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Adrenocorticoids amp Adrenocorticoids amp adrenocortical adrenocortical
antagonists antagonists
Huifang TangEmail tanghuifangzjueducn
History(1)bull In 1849 In 1849 AddisonAddison first appreciated the importance of the adrenal first appreciated the importance of the adrenal
glandsglands
bull Addison T On the Constitutional and Local Effects of Disease of the Supra-renal Capsules LoAddison T On the Constitutional and Local Effects of Disease of the Supra-renal Capsules London UK Samuel Highley 1855 ndon UK Samuel Highley 1855
Structure and function of adrenal Structure and function of adrenal cortexcortex
ZonaZonaReticularisReticularis
AdrenalineAdrenaline
ZonaZonaFaseciculataFaseciculata
AndrogensAndrogens
bull Adrenocortical Adrenocortical hormoneshormones
bull MineralocorticoidsMineralocorticoids aldosteron aldosteronee
bull Glucocorticoids Glucocorticoids (Glucocorticosteroids)(Glucocorticosteroids) cortisol cortisol
bull Sex hormonesSex hormones androgens androgens
History(2)bull As early as 1912 Cushing described
patients with hypercorticism and later recongized that pituitary basophilism represented the cause of the adrenal overactivity
History(3)
bull In 1948 the role of hypothalamus in pituitary control was established by Harris
bull In 1949 Hench and colleagues demonstrated the dramatic effect of glucocorticoids and ACTH in the treatment of rheumatoid arthritis
ContentsContents
bull AA Glucocorticoid drugs Glucocorticoid drugsbull BB Mineralocorticoid drugsMineralocorticoid drugsbull CC ACTH and corticosteroid ACTH and corticosteroid
synthetase inhibitorssynthetase inhibitors
Basic structure of glucocorticoid Basic structure of glucocorticoid drugsdrugs
AA BB
CC DD
甾甾
甾体结构甾体结构
HH
AA Glucocorticoid drugs Glucocorticoid drugs
Structure and Activity Structure and Activity RelationshipRelationship(1)1(1)1 位和位和 22 位碳之间改成不饱和的双键位碳之间改成不饱和的双键 cortisone cortisone prednisone prednisone hydrocortisone hydrocortisone prednisolone prednisolone(2)16(2)16 引入羟基引入羟基 triamcinolone(triamcinolone( 曲安西龙曲安西龙 ))(3)6(3)6 引入甲基引入甲基 66-methylprednisone-methylprednisone (6(6 甲基泼尼松甲基泼尼松 ))(4)9(4)9 引入氟原子引入氟原子 fludrocortosonefludrocortosone (( 氟氢可的松氟氢可的松 ))
11 22
33 44
5566 77
881010 99
121213131414 1515
1616 1818
1919
AA BB
CC DD
基本结构基本结构
HH
AA Glucocorticoid drugs Glucocorticoid drugs
HH
Cortisone( 可的松 )
Prednisone( 泼尼松 )
(( 地塞米地塞米松松 ))
Hydrocortisone( 氢化可的松
Cortisol)
Prednisolone( 泼尼松龙 )
Fluocinolone( 氟轻松 )
HH
Mechanisms of glucocorticoid Mechanisms of glucocorticoid actionsactions
binding to glucocorticoid receptor binding to glucocorticoid receptor (GR) (GR)
nuclear translocationnuclear translocation
binding to GRE or nGREbinding to GRE or nGRE
regulating related gene regulating related gene transcriptiontranscription
biological effects (usually slow) biological effects (usually slow)
AA Glucocorticoid drugs
Action mode of glucocorticoid drugs
CBG corticosteroid binding globulin
S glucocorticoid steroids
GR glucocorticoid receptor
HSP heat shock protein
IP immunophilin
GRE glucocorticoid-response element
Nuclear translocation of glucocorticoid receptors (GR)
Dexamethasone was used
GR was labeled with green fluorescent protein
1 Pharmacological effects
Mechanisms of glucocorticoid actions(1) Effects on metabolisms (2) Permissive action(3) Anti-inflammatory effects(4) Effects on immune and allergy (5) Anti-shock(6) Other effects antipyretic effects effects on blood and blood-forming organs skeletal system CNS effects
AA Glucocorticoid drugs Glucocorticoid drugs
(1) Effects on metabolisms
①Glucose metabolism gluconeogenesis glucose
utilization blood glucose ②Protein metabolism synthesis degradation ③Lipid metabolism plasma cholesterol fat
redistribution (central obesity moon face buffalo hump etc)
④Water and electrolytic metabolism
water excretion Na+ excretion
K+ excretion Ca2+ excretion and absorption
AA Glucocorticoid drugs Glucocorticoid drugs
Weaker action of glucocorticoid drugs (cortisol) on mineralocorticoid receptor
(2) Permissive actionPotentiating the effects of catecholamines and
glucagon (3) Anti-inflammatory effectsAcute inhibiting microvascular leakage leukocyte infiltrationChronic inhibiting fibroblast proliferation deposition of collagen cicatrization ( 瘢痕形成 )
AA Glucocorticoid drugs Glucocorticoid drugs
One of glucocorticoidrsquos anti-inflammatory actions
Inhibition of proinflammatory gene transcription (AP-1 and NFB)
AA Glucocorticoid drugs Glucocorticoid drugs
a) Increasing inflammation related proteins or enzymes
inducing lipocortin inhibiting phospholipase A2 activity decreasing mediators PGs LTs PAF
inducing vasocortin decreasing microvascular permeability
inhibiting the expression of PLA2 COX-2 inducible NOS etc
b) Inhibiting cytokinins decreasing the transcription and activities of TNFα IL-1 IL-2 IL-5 IL-6 IL-8 etc
c) Inhibiting adhesion molecules
d) Inducing the apoptosis of inflammatory cells
AA Glucocorticoid drugs Glucocorticoid drugs
(4) Effects on immune and allergy
Suppressing immunological functions and allergy
a) inducing apoptosis of T and B lymphocytes
b) inhibiting transcription factor activity(eg AP-1 NFB)
AA Glucocorticoid drugs Glucocorticoid drugs
(5) Anti-shock Septic shock
a) improving cardiovascular functions
b) inhibiting the production of inflammatory factors
c) stabilizing lysosome membrane decreasing the release of myocardial depressant factor (MDF)
d) increasing the tolerance to endotoxin from bacteria
AA Glucocorticoid drugs Glucocorticoid drugs
(6) Other effects
a) antipyretic effects
b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )
eosinophils platelets
c) skeletal system osteoporosis
d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)
AA Glucocorticoid drugs Glucocorticoid drugs
2 ADME and properties of commonly used drugs
Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver
Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)
AA Glucocorticoid drugs Glucocorticoid drugs
Commonly used drugs
Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松
Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙
Long-acting dexamethasone 地塞米松
Topical fluocinolone 氟轻松
AA Glucocorticoid drugs Glucocorticoid drugs
CortisonCortisonee
可的松可的松
HydrocortisoHydrocortisonene
氢化可的松氢化可的松
CortisolCortisol
PrednisoPrednisonene
泼尼松泼尼松
PrednisolPrednisoloneone
泼尼松龙泼尼松龙
FluocinoloFluocinolonene
氟轻松氟轻松地塞米松地塞米松
HH
3 Clinical uses
(1) Immune diseases
a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc
b) rejection of organ transplantation
c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc
AA Glucocorticoid drugs Glucocorticoid drugs
(2) Severe infection and inflammation
a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving
Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration
Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms
b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc
AA Glucocorticoid drugsGlucocorticoid drugs
(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined
with antimicrobial drugswith antimicrobial drugs
(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc
(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)
(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc
AA Glucocorticoid drugs
4 Adverse effects of glucocorticoid
drugs
Effects resulting from continued used of large doses
AA Glucocorticoid drugs
4 Adverse effects
(1) Effects resulting from continued used of large doses
a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc
b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be
administered with GCs
c) Ingestive system peptic ulcers etc
AA Glucocorticoid drugsGlucocorticoid drugs
d) Cardiovascular system hypertension arteriosclerosis
e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women
f) CNS behavioral disturbances induction of epileptic seizures
g) Inhibition or arrest of growth in children
AA Glucocorticoid drugsGlucocorticoid drugs
Suppression of hypothalamic-pituitary-adrenal axis
and glucocorticoid drugs
‒‒
ACTH
(2) Withdrawal syndrome
a) Suppression of hypothalamic-pituitary-adrenal axis
b) Exacerbation of the underlying diseases (rebound)
(3) Contraindications
psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc
AA Glucocorticoid drugs Glucocorticoid drugs
Balance the ratio of benefit risk before the use of GCs
AA Glucocorticoid drugsGlucocorticoid drugs
5 Applications
(1) Replacement therapy usually using hydrocortisone
(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone
(3) Long-term therapy oral prednisone or prednisolone
morning single dose
alternate-day therapy
Notes for less severe and less sustained patients
less suppression on hypothalamic-pituitary-adrenal (HPA) axis
(4) Tipical applications skin eye respiratory tract
AA Glucocorticoid drugsGlucocorticoid drugs
bull Aldosterone 醛固酮
bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of
water and electrolytes
BB Mineralocorticoid drugsMineralocorticoid drugs
Action of aldosterone on mineralocorticoid receptor
Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein
AIP
bull 1 Adrenocorticotropic hormone (ACTH)
bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of
adrenocortical hoemones after long-term glucocorticoid drug use
bull Easily inducing allergy to ACTH
CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase
inhibitorsinhibitors
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response
ndash plasma cortisol levels are elevated
bull Abnormal responsendash plasma cortisol level are unchanged
bull 2 Corticosteroid synthetase inhibitors
bull Mitotane 米托坦
bull Metyrapone 美替拉酮
bull Aminoglutethimide 氨鲁米特
bull Used for adrenocortical tumors or hypercorticism
C Adrenocorticotropic hormone and corticosteroid synthetase
inhibitors
Cortisol Suppression Tests
bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
History(1)bull In 1849 In 1849 AddisonAddison first appreciated the importance of the adrenal first appreciated the importance of the adrenal
glandsglands
bull Addison T On the Constitutional and Local Effects of Disease of the Supra-renal Capsules LoAddison T On the Constitutional and Local Effects of Disease of the Supra-renal Capsules London UK Samuel Highley 1855 ndon UK Samuel Highley 1855
Structure and function of adrenal Structure and function of adrenal cortexcortex
ZonaZonaReticularisReticularis
AdrenalineAdrenaline
ZonaZonaFaseciculataFaseciculata
AndrogensAndrogens
bull Adrenocortical Adrenocortical hormoneshormones
bull MineralocorticoidsMineralocorticoids aldosteron aldosteronee
bull Glucocorticoids Glucocorticoids (Glucocorticosteroids)(Glucocorticosteroids) cortisol cortisol
bull Sex hormonesSex hormones androgens androgens
History(2)bull As early as 1912 Cushing described
patients with hypercorticism and later recongized that pituitary basophilism represented the cause of the adrenal overactivity
History(3)
bull In 1948 the role of hypothalamus in pituitary control was established by Harris
bull In 1949 Hench and colleagues demonstrated the dramatic effect of glucocorticoids and ACTH in the treatment of rheumatoid arthritis
ContentsContents
bull AA Glucocorticoid drugs Glucocorticoid drugsbull BB Mineralocorticoid drugsMineralocorticoid drugsbull CC ACTH and corticosteroid ACTH and corticosteroid
synthetase inhibitorssynthetase inhibitors
Basic structure of glucocorticoid Basic structure of glucocorticoid drugsdrugs
AA BB
CC DD
甾甾
甾体结构甾体结构
HH
AA Glucocorticoid drugs Glucocorticoid drugs
Structure and Activity Structure and Activity RelationshipRelationship(1)1(1)1 位和位和 22 位碳之间改成不饱和的双键位碳之间改成不饱和的双键 cortisone cortisone prednisone prednisone hydrocortisone hydrocortisone prednisolone prednisolone(2)16(2)16 引入羟基引入羟基 triamcinolone(triamcinolone( 曲安西龙曲安西龙 ))(3)6(3)6 引入甲基引入甲基 66-methylprednisone-methylprednisone (6(6 甲基泼尼松甲基泼尼松 ))(4)9(4)9 引入氟原子引入氟原子 fludrocortosonefludrocortosone (( 氟氢可的松氟氢可的松 ))
11 22
33 44
5566 77
881010 99
121213131414 1515
1616 1818
1919
AA BB
CC DD
基本结构基本结构
HH
AA Glucocorticoid drugs Glucocorticoid drugs
HH
Cortisone( 可的松 )
Prednisone( 泼尼松 )
(( 地塞米地塞米松松 ))
Hydrocortisone( 氢化可的松
Cortisol)
Prednisolone( 泼尼松龙 )
Fluocinolone( 氟轻松 )
HH
Mechanisms of glucocorticoid Mechanisms of glucocorticoid actionsactions
binding to glucocorticoid receptor binding to glucocorticoid receptor (GR) (GR)
nuclear translocationnuclear translocation
binding to GRE or nGREbinding to GRE or nGRE
regulating related gene regulating related gene transcriptiontranscription
biological effects (usually slow) biological effects (usually slow)
AA Glucocorticoid drugs
Action mode of glucocorticoid drugs
CBG corticosteroid binding globulin
S glucocorticoid steroids
GR glucocorticoid receptor
HSP heat shock protein
IP immunophilin
GRE glucocorticoid-response element
Nuclear translocation of glucocorticoid receptors (GR)
Dexamethasone was used
GR was labeled with green fluorescent protein
1 Pharmacological effects
Mechanisms of glucocorticoid actions(1) Effects on metabolisms (2) Permissive action(3) Anti-inflammatory effects(4) Effects on immune and allergy (5) Anti-shock(6) Other effects antipyretic effects effects on blood and blood-forming organs skeletal system CNS effects
AA Glucocorticoid drugs Glucocorticoid drugs
(1) Effects on metabolisms
①Glucose metabolism gluconeogenesis glucose
utilization blood glucose ②Protein metabolism synthesis degradation ③Lipid metabolism plasma cholesterol fat
redistribution (central obesity moon face buffalo hump etc)
④Water and electrolytic metabolism
water excretion Na+ excretion
K+ excretion Ca2+ excretion and absorption
AA Glucocorticoid drugs Glucocorticoid drugs
Weaker action of glucocorticoid drugs (cortisol) on mineralocorticoid receptor
(2) Permissive actionPotentiating the effects of catecholamines and
glucagon (3) Anti-inflammatory effectsAcute inhibiting microvascular leakage leukocyte infiltrationChronic inhibiting fibroblast proliferation deposition of collagen cicatrization ( 瘢痕形成 )
AA Glucocorticoid drugs Glucocorticoid drugs
One of glucocorticoidrsquos anti-inflammatory actions
Inhibition of proinflammatory gene transcription (AP-1 and NFB)
AA Glucocorticoid drugs Glucocorticoid drugs
a) Increasing inflammation related proteins or enzymes
inducing lipocortin inhibiting phospholipase A2 activity decreasing mediators PGs LTs PAF
inducing vasocortin decreasing microvascular permeability
inhibiting the expression of PLA2 COX-2 inducible NOS etc
b) Inhibiting cytokinins decreasing the transcription and activities of TNFα IL-1 IL-2 IL-5 IL-6 IL-8 etc
c) Inhibiting adhesion molecules
d) Inducing the apoptosis of inflammatory cells
AA Glucocorticoid drugs Glucocorticoid drugs
(4) Effects on immune and allergy
Suppressing immunological functions and allergy
a) inducing apoptosis of T and B lymphocytes
b) inhibiting transcription factor activity(eg AP-1 NFB)
AA Glucocorticoid drugs Glucocorticoid drugs
(5) Anti-shock Septic shock
a) improving cardiovascular functions
b) inhibiting the production of inflammatory factors
c) stabilizing lysosome membrane decreasing the release of myocardial depressant factor (MDF)
d) increasing the tolerance to endotoxin from bacteria
AA Glucocorticoid drugs Glucocorticoid drugs
(6) Other effects
a) antipyretic effects
b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )
eosinophils platelets
c) skeletal system osteoporosis
d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)
AA Glucocorticoid drugs Glucocorticoid drugs
2 ADME and properties of commonly used drugs
Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver
Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)
AA Glucocorticoid drugs Glucocorticoid drugs
Commonly used drugs
Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松
Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙
Long-acting dexamethasone 地塞米松
Topical fluocinolone 氟轻松
AA Glucocorticoid drugs Glucocorticoid drugs
CortisonCortisonee
可的松可的松
HydrocortisoHydrocortisonene
氢化可的松氢化可的松
CortisolCortisol
PrednisoPrednisonene
泼尼松泼尼松
PrednisolPrednisoloneone
泼尼松龙泼尼松龙
FluocinoloFluocinolonene
氟轻松氟轻松地塞米松地塞米松
HH
3 Clinical uses
(1) Immune diseases
a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc
b) rejection of organ transplantation
c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc
AA Glucocorticoid drugs Glucocorticoid drugs
(2) Severe infection and inflammation
a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving
Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration
Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms
b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc
AA Glucocorticoid drugsGlucocorticoid drugs
(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined
with antimicrobial drugswith antimicrobial drugs
(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc
(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)
(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc
AA Glucocorticoid drugs
4 Adverse effects of glucocorticoid
drugs
Effects resulting from continued used of large doses
AA Glucocorticoid drugs
4 Adverse effects
(1) Effects resulting from continued used of large doses
a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc
b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be
administered with GCs
c) Ingestive system peptic ulcers etc
AA Glucocorticoid drugsGlucocorticoid drugs
d) Cardiovascular system hypertension arteriosclerosis
e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women
f) CNS behavioral disturbances induction of epileptic seizures
g) Inhibition or arrest of growth in children
AA Glucocorticoid drugsGlucocorticoid drugs
Suppression of hypothalamic-pituitary-adrenal axis
and glucocorticoid drugs
‒‒
ACTH
(2) Withdrawal syndrome
a) Suppression of hypothalamic-pituitary-adrenal axis
b) Exacerbation of the underlying diseases (rebound)
(3) Contraindications
psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc
AA Glucocorticoid drugs Glucocorticoid drugs
Balance the ratio of benefit risk before the use of GCs
AA Glucocorticoid drugsGlucocorticoid drugs
5 Applications
(1) Replacement therapy usually using hydrocortisone
(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone
(3) Long-term therapy oral prednisone or prednisolone
morning single dose
alternate-day therapy
Notes for less severe and less sustained patients
less suppression on hypothalamic-pituitary-adrenal (HPA) axis
(4) Tipical applications skin eye respiratory tract
AA Glucocorticoid drugsGlucocorticoid drugs
bull Aldosterone 醛固酮
bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of
water and electrolytes
BB Mineralocorticoid drugsMineralocorticoid drugs
Action of aldosterone on mineralocorticoid receptor
Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein
AIP
bull 1 Adrenocorticotropic hormone (ACTH)
bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of
adrenocortical hoemones after long-term glucocorticoid drug use
bull Easily inducing allergy to ACTH
CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase
inhibitorsinhibitors
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response
ndash plasma cortisol levels are elevated
bull Abnormal responsendash plasma cortisol level are unchanged
bull 2 Corticosteroid synthetase inhibitors
bull Mitotane 米托坦
bull Metyrapone 美替拉酮
bull Aminoglutethimide 氨鲁米特
bull Used for adrenocortical tumors or hypercorticism
C Adrenocorticotropic hormone and corticosteroid synthetase
inhibitors
Cortisol Suppression Tests
bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
Structure and function of adrenal Structure and function of adrenal cortexcortex
ZonaZonaReticularisReticularis
AdrenalineAdrenaline
ZonaZonaFaseciculataFaseciculata
AndrogensAndrogens
bull Adrenocortical Adrenocortical hormoneshormones
bull MineralocorticoidsMineralocorticoids aldosteron aldosteronee
bull Glucocorticoids Glucocorticoids (Glucocorticosteroids)(Glucocorticosteroids) cortisol cortisol
bull Sex hormonesSex hormones androgens androgens
History(2)bull As early as 1912 Cushing described
patients with hypercorticism and later recongized that pituitary basophilism represented the cause of the adrenal overactivity
History(3)
bull In 1948 the role of hypothalamus in pituitary control was established by Harris
bull In 1949 Hench and colleagues demonstrated the dramatic effect of glucocorticoids and ACTH in the treatment of rheumatoid arthritis
ContentsContents
bull AA Glucocorticoid drugs Glucocorticoid drugsbull BB Mineralocorticoid drugsMineralocorticoid drugsbull CC ACTH and corticosteroid ACTH and corticosteroid
synthetase inhibitorssynthetase inhibitors
Basic structure of glucocorticoid Basic structure of glucocorticoid drugsdrugs
AA BB
CC DD
甾甾
甾体结构甾体结构
HH
AA Glucocorticoid drugs Glucocorticoid drugs
Structure and Activity Structure and Activity RelationshipRelationship(1)1(1)1 位和位和 22 位碳之间改成不饱和的双键位碳之间改成不饱和的双键 cortisone cortisone prednisone prednisone hydrocortisone hydrocortisone prednisolone prednisolone(2)16(2)16 引入羟基引入羟基 triamcinolone(triamcinolone( 曲安西龙曲安西龙 ))(3)6(3)6 引入甲基引入甲基 66-methylprednisone-methylprednisone (6(6 甲基泼尼松甲基泼尼松 ))(4)9(4)9 引入氟原子引入氟原子 fludrocortosonefludrocortosone (( 氟氢可的松氟氢可的松 ))
11 22
33 44
5566 77
881010 99
121213131414 1515
1616 1818
1919
AA BB
CC DD
基本结构基本结构
HH
AA Glucocorticoid drugs Glucocorticoid drugs
HH
Cortisone( 可的松 )
Prednisone( 泼尼松 )
(( 地塞米地塞米松松 ))
Hydrocortisone( 氢化可的松
Cortisol)
Prednisolone( 泼尼松龙 )
Fluocinolone( 氟轻松 )
HH
Mechanisms of glucocorticoid Mechanisms of glucocorticoid actionsactions
binding to glucocorticoid receptor binding to glucocorticoid receptor (GR) (GR)
nuclear translocationnuclear translocation
binding to GRE or nGREbinding to GRE or nGRE
regulating related gene regulating related gene transcriptiontranscription
biological effects (usually slow) biological effects (usually slow)
AA Glucocorticoid drugs
Action mode of glucocorticoid drugs
CBG corticosteroid binding globulin
S glucocorticoid steroids
GR glucocorticoid receptor
HSP heat shock protein
IP immunophilin
GRE glucocorticoid-response element
Nuclear translocation of glucocorticoid receptors (GR)
Dexamethasone was used
GR was labeled with green fluorescent protein
1 Pharmacological effects
Mechanisms of glucocorticoid actions(1) Effects on metabolisms (2) Permissive action(3) Anti-inflammatory effects(4) Effects on immune and allergy (5) Anti-shock(6) Other effects antipyretic effects effects on blood and blood-forming organs skeletal system CNS effects
AA Glucocorticoid drugs Glucocorticoid drugs
(1) Effects on metabolisms
①Glucose metabolism gluconeogenesis glucose
utilization blood glucose ②Protein metabolism synthesis degradation ③Lipid metabolism plasma cholesterol fat
redistribution (central obesity moon face buffalo hump etc)
④Water and electrolytic metabolism
water excretion Na+ excretion
K+ excretion Ca2+ excretion and absorption
AA Glucocorticoid drugs Glucocorticoid drugs
Weaker action of glucocorticoid drugs (cortisol) on mineralocorticoid receptor
(2) Permissive actionPotentiating the effects of catecholamines and
glucagon (3) Anti-inflammatory effectsAcute inhibiting microvascular leakage leukocyte infiltrationChronic inhibiting fibroblast proliferation deposition of collagen cicatrization ( 瘢痕形成 )
AA Glucocorticoid drugs Glucocorticoid drugs
One of glucocorticoidrsquos anti-inflammatory actions
Inhibition of proinflammatory gene transcription (AP-1 and NFB)
AA Glucocorticoid drugs Glucocorticoid drugs
a) Increasing inflammation related proteins or enzymes
inducing lipocortin inhibiting phospholipase A2 activity decreasing mediators PGs LTs PAF
inducing vasocortin decreasing microvascular permeability
inhibiting the expression of PLA2 COX-2 inducible NOS etc
b) Inhibiting cytokinins decreasing the transcription and activities of TNFα IL-1 IL-2 IL-5 IL-6 IL-8 etc
c) Inhibiting adhesion molecules
d) Inducing the apoptosis of inflammatory cells
AA Glucocorticoid drugs Glucocorticoid drugs
(4) Effects on immune and allergy
Suppressing immunological functions and allergy
a) inducing apoptosis of T and B lymphocytes
b) inhibiting transcription factor activity(eg AP-1 NFB)
AA Glucocorticoid drugs Glucocorticoid drugs
(5) Anti-shock Septic shock
a) improving cardiovascular functions
b) inhibiting the production of inflammatory factors
c) stabilizing lysosome membrane decreasing the release of myocardial depressant factor (MDF)
d) increasing the tolerance to endotoxin from bacteria
AA Glucocorticoid drugs Glucocorticoid drugs
(6) Other effects
a) antipyretic effects
b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )
eosinophils platelets
c) skeletal system osteoporosis
d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)
AA Glucocorticoid drugs Glucocorticoid drugs
2 ADME and properties of commonly used drugs
Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver
Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)
AA Glucocorticoid drugs Glucocorticoid drugs
Commonly used drugs
Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松
Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙
Long-acting dexamethasone 地塞米松
Topical fluocinolone 氟轻松
AA Glucocorticoid drugs Glucocorticoid drugs
CortisonCortisonee
可的松可的松
HydrocortisoHydrocortisonene
氢化可的松氢化可的松
CortisolCortisol
PrednisoPrednisonene
泼尼松泼尼松
PrednisolPrednisoloneone
泼尼松龙泼尼松龙
FluocinoloFluocinolonene
氟轻松氟轻松地塞米松地塞米松
HH
3 Clinical uses
(1) Immune diseases
a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc
b) rejection of organ transplantation
c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc
AA Glucocorticoid drugs Glucocorticoid drugs
(2) Severe infection and inflammation
a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving
Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration
Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms
b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc
AA Glucocorticoid drugsGlucocorticoid drugs
(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined
with antimicrobial drugswith antimicrobial drugs
(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc
(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)
(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc
AA Glucocorticoid drugs
4 Adverse effects of glucocorticoid
drugs
Effects resulting from continued used of large doses
AA Glucocorticoid drugs
4 Adverse effects
(1) Effects resulting from continued used of large doses
a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc
b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be
administered with GCs
c) Ingestive system peptic ulcers etc
AA Glucocorticoid drugsGlucocorticoid drugs
d) Cardiovascular system hypertension arteriosclerosis
e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women
f) CNS behavioral disturbances induction of epileptic seizures
g) Inhibition or arrest of growth in children
AA Glucocorticoid drugsGlucocorticoid drugs
Suppression of hypothalamic-pituitary-adrenal axis
and glucocorticoid drugs
‒‒
ACTH
(2) Withdrawal syndrome
a) Suppression of hypothalamic-pituitary-adrenal axis
b) Exacerbation of the underlying diseases (rebound)
(3) Contraindications
psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc
AA Glucocorticoid drugs Glucocorticoid drugs
Balance the ratio of benefit risk before the use of GCs
AA Glucocorticoid drugsGlucocorticoid drugs
5 Applications
(1) Replacement therapy usually using hydrocortisone
(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone
(3) Long-term therapy oral prednisone or prednisolone
morning single dose
alternate-day therapy
Notes for less severe and less sustained patients
less suppression on hypothalamic-pituitary-adrenal (HPA) axis
(4) Tipical applications skin eye respiratory tract
AA Glucocorticoid drugsGlucocorticoid drugs
bull Aldosterone 醛固酮
bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of
water and electrolytes
BB Mineralocorticoid drugsMineralocorticoid drugs
Action of aldosterone on mineralocorticoid receptor
Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein
AIP
bull 1 Adrenocorticotropic hormone (ACTH)
bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of
adrenocortical hoemones after long-term glucocorticoid drug use
bull Easily inducing allergy to ACTH
CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase
inhibitorsinhibitors
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response
ndash plasma cortisol levels are elevated
bull Abnormal responsendash plasma cortisol level are unchanged
bull 2 Corticosteroid synthetase inhibitors
bull Mitotane 米托坦
bull Metyrapone 美替拉酮
bull Aminoglutethimide 氨鲁米特
bull Used for adrenocortical tumors or hypercorticism
C Adrenocorticotropic hormone and corticosteroid synthetase
inhibitors
Cortisol Suppression Tests
bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
bull Adrenocortical Adrenocortical hormoneshormones
bull MineralocorticoidsMineralocorticoids aldosteron aldosteronee
bull Glucocorticoids Glucocorticoids (Glucocorticosteroids)(Glucocorticosteroids) cortisol cortisol
bull Sex hormonesSex hormones androgens androgens
History(2)bull As early as 1912 Cushing described
patients with hypercorticism and later recongized that pituitary basophilism represented the cause of the adrenal overactivity
History(3)
bull In 1948 the role of hypothalamus in pituitary control was established by Harris
bull In 1949 Hench and colleagues demonstrated the dramatic effect of glucocorticoids and ACTH in the treatment of rheumatoid arthritis
ContentsContents
bull AA Glucocorticoid drugs Glucocorticoid drugsbull BB Mineralocorticoid drugsMineralocorticoid drugsbull CC ACTH and corticosteroid ACTH and corticosteroid
synthetase inhibitorssynthetase inhibitors
Basic structure of glucocorticoid Basic structure of glucocorticoid drugsdrugs
AA BB
CC DD
甾甾
甾体结构甾体结构
HH
AA Glucocorticoid drugs Glucocorticoid drugs
Structure and Activity Structure and Activity RelationshipRelationship(1)1(1)1 位和位和 22 位碳之间改成不饱和的双键位碳之间改成不饱和的双键 cortisone cortisone prednisone prednisone hydrocortisone hydrocortisone prednisolone prednisolone(2)16(2)16 引入羟基引入羟基 triamcinolone(triamcinolone( 曲安西龙曲安西龙 ))(3)6(3)6 引入甲基引入甲基 66-methylprednisone-methylprednisone (6(6 甲基泼尼松甲基泼尼松 ))(4)9(4)9 引入氟原子引入氟原子 fludrocortosonefludrocortosone (( 氟氢可的松氟氢可的松 ))
11 22
33 44
5566 77
881010 99
121213131414 1515
1616 1818
1919
AA BB
CC DD
基本结构基本结构
HH
AA Glucocorticoid drugs Glucocorticoid drugs
HH
Cortisone( 可的松 )
Prednisone( 泼尼松 )
(( 地塞米地塞米松松 ))
Hydrocortisone( 氢化可的松
Cortisol)
Prednisolone( 泼尼松龙 )
Fluocinolone( 氟轻松 )
HH
Mechanisms of glucocorticoid Mechanisms of glucocorticoid actionsactions
binding to glucocorticoid receptor binding to glucocorticoid receptor (GR) (GR)
nuclear translocationnuclear translocation
binding to GRE or nGREbinding to GRE or nGRE
regulating related gene regulating related gene transcriptiontranscription
biological effects (usually slow) biological effects (usually slow)
AA Glucocorticoid drugs
Action mode of glucocorticoid drugs
CBG corticosteroid binding globulin
S glucocorticoid steroids
GR glucocorticoid receptor
HSP heat shock protein
IP immunophilin
GRE glucocorticoid-response element
Nuclear translocation of glucocorticoid receptors (GR)
Dexamethasone was used
GR was labeled with green fluorescent protein
1 Pharmacological effects
Mechanisms of glucocorticoid actions(1) Effects on metabolisms (2) Permissive action(3) Anti-inflammatory effects(4) Effects on immune and allergy (5) Anti-shock(6) Other effects antipyretic effects effects on blood and blood-forming organs skeletal system CNS effects
AA Glucocorticoid drugs Glucocorticoid drugs
(1) Effects on metabolisms
①Glucose metabolism gluconeogenesis glucose
utilization blood glucose ②Protein metabolism synthesis degradation ③Lipid metabolism plasma cholesterol fat
redistribution (central obesity moon face buffalo hump etc)
④Water and electrolytic metabolism
water excretion Na+ excretion
K+ excretion Ca2+ excretion and absorption
AA Glucocorticoid drugs Glucocorticoid drugs
Weaker action of glucocorticoid drugs (cortisol) on mineralocorticoid receptor
(2) Permissive actionPotentiating the effects of catecholamines and
glucagon (3) Anti-inflammatory effectsAcute inhibiting microvascular leakage leukocyte infiltrationChronic inhibiting fibroblast proliferation deposition of collagen cicatrization ( 瘢痕形成 )
AA Glucocorticoid drugs Glucocorticoid drugs
One of glucocorticoidrsquos anti-inflammatory actions
Inhibition of proinflammatory gene transcription (AP-1 and NFB)
AA Glucocorticoid drugs Glucocorticoid drugs
a) Increasing inflammation related proteins or enzymes
inducing lipocortin inhibiting phospholipase A2 activity decreasing mediators PGs LTs PAF
inducing vasocortin decreasing microvascular permeability
inhibiting the expression of PLA2 COX-2 inducible NOS etc
b) Inhibiting cytokinins decreasing the transcription and activities of TNFα IL-1 IL-2 IL-5 IL-6 IL-8 etc
c) Inhibiting adhesion molecules
d) Inducing the apoptosis of inflammatory cells
AA Glucocorticoid drugs Glucocorticoid drugs
(4) Effects on immune and allergy
Suppressing immunological functions and allergy
a) inducing apoptosis of T and B lymphocytes
b) inhibiting transcription factor activity(eg AP-1 NFB)
AA Glucocorticoid drugs Glucocorticoid drugs
(5) Anti-shock Septic shock
a) improving cardiovascular functions
b) inhibiting the production of inflammatory factors
c) stabilizing lysosome membrane decreasing the release of myocardial depressant factor (MDF)
d) increasing the tolerance to endotoxin from bacteria
AA Glucocorticoid drugs Glucocorticoid drugs
(6) Other effects
a) antipyretic effects
b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )
eosinophils platelets
c) skeletal system osteoporosis
d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)
AA Glucocorticoid drugs Glucocorticoid drugs
2 ADME and properties of commonly used drugs
Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver
Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)
AA Glucocorticoid drugs Glucocorticoid drugs
Commonly used drugs
Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松
Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙
Long-acting dexamethasone 地塞米松
Topical fluocinolone 氟轻松
AA Glucocorticoid drugs Glucocorticoid drugs
CortisonCortisonee
可的松可的松
HydrocortisoHydrocortisonene
氢化可的松氢化可的松
CortisolCortisol
PrednisoPrednisonene
泼尼松泼尼松
PrednisolPrednisoloneone
泼尼松龙泼尼松龙
FluocinoloFluocinolonene
氟轻松氟轻松地塞米松地塞米松
HH
3 Clinical uses
(1) Immune diseases
a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc
b) rejection of organ transplantation
c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc
AA Glucocorticoid drugs Glucocorticoid drugs
(2) Severe infection and inflammation
a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving
Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration
Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms
b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc
AA Glucocorticoid drugsGlucocorticoid drugs
(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined
with antimicrobial drugswith antimicrobial drugs
(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc
(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)
(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc
AA Glucocorticoid drugs
4 Adverse effects of glucocorticoid
drugs
Effects resulting from continued used of large doses
AA Glucocorticoid drugs
4 Adverse effects
(1) Effects resulting from continued used of large doses
a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc
b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be
administered with GCs
c) Ingestive system peptic ulcers etc
AA Glucocorticoid drugsGlucocorticoid drugs
d) Cardiovascular system hypertension arteriosclerosis
e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women
f) CNS behavioral disturbances induction of epileptic seizures
g) Inhibition or arrest of growth in children
AA Glucocorticoid drugsGlucocorticoid drugs
Suppression of hypothalamic-pituitary-adrenal axis
and glucocorticoid drugs
‒‒
ACTH
(2) Withdrawal syndrome
a) Suppression of hypothalamic-pituitary-adrenal axis
b) Exacerbation of the underlying diseases (rebound)
(3) Contraindications
psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc
AA Glucocorticoid drugs Glucocorticoid drugs
Balance the ratio of benefit risk before the use of GCs
AA Glucocorticoid drugsGlucocorticoid drugs
5 Applications
(1) Replacement therapy usually using hydrocortisone
(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone
(3) Long-term therapy oral prednisone or prednisolone
morning single dose
alternate-day therapy
Notes for less severe and less sustained patients
less suppression on hypothalamic-pituitary-adrenal (HPA) axis
(4) Tipical applications skin eye respiratory tract
AA Glucocorticoid drugsGlucocorticoid drugs
bull Aldosterone 醛固酮
bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of
water and electrolytes
BB Mineralocorticoid drugsMineralocorticoid drugs
Action of aldosterone on mineralocorticoid receptor
Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein
AIP
bull 1 Adrenocorticotropic hormone (ACTH)
bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of
adrenocortical hoemones after long-term glucocorticoid drug use
bull Easily inducing allergy to ACTH
CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase
inhibitorsinhibitors
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response
ndash plasma cortisol levels are elevated
bull Abnormal responsendash plasma cortisol level are unchanged
bull 2 Corticosteroid synthetase inhibitors
bull Mitotane 米托坦
bull Metyrapone 美替拉酮
bull Aminoglutethimide 氨鲁米特
bull Used for adrenocortical tumors or hypercorticism
C Adrenocorticotropic hormone and corticosteroid synthetase
inhibitors
Cortisol Suppression Tests
bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
History(2)bull As early as 1912 Cushing described
patients with hypercorticism and later recongized that pituitary basophilism represented the cause of the adrenal overactivity
History(3)
bull In 1948 the role of hypothalamus in pituitary control was established by Harris
bull In 1949 Hench and colleagues demonstrated the dramatic effect of glucocorticoids and ACTH in the treatment of rheumatoid arthritis
ContentsContents
bull AA Glucocorticoid drugs Glucocorticoid drugsbull BB Mineralocorticoid drugsMineralocorticoid drugsbull CC ACTH and corticosteroid ACTH and corticosteroid
synthetase inhibitorssynthetase inhibitors
Basic structure of glucocorticoid Basic structure of glucocorticoid drugsdrugs
AA BB
CC DD
甾甾
甾体结构甾体结构
HH
AA Glucocorticoid drugs Glucocorticoid drugs
Structure and Activity Structure and Activity RelationshipRelationship(1)1(1)1 位和位和 22 位碳之间改成不饱和的双键位碳之间改成不饱和的双键 cortisone cortisone prednisone prednisone hydrocortisone hydrocortisone prednisolone prednisolone(2)16(2)16 引入羟基引入羟基 triamcinolone(triamcinolone( 曲安西龙曲安西龙 ))(3)6(3)6 引入甲基引入甲基 66-methylprednisone-methylprednisone (6(6 甲基泼尼松甲基泼尼松 ))(4)9(4)9 引入氟原子引入氟原子 fludrocortosonefludrocortosone (( 氟氢可的松氟氢可的松 ))
11 22
33 44
5566 77
881010 99
121213131414 1515
1616 1818
1919
AA BB
CC DD
基本结构基本结构
HH
AA Glucocorticoid drugs Glucocorticoid drugs
HH
Cortisone( 可的松 )
Prednisone( 泼尼松 )
(( 地塞米地塞米松松 ))
Hydrocortisone( 氢化可的松
Cortisol)
Prednisolone( 泼尼松龙 )
Fluocinolone( 氟轻松 )
HH
Mechanisms of glucocorticoid Mechanisms of glucocorticoid actionsactions
binding to glucocorticoid receptor binding to glucocorticoid receptor (GR) (GR)
nuclear translocationnuclear translocation
binding to GRE or nGREbinding to GRE or nGRE
regulating related gene regulating related gene transcriptiontranscription
biological effects (usually slow) biological effects (usually slow)
AA Glucocorticoid drugs
Action mode of glucocorticoid drugs
CBG corticosteroid binding globulin
S glucocorticoid steroids
GR glucocorticoid receptor
HSP heat shock protein
IP immunophilin
GRE glucocorticoid-response element
Nuclear translocation of glucocorticoid receptors (GR)
Dexamethasone was used
GR was labeled with green fluorescent protein
1 Pharmacological effects
Mechanisms of glucocorticoid actions(1) Effects on metabolisms (2) Permissive action(3) Anti-inflammatory effects(4) Effects on immune and allergy (5) Anti-shock(6) Other effects antipyretic effects effects on blood and blood-forming organs skeletal system CNS effects
AA Glucocorticoid drugs Glucocorticoid drugs
(1) Effects on metabolisms
①Glucose metabolism gluconeogenesis glucose
utilization blood glucose ②Protein metabolism synthesis degradation ③Lipid metabolism plasma cholesterol fat
redistribution (central obesity moon face buffalo hump etc)
④Water and electrolytic metabolism
water excretion Na+ excretion
K+ excretion Ca2+ excretion and absorption
AA Glucocorticoid drugs Glucocorticoid drugs
Weaker action of glucocorticoid drugs (cortisol) on mineralocorticoid receptor
(2) Permissive actionPotentiating the effects of catecholamines and
glucagon (3) Anti-inflammatory effectsAcute inhibiting microvascular leakage leukocyte infiltrationChronic inhibiting fibroblast proliferation deposition of collagen cicatrization ( 瘢痕形成 )
AA Glucocorticoid drugs Glucocorticoid drugs
One of glucocorticoidrsquos anti-inflammatory actions
Inhibition of proinflammatory gene transcription (AP-1 and NFB)
AA Glucocorticoid drugs Glucocorticoid drugs
a) Increasing inflammation related proteins or enzymes
inducing lipocortin inhibiting phospholipase A2 activity decreasing mediators PGs LTs PAF
inducing vasocortin decreasing microvascular permeability
inhibiting the expression of PLA2 COX-2 inducible NOS etc
b) Inhibiting cytokinins decreasing the transcription and activities of TNFα IL-1 IL-2 IL-5 IL-6 IL-8 etc
c) Inhibiting adhesion molecules
d) Inducing the apoptosis of inflammatory cells
AA Glucocorticoid drugs Glucocorticoid drugs
(4) Effects on immune and allergy
Suppressing immunological functions and allergy
a) inducing apoptosis of T and B lymphocytes
b) inhibiting transcription factor activity(eg AP-1 NFB)
AA Glucocorticoid drugs Glucocorticoid drugs
(5) Anti-shock Septic shock
a) improving cardiovascular functions
b) inhibiting the production of inflammatory factors
c) stabilizing lysosome membrane decreasing the release of myocardial depressant factor (MDF)
d) increasing the tolerance to endotoxin from bacteria
AA Glucocorticoid drugs Glucocorticoid drugs
(6) Other effects
a) antipyretic effects
b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )
eosinophils platelets
c) skeletal system osteoporosis
d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)
AA Glucocorticoid drugs Glucocorticoid drugs
2 ADME and properties of commonly used drugs
Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver
Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)
AA Glucocorticoid drugs Glucocorticoid drugs
Commonly used drugs
Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松
Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙
Long-acting dexamethasone 地塞米松
Topical fluocinolone 氟轻松
AA Glucocorticoid drugs Glucocorticoid drugs
CortisonCortisonee
可的松可的松
HydrocortisoHydrocortisonene
氢化可的松氢化可的松
CortisolCortisol
PrednisoPrednisonene
泼尼松泼尼松
PrednisolPrednisoloneone
泼尼松龙泼尼松龙
FluocinoloFluocinolonene
氟轻松氟轻松地塞米松地塞米松
HH
3 Clinical uses
(1) Immune diseases
a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc
b) rejection of organ transplantation
c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc
AA Glucocorticoid drugs Glucocorticoid drugs
(2) Severe infection and inflammation
a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving
Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration
Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms
b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc
AA Glucocorticoid drugsGlucocorticoid drugs
(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined
with antimicrobial drugswith antimicrobial drugs
(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc
(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)
(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc
AA Glucocorticoid drugs
4 Adverse effects of glucocorticoid
drugs
Effects resulting from continued used of large doses
AA Glucocorticoid drugs
4 Adverse effects
(1) Effects resulting from continued used of large doses
a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc
b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be
administered with GCs
c) Ingestive system peptic ulcers etc
AA Glucocorticoid drugsGlucocorticoid drugs
d) Cardiovascular system hypertension arteriosclerosis
e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women
f) CNS behavioral disturbances induction of epileptic seizures
g) Inhibition or arrest of growth in children
AA Glucocorticoid drugsGlucocorticoid drugs
Suppression of hypothalamic-pituitary-adrenal axis
and glucocorticoid drugs
‒‒
ACTH
(2) Withdrawal syndrome
a) Suppression of hypothalamic-pituitary-adrenal axis
b) Exacerbation of the underlying diseases (rebound)
(3) Contraindications
psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc
AA Glucocorticoid drugs Glucocorticoid drugs
Balance the ratio of benefit risk before the use of GCs
AA Glucocorticoid drugsGlucocorticoid drugs
5 Applications
(1) Replacement therapy usually using hydrocortisone
(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone
(3) Long-term therapy oral prednisone or prednisolone
morning single dose
alternate-day therapy
Notes for less severe and less sustained patients
less suppression on hypothalamic-pituitary-adrenal (HPA) axis
(4) Tipical applications skin eye respiratory tract
AA Glucocorticoid drugsGlucocorticoid drugs
bull Aldosterone 醛固酮
bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of
water and electrolytes
BB Mineralocorticoid drugsMineralocorticoid drugs
Action of aldosterone on mineralocorticoid receptor
Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein
AIP
bull 1 Adrenocorticotropic hormone (ACTH)
bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of
adrenocortical hoemones after long-term glucocorticoid drug use
bull Easily inducing allergy to ACTH
CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase
inhibitorsinhibitors
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response
ndash plasma cortisol levels are elevated
bull Abnormal responsendash plasma cortisol level are unchanged
bull 2 Corticosteroid synthetase inhibitors
bull Mitotane 米托坦
bull Metyrapone 美替拉酮
bull Aminoglutethimide 氨鲁米特
bull Used for adrenocortical tumors or hypercorticism
C Adrenocorticotropic hormone and corticosteroid synthetase
inhibitors
Cortisol Suppression Tests
bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
History(3)
bull In 1948 the role of hypothalamus in pituitary control was established by Harris
bull In 1949 Hench and colleagues demonstrated the dramatic effect of glucocorticoids and ACTH in the treatment of rheumatoid arthritis
ContentsContents
bull AA Glucocorticoid drugs Glucocorticoid drugsbull BB Mineralocorticoid drugsMineralocorticoid drugsbull CC ACTH and corticosteroid ACTH and corticosteroid
synthetase inhibitorssynthetase inhibitors
Basic structure of glucocorticoid Basic structure of glucocorticoid drugsdrugs
AA BB
CC DD
甾甾
甾体结构甾体结构
HH
AA Glucocorticoid drugs Glucocorticoid drugs
Structure and Activity Structure and Activity RelationshipRelationship(1)1(1)1 位和位和 22 位碳之间改成不饱和的双键位碳之间改成不饱和的双键 cortisone cortisone prednisone prednisone hydrocortisone hydrocortisone prednisolone prednisolone(2)16(2)16 引入羟基引入羟基 triamcinolone(triamcinolone( 曲安西龙曲安西龙 ))(3)6(3)6 引入甲基引入甲基 66-methylprednisone-methylprednisone (6(6 甲基泼尼松甲基泼尼松 ))(4)9(4)9 引入氟原子引入氟原子 fludrocortosonefludrocortosone (( 氟氢可的松氟氢可的松 ))
11 22
33 44
5566 77
881010 99
121213131414 1515
1616 1818
1919
AA BB
CC DD
基本结构基本结构
HH
AA Glucocorticoid drugs Glucocorticoid drugs
HH
Cortisone( 可的松 )
Prednisone( 泼尼松 )
(( 地塞米地塞米松松 ))
Hydrocortisone( 氢化可的松
Cortisol)
Prednisolone( 泼尼松龙 )
Fluocinolone( 氟轻松 )
HH
Mechanisms of glucocorticoid Mechanisms of glucocorticoid actionsactions
binding to glucocorticoid receptor binding to glucocorticoid receptor (GR) (GR)
nuclear translocationnuclear translocation
binding to GRE or nGREbinding to GRE or nGRE
regulating related gene regulating related gene transcriptiontranscription
biological effects (usually slow) biological effects (usually slow)
AA Glucocorticoid drugs
Action mode of glucocorticoid drugs
CBG corticosteroid binding globulin
S glucocorticoid steroids
GR glucocorticoid receptor
HSP heat shock protein
IP immunophilin
GRE glucocorticoid-response element
Nuclear translocation of glucocorticoid receptors (GR)
Dexamethasone was used
GR was labeled with green fluorescent protein
1 Pharmacological effects
Mechanisms of glucocorticoid actions(1) Effects on metabolisms (2) Permissive action(3) Anti-inflammatory effects(4) Effects on immune and allergy (5) Anti-shock(6) Other effects antipyretic effects effects on blood and blood-forming organs skeletal system CNS effects
AA Glucocorticoid drugs Glucocorticoid drugs
(1) Effects on metabolisms
①Glucose metabolism gluconeogenesis glucose
utilization blood glucose ②Protein metabolism synthesis degradation ③Lipid metabolism plasma cholesterol fat
redistribution (central obesity moon face buffalo hump etc)
④Water and electrolytic metabolism
water excretion Na+ excretion
K+ excretion Ca2+ excretion and absorption
AA Glucocorticoid drugs Glucocorticoid drugs
Weaker action of glucocorticoid drugs (cortisol) on mineralocorticoid receptor
(2) Permissive actionPotentiating the effects of catecholamines and
glucagon (3) Anti-inflammatory effectsAcute inhibiting microvascular leakage leukocyte infiltrationChronic inhibiting fibroblast proliferation deposition of collagen cicatrization ( 瘢痕形成 )
AA Glucocorticoid drugs Glucocorticoid drugs
One of glucocorticoidrsquos anti-inflammatory actions
Inhibition of proinflammatory gene transcription (AP-1 and NFB)
AA Glucocorticoid drugs Glucocorticoid drugs
a) Increasing inflammation related proteins or enzymes
inducing lipocortin inhibiting phospholipase A2 activity decreasing mediators PGs LTs PAF
inducing vasocortin decreasing microvascular permeability
inhibiting the expression of PLA2 COX-2 inducible NOS etc
b) Inhibiting cytokinins decreasing the transcription and activities of TNFα IL-1 IL-2 IL-5 IL-6 IL-8 etc
c) Inhibiting adhesion molecules
d) Inducing the apoptosis of inflammatory cells
AA Glucocorticoid drugs Glucocorticoid drugs
(4) Effects on immune and allergy
Suppressing immunological functions and allergy
a) inducing apoptosis of T and B lymphocytes
b) inhibiting transcription factor activity(eg AP-1 NFB)
AA Glucocorticoid drugs Glucocorticoid drugs
(5) Anti-shock Septic shock
a) improving cardiovascular functions
b) inhibiting the production of inflammatory factors
c) stabilizing lysosome membrane decreasing the release of myocardial depressant factor (MDF)
d) increasing the tolerance to endotoxin from bacteria
AA Glucocorticoid drugs Glucocorticoid drugs
(6) Other effects
a) antipyretic effects
b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )
eosinophils platelets
c) skeletal system osteoporosis
d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)
AA Glucocorticoid drugs Glucocorticoid drugs
2 ADME and properties of commonly used drugs
Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver
Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)
AA Glucocorticoid drugs Glucocorticoid drugs
Commonly used drugs
Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松
Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙
Long-acting dexamethasone 地塞米松
Topical fluocinolone 氟轻松
AA Glucocorticoid drugs Glucocorticoid drugs
CortisonCortisonee
可的松可的松
HydrocortisoHydrocortisonene
氢化可的松氢化可的松
CortisolCortisol
PrednisoPrednisonene
泼尼松泼尼松
PrednisolPrednisoloneone
泼尼松龙泼尼松龙
FluocinoloFluocinolonene
氟轻松氟轻松地塞米松地塞米松
HH
3 Clinical uses
(1) Immune diseases
a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc
b) rejection of organ transplantation
c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc
AA Glucocorticoid drugs Glucocorticoid drugs
(2) Severe infection and inflammation
a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving
Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration
Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms
b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc
AA Glucocorticoid drugsGlucocorticoid drugs
(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined
with antimicrobial drugswith antimicrobial drugs
(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc
(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)
(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc
AA Glucocorticoid drugs
4 Adverse effects of glucocorticoid
drugs
Effects resulting from continued used of large doses
AA Glucocorticoid drugs
4 Adverse effects
(1) Effects resulting from continued used of large doses
a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc
b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be
administered with GCs
c) Ingestive system peptic ulcers etc
AA Glucocorticoid drugsGlucocorticoid drugs
d) Cardiovascular system hypertension arteriosclerosis
e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women
f) CNS behavioral disturbances induction of epileptic seizures
g) Inhibition or arrest of growth in children
AA Glucocorticoid drugsGlucocorticoid drugs
Suppression of hypothalamic-pituitary-adrenal axis
and glucocorticoid drugs
‒‒
ACTH
(2) Withdrawal syndrome
a) Suppression of hypothalamic-pituitary-adrenal axis
b) Exacerbation of the underlying diseases (rebound)
(3) Contraindications
psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc
AA Glucocorticoid drugs Glucocorticoid drugs
Balance the ratio of benefit risk before the use of GCs
AA Glucocorticoid drugsGlucocorticoid drugs
5 Applications
(1) Replacement therapy usually using hydrocortisone
(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone
(3) Long-term therapy oral prednisone or prednisolone
morning single dose
alternate-day therapy
Notes for less severe and less sustained patients
less suppression on hypothalamic-pituitary-adrenal (HPA) axis
(4) Tipical applications skin eye respiratory tract
AA Glucocorticoid drugsGlucocorticoid drugs
bull Aldosterone 醛固酮
bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of
water and electrolytes
BB Mineralocorticoid drugsMineralocorticoid drugs
Action of aldosterone on mineralocorticoid receptor
Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein
AIP
bull 1 Adrenocorticotropic hormone (ACTH)
bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of
adrenocortical hoemones after long-term glucocorticoid drug use
bull Easily inducing allergy to ACTH
CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase
inhibitorsinhibitors
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response
ndash plasma cortisol levels are elevated
bull Abnormal responsendash plasma cortisol level are unchanged
bull 2 Corticosteroid synthetase inhibitors
bull Mitotane 米托坦
bull Metyrapone 美替拉酮
bull Aminoglutethimide 氨鲁米特
bull Used for adrenocortical tumors or hypercorticism
C Adrenocorticotropic hormone and corticosteroid synthetase
inhibitors
Cortisol Suppression Tests
bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
ContentsContents
bull AA Glucocorticoid drugs Glucocorticoid drugsbull BB Mineralocorticoid drugsMineralocorticoid drugsbull CC ACTH and corticosteroid ACTH and corticosteroid
synthetase inhibitorssynthetase inhibitors
Basic structure of glucocorticoid Basic structure of glucocorticoid drugsdrugs
AA BB
CC DD
甾甾
甾体结构甾体结构
HH
AA Glucocorticoid drugs Glucocorticoid drugs
Structure and Activity Structure and Activity RelationshipRelationship(1)1(1)1 位和位和 22 位碳之间改成不饱和的双键位碳之间改成不饱和的双键 cortisone cortisone prednisone prednisone hydrocortisone hydrocortisone prednisolone prednisolone(2)16(2)16 引入羟基引入羟基 triamcinolone(triamcinolone( 曲安西龙曲安西龙 ))(3)6(3)6 引入甲基引入甲基 66-methylprednisone-methylprednisone (6(6 甲基泼尼松甲基泼尼松 ))(4)9(4)9 引入氟原子引入氟原子 fludrocortosonefludrocortosone (( 氟氢可的松氟氢可的松 ))
11 22
33 44
5566 77
881010 99
121213131414 1515
1616 1818
1919
AA BB
CC DD
基本结构基本结构
HH
AA Glucocorticoid drugs Glucocorticoid drugs
HH
Cortisone( 可的松 )
Prednisone( 泼尼松 )
(( 地塞米地塞米松松 ))
Hydrocortisone( 氢化可的松
Cortisol)
Prednisolone( 泼尼松龙 )
Fluocinolone( 氟轻松 )
HH
Mechanisms of glucocorticoid Mechanisms of glucocorticoid actionsactions
binding to glucocorticoid receptor binding to glucocorticoid receptor (GR) (GR)
nuclear translocationnuclear translocation
binding to GRE or nGREbinding to GRE or nGRE
regulating related gene regulating related gene transcriptiontranscription
biological effects (usually slow) biological effects (usually slow)
AA Glucocorticoid drugs
Action mode of glucocorticoid drugs
CBG corticosteroid binding globulin
S glucocorticoid steroids
GR glucocorticoid receptor
HSP heat shock protein
IP immunophilin
GRE glucocorticoid-response element
Nuclear translocation of glucocorticoid receptors (GR)
Dexamethasone was used
GR was labeled with green fluorescent protein
1 Pharmacological effects
Mechanisms of glucocorticoid actions(1) Effects on metabolisms (2) Permissive action(3) Anti-inflammatory effects(4) Effects on immune and allergy (5) Anti-shock(6) Other effects antipyretic effects effects on blood and blood-forming organs skeletal system CNS effects
AA Glucocorticoid drugs Glucocorticoid drugs
(1) Effects on metabolisms
①Glucose metabolism gluconeogenesis glucose
utilization blood glucose ②Protein metabolism synthesis degradation ③Lipid metabolism plasma cholesterol fat
redistribution (central obesity moon face buffalo hump etc)
④Water and electrolytic metabolism
water excretion Na+ excretion
K+ excretion Ca2+ excretion and absorption
AA Glucocorticoid drugs Glucocorticoid drugs
Weaker action of glucocorticoid drugs (cortisol) on mineralocorticoid receptor
(2) Permissive actionPotentiating the effects of catecholamines and
glucagon (3) Anti-inflammatory effectsAcute inhibiting microvascular leakage leukocyte infiltrationChronic inhibiting fibroblast proliferation deposition of collagen cicatrization ( 瘢痕形成 )
AA Glucocorticoid drugs Glucocorticoid drugs
One of glucocorticoidrsquos anti-inflammatory actions
Inhibition of proinflammatory gene transcription (AP-1 and NFB)
AA Glucocorticoid drugs Glucocorticoid drugs
a) Increasing inflammation related proteins or enzymes
inducing lipocortin inhibiting phospholipase A2 activity decreasing mediators PGs LTs PAF
inducing vasocortin decreasing microvascular permeability
inhibiting the expression of PLA2 COX-2 inducible NOS etc
b) Inhibiting cytokinins decreasing the transcription and activities of TNFα IL-1 IL-2 IL-5 IL-6 IL-8 etc
c) Inhibiting adhesion molecules
d) Inducing the apoptosis of inflammatory cells
AA Glucocorticoid drugs Glucocorticoid drugs
(4) Effects on immune and allergy
Suppressing immunological functions and allergy
a) inducing apoptosis of T and B lymphocytes
b) inhibiting transcription factor activity(eg AP-1 NFB)
AA Glucocorticoid drugs Glucocorticoid drugs
(5) Anti-shock Septic shock
a) improving cardiovascular functions
b) inhibiting the production of inflammatory factors
c) stabilizing lysosome membrane decreasing the release of myocardial depressant factor (MDF)
d) increasing the tolerance to endotoxin from bacteria
AA Glucocorticoid drugs Glucocorticoid drugs
(6) Other effects
a) antipyretic effects
b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )
eosinophils platelets
c) skeletal system osteoporosis
d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)
AA Glucocorticoid drugs Glucocorticoid drugs
2 ADME and properties of commonly used drugs
Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver
Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)
AA Glucocorticoid drugs Glucocorticoid drugs
Commonly used drugs
Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松
Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙
Long-acting dexamethasone 地塞米松
Topical fluocinolone 氟轻松
AA Glucocorticoid drugs Glucocorticoid drugs
CortisonCortisonee
可的松可的松
HydrocortisoHydrocortisonene
氢化可的松氢化可的松
CortisolCortisol
PrednisoPrednisonene
泼尼松泼尼松
PrednisolPrednisoloneone
泼尼松龙泼尼松龙
FluocinoloFluocinolonene
氟轻松氟轻松地塞米松地塞米松
HH
3 Clinical uses
(1) Immune diseases
a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc
b) rejection of organ transplantation
c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc
AA Glucocorticoid drugs Glucocorticoid drugs
(2) Severe infection and inflammation
a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving
Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration
Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms
b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc
AA Glucocorticoid drugsGlucocorticoid drugs
(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined
with antimicrobial drugswith antimicrobial drugs
(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc
(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)
(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc
AA Glucocorticoid drugs
4 Adverse effects of glucocorticoid
drugs
Effects resulting from continued used of large doses
AA Glucocorticoid drugs
4 Adverse effects
(1) Effects resulting from continued used of large doses
a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc
b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be
administered with GCs
c) Ingestive system peptic ulcers etc
AA Glucocorticoid drugsGlucocorticoid drugs
d) Cardiovascular system hypertension arteriosclerosis
e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women
f) CNS behavioral disturbances induction of epileptic seizures
g) Inhibition or arrest of growth in children
AA Glucocorticoid drugsGlucocorticoid drugs
Suppression of hypothalamic-pituitary-adrenal axis
and glucocorticoid drugs
‒‒
ACTH
(2) Withdrawal syndrome
a) Suppression of hypothalamic-pituitary-adrenal axis
b) Exacerbation of the underlying diseases (rebound)
(3) Contraindications
psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc
AA Glucocorticoid drugs Glucocorticoid drugs
Balance the ratio of benefit risk before the use of GCs
AA Glucocorticoid drugsGlucocorticoid drugs
5 Applications
(1) Replacement therapy usually using hydrocortisone
(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone
(3) Long-term therapy oral prednisone or prednisolone
morning single dose
alternate-day therapy
Notes for less severe and less sustained patients
less suppression on hypothalamic-pituitary-adrenal (HPA) axis
(4) Tipical applications skin eye respiratory tract
AA Glucocorticoid drugsGlucocorticoid drugs
bull Aldosterone 醛固酮
bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of
water and electrolytes
BB Mineralocorticoid drugsMineralocorticoid drugs
Action of aldosterone on mineralocorticoid receptor
Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein
AIP
bull 1 Adrenocorticotropic hormone (ACTH)
bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of
adrenocortical hoemones after long-term glucocorticoid drug use
bull Easily inducing allergy to ACTH
CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase
inhibitorsinhibitors
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response
ndash plasma cortisol levels are elevated
bull Abnormal responsendash plasma cortisol level are unchanged
bull 2 Corticosteroid synthetase inhibitors
bull Mitotane 米托坦
bull Metyrapone 美替拉酮
bull Aminoglutethimide 氨鲁米特
bull Used for adrenocortical tumors or hypercorticism
C Adrenocorticotropic hormone and corticosteroid synthetase
inhibitors
Cortisol Suppression Tests
bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
Basic structure of glucocorticoid Basic structure of glucocorticoid drugsdrugs
AA BB
CC DD
甾甾
甾体结构甾体结构
HH
AA Glucocorticoid drugs Glucocorticoid drugs
Structure and Activity Structure and Activity RelationshipRelationship(1)1(1)1 位和位和 22 位碳之间改成不饱和的双键位碳之间改成不饱和的双键 cortisone cortisone prednisone prednisone hydrocortisone hydrocortisone prednisolone prednisolone(2)16(2)16 引入羟基引入羟基 triamcinolone(triamcinolone( 曲安西龙曲安西龙 ))(3)6(3)6 引入甲基引入甲基 66-methylprednisone-methylprednisone (6(6 甲基泼尼松甲基泼尼松 ))(4)9(4)9 引入氟原子引入氟原子 fludrocortosonefludrocortosone (( 氟氢可的松氟氢可的松 ))
11 22
33 44
5566 77
881010 99
121213131414 1515
1616 1818
1919
AA BB
CC DD
基本结构基本结构
HH
AA Glucocorticoid drugs Glucocorticoid drugs
HH
Cortisone( 可的松 )
Prednisone( 泼尼松 )
(( 地塞米地塞米松松 ))
Hydrocortisone( 氢化可的松
Cortisol)
Prednisolone( 泼尼松龙 )
Fluocinolone( 氟轻松 )
HH
Mechanisms of glucocorticoid Mechanisms of glucocorticoid actionsactions
binding to glucocorticoid receptor binding to glucocorticoid receptor (GR) (GR)
nuclear translocationnuclear translocation
binding to GRE or nGREbinding to GRE or nGRE
regulating related gene regulating related gene transcriptiontranscription
biological effects (usually slow) biological effects (usually slow)
AA Glucocorticoid drugs
Action mode of glucocorticoid drugs
CBG corticosteroid binding globulin
S glucocorticoid steroids
GR glucocorticoid receptor
HSP heat shock protein
IP immunophilin
GRE glucocorticoid-response element
Nuclear translocation of glucocorticoid receptors (GR)
Dexamethasone was used
GR was labeled with green fluorescent protein
1 Pharmacological effects
Mechanisms of glucocorticoid actions(1) Effects on metabolisms (2) Permissive action(3) Anti-inflammatory effects(4) Effects on immune and allergy (5) Anti-shock(6) Other effects antipyretic effects effects on blood and blood-forming organs skeletal system CNS effects
AA Glucocorticoid drugs Glucocorticoid drugs
(1) Effects on metabolisms
①Glucose metabolism gluconeogenesis glucose
utilization blood glucose ②Protein metabolism synthesis degradation ③Lipid metabolism plasma cholesterol fat
redistribution (central obesity moon face buffalo hump etc)
④Water and electrolytic metabolism
water excretion Na+ excretion
K+ excretion Ca2+ excretion and absorption
AA Glucocorticoid drugs Glucocorticoid drugs
Weaker action of glucocorticoid drugs (cortisol) on mineralocorticoid receptor
(2) Permissive actionPotentiating the effects of catecholamines and
glucagon (3) Anti-inflammatory effectsAcute inhibiting microvascular leakage leukocyte infiltrationChronic inhibiting fibroblast proliferation deposition of collagen cicatrization ( 瘢痕形成 )
AA Glucocorticoid drugs Glucocorticoid drugs
One of glucocorticoidrsquos anti-inflammatory actions
Inhibition of proinflammatory gene transcription (AP-1 and NFB)
AA Glucocorticoid drugs Glucocorticoid drugs
a) Increasing inflammation related proteins or enzymes
inducing lipocortin inhibiting phospholipase A2 activity decreasing mediators PGs LTs PAF
inducing vasocortin decreasing microvascular permeability
inhibiting the expression of PLA2 COX-2 inducible NOS etc
b) Inhibiting cytokinins decreasing the transcription and activities of TNFα IL-1 IL-2 IL-5 IL-6 IL-8 etc
c) Inhibiting adhesion molecules
d) Inducing the apoptosis of inflammatory cells
AA Glucocorticoid drugs Glucocorticoid drugs
(4) Effects on immune and allergy
Suppressing immunological functions and allergy
a) inducing apoptosis of T and B lymphocytes
b) inhibiting transcription factor activity(eg AP-1 NFB)
AA Glucocorticoid drugs Glucocorticoid drugs
(5) Anti-shock Septic shock
a) improving cardiovascular functions
b) inhibiting the production of inflammatory factors
c) stabilizing lysosome membrane decreasing the release of myocardial depressant factor (MDF)
d) increasing the tolerance to endotoxin from bacteria
AA Glucocorticoid drugs Glucocorticoid drugs
(6) Other effects
a) antipyretic effects
b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )
eosinophils platelets
c) skeletal system osteoporosis
d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)
AA Glucocorticoid drugs Glucocorticoid drugs
2 ADME and properties of commonly used drugs
Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver
Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)
AA Glucocorticoid drugs Glucocorticoid drugs
Commonly used drugs
Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松
Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙
Long-acting dexamethasone 地塞米松
Topical fluocinolone 氟轻松
AA Glucocorticoid drugs Glucocorticoid drugs
CortisonCortisonee
可的松可的松
HydrocortisoHydrocortisonene
氢化可的松氢化可的松
CortisolCortisol
PrednisoPrednisonene
泼尼松泼尼松
PrednisolPrednisoloneone
泼尼松龙泼尼松龙
FluocinoloFluocinolonene
氟轻松氟轻松地塞米松地塞米松
HH
3 Clinical uses
(1) Immune diseases
a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc
b) rejection of organ transplantation
c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc
AA Glucocorticoid drugs Glucocorticoid drugs
(2) Severe infection and inflammation
a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving
Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration
Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms
b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc
AA Glucocorticoid drugsGlucocorticoid drugs
(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined
with antimicrobial drugswith antimicrobial drugs
(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc
(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)
(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc
AA Glucocorticoid drugs
4 Adverse effects of glucocorticoid
drugs
Effects resulting from continued used of large doses
AA Glucocorticoid drugs
4 Adverse effects
(1) Effects resulting from continued used of large doses
a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc
b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be
administered with GCs
c) Ingestive system peptic ulcers etc
AA Glucocorticoid drugsGlucocorticoid drugs
d) Cardiovascular system hypertension arteriosclerosis
e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women
f) CNS behavioral disturbances induction of epileptic seizures
g) Inhibition or arrest of growth in children
AA Glucocorticoid drugsGlucocorticoid drugs
Suppression of hypothalamic-pituitary-adrenal axis
and glucocorticoid drugs
‒‒
ACTH
(2) Withdrawal syndrome
a) Suppression of hypothalamic-pituitary-adrenal axis
b) Exacerbation of the underlying diseases (rebound)
(3) Contraindications
psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc
AA Glucocorticoid drugs Glucocorticoid drugs
Balance the ratio of benefit risk before the use of GCs
AA Glucocorticoid drugsGlucocorticoid drugs
5 Applications
(1) Replacement therapy usually using hydrocortisone
(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone
(3) Long-term therapy oral prednisone or prednisolone
morning single dose
alternate-day therapy
Notes for less severe and less sustained patients
less suppression on hypothalamic-pituitary-adrenal (HPA) axis
(4) Tipical applications skin eye respiratory tract
AA Glucocorticoid drugsGlucocorticoid drugs
bull Aldosterone 醛固酮
bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of
water and electrolytes
BB Mineralocorticoid drugsMineralocorticoid drugs
Action of aldosterone on mineralocorticoid receptor
Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein
AIP
bull 1 Adrenocorticotropic hormone (ACTH)
bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of
adrenocortical hoemones after long-term glucocorticoid drug use
bull Easily inducing allergy to ACTH
CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase
inhibitorsinhibitors
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response
ndash plasma cortisol levels are elevated
bull Abnormal responsendash plasma cortisol level are unchanged
bull 2 Corticosteroid synthetase inhibitors
bull Mitotane 米托坦
bull Metyrapone 美替拉酮
bull Aminoglutethimide 氨鲁米特
bull Used for adrenocortical tumors or hypercorticism
C Adrenocorticotropic hormone and corticosteroid synthetase
inhibitors
Cortisol Suppression Tests
bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
Structure and Activity Structure and Activity RelationshipRelationship(1)1(1)1 位和位和 22 位碳之间改成不饱和的双键位碳之间改成不饱和的双键 cortisone cortisone prednisone prednisone hydrocortisone hydrocortisone prednisolone prednisolone(2)16(2)16 引入羟基引入羟基 triamcinolone(triamcinolone( 曲安西龙曲安西龙 ))(3)6(3)6 引入甲基引入甲基 66-methylprednisone-methylprednisone (6(6 甲基泼尼松甲基泼尼松 ))(4)9(4)9 引入氟原子引入氟原子 fludrocortosonefludrocortosone (( 氟氢可的松氟氢可的松 ))
11 22
33 44
5566 77
881010 99
121213131414 1515
1616 1818
1919
AA BB
CC DD
基本结构基本结构
HH
AA Glucocorticoid drugs Glucocorticoid drugs
HH
Cortisone( 可的松 )
Prednisone( 泼尼松 )
(( 地塞米地塞米松松 ))
Hydrocortisone( 氢化可的松
Cortisol)
Prednisolone( 泼尼松龙 )
Fluocinolone( 氟轻松 )
HH
Mechanisms of glucocorticoid Mechanisms of glucocorticoid actionsactions
binding to glucocorticoid receptor binding to glucocorticoid receptor (GR) (GR)
nuclear translocationnuclear translocation
binding to GRE or nGREbinding to GRE or nGRE
regulating related gene regulating related gene transcriptiontranscription
biological effects (usually slow) biological effects (usually slow)
AA Glucocorticoid drugs
Action mode of glucocorticoid drugs
CBG corticosteroid binding globulin
S glucocorticoid steroids
GR glucocorticoid receptor
HSP heat shock protein
IP immunophilin
GRE glucocorticoid-response element
Nuclear translocation of glucocorticoid receptors (GR)
Dexamethasone was used
GR was labeled with green fluorescent protein
1 Pharmacological effects
Mechanisms of glucocorticoid actions(1) Effects on metabolisms (2) Permissive action(3) Anti-inflammatory effects(4) Effects on immune and allergy (5) Anti-shock(6) Other effects antipyretic effects effects on blood and blood-forming organs skeletal system CNS effects
AA Glucocorticoid drugs Glucocorticoid drugs
(1) Effects on metabolisms
①Glucose metabolism gluconeogenesis glucose
utilization blood glucose ②Protein metabolism synthesis degradation ③Lipid metabolism plasma cholesterol fat
redistribution (central obesity moon face buffalo hump etc)
④Water and electrolytic metabolism
water excretion Na+ excretion
K+ excretion Ca2+ excretion and absorption
AA Glucocorticoid drugs Glucocorticoid drugs
Weaker action of glucocorticoid drugs (cortisol) on mineralocorticoid receptor
(2) Permissive actionPotentiating the effects of catecholamines and
glucagon (3) Anti-inflammatory effectsAcute inhibiting microvascular leakage leukocyte infiltrationChronic inhibiting fibroblast proliferation deposition of collagen cicatrization ( 瘢痕形成 )
AA Glucocorticoid drugs Glucocorticoid drugs
One of glucocorticoidrsquos anti-inflammatory actions
Inhibition of proinflammatory gene transcription (AP-1 and NFB)
AA Glucocorticoid drugs Glucocorticoid drugs
a) Increasing inflammation related proteins or enzymes
inducing lipocortin inhibiting phospholipase A2 activity decreasing mediators PGs LTs PAF
inducing vasocortin decreasing microvascular permeability
inhibiting the expression of PLA2 COX-2 inducible NOS etc
b) Inhibiting cytokinins decreasing the transcription and activities of TNFα IL-1 IL-2 IL-5 IL-6 IL-8 etc
c) Inhibiting adhesion molecules
d) Inducing the apoptosis of inflammatory cells
AA Glucocorticoid drugs Glucocorticoid drugs
(4) Effects on immune and allergy
Suppressing immunological functions and allergy
a) inducing apoptosis of T and B lymphocytes
b) inhibiting transcription factor activity(eg AP-1 NFB)
AA Glucocorticoid drugs Glucocorticoid drugs
(5) Anti-shock Septic shock
a) improving cardiovascular functions
b) inhibiting the production of inflammatory factors
c) stabilizing lysosome membrane decreasing the release of myocardial depressant factor (MDF)
d) increasing the tolerance to endotoxin from bacteria
AA Glucocorticoid drugs Glucocorticoid drugs
(6) Other effects
a) antipyretic effects
b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )
eosinophils platelets
c) skeletal system osteoporosis
d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)
AA Glucocorticoid drugs Glucocorticoid drugs
2 ADME and properties of commonly used drugs
Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver
Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)
AA Glucocorticoid drugs Glucocorticoid drugs
Commonly used drugs
Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松
Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙
Long-acting dexamethasone 地塞米松
Topical fluocinolone 氟轻松
AA Glucocorticoid drugs Glucocorticoid drugs
CortisonCortisonee
可的松可的松
HydrocortisoHydrocortisonene
氢化可的松氢化可的松
CortisolCortisol
PrednisoPrednisonene
泼尼松泼尼松
PrednisolPrednisoloneone
泼尼松龙泼尼松龙
FluocinoloFluocinolonene
氟轻松氟轻松地塞米松地塞米松
HH
3 Clinical uses
(1) Immune diseases
a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc
b) rejection of organ transplantation
c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc
AA Glucocorticoid drugs Glucocorticoid drugs
(2) Severe infection and inflammation
a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving
Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration
Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms
b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc
AA Glucocorticoid drugsGlucocorticoid drugs
(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined
with antimicrobial drugswith antimicrobial drugs
(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc
(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)
(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc
AA Glucocorticoid drugs
4 Adverse effects of glucocorticoid
drugs
Effects resulting from continued used of large doses
AA Glucocorticoid drugs
4 Adverse effects
(1) Effects resulting from continued used of large doses
a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc
b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be
administered with GCs
c) Ingestive system peptic ulcers etc
AA Glucocorticoid drugsGlucocorticoid drugs
d) Cardiovascular system hypertension arteriosclerosis
e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women
f) CNS behavioral disturbances induction of epileptic seizures
g) Inhibition or arrest of growth in children
AA Glucocorticoid drugsGlucocorticoid drugs
Suppression of hypothalamic-pituitary-adrenal axis
and glucocorticoid drugs
‒‒
ACTH
(2) Withdrawal syndrome
a) Suppression of hypothalamic-pituitary-adrenal axis
b) Exacerbation of the underlying diseases (rebound)
(3) Contraindications
psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc
AA Glucocorticoid drugs Glucocorticoid drugs
Balance the ratio of benefit risk before the use of GCs
AA Glucocorticoid drugsGlucocorticoid drugs
5 Applications
(1) Replacement therapy usually using hydrocortisone
(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone
(3) Long-term therapy oral prednisone or prednisolone
morning single dose
alternate-day therapy
Notes for less severe and less sustained patients
less suppression on hypothalamic-pituitary-adrenal (HPA) axis
(4) Tipical applications skin eye respiratory tract
AA Glucocorticoid drugsGlucocorticoid drugs
bull Aldosterone 醛固酮
bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of
water and electrolytes
BB Mineralocorticoid drugsMineralocorticoid drugs
Action of aldosterone on mineralocorticoid receptor
Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein
AIP
bull 1 Adrenocorticotropic hormone (ACTH)
bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of
adrenocortical hoemones after long-term glucocorticoid drug use
bull Easily inducing allergy to ACTH
CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase
inhibitorsinhibitors
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response
ndash plasma cortisol levels are elevated
bull Abnormal responsendash plasma cortisol level are unchanged
bull 2 Corticosteroid synthetase inhibitors
bull Mitotane 米托坦
bull Metyrapone 美替拉酮
bull Aminoglutethimide 氨鲁米特
bull Used for adrenocortical tumors or hypercorticism
C Adrenocorticotropic hormone and corticosteroid synthetase
inhibitors
Cortisol Suppression Tests
bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
HH
Cortisone( 可的松 )
Prednisone( 泼尼松 )
(( 地塞米地塞米松松 ))
Hydrocortisone( 氢化可的松
Cortisol)
Prednisolone( 泼尼松龙 )
Fluocinolone( 氟轻松 )
HH
Mechanisms of glucocorticoid Mechanisms of glucocorticoid actionsactions
binding to glucocorticoid receptor binding to glucocorticoid receptor (GR) (GR)
nuclear translocationnuclear translocation
binding to GRE or nGREbinding to GRE or nGRE
regulating related gene regulating related gene transcriptiontranscription
biological effects (usually slow) biological effects (usually slow)
AA Glucocorticoid drugs
Action mode of glucocorticoid drugs
CBG corticosteroid binding globulin
S glucocorticoid steroids
GR glucocorticoid receptor
HSP heat shock protein
IP immunophilin
GRE glucocorticoid-response element
Nuclear translocation of glucocorticoid receptors (GR)
Dexamethasone was used
GR was labeled with green fluorescent protein
1 Pharmacological effects
Mechanisms of glucocorticoid actions(1) Effects on metabolisms (2) Permissive action(3) Anti-inflammatory effects(4) Effects on immune and allergy (5) Anti-shock(6) Other effects antipyretic effects effects on blood and blood-forming organs skeletal system CNS effects
AA Glucocorticoid drugs Glucocorticoid drugs
(1) Effects on metabolisms
①Glucose metabolism gluconeogenesis glucose
utilization blood glucose ②Protein metabolism synthesis degradation ③Lipid metabolism plasma cholesterol fat
redistribution (central obesity moon face buffalo hump etc)
④Water and electrolytic metabolism
water excretion Na+ excretion
K+ excretion Ca2+ excretion and absorption
AA Glucocorticoid drugs Glucocorticoid drugs
Weaker action of glucocorticoid drugs (cortisol) on mineralocorticoid receptor
(2) Permissive actionPotentiating the effects of catecholamines and
glucagon (3) Anti-inflammatory effectsAcute inhibiting microvascular leakage leukocyte infiltrationChronic inhibiting fibroblast proliferation deposition of collagen cicatrization ( 瘢痕形成 )
AA Glucocorticoid drugs Glucocorticoid drugs
One of glucocorticoidrsquos anti-inflammatory actions
Inhibition of proinflammatory gene transcription (AP-1 and NFB)
AA Glucocorticoid drugs Glucocorticoid drugs
a) Increasing inflammation related proteins or enzymes
inducing lipocortin inhibiting phospholipase A2 activity decreasing mediators PGs LTs PAF
inducing vasocortin decreasing microvascular permeability
inhibiting the expression of PLA2 COX-2 inducible NOS etc
b) Inhibiting cytokinins decreasing the transcription and activities of TNFα IL-1 IL-2 IL-5 IL-6 IL-8 etc
c) Inhibiting adhesion molecules
d) Inducing the apoptosis of inflammatory cells
AA Glucocorticoid drugs Glucocorticoid drugs
(4) Effects on immune and allergy
Suppressing immunological functions and allergy
a) inducing apoptosis of T and B lymphocytes
b) inhibiting transcription factor activity(eg AP-1 NFB)
AA Glucocorticoid drugs Glucocorticoid drugs
(5) Anti-shock Septic shock
a) improving cardiovascular functions
b) inhibiting the production of inflammatory factors
c) stabilizing lysosome membrane decreasing the release of myocardial depressant factor (MDF)
d) increasing the tolerance to endotoxin from bacteria
AA Glucocorticoid drugs Glucocorticoid drugs
(6) Other effects
a) antipyretic effects
b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )
eosinophils platelets
c) skeletal system osteoporosis
d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)
AA Glucocorticoid drugs Glucocorticoid drugs
2 ADME and properties of commonly used drugs
Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver
Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)
AA Glucocorticoid drugs Glucocorticoid drugs
Commonly used drugs
Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松
Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙
Long-acting dexamethasone 地塞米松
Topical fluocinolone 氟轻松
AA Glucocorticoid drugs Glucocorticoid drugs
CortisonCortisonee
可的松可的松
HydrocortisoHydrocortisonene
氢化可的松氢化可的松
CortisolCortisol
PrednisoPrednisonene
泼尼松泼尼松
PrednisolPrednisoloneone
泼尼松龙泼尼松龙
FluocinoloFluocinolonene
氟轻松氟轻松地塞米松地塞米松
HH
3 Clinical uses
(1) Immune diseases
a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc
b) rejection of organ transplantation
c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc
AA Glucocorticoid drugs Glucocorticoid drugs
(2) Severe infection and inflammation
a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving
Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration
Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms
b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc
AA Glucocorticoid drugsGlucocorticoid drugs
(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined
with antimicrobial drugswith antimicrobial drugs
(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc
(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)
(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc
AA Glucocorticoid drugs
4 Adverse effects of glucocorticoid
drugs
Effects resulting from continued used of large doses
AA Glucocorticoid drugs
4 Adverse effects
(1) Effects resulting from continued used of large doses
a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc
b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be
administered with GCs
c) Ingestive system peptic ulcers etc
AA Glucocorticoid drugsGlucocorticoid drugs
d) Cardiovascular system hypertension arteriosclerosis
e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women
f) CNS behavioral disturbances induction of epileptic seizures
g) Inhibition or arrest of growth in children
AA Glucocorticoid drugsGlucocorticoid drugs
Suppression of hypothalamic-pituitary-adrenal axis
and glucocorticoid drugs
‒‒
ACTH
(2) Withdrawal syndrome
a) Suppression of hypothalamic-pituitary-adrenal axis
b) Exacerbation of the underlying diseases (rebound)
(3) Contraindications
psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc
AA Glucocorticoid drugs Glucocorticoid drugs
Balance the ratio of benefit risk before the use of GCs
AA Glucocorticoid drugsGlucocorticoid drugs
5 Applications
(1) Replacement therapy usually using hydrocortisone
(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone
(3) Long-term therapy oral prednisone or prednisolone
morning single dose
alternate-day therapy
Notes for less severe and less sustained patients
less suppression on hypothalamic-pituitary-adrenal (HPA) axis
(4) Tipical applications skin eye respiratory tract
AA Glucocorticoid drugsGlucocorticoid drugs
bull Aldosterone 醛固酮
bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of
water and electrolytes
BB Mineralocorticoid drugsMineralocorticoid drugs
Action of aldosterone on mineralocorticoid receptor
Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein
AIP
bull 1 Adrenocorticotropic hormone (ACTH)
bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of
adrenocortical hoemones after long-term glucocorticoid drug use
bull Easily inducing allergy to ACTH
CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase
inhibitorsinhibitors
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response
ndash plasma cortisol levels are elevated
bull Abnormal responsendash plasma cortisol level are unchanged
bull 2 Corticosteroid synthetase inhibitors
bull Mitotane 米托坦
bull Metyrapone 美替拉酮
bull Aminoglutethimide 氨鲁米特
bull Used for adrenocortical tumors or hypercorticism
C Adrenocorticotropic hormone and corticosteroid synthetase
inhibitors
Cortisol Suppression Tests
bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
Mechanisms of glucocorticoid Mechanisms of glucocorticoid actionsactions
binding to glucocorticoid receptor binding to glucocorticoid receptor (GR) (GR)
nuclear translocationnuclear translocation
binding to GRE or nGREbinding to GRE or nGRE
regulating related gene regulating related gene transcriptiontranscription
biological effects (usually slow) biological effects (usually slow)
AA Glucocorticoid drugs
Action mode of glucocorticoid drugs
CBG corticosteroid binding globulin
S glucocorticoid steroids
GR glucocorticoid receptor
HSP heat shock protein
IP immunophilin
GRE glucocorticoid-response element
Nuclear translocation of glucocorticoid receptors (GR)
Dexamethasone was used
GR was labeled with green fluorescent protein
1 Pharmacological effects
Mechanisms of glucocorticoid actions(1) Effects on metabolisms (2) Permissive action(3) Anti-inflammatory effects(4) Effects on immune and allergy (5) Anti-shock(6) Other effects antipyretic effects effects on blood and blood-forming organs skeletal system CNS effects
AA Glucocorticoid drugs Glucocorticoid drugs
(1) Effects on metabolisms
①Glucose metabolism gluconeogenesis glucose
utilization blood glucose ②Protein metabolism synthesis degradation ③Lipid metabolism plasma cholesterol fat
redistribution (central obesity moon face buffalo hump etc)
④Water and electrolytic metabolism
water excretion Na+ excretion
K+ excretion Ca2+ excretion and absorption
AA Glucocorticoid drugs Glucocorticoid drugs
Weaker action of glucocorticoid drugs (cortisol) on mineralocorticoid receptor
(2) Permissive actionPotentiating the effects of catecholamines and
glucagon (3) Anti-inflammatory effectsAcute inhibiting microvascular leakage leukocyte infiltrationChronic inhibiting fibroblast proliferation deposition of collagen cicatrization ( 瘢痕形成 )
AA Glucocorticoid drugs Glucocorticoid drugs
One of glucocorticoidrsquos anti-inflammatory actions
Inhibition of proinflammatory gene transcription (AP-1 and NFB)
AA Glucocorticoid drugs Glucocorticoid drugs
a) Increasing inflammation related proteins or enzymes
inducing lipocortin inhibiting phospholipase A2 activity decreasing mediators PGs LTs PAF
inducing vasocortin decreasing microvascular permeability
inhibiting the expression of PLA2 COX-2 inducible NOS etc
b) Inhibiting cytokinins decreasing the transcription and activities of TNFα IL-1 IL-2 IL-5 IL-6 IL-8 etc
c) Inhibiting adhesion molecules
d) Inducing the apoptosis of inflammatory cells
AA Glucocorticoid drugs Glucocorticoid drugs
(4) Effects on immune and allergy
Suppressing immunological functions and allergy
a) inducing apoptosis of T and B lymphocytes
b) inhibiting transcription factor activity(eg AP-1 NFB)
AA Glucocorticoid drugs Glucocorticoid drugs
(5) Anti-shock Septic shock
a) improving cardiovascular functions
b) inhibiting the production of inflammatory factors
c) stabilizing lysosome membrane decreasing the release of myocardial depressant factor (MDF)
d) increasing the tolerance to endotoxin from bacteria
AA Glucocorticoid drugs Glucocorticoid drugs
(6) Other effects
a) antipyretic effects
b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )
eosinophils platelets
c) skeletal system osteoporosis
d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)
AA Glucocorticoid drugs Glucocorticoid drugs
2 ADME and properties of commonly used drugs
Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver
Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)
AA Glucocorticoid drugs Glucocorticoid drugs
Commonly used drugs
Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松
Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙
Long-acting dexamethasone 地塞米松
Topical fluocinolone 氟轻松
AA Glucocorticoid drugs Glucocorticoid drugs
CortisonCortisonee
可的松可的松
HydrocortisoHydrocortisonene
氢化可的松氢化可的松
CortisolCortisol
PrednisoPrednisonene
泼尼松泼尼松
PrednisolPrednisoloneone
泼尼松龙泼尼松龙
FluocinoloFluocinolonene
氟轻松氟轻松地塞米松地塞米松
HH
3 Clinical uses
(1) Immune diseases
a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc
b) rejection of organ transplantation
c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc
AA Glucocorticoid drugs Glucocorticoid drugs
(2) Severe infection and inflammation
a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving
Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration
Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms
b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc
AA Glucocorticoid drugsGlucocorticoid drugs
(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined
with antimicrobial drugswith antimicrobial drugs
(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc
(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)
(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc
AA Glucocorticoid drugs
4 Adverse effects of glucocorticoid
drugs
Effects resulting from continued used of large doses
AA Glucocorticoid drugs
4 Adverse effects
(1) Effects resulting from continued used of large doses
a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc
b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be
administered with GCs
c) Ingestive system peptic ulcers etc
AA Glucocorticoid drugsGlucocorticoid drugs
d) Cardiovascular system hypertension arteriosclerosis
e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women
f) CNS behavioral disturbances induction of epileptic seizures
g) Inhibition or arrest of growth in children
AA Glucocorticoid drugsGlucocorticoid drugs
Suppression of hypothalamic-pituitary-adrenal axis
and glucocorticoid drugs
‒‒
ACTH
(2) Withdrawal syndrome
a) Suppression of hypothalamic-pituitary-adrenal axis
b) Exacerbation of the underlying diseases (rebound)
(3) Contraindications
psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc
AA Glucocorticoid drugs Glucocorticoid drugs
Balance the ratio of benefit risk before the use of GCs
AA Glucocorticoid drugsGlucocorticoid drugs
5 Applications
(1) Replacement therapy usually using hydrocortisone
(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone
(3) Long-term therapy oral prednisone or prednisolone
morning single dose
alternate-day therapy
Notes for less severe and less sustained patients
less suppression on hypothalamic-pituitary-adrenal (HPA) axis
(4) Tipical applications skin eye respiratory tract
AA Glucocorticoid drugsGlucocorticoid drugs
bull Aldosterone 醛固酮
bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of
water and electrolytes
BB Mineralocorticoid drugsMineralocorticoid drugs
Action of aldosterone on mineralocorticoid receptor
Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein
AIP
bull 1 Adrenocorticotropic hormone (ACTH)
bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of
adrenocortical hoemones after long-term glucocorticoid drug use
bull Easily inducing allergy to ACTH
CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase
inhibitorsinhibitors
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response
ndash plasma cortisol levels are elevated
bull Abnormal responsendash plasma cortisol level are unchanged
bull 2 Corticosteroid synthetase inhibitors
bull Mitotane 米托坦
bull Metyrapone 美替拉酮
bull Aminoglutethimide 氨鲁米特
bull Used for adrenocortical tumors or hypercorticism
C Adrenocorticotropic hormone and corticosteroid synthetase
inhibitors
Cortisol Suppression Tests
bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
Action mode of glucocorticoid drugs
CBG corticosteroid binding globulin
S glucocorticoid steroids
GR glucocorticoid receptor
HSP heat shock protein
IP immunophilin
GRE glucocorticoid-response element
Nuclear translocation of glucocorticoid receptors (GR)
Dexamethasone was used
GR was labeled with green fluorescent protein
1 Pharmacological effects
Mechanisms of glucocorticoid actions(1) Effects on metabolisms (2) Permissive action(3) Anti-inflammatory effects(4) Effects on immune and allergy (5) Anti-shock(6) Other effects antipyretic effects effects on blood and blood-forming organs skeletal system CNS effects
AA Glucocorticoid drugs Glucocorticoid drugs
(1) Effects on metabolisms
①Glucose metabolism gluconeogenesis glucose
utilization blood glucose ②Protein metabolism synthesis degradation ③Lipid metabolism plasma cholesterol fat
redistribution (central obesity moon face buffalo hump etc)
④Water and electrolytic metabolism
water excretion Na+ excretion
K+ excretion Ca2+ excretion and absorption
AA Glucocorticoid drugs Glucocorticoid drugs
Weaker action of glucocorticoid drugs (cortisol) on mineralocorticoid receptor
(2) Permissive actionPotentiating the effects of catecholamines and
glucagon (3) Anti-inflammatory effectsAcute inhibiting microvascular leakage leukocyte infiltrationChronic inhibiting fibroblast proliferation deposition of collagen cicatrization ( 瘢痕形成 )
AA Glucocorticoid drugs Glucocorticoid drugs
One of glucocorticoidrsquos anti-inflammatory actions
Inhibition of proinflammatory gene transcription (AP-1 and NFB)
AA Glucocorticoid drugs Glucocorticoid drugs
a) Increasing inflammation related proteins or enzymes
inducing lipocortin inhibiting phospholipase A2 activity decreasing mediators PGs LTs PAF
inducing vasocortin decreasing microvascular permeability
inhibiting the expression of PLA2 COX-2 inducible NOS etc
b) Inhibiting cytokinins decreasing the transcription and activities of TNFα IL-1 IL-2 IL-5 IL-6 IL-8 etc
c) Inhibiting adhesion molecules
d) Inducing the apoptosis of inflammatory cells
AA Glucocorticoid drugs Glucocorticoid drugs
(4) Effects on immune and allergy
Suppressing immunological functions and allergy
a) inducing apoptosis of T and B lymphocytes
b) inhibiting transcription factor activity(eg AP-1 NFB)
AA Glucocorticoid drugs Glucocorticoid drugs
(5) Anti-shock Septic shock
a) improving cardiovascular functions
b) inhibiting the production of inflammatory factors
c) stabilizing lysosome membrane decreasing the release of myocardial depressant factor (MDF)
d) increasing the tolerance to endotoxin from bacteria
AA Glucocorticoid drugs Glucocorticoid drugs
(6) Other effects
a) antipyretic effects
b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )
eosinophils platelets
c) skeletal system osteoporosis
d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)
AA Glucocorticoid drugs Glucocorticoid drugs
2 ADME and properties of commonly used drugs
Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver
Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)
AA Glucocorticoid drugs Glucocorticoid drugs
Commonly used drugs
Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松
Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙
Long-acting dexamethasone 地塞米松
Topical fluocinolone 氟轻松
AA Glucocorticoid drugs Glucocorticoid drugs
CortisonCortisonee
可的松可的松
HydrocortisoHydrocortisonene
氢化可的松氢化可的松
CortisolCortisol
PrednisoPrednisonene
泼尼松泼尼松
PrednisolPrednisoloneone
泼尼松龙泼尼松龙
FluocinoloFluocinolonene
氟轻松氟轻松地塞米松地塞米松
HH
3 Clinical uses
(1) Immune diseases
a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc
b) rejection of organ transplantation
c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc
AA Glucocorticoid drugs Glucocorticoid drugs
(2) Severe infection and inflammation
a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving
Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration
Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms
b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc
AA Glucocorticoid drugsGlucocorticoid drugs
(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined
with antimicrobial drugswith antimicrobial drugs
(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc
(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)
(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc
AA Glucocorticoid drugs
4 Adverse effects of glucocorticoid
drugs
Effects resulting from continued used of large doses
AA Glucocorticoid drugs
4 Adverse effects
(1) Effects resulting from continued used of large doses
a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc
b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be
administered with GCs
c) Ingestive system peptic ulcers etc
AA Glucocorticoid drugsGlucocorticoid drugs
d) Cardiovascular system hypertension arteriosclerosis
e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women
f) CNS behavioral disturbances induction of epileptic seizures
g) Inhibition or arrest of growth in children
AA Glucocorticoid drugsGlucocorticoid drugs
Suppression of hypothalamic-pituitary-adrenal axis
and glucocorticoid drugs
‒‒
ACTH
(2) Withdrawal syndrome
a) Suppression of hypothalamic-pituitary-adrenal axis
b) Exacerbation of the underlying diseases (rebound)
(3) Contraindications
psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc
AA Glucocorticoid drugs Glucocorticoid drugs
Balance the ratio of benefit risk before the use of GCs
AA Glucocorticoid drugsGlucocorticoid drugs
5 Applications
(1) Replacement therapy usually using hydrocortisone
(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone
(3) Long-term therapy oral prednisone or prednisolone
morning single dose
alternate-day therapy
Notes for less severe and less sustained patients
less suppression on hypothalamic-pituitary-adrenal (HPA) axis
(4) Tipical applications skin eye respiratory tract
AA Glucocorticoid drugsGlucocorticoid drugs
bull Aldosterone 醛固酮
bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of
water and electrolytes
BB Mineralocorticoid drugsMineralocorticoid drugs
Action of aldosterone on mineralocorticoid receptor
Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein
AIP
bull 1 Adrenocorticotropic hormone (ACTH)
bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of
adrenocortical hoemones after long-term glucocorticoid drug use
bull Easily inducing allergy to ACTH
CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase
inhibitorsinhibitors
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response
ndash plasma cortisol levels are elevated
bull Abnormal responsendash plasma cortisol level are unchanged
bull 2 Corticosteroid synthetase inhibitors
bull Mitotane 米托坦
bull Metyrapone 美替拉酮
bull Aminoglutethimide 氨鲁米特
bull Used for adrenocortical tumors or hypercorticism
C Adrenocorticotropic hormone and corticosteroid synthetase
inhibitors
Cortisol Suppression Tests
bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
Nuclear translocation of glucocorticoid receptors (GR)
Dexamethasone was used
GR was labeled with green fluorescent protein
1 Pharmacological effects
Mechanisms of glucocorticoid actions(1) Effects on metabolisms (2) Permissive action(3) Anti-inflammatory effects(4) Effects on immune and allergy (5) Anti-shock(6) Other effects antipyretic effects effects on blood and blood-forming organs skeletal system CNS effects
AA Glucocorticoid drugs Glucocorticoid drugs
(1) Effects on metabolisms
①Glucose metabolism gluconeogenesis glucose
utilization blood glucose ②Protein metabolism synthesis degradation ③Lipid metabolism plasma cholesterol fat
redistribution (central obesity moon face buffalo hump etc)
④Water and electrolytic metabolism
water excretion Na+ excretion
K+ excretion Ca2+ excretion and absorption
AA Glucocorticoid drugs Glucocorticoid drugs
Weaker action of glucocorticoid drugs (cortisol) on mineralocorticoid receptor
(2) Permissive actionPotentiating the effects of catecholamines and
glucagon (3) Anti-inflammatory effectsAcute inhibiting microvascular leakage leukocyte infiltrationChronic inhibiting fibroblast proliferation deposition of collagen cicatrization ( 瘢痕形成 )
AA Glucocorticoid drugs Glucocorticoid drugs
One of glucocorticoidrsquos anti-inflammatory actions
Inhibition of proinflammatory gene transcription (AP-1 and NFB)
AA Glucocorticoid drugs Glucocorticoid drugs
a) Increasing inflammation related proteins or enzymes
inducing lipocortin inhibiting phospholipase A2 activity decreasing mediators PGs LTs PAF
inducing vasocortin decreasing microvascular permeability
inhibiting the expression of PLA2 COX-2 inducible NOS etc
b) Inhibiting cytokinins decreasing the transcription and activities of TNFα IL-1 IL-2 IL-5 IL-6 IL-8 etc
c) Inhibiting adhesion molecules
d) Inducing the apoptosis of inflammatory cells
AA Glucocorticoid drugs Glucocorticoid drugs
(4) Effects on immune and allergy
Suppressing immunological functions and allergy
a) inducing apoptosis of T and B lymphocytes
b) inhibiting transcription factor activity(eg AP-1 NFB)
AA Glucocorticoid drugs Glucocorticoid drugs
(5) Anti-shock Septic shock
a) improving cardiovascular functions
b) inhibiting the production of inflammatory factors
c) stabilizing lysosome membrane decreasing the release of myocardial depressant factor (MDF)
d) increasing the tolerance to endotoxin from bacteria
AA Glucocorticoid drugs Glucocorticoid drugs
(6) Other effects
a) antipyretic effects
b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )
eosinophils platelets
c) skeletal system osteoporosis
d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)
AA Glucocorticoid drugs Glucocorticoid drugs
2 ADME and properties of commonly used drugs
Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver
Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)
AA Glucocorticoid drugs Glucocorticoid drugs
Commonly used drugs
Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松
Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙
Long-acting dexamethasone 地塞米松
Topical fluocinolone 氟轻松
AA Glucocorticoid drugs Glucocorticoid drugs
CortisonCortisonee
可的松可的松
HydrocortisoHydrocortisonene
氢化可的松氢化可的松
CortisolCortisol
PrednisoPrednisonene
泼尼松泼尼松
PrednisolPrednisoloneone
泼尼松龙泼尼松龙
FluocinoloFluocinolonene
氟轻松氟轻松地塞米松地塞米松
HH
3 Clinical uses
(1) Immune diseases
a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc
b) rejection of organ transplantation
c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc
AA Glucocorticoid drugs Glucocorticoid drugs
(2) Severe infection and inflammation
a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving
Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration
Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms
b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc
AA Glucocorticoid drugsGlucocorticoid drugs
(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined
with antimicrobial drugswith antimicrobial drugs
(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc
(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)
(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc
AA Glucocorticoid drugs
4 Adverse effects of glucocorticoid
drugs
Effects resulting from continued used of large doses
AA Glucocorticoid drugs
4 Adverse effects
(1) Effects resulting from continued used of large doses
a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc
b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be
administered with GCs
c) Ingestive system peptic ulcers etc
AA Glucocorticoid drugsGlucocorticoid drugs
d) Cardiovascular system hypertension arteriosclerosis
e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women
f) CNS behavioral disturbances induction of epileptic seizures
g) Inhibition or arrest of growth in children
AA Glucocorticoid drugsGlucocorticoid drugs
Suppression of hypothalamic-pituitary-adrenal axis
and glucocorticoid drugs
‒‒
ACTH
(2) Withdrawal syndrome
a) Suppression of hypothalamic-pituitary-adrenal axis
b) Exacerbation of the underlying diseases (rebound)
(3) Contraindications
psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc
AA Glucocorticoid drugs Glucocorticoid drugs
Balance the ratio of benefit risk before the use of GCs
AA Glucocorticoid drugsGlucocorticoid drugs
5 Applications
(1) Replacement therapy usually using hydrocortisone
(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone
(3) Long-term therapy oral prednisone or prednisolone
morning single dose
alternate-day therapy
Notes for less severe and less sustained patients
less suppression on hypothalamic-pituitary-adrenal (HPA) axis
(4) Tipical applications skin eye respiratory tract
AA Glucocorticoid drugsGlucocorticoid drugs
bull Aldosterone 醛固酮
bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of
water and electrolytes
BB Mineralocorticoid drugsMineralocorticoid drugs
Action of aldosterone on mineralocorticoid receptor
Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein
AIP
bull 1 Adrenocorticotropic hormone (ACTH)
bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of
adrenocortical hoemones after long-term glucocorticoid drug use
bull Easily inducing allergy to ACTH
CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase
inhibitorsinhibitors
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response
ndash plasma cortisol levels are elevated
bull Abnormal responsendash plasma cortisol level are unchanged
bull 2 Corticosteroid synthetase inhibitors
bull Mitotane 米托坦
bull Metyrapone 美替拉酮
bull Aminoglutethimide 氨鲁米特
bull Used for adrenocortical tumors or hypercorticism
C Adrenocorticotropic hormone and corticosteroid synthetase
inhibitors
Cortisol Suppression Tests
bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
1 Pharmacological effects
Mechanisms of glucocorticoid actions(1) Effects on metabolisms (2) Permissive action(3) Anti-inflammatory effects(4) Effects on immune and allergy (5) Anti-shock(6) Other effects antipyretic effects effects on blood and blood-forming organs skeletal system CNS effects
AA Glucocorticoid drugs Glucocorticoid drugs
(1) Effects on metabolisms
①Glucose metabolism gluconeogenesis glucose
utilization blood glucose ②Protein metabolism synthesis degradation ③Lipid metabolism plasma cholesterol fat
redistribution (central obesity moon face buffalo hump etc)
④Water and electrolytic metabolism
water excretion Na+ excretion
K+ excretion Ca2+ excretion and absorption
AA Glucocorticoid drugs Glucocorticoid drugs
Weaker action of glucocorticoid drugs (cortisol) on mineralocorticoid receptor
(2) Permissive actionPotentiating the effects of catecholamines and
glucagon (3) Anti-inflammatory effectsAcute inhibiting microvascular leakage leukocyte infiltrationChronic inhibiting fibroblast proliferation deposition of collagen cicatrization ( 瘢痕形成 )
AA Glucocorticoid drugs Glucocorticoid drugs
One of glucocorticoidrsquos anti-inflammatory actions
Inhibition of proinflammatory gene transcription (AP-1 and NFB)
AA Glucocorticoid drugs Glucocorticoid drugs
a) Increasing inflammation related proteins or enzymes
inducing lipocortin inhibiting phospholipase A2 activity decreasing mediators PGs LTs PAF
inducing vasocortin decreasing microvascular permeability
inhibiting the expression of PLA2 COX-2 inducible NOS etc
b) Inhibiting cytokinins decreasing the transcription and activities of TNFα IL-1 IL-2 IL-5 IL-6 IL-8 etc
c) Inhibiting adhesion molecules
d) Inducing the apoptosis of inflammatory cells
AA Glucocorticoid drugs Glucocorticoid drugs
(4) Effects on immune and allergy
Suppressing immunological functions and allergy
a) inducing apoptosis of T and B lymphocytes
b) inhibiting transcription factor activity(eg AP-1 NFB)
AA Glucocorticoid drugs Glucocorticoid drugs
(5) Anti-shock Septic shock
a) improving cardiovascular functions
b) inhibiting the production of inflammatory factors
c) stabilizing lysosome membrane decreasing the release of myocardial depressant factor (MDF)
d) increasing the tolerance to endotoxin from bacteria
AA Glucocorticoid drugs Glucocorticoid drugs
(6) Other effects
a) antipyretic effects
b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )
eosinophils platelets
c) skeletal system osteoporosis
d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)
AA Glucocorticoid drugs Glucocorticoid drugs
2 ADME and properties of commonly used drugs
Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver
Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)
AA Glucocorticoid drugs Glucocorticoid drugs
Commonly used drugs
Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松
Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙
Long-acting dexamethasone 地塞米松
Topical fluocinolone 氟轻松
AA Glucocorticoid drugs Glucocorticoid drugs
CortisonCortisonee
可的松可的松
HydrocortisoHydrocortisonene
氢化可的松氢化可的松
CortisolCortisol
PrednisoPrednisonene
泼尼松泼尼松
PrednisolPrednisoloneone
泼尼松龙泼尼松龙
FluocinoloFluocinolonene
氟轻松氟轻松地塞米松地塞米松
HH
3 Clinical uses
(1) Immune diseases
a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc
b) rejection of organ transplantation
c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc
AA Glucocorticoid drugs Glucocorticoid drugs
(2) Severe infection and inflammation
a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving
Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration
Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms
b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc
AA Glucocorticoid drugsGlucocorticoid drugs
(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined
with antimicrobial drugswith antimicrobial drugs
(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc
(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)
(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc
AA Glucocorticoid drugs
4 Adverse effects of glucocorticoid
drugs
Effects resulting from continued used of large doses
AA Glucocorticoid drugs
4 Adverse effects
(1) Effects resulting from continued used of large doses
a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc
b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be
administered with GCs
c) Ingestive system peptic ulcers etc
AA Glucocorticoid drugsGlucocorticoid drugs
d) Cardiovascular system hypertension arteriosclerosis
e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women
f) CNS behavioral disturbances induction of epileptic seizures
g) Inhibition or arrest of growth in children
AA Glucocorticoid drugsGlucocorticoid drugs
Suppression of hypothalamic-pituitary-adrenal axis
and glucocorticoid drugs
‒‒
ACTH
(2) Withdrawal syndrome
a) Suppression of hypothalamic-pituitary-adrenal axis
b) Exacerbation of the underlying diseases (rebound)
(3) Contraindications
psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc
AA Glucocorticoid drugs Glucocorticoid drugs
Balance the ratio of benefit risk before the use of GCs
AA Glucocorticoid drugsGlucocorticoid drugs
5 Applications
(1) Replacement therapy usually using hydrocortisone
(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone
(3) Long-term therapy oral prednisone or prednisolone
morning single dose
alternate-day therapy
Notes for less severe and less sustained patients
less suppression on hypothalamic-pituitary-adrenal (HPA) axis
(4) Tipical applications skin eye respiratory tract
AA Glucocorticoid drugsGlucocorticoid drugs
bull Aldosterone 醛固酮
bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of
water and electrolytes
BB Mineralocorticoid drugsMineralocorticoid drugs
Action of aldosterone on mineralocorticoid receptor
Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein
AIP
bull 1 Adrenocorticotropic hormone (ACTH)
bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of
adrenocortical hoemones after long-term glucocorticoid drug use
bull Easily inducing allergy to ACTH
CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase
inhibitorsinhibitors
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response
ndash plasma cortisol levels are elevated
bull Abnormal responsendash plasma cortisol level are unchanged
bull 2 Corticosteroid synthetase inhibitors
bull Mitotane 米托坦
bull Metyrapone 美替拉酮
bull Aminoglutethimide 氨鲁米特
bull Used for adrenocortical tumors or hypercorticism
C Adrenocorticotropic hormone and corticosteroid synthetase
inhibitors
Cortisol Suppression Tests
bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
(1) Effects on metabolisms
①Glucose metabolism gluconeogenesis glucose
utilization blood glucose ②Protein metabolism synthesis degradation ③Lipid metabolism plasma cholesterol fat
redistribution (central obesity moon face buffalo hump etc)
④Water and electrolytic metabolism
water excretion Na+ excretion
K+ excretion Ca2+ excretion and absorption
AA Glucocorticoid drugs Glucocorticoid drugs
Weaker action of glucocorticoid drugs (cortisol) on mineralocorticoid receptor
(2) Permissive actionPotentiating the effects of catecholamines and
glucagon (3) Anti-inflammatory effectsAcute inhibiting microvascular leakage leukocyte infiltrationChronic inhibiting fibroblast proliferation deposition of collagen cicatrization ( 瘢痕形成 )
AA Glucocorticoid drugs Glucocorticoid drugs
One of glucocorticoidrsquos anti-inflammatory actions
Inhibition of proinflammatory gene transcription (AP-1 and NFB)
AA Glucocorticoid drugs Glucocorticoid drugs
a) Increasing inflammation related proteins or enzymes
inducing lipocortin inhibiting phospholipase A2 activity decreasing mediators PGs LTs PAF
inducing vasocortin decreasing microvascular permeability
inhibiting the expression of PLA2 COX-2 inducible NOS etc
b) Inhibiting cytokinins decreasing the transcription and activities of TNFα IL-1 IL-2 IL-5 IL-6 IL-8 etc
c) Inhibiting adhesion molecules
d) Inducing the apoptosis of inflammatory cells
AA Glucocorticoid drugs Glucocorticoid drugs
(4) Effects on immune and allergy
Suppressing immunological functions and allergy
a) inducing apoptosis of T and B lymphocytes
b) inhibiting transcription factor activity(eg AP-1 NFB)
AA Glucocorticoid drugs Glucocorticoid drugs
(5) Anti-shock Septic shock
a) improving cardiovascular functions
b) inhibiting the production of inflammatory factors
c) stabilizing lysosome membrane decreasing the release of myocardial depressant factor (MDF)
d) increasing the tolerance to endotoxin from bacteria
AA Glucocorticoid drugs Glucocorticoid drugs
(6) Other effects
a) antipyretic effects
b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )
eosinophils platelets
c) skeletal system osteoporosis
d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)
AA Glucocorticoid drugs Glucocorticoid drugs
2 ADME and properties of commonly used drugs
Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver
Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)
AA Glucocorticoid drugs Glucocorticoid drugs
Commonly used drugs
Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松
Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙
Long-acting dexamethasone 地塞米松
Topical fluocinolone 氟轻松
AA Glucocorticoid drugs Glucocorticoid drugs
CortisonCortisonee
可的松可的松
HydrocortisoHydrocortisonene
氢化可的松氢化可的松
CortisolCortisol
PrednisoPrednisonene
泼尼松泼尼松
PrednisolPrednisoloneone
泼尼松龙泼尼松龙
FluocinoloFluocinolonene
氟轻松氟轻松地塞米松地塞米松
HH
3 Clinical uses
(1) Immune diseases
a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc
b) rejection of organ transplantation
c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc
AA Glucocorticoid drugs Glucocorticoid drugs
(2) Severe infection and inflammation
a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving
Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration
Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms
b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc
AA Glucocorticoid drugsGlucocorticoid drugs
(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined
with antimicrobial drugswith antimicrobial drugs
(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc
(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)
(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc
AA Glucocorticoid drugs
4 Adverse effects of glucocorticoid
drugs
Effects resulting from continued used of large doses
AA Glucocorticoid drugs
4 Adverse effects
(1) Effects resulting from continued used of large doses
a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc
b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be
administered with GCs
c) Ingestive system peptic ulcers etc
AA Glucocorticoid drugsGlucocorticoid drugs
d) Cardiovascular system hypertension arteriosclerosis
e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women
f) CNS behavioral disturbances induction of epileptic seizures
g) Inhibition or arrest of growth in children
AA Glucocorticoid drugsGlucocorticoid drugs
Suppression of hypothalamic-pituitary-adrenal axis
and glucocorticoid drugs
‒‒
ACTH
(2) Withdrawal syndrome
a) Suppression of hypothalamic-pituitary-adrenal axis
b) Exacerbation of the underlying diseases (rebound)
(3) Contraindications
psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc
AA Glucocorticoid drugs Glucocorticoid drugs
Balance the ratio of benefit risk before the use of GCs
AA Glucocorticoid drugsGlucocorticoid drugs
5 Applications
(1) Replacement therapy usually using hydrocortisone
(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone
(3) Long-term therapy oral prednisone or prednisolone
morning single dose
alternate-day therapy
Notes for less severe and less sustained patients
less suppression on hypothalamic-pituitary-adrenal (HPA) axis
(4) Tipical applications skin eye respiratory tract
AA Glucocorticoid drugsGlucocorticoid drugs
bull Aldosterone 醛固酮
bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of
water and electrolytes
BB Mineralocorticoid drugsMineralocorticoid drugs
Action of aldosterone on mineralocorticoid receptor
Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein
AIP
bull 1 Adrenocorticotropic hormone (ACTH)
bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of
adrenocortical hoemones after long-term glucocorticoid drug use
bull Easily inducing allergy to ACTH
CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase
inhibitorsinhibitors
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response
ndash plasma cortisol levels are elevated
bull Abnormal responsendash plasma cortisol level are unchanged
bull 2 Corticosteroid synthetase inhibitors
bull Mitotane 米托坦
bull Metyrapone 美替拉酮
bull Aminoglutethimide 氨鲁米特
bull Used for adrenocortical tumors or hypercorticism
C Adrenocorticotropic hormone and corticosteroid synthetase
inhibitors
Cortisol Suppression Tests
bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
Weaker action of glucocorticoid drugs (cortisol) on mineralocorticoid receptor
(2) Permissive actionPotentiating the effects of catecholamines and
glucagon (3) Anti-inflammatory effectsAcute inhibiting microvascular leakage leukocyte infiltrationChronic inhibiting fibroblast proliferation deposition of collagen cicatrization ( 瘢痕形成 )
AA Glucocorticoid drugs Glucocorticoid drugs
One of glucocorticoidrsquos anti-inflammatory actions
Inhibition of proinflammatory gene transcription (AP-1 and NFB)
AA Glucocorticoid drugs Glucocorticoid drugs
a) Increasing inflammation related proteins or enzymes
inducing lipocortin inhibiting phospholipase A2 activity decreasing mediators PGs LTs PAF
inducing vasocortin decreasing microvascular permeability
inhibiting the expression of PLA2 COX-2 inducible NOS etc
b) Inhibiting cytokinins decreasing the transcription and activities of TNFα IL-1 IL-2 IL-5 IL-6 IL-8 etc
c) Inhibiting adhesion molecules
d) Inducing the apoptosis of inflammatory cells
AA Glucocorticoid drugs Glucocorticoid drugs
(4) Effects on immune and allergy
Suppressing immunological functions and allergy
a) inducing apoptosis of T and B lymphocytes
b) inhibiting transcription factor activity(eg AP-1 NFB)
AA Glucocorticoid drugs Glucocorticoid drugs
(5) Anti-shock Septic shock
a) improving cardiovascular functions
b) inhibiting the production of inflammatory factors
c) stabilizing lysosome membrane decreasing the release of myocardial depressant factor (MDF)
d) increasing the tolerance to endotoxin from bacteria
AA Glucocorticoid drugs Glucocorticoid drugs
(6) Other effects
a) antipyretic effects
b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )
eosinophils platelets
c) skeletal system osteoporosis
d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)
AA Glucocorticoid drugs Glucocorticoid drugs
2 ADME and properties of commonly used drugs
Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver
Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)
AA Glucocorticoid drugs Glucocorticoid drugs
Commonly used drugs
Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松
Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙
Long-acting dexamethasone 地塞米松
Topical fluocinolone 氟轻松
AA Glucocorticoid drugs Glucocorticoid drugs
CortisonCortisonee
可的松可的松
HydrocortisoHydrocortisonene
氢化可的松氢化可的松
CortisolCortisol
PrednisoPrednisonene
泼尼松泼尼松
PrednisolPrednisoloneone
泼尼松龙泼尼松龙
FluocinoloFluocinolonene
氟轻松氟轻松地塞米松地塞米松
HH
3 Clinical uses
(1) Immune diseases
a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc
b) rejection of organ transplantation
c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc
AA Glucocorticoid drugs Glucocorticoid drugs
(2) Severe infection and inflammation
a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving
Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration
Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms
b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc
AA Glucocorticoid drugsGlucocorticoid drugs
(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined
with antimicrobial drugswith antimicrobial drugs
(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc
(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)
(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc
AA Glucocorticoid drugs
4 Adverse effects of glucocorticoid
drugs
Effects resulting from continued used of large doses
AA Glucocorticoid drugs
4 Adverse effects
(1) Effects resulting from continued used of large doses
a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc
b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be
administered with GCs
c) Ingestive system peptic ulcers etc
AA Glucocorticoid drugsGlucocorticoid drugs
d) Cardiovascular system hypertension arteriosclerosis
e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women
f) CNS behavioral disturbances induction of epileptic seizures
g) Inhibition or arrest of growth in children
AA Glucocorticoid drugsGlucocorticoid drugs
Suppression of hypothalamic-pituitary-adrenal axis
and glucocorticoid drugs
‒‒
ACTH
(2) Withdrawal syndrome
a) Suppression of hypothalamic-pituitary-adrenal axis
b) Exacerbation of the underlying diseases (rebound)
(3) Contraindications
psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc
AA Glucocorticoid drugs Glucocorticoid drugs
Balance the ratio of benefit risk before the use of GCs
AA Glucocorticoid drugsGlucocorticoid drugs
5 Applications
(1) Replacement therapy usually using hydrocortisone
(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone
(3) Long-term therapy oral prednisone or prednisolone
morning single dose
alternate-day therapy
Notes for less severe and less sustained patients
less suppression on hypothalamic-pituitary-adrenal (HPA) axis
(4) Tipical applications skin eye respiratory tract
AA Glucocorticoid drugsGlucocorticoid drugs
bull Aldosterone 醛固酮
bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of
water and electrolytes
BB Mineralocorticoid drugsMineralocorticoid drugs
Action of aldosterone on mineralocorticoid receptor
Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein
AIP
bull 1 Adrenocorticotropic hormone (ACTH)
bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of
adrenocortical hoemones after long-term glucocorticoid drug use
bull Easily inducing allergy to ACTH
CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase
inhibitorsinhibitors
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response
ndash plasma cortisol levels are elevated
bull Abnormal responsendash plasma cortisol level are unchanged
bull 2 Corticosteroid synthetase inhibitors
bull Mitotane 米托坦
bull Metyrapone 美替拉酮
bull Aminoglutethimide 氨鲁米特
bull Used for adrenocortical tumors or hypercorticism
C Adrenocorticotropic hormone and corticosteroid synthetase
inhibitors
Cortisol Suppression Tests
bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
(2) Permissive actionPotentiating the effects of catecholamines and
glucagon (3) Anti-inflammatory effectsAcute inhibiting microvascular leakage leukocyte infiltrationChronic inhibiting fibroblast proliferation deposition of collagen cicatrization ( 瘢痕形成 )
AA Glucocorticoid drugs Glucocorticoid drugs
One of glucocorticoidrsquos anti-inflammatory actions
Inhibition of proinflammatory gene transcription (AP-1 and NFB)
AA Glucocorticoid drugs Glucocorticoid drugs
a) Increasing inflammation related proteins or enzymes
inducing lipocortin inhibiting phospholipase A2 activity decreasing mediators PGs LTs PAF
inducing vasocortin decreasing microvascular permeability
inhibiting the expression of PLA2 COX-2 inducible NOS etc
b) Inhibiting cytokinins decreasing the transcription and activities of TNFα IL-1 IL-2 IL-5 IL-6 IL-8 etc
c) Inhibiting adhesion molecules
d) Inducing the apoptosis of inflammatory cells
AA Glucocorticoid drugs Glucocorticoid drugs
(4) Effects on immune and allergy
Suppressing immunological functions and allergy
a) inducing apoptosis of T and B lymphocytes
b) inhibiting transcription factor activity(eg AP-1 NFB)
AA Glucocorticoid drugs Glucocorticoid drugs
(5) Anti-shock Septic shock
a) improving cardiovascular functions
b) inhibiting the production of inflammatory factors
c) stabilizing lysosome membrane decreasing the release of myocardial depressant factor (MDF)
d) increasing the tolerance to endotoxin from bacteria
AA Glucocorticoid drugs Glucocorticoid drugs
(6) Other effects
a) antipyretic effects
b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )
eosinophils platelets
c) skeletal system osteoporosis
d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)
AA Glucocorticoid drugs Glucocorticoid drugs
2 ADME and properties of commonly used drugs
Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver
Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)
AA Glucocorticoid drugs Glucocorticoid drugs
Commonly used drugs
Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松
Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙
Long-acting dexamethasone 地塞米松
Topical fluocinolone 氟轻松
AA Glucocorticoid drugs Glucocorticoid drugs
CortisonCortisonee
可的松可的松
HydrocortisoHydrocortisonene
氢化可的松氢化可的松
CortisolCortisol
PrednisoPrednisonene
泼尼松泼尼松
PrednisolPrednisoloneone
泼尼松龙泼尼松龙
FluocinoloFluocinolonene
氟轻松氟轻松地塞米松地塞米松
HH
3 Clinical uses
(1) Immune diseases
a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc
b) rejection of organ transplantation
c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc
AA Glucocorticoid drugs Glucocorticoid drugs
(2) Severe infection and inflammation
a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving
Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration
Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms
b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc
AA Glucocorticoid drugsGlucocorticoid drugs
(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined
with antimicrobial drugswith antimicrobial drugs
(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc
(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)
(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc
AA Glucocorticoid drugs
4 Adverse effects of glucocorticoid
drugs
Effects resulting from continued used of large doses
AA Glucocorticoid drugs
4 Adverse effects
(1) Effects resulting from continued used of large doses
a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc
b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be
administered with GCs
c) Ingestive system peptic ulcers etc
AA Glucocorticoid drugsGlucocorticoid drugs
d) Cardiovascular system hypertension arteriosclerosis
e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women
f) CNS behavioral disturbances induction of epileptic seizures
g) Inhibition or arrest of growth in children
AA Glucocorticoid drugsGlucocorticoid drugs
Suppression of hypothalamic-pituitary-adrenal axis
and glucocorticoid drugs
‒‒
ACTH
(2) Withdrawal syndrome
a) Suppression of hypothalamic-pituitary-adrenal axis
b) Exacerbation of the underlying diseases (rebound)
(3) Contraindications
psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc
AA Glucocorticoid drugs Glucocorticoid drugs
Balance the ratio of benefit risk before the use of GCs
AA Glucocorticoid drugsGlucocorticoid drugs
5 Applications
(1) Replacement therapy usually using hydrocortisone
(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone
(3) Long-term therapy oral prednisone or prednisolone
morning single dose
alternate-day therapy
Notes for less severe and less sustained patients
less suppression on hypothalamic-pituitary-adrenal (HPA) axis
(4) Tipical applications skin eye respiratory tract
AA Glucocorticoid drugsGlucocorticoid drugs
bull Aldosterone 醛固酮
bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of
water and electrolytes
BB Mineralocorticoid drugsMineralocorticoid drugs
Action of aldosterone on mineralocorticoid receptor
Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein
AIP
bull 1 Adrenocorticotropic hormone (ACTH)
bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of
adrenocortical hoemones after long-term glucocorticoid drug use
bull Easily inducing allergy to ACTH
CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase
inhibitorsinhibitors
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response
ndash plasma cortisol levels are elevated
bull Abnormal responsendash plasma cortisol level are unchanged
bull 2 Corticosteroid synthetase inhibitors
bull Mitotane 米托坦
bull Metyrapone 美替拉酮
bull Aminoglutethimide 氨鲁米特
bull Used for adrenocortical tumors or hypercorticism
C Adrenocorticotropic hormone and corticosteroid synthetase
inhibitors
Cortisol Suppression Tests
bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
One of glucocorticoidrsquos anti-inflammatory actions
Inhibition of proinflammatory gene transcription (AP-1 and NFB)
AA Glucocorticoid drugs Glucocorticoid drugs
a) Increasing inflammation related proteins or enzymes
inducing lipocortin inhibiting phospholipase A2 activity decreasing mediators PGs LTs PAF
inducing vasocortin decreasing microvascular permeability
inhibiting the expression of PLA2 COX-2 inducible NOS etc
b) Inhibiting cytokinins decreasing the transcription and activities of TNFα IL-1 IL-2 IL-5 IL-6 IL-8 etc
c) Inhibiting adhesion molecules
d) Inducing the apoptosis of inflammatory cells
AA Glucocorticoid drugs Glucocorticoid drugs
(4) Effects on immune and allergy
Suppressing immunological functions and allergy
a) inducing apoptosis of T and B lymphocytes
b) inhibiting transcription factor activity(eg AP-1 NFB)
AA Glucocorticoid drugs Glucocorticoid drugs
(5) Anti-shock Septic shock
a) improving cardiovascular functions
b) inhibiting the production of inflammatory factors
c) stabilizing lysosome membrane decreasing the release of myocardial depressant factor (MDF)
d) increasing the tolerance to endotoxin from bacteria
AA Glucocorticoid drugs Glucocorticoid drugs
(6) Other effects
a) antipyretic effects
b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )
eosinophils platelets
c) skeletal system osteoporosis
d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)
AA Glucocorticoid drugs Glucocorticoid drugs
2 ADME and properties of commonly used drugs
Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver
Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)
AA Glucocorticoid drugs Glucocorticoid drugs
Commonly used drugs
Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松
Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙
Long-acting dexamethasone 地塞米松
Topical fluocinolone 氟轻松
AA Glucocorticoid drugs Glucocorticoid drugs
CortisonCortisonee
可的松可的松
HydrocortisoHydrocortisonene
氢化可的松氢化可的松
CortisolCortisol
PrednisoPrednisonene
泼尼松泼尼松
PrednisolPrednisoloneone
泼尼松龙泼尼松龙
FluocinoloFluocinolonene
氟轻松氟轻松地塞米松地塞米松
HH
3 Clinical uses
(1) Immune diseases
a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc
b) rejection of organ transplantation
c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc
AA Glucocorticoid drugs Glucocorticoid drugs
(2) Severe infection and inflammation
a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving
Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration
Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms
b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc
AA Glucocorticoid drugsGlucocorticoid drugs
(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined
with antimicrobial drugswith antimicrobial drugs
(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc
(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)
(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc
AA Glucocorticoid drugs
4 Adverse effects of glucocorticoid
drugs
Effects resulting from continued used of large doses
AA Glucocorticoid drugs
4 Adverse effects
(1) Effects resulting from continued used of large doses
a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc
b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be
administered with GCs
c) Ingestive system peptic ulcers etc
AA Glucocorticoid drugsGlucocorticoid drugs
d) Cardiovascular system hypertension arteriosclerosis
e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women
f) CNS behavioral disturbances induction of epileptic seizures
g) Inhibition or arrest of growth in children
AA Glucocorticoid drugsGlucocorticoid drugs
Suppression of hypothalamic-pituitary-adrenal axis
and glucocorticoid drugs
‒‒
ACTH
(2) Withdrawal syndrome
a) Suppression of hypothalamic-pituitary-adrenal axis
b) Exacerbation of the underlying diseases (rebound)
(3) Contraindications
psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc
AA Glucocorticoid drugs Glucocorticoid drugs
Balance the ratio of benefit risk before the use of GCs
AA Glucocorticoid drugsGlucocorticoid drugs
5 Applications
(1) Replacement therapy usually using hydrocortisone
(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone
(3) Long-term therapy oral prednisone or prednisolone
morning single dose
alternate-day therapy
Notes for less severe and less sustained patients
less suppression on hypothalamic-pituitary-adrenal (HPA) axis
(4) Tipical applications skin eye respiratory tract
AA Glucocorticoid drugsGlucocorticoid drugs
bull Aldosterone 醛固酮
bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of
water and electrolytes
BB Mineralocorticoid drugsMineralocorticoid drugs
Action of aldosterone on mineralocorticoid receptor
Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein
AIP
bull 1 Adrenocorticotropic hormone (ACTH)
bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of
adrenocortical hoemones after long-term glucocorticoid drug use
bull Easily inducing allergy to ACTH
CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase
inhibitorsinhibitors
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response
ndash plasma cortisol levels are elevated
bull Abnormal responsendash plasma cortisol level are unchanged
bull 2 Corticosteroid synthetase inhibitors
bull Mitotane 米托坦
bull Metyrapone 美替拉酮
bull Aminoglutethimide 氨鲁米特
bull Used for adrenocortical tumors or hypercorticism
C Adrenocorticotropic hormone and corticosteroid synthetase
inhibitors
Cortisol Suppression Tests
bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
a) Increasing inflammation related proteins or enzymes
inducing lipocortin inhibiting phospholipase A2 activity decreasing mediators PGs LTs PAF
inducing vasocortin decreasing microvascular permeability
inhibiting the expression of PLA2 COX-2 inducible NOS etc
b) Inhibiting cytokinins decreasing the transcription and activities of TNFα IL-1 IL-2 IL-5 IL-6 IL-8 etc
c) Inhibiting adhesion molecules
d) Inducing the apoptosis of inflammatory cells
AA Glucocorticoid drugs Glucocorticoid drugs
(4) Effects on immune and allergy
Suppressing immunological functions and allergy
a) inducing apoptosis of T and B lymphocytes
b) inhibiting transcription factor activity(eg AP-1 NFB)
AA Glucocorticoid drugs Glucocorticoid drugs
(5) Anti-shock Septic shock
a) improving cardiovascular functions
b) inhibiting the production of inflammatory factors
c) stabilizing lysosome membrane decreasing the release of myocardial depressant factor (MDF)
d) increasing the tolerance to endotoxin from bacteria
AA Glucocorticoid drugs Glucocorticoid drugs
(6) Other effects
a) antipyretic effects
b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )
eosinophils platelets
c) skeletal system osteoporosis
d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)
AA Glucocorticoid drugs Glucocorticoid drugs
2 ADME and properties of commonly used drugs
Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver
Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)
AA Glucocorticoid drugs Glucocorticoid drugs
Commonly used drugs
Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松
Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙
Long-acting dexamethasone 地塞米松
Topical fluocinolone 氟轻松
AA Glucocorticoid drugs Glucocorticoid drugs
CortisonCortisonee
可的松可的松
HydrocortisoHydrocortisonene
氢化可的松氢化可的松
CortisolCortisol
PrednisoPrednisonene
泼尼松泼尼松
PrednisolPrednisoloneone
泼尼松龙泼尼松龙
FluocinoloFluocinolonene
氟轻松氟轻松地塞米松地塞米松
HH
3 Clinical uses
(1) Immune diseases
a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc
b) rejection of organ transplantation
c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc
AA Glucocorticoid drugs Glucocorticoid drugs
(2) Severe infection and inflammation
a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving
Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration
Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms
b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc
AA Glucocorticoid drugsGlucocorticoid drugs
(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined
with antimicrobial drugswith antimicrobial drugs
(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc
(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)
(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc
AA Glucocorticoid drugs
4 Adverse effects of glucocorticoid
drugs
Effects resulting from continued used of large doses
AA Glucocorticoid drugs
4 Adverse effects
(1) Effects resulting from continued used of large doses
a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc
b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be
administered with GCs
c) Ingestive system peptic ulcers etc
AA Glucocorticoid drugsGlucocorticoid drugs
d) Cardiovascular system hypertension arteriosclerosis
e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women
f) CNS behavioral disturbances induction of epileptic seizures
g) Inhibition or arrest of growth in children
AA Glucocorticoid drugsGlucocorticoid drugs
Suppression of hypothalamic-pituitary-adrenal axis
and glucocorticoid drugs
‒‒
ACTH
(2) Withdrawal syndrome
a) Suppression of hypothalamic-pituitary-adrenal axis
b) Exacerbation of the underlying diseases (rebound)
(3) Contraindications
psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc
AA Glucocorticoid drugs Glucocorticoid drugs
Balance the ratio of benefit risk before the use of GCs
AA Glucocorticoid drugsGlucocorticoid drugs
5 Applications
(1) Replacement therapy usually using hydrocortisone
(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone
(3) Long-term therapy oral prednisone or prednisolone
morning single dose
alternate-day therapy
Notes for less severe and less sustained patients
less suppression on hypothalamic-pituitary-adrenal (HPA) axis
(4) Tipical applications skin eye respiratory tract
AA Glucocorticoid drugsGlucocorticoid drugs
bull Aldosterone 醛固酮
bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of
water and electrolytes
BB Mineralocorticoid drugsMineralocorticoid drugs
Action of aldosterone on mineralocorticoid receptor
Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein
AIP
bull 1 Adrenocorticotropic hormone (ACTH)
bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of
adrenocortical hoemones after long-term glucocorticoid drug use
bull Easily inducing allergy to ACTH
CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase
inhibitorsinhibitors
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response
ndash plasma cortisol levels are elevated
bull Abnormal responsendash plasma cortisol level are unchanged
bull 2 Corticosteroid synthetase inhibitors
bull Mitotane 米托坦
bull Metyrapone 美替拉酮
bull Aminoglutethimide 氨鲁米特
bull Used for adrenocortical tumors or hypercorticism
C Adrenocorticotropic hormone and corticosteroid synthetase
inhibitors
Cortisol Suppression Tests
bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
(4) Effects on immune and allergy
Suppressing immunological functions and allergy
a) inducing apoptosis of T and B lymphocytes
b) inhibiting transcription factor activity(eg AP-1 NFB)
AA Glucocorticoid drugs Glucocorticoid drugs
(5) Anti-shock Septic shock
a) improving cardiovascular functions
b) inhibiting the production of inflammatory factors
c) stabilizing lysosome membrane decreasing the release of myocardial depressant factor (MDF)
d) increasing the tolerance to endotoxin from bacteria
AA Glucocorticoid drugs Glucocorticoid drugs
(6) Other effects
a) antipyretic effects
b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )
eosinophils platelets
c) skeletal system osteoporosis
d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)
AA Glucocorticoid drugs Glucocorticoid drugs
2 ADME and properties of commonly used drugs
Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver
Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)
AA Glucocorticoid drugs Glucocorticoid drugs
Commonly used drugs
Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松
Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙
Long-acting dexamethasone 地塞米松
Topical fluocinolone 氟轻松
AA Glucocorticoid drugs Glucocorticoid drugs
CortisonCortisonee
可的松可的松
HydrocortisoHydrocortisonene
氢化可的松氢化可的松
CortisolCortisol
PrednisoPrednisonene
泼尼松泼尼松
PrednisolPrednisoloneone
泼尼松龙泼尼松龙
FluocinoloFluocinolonene
氟轻松氟轻松地塞米松地塞米松
HH
3 Clinical uses
(1) Immune diseases
a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc
b) rejection of organ transplantation
c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc
AA Glucocorticoid drugs Glucocorticoid drugs
(2) Severe infection and inflammation
a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving
Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration
Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms
b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc
AA Glucocorticoid drugsGlucocorticoid drugs
(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined
with antimicrobial drugswith antimicrobial drugs
(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc
(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)
(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc
AA Glucocorticoid drugs
4 Adverse effects of glucocorticoid
drugs
Effects resulting from continued used of large doses
AA Glucocorticoid drugs
4 Adverse effects
(1) Effects resulting from continued used of large doses
a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc
b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be
administered with GCs
c) Ingestive system peptic ulcers etc
AA Glucocorticoid drugsGlucocorticoid drugs
d) Cardiovascular system hypertension arteriosclerosis
e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women
f) CNS behavioral disturbances induction of epileptic seizures
g) Inhibition or arrest of growth in children
AA Glucocorticoid drugsGlucocorticoid drugs
Suppression of hypothalamic-pituitary-adrenal axis
and glucocorticoid drugs
‒‒
ACTH
(2) Withdrawal syndrome
a) Suppression of hypothalamic-pituitary-adrenal axis
b) Exacerbation of the underlying diseases (rebound)
(3) Contraindications
psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc
AA Glucocorticoid drugs Glucocorticoid drugs
Balance the ratio of benefit risk before the use of GCs
AA Glucocorticoid drugsGlucocorticoid drugs
5 Applications
(1) Replacement therapy usually using hydrocortisone
(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone
(3) Long-term therapy oral prednisone or prednisolone
morning single dose
alternate-day therapy
Notes for less severe and less sustained patients
less suppression on hypothalamic-pituitary-adrenal (HPA) axis
(4) Tipical applications skin eye respiratory tract
AA Glucocorticoid drugsGlucocorticoid drugs
bull Aldosterone 醛固酮
bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of
water and electrolytes
BB Mineralocorticoid drugsMineralocorticoid drugs
Action of aldosterone on mineralocorticoid receptor
Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein
AIP
bull 1 Adrenocorticotropic hormone (ACTH)
bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of
adrenocortical hoemones after long-term glucocorticoid drug use
bull Easily inducing allergy to ACTH
CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase
inhibitorsinhibitors
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response
ndash plasma cortisol levels are elevated
bull Abnormal responsendash plasma cortisol level are unchanged
bull 2 Corticosteroid synthetase inhibitors
bull Mitotane 米托坦
bull Metyrapone 美替拉酮
bull Aminoglutethimide 氨鲁米特
bull Used for adrenocortical tumors or hypercorticism
C Adrenocorticotropic hormone and corticosteroid synthetase
inhibitors
Cortisol Suppression Tests
bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
(5) Anti-shock Septic shock
a) improving cardiovascular functions
b) inhibiting the production of inflammatory factors
c) stabilizing lysosome membrane decreasing the release of myocardial depressant factor (MDF)
d) increasing the tolerance to endotoxin from bacteria
AA Glucocorticoid drugs Glucocorticoid drugs
(6) Other effects
a) antipyretic effects
b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )
eosinophils platelets
c) skeletal system osteoporosis
d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)
AA Glucocorticoid drugs Glucocorticoid drugs
2 ADME and properties of commonly used drugs
Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver
Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)
AA Glucocorticoid drugs Glucocorticoid drugs
Commonly used drugs
Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松
Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙
Long-acting dexamethasone 地塞米松
Topical fluocinolone 氟轻松
AA Glucocorticoid drugs Glucocorticoid drugs
CortisonCortisonee
可的松可的松
HydrocortisoHydrocortisonene
氢化可的松氢化可的松
CortisolCortisol
PrednisoPrednisonene
泼尼松泼尼松
PrednisolPrednisoloneone
泼尼松龙泼尼松龙
FluocinoloFluocinolonene
氟轻松氟轻松地塞米松地塞米松
HH
3 Clinical uses
(1) Immune diseases
a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc
b) rejection of organ transplantation
c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc
AA Glucocorticoid drugs Glucocorticoid drugs
(2) Severe infection and inflammation
a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving
Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration
Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms
b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc
AA Glucocorticoid drugsGlucocorticoid drugs
(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined
with antimicrobial drugswith antimicrobial drugs
(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc
(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)
(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc
AA Glucocorticoid drugs
4 Adverse effects of glucocorticoid
drugs
Effects resulting from continued used of large doses
AA Glucocorticoid drugs
4 Adverse effects
(1) Effects resulting from continued used of large doses
a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc
b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be
administered with GCs
c) Ingestive system peptic ulcers etc
AA Glucocorticoid drugsGlucocorticoid drugs
d) Cardiovascular system hypertension arteriosclerosis
e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women
f) CNS behavioral disturbances induction of epileptic seizures
g) Inhibition or arrest of growth in children
AA Glucocorticoid drugsGlucocorticoid drugs
Suppression of hypothalamic-pituitary-adrenal axis
and glucocorticoid drugs
‒‒
ACTH
(2) Withdrawal syndrome
a) Suppression of hypothalamic-pituitary-adrenal axis
b) Exacerbation of the underlying diseases (rebound)
(3) Contraindications
psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc
AA Glucocorticoid drugs Glucocorticoid drugs
Balance the ratio of benefit risk before the use of GCs
AA Glucocorticoid drugsGlucocorticoid drugs
5 Applications
(1) Replacement therapy usually using hydrocortisone
(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone
(3) Long-term therapy oral prednisone or prednisolone
morning single dose
alternate-day therapy
Notes for less severe and less sustained patients
less suppression on hypothalamic-pituitary-adrenal (HPA) axis
(4) Tipical applications skin eye respiratory tract
AA Glucocorticoid drugsGlucocorticoid drugs
bull Aldosterone 醛固酮
bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of
water and electrolytes
BB Mineralocorticoid drugsMineralocorticoid drugs
Action of aldosterone on mineralocorticoid receptor
Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein
AIP
bull 1 Adrenocorticotropic hormone (ACTH)
bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of
adrenocortical hoemones after long-term glucocorticoid drug use
bull Easily inducing allergy to ACTH
CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase
inhibitorsinhibitors
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response
ndash plasma cortisol levels are elevated
bull Abnormal responsendash plasma cortisol level are unchanged
bull 2 Corticosteroid synthetase inhibitors
bull Mitotane 米托坦
bull Metyrapone 美替拉酮
bull Aminoglutethimide 氨鲁米特
bull Used for adrenocortical tumors or hypercorticism
C Adrenocorticotropic hormone and corticosteroid synthetase
inhibitors
Cortisol Suppression Tests
bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
(6) Other effects
a) antipyretic effects
b) effects on blood and blood-forming organsred cell lymphocytes neutrophils (function )
eosinophils platelets
c) skeletal system osteoporosis
d) CNS increasing excitability (elevated mood euphoria insomnia restlessness increased motor activity)
AA Glucocorticoid drugs Glucocorticoid drugs
2 ADME and properties of commonly used drugs
Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver
Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)
AA Glucocorticoid drugs Glucocorticoid drugs
Commonly used drugs
Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松
Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙
Long-acting dexamethasone 地塞米松
Topical fluocinolone 氟轻松
AA Glucocorticoid drugs Glucocorticoid drugs
CortisonCortisonee
可的松可的松
HydrocortisoHydrocortisonene
氢化可的松氢化可的松
CortisolCortisol
PrednisoPrednisonene
泼尼松泼尼松
PrednisolPrednisoloneone
泼尼松龙泼尼松龙
FluocinoloFluocinolonene
氟轻松氟轻松地塞米松地塞米松
HH
3 Clinical uses
(1) Immune diseases
a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc
b) rejection of organ transplantation
c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc
AA Glucocorticoid drugs Glucocorticoid drugs
(2) Severe infection and inflammation
a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving
Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration
Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms
b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc
AA Glucocorticoid drugsGlucocorticoid drugs
(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined
with antimicrobial drugswith antimicrobial drugs
(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc
(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)
(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc
AA Glucocorticoid drugs
4 Adverse effects of glucocorticoid
drugs
Effects resulting from continued used of large doses
AA Glucocorticoid drugs
4 Adverse effects
(1) Effects resulting from continued used of large doses
a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc
b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be
administered with GCs
c) Ingestive system peptic ulcers etc
AA Glucocorticoid drugsGlucocorticoid drugs
d) Cardiovascular system hypertension arteriosclerosis
e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women
f) CNS behavioral disturbances induction of epileptic seizures
g) Inhibition or arrest of growth in children
AA Glucocorticoid drugsGlucocorticoid drugs
Suppression of hypothalamic-pituitary-adrenal axis
and glucocorticoid drugs
‒‒
ACTH
(2) Withdrawal syndrome
a) Suppression of hypothalamic-pituitary-adrenal axis
b) Exacerbation of the underlying diseases (rebound)
(3) Contraindications
psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc
AA Glucocorticoid drugs Glucocorticoid drugs
Balance the ratio of benefit risk before the use of GCs
AA Glucocorticoid drugsGlucocorticoid drugs
5 Applications
(1) Replacement therapy usually using hydrocortisone
(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone
(3) Long-term therapy oral prednisone or prednisolone
morning single dose
alternate-day therapy
Notes for less severe and less sustained patients
less suppression on hypothalamic-pituitary-adrenal (HPA) axis
(4) Tipical applications skin eye respiratory tract
AA Glucocorticoid drugsGlucocorticoid drugs
bull Aldosterone 醛固酮
bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of
water and electrolytes
BB Mineralocorticoid drugsMineralocorticoid drugs
Action of aldosterone on mineralocorticoid receptor
Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein
AIP
bull 1 Adrenocorticotropic hormone (ACTH)
bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of
adrenocortical hoemones after long-term glucocorticoid drug use
bull Easily inducing allergy to ACTH
CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase
inhibitorsinhibitors
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response
ndash plasma cortisol levels are elevated
bull Abnormal responsendash plasma cortisol level are unchanged
bull 2 Corticosteroid synthetase inhibitors
bull Mitotane 米托坦
bull Metyrapone 美替拉酮
bull Aminoglutethimide 氨鲁米特
bull Used for adrenocortical tumors or hypercorticism
C Adrenocorticotropic hormone and corticosteroid synthetase
inhibitors
Cortisol Suppression Tests
bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
2 ADME and properties of commonly used drugs
Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver
Metabolism will be increased by hepatic enzyme inductors (phenobarbital phenytoin rifampine etc)
AA Glucocorticoid drugs Glucocorticoid drugs
Commonly used drugs
Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松
Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙
Long-acting dexamethasone 地塞米松
Topical fluocinolone 氟轻松
AA Glucocorticoid drugs Glucocorticoid drugs
CortisonCortisonee
可的松可的松
HydrocortisoHydrocortisonene
氢化可的松氢化可的松
CortisolCortisol
PrednisoPrednisonene
泼尼松泼尼松
PrednisolPrednisoloneone
泼尼松龙泼尼松龙
FluocinoloFluocinolonene
氟轻松氟轻松地塞米松地塞米松
HH
3 Clinical uses
(1) Immune diseases
a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc
b) rejection of organ transplantation
c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc
AA Glucocorticoid drugs Glucocorticoid drugs
(2) Severe infection and inflammation
a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving
Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration
Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms
b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc
AA Glucocorticoid drugsGlucocorticoid drugs
(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined
with antimicrobial drugswith antimicrobial drugs
(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc
(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)
(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc
AA Glucocorticoid drugs
4 Adverse effects of glucocorticoid
drugs
Effects resulting from continued used of large doses
AA Glucocorticoid drugs
4 Adverse effects
(1) Effects resulting from continued used of large doses
a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc
b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be
administered with GCs
c) Ingestive system peptic ulcers etc
AA Glucocorticoid drugsGlucocorticoid drugs
d) Cardiovascular system hypertension arteriosclerosis
e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women
f) CNS behavioral disturbances induction of epileptic seizures
g) Inhibition or arrest of growth in children
AA Glucocorticoid drugsGlucocorticoid drugs
Suppression of hypothalamic-pituitary-adrenal axis
and glucocorticoid drugs
‒‒
ACTH
(2) Withdrawal syndrome
a) Suppression of hypothalamic-pituitary-adrenal axis
b) Exacerbation of the underlying diseases (rebound)
(3) Contraindications
psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc
AA Glucocorticoid drugs Glucocorticoid drugs
Balance the ratio of benefit risk before the use of GCs
AA Glucocorticoid drugsGlucocorticoid drugs
5 Applications
(1) Replacement therapy usually using hydrocortisone
(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone
(3) Long-term therapy oral prednisone or prednisolone
morning single dose
alternate-day therapy
Notes for less severe and less sustained patients
less suppression on hypothalamic-pituitary-adrenal (HPA) axis
(4) Tipical applications skin eye respiratory tract
AA Glucocorticoid drugsGlucocorticoid drugs
bull Aldosterone 醛固酮
bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of
water and electrolytes
BB Mineralocorticoid drugsMineralocorticoid drugs
Action of aldosterone on mineralocorticoid receptor
Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein
AIP
bull 1 Adrenocorticotropic hormone (ACTH)
bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of
adrenocortical hoemones after long-term glucocorticoid drug use
bull Easily inducing allergy to ACTH
CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase
inhibitorsinhibitors
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response
ndash plasma cortisol levels are elevated
bull Abnormal responsendash plasma cortisol level are unchanged
bull 2 Corticosteroid synthetase inhibitors
bull Mitotane 米托坦
bull Metyrapone 美替拉酮
bull Aminoglutethimide 氨鲁米特
bull Used for adrenocortical tumors or hypercorticism
C Adrenocorticotropic hormone and corticosteroid synthetase
inhibitors
Cortisol Suppression Tests
bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
Commonly used drugs
Short-acting hydrocortisone (cortisol) 氢化可的松 cortisone 可的松
Intermediate-acting prednisone 泼尼松 强的松 prednisolone 泼尼松龙 强的松龙
Long-acting dexamethasone 地塞米松
Topical fluocinolone 氟轻松
AA Glucocorticoid drugs Glucocorticoid drugs
CortisonCortisonee
可的松可的松
HydrocortisoHydrocortisonene
氢化可的松氢化可的松
CortisolCortisol
PrednisoPrednisonene
泼尼松泼尼松
PrednisolPrednisoloneone
泼尼松龙泼尼松龙
FluocinoloFluocinolonene
氟轻松氟轻松地塞米松地塞米松
HH
3 Clinical uses
(1) Immune diseases
a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc
b) rejection of organ transplantation
c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc
AA Glucocorticoid drugs Glucocorticoid drugs
(2) Severe infection and inflammation
a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving
Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration
Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms
b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc
AA Glucocorticoid drugsGlucocorticoid drugs
(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined
with antimicrobial drugswith antimicrobial drugs
(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc
(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)
(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc
AA Glucocorticoid drugs
4 Adverse effects of glucocorticoid
drugs
Effects resulting from continued used of large doses
AA Glucocorticoid drugs
4 Adverse effects
(1) Effects resulting from continued used of large doses
a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc
b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be
administered with GCs
c) Ingestive system peptic ulcers etc
AA Glucocorticoid drugsGlucocorticoid drugs
d) Cardiovascular system hypertension arteriosclerosis
e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women
f) CNS behavioral disturbances induction of epileptic seizures
g) Inhibition or arrest of growth in children
AA Glucocorticoid drugsGlucocorticoid drugs
Suppression of hypothalamic-pituitary-adrenal axis
and glucocorticoid drugs
‒‒
ACTH
(2) Withdrawal syndrome
a) Suppression of hypothalamic-pituitary-adrenal axis
b) Exacerbation of the underlying diseases (rebound)
(3) Contraindications
psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc
AA Glucocorticoid drugs Glucocorticoid drugs
Balance the ratio of benefit risk before the use of GCs
AA Glucocorticoid drugsGlucocorticoid drugs
5 Applications
(1) Replacement therapy usually using hydrocortisone
(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone
(3) Long-term therapy oral prednisone or prednisolone
morning single dose
alternate-day therapy
Notes for less severe and less sustained patients
less suppression on hypothalamic-pituitary-adrenal (HPA) axis
(4) Tipical applications skin eye respiratory tract
AA Glucocorticoid drugsGlucocorticoid drugs
bull Aldosterone 醛固酮
bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of
water and electrolytes
BB Mineralocorticoid drugsMineralocorticoid drugs
Action of aldosterone on mineralocorticoid receptor
Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein
AIP
bull 1 Adrenocorticotropic hormone (ACTH)
bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of
adrenocortical hoemones after long-term glucocorticoid drug use
bull Easily inducing allergy to ACTH
CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase
inhibitorsinhibitors
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response
ndash plasma cortisol levels are elevated
bull Abnormal responsendash plasma cortisol level are unchanged
bull 2 Corticosteroid synthetase inhibitors
bull Mitotane 米托坦
bull Metyrapone 美替拉酮
bull Aminoglutethimide 氨鲁米特
bull Used for adrenocortical tumors or hypercorticism
C Adrenocorticotropic hormone and corticosteroid synthetase
inhibitors
Cortisol Suppression Tests
bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
CortisonCortisonee
可的松可的松
HydrocortisoHydrocortisonene
氢化可的松氢化可的松
CortisolCortisol
PrednisoPrednisonene
泼尼松泼尼松
PrednisolPrednisoloneone
泼尼松龙泼尼松龙
FluocinoloFluocinolonene
氟轻松氟轻松地塞米松地塞米松
HH
3 Clinical uses
(1) Immune diseases
a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc
b) rejection of organ transplantation
c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc
AA Glucocorticoid drugs Glucocorticoid drugs
(2) Severe infection and inflammation
a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving
Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration
Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms
b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc
AA Glucocorticoid drugsGlucocorticoid drugs
(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined
with antimicrobial drugswith antimicrobial drugs
(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc
(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)
(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc
AA Glucocorticoid drugs
4 Adverse effects of glucocorticoid
drugs
Effects resulting from continued used of large doses
AA Glucocorticoid drugs
4 Adverse effects
(1) Effects resulting from continued used of large doses
a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc
b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be
administered with GCs
c) Ingestive system peptic ulcers etc
AA Glucocorticoid drugsGlucocorticoid drugs
d) Cardiovascular system hypertension arteriosclerosis
e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women
f) CNS behavioral disturbances induction of epileptic seizures
g) Inhibition or arrest of growth in children
AA Glucocorticoid drugsGlucocorticoid drugs
Suppression of hypothalamic-pituitary-adrenal axis
and glucocorticoid drugs
‒‒
ACTH
(2) Withdrawal syndrome
a) Suppression of hypothalamic-pituitary-adrenal axis
b) Exacerbation of the underlying diseases (rebound)
(3) Contraindications
psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc
AA Glucocorticoid drugs Glucocorticoid drugs
Balance the ratio of benefit risk before the use of GCs
AA Glucocorticoid drugsGlucocorticoid drugs
5 Applications
(1) Replacement therapy usually using hydrocortisone
(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone
(3) Long-term therapy oral prednisone or prednisolone
morning single dose
alternate-day therapy
Notes for less severe and less sustained patients
less suppression on hypothalamic-pituitary-adrenal (HPA) axis
(4) Tipical applications skin eye respiratory tract
AA Glucocorticoid drugsGlucocorticoid drugs
bull Aldosterone 醛固酮
bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of
water and electrolytes
BB Mineralocorticoid drugsMineralocorticoid drugs
Action of aldosterone on mineralocorticoid receptor
Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein
AIP
bull 1 Adrenocorticotropic hormone (ACTH)
bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of
adrenocortical hoemones after long-term glucocorticoid drug use
bull Easily inducing allergy to ACTH
CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase
inhibitorsinhibitors
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response
ndash plasma cortisol levels are elevated
bull Abnormal responsendash plasma cortisol level are unchanged
bull 2 Corticosteroid synthetase inhibitors
bull Mitotane 米托坦
bull Metyrapone 美替拉酮
bull Aminoglutethimide 氨鲁米特
bull Used for adrenocortical tumors or hypercorticism
C Adrenocorticotropic hormone and corticosteroid synthetase
inhibitors
Cortisol Suppression Tests
bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
3 Clinical uses
(1) Immune diseases
a) autoimmune disorders reumatic fever reumatic carditis rhumatic arthritis rheumatoid arthritis osteoarthritis systemic lupus erythematosus polyarthritis nodosa nephritic syndrome etc
b) rejection of organ transplantation
c) allergic diseases urticaria serum sickenss contact dermatitis drug allergic reactions chronic severe asthma status asthmaticus angioneurotic edema etc
AA Glucocorticoid drugs Glucocorticoid drugs
(2) Severe infection and inflammation
a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving
Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration
Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms
b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc
AA Glucocorticoid drugsGlucocorticoid drugs
(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined
with antimicrobial drugswith antimicrobial drugs
(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc
(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)
(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc
AA Glucocorticoid drugs
4 Adverse effects of glucocorticoid
drugs
Effects resulting from continued used of large doses
AA Glucocorticoid drugs
4 Adverse effects
(1) Effects resulting from continued used of large doses
a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc
b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be
administered with GCs
c) Ingestive system peptic ulcers etc
AA Glucocorticoid drugsGlucocorticoid drugs
d) Cardiovascular system hypertension arteriosclerosis
e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women
f) CNS behavioral disturbances induction of epileptic seizures
g) Inhibition or arrest of growth in children
AA Glucocorticoid drugsGlucocorticoid drugs
Suppression of hypothalamic-pituitary-adrenal axis
and glucocorticoid drugs
‒‒
ACTH
(2) Withdrawal syndrome
a) Suppression of hypothalamic-pituitary-adrenal axis
b) Exacerbation of the underlying diseases (rebound)
(3) Contraindications
psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc
AA Glucocorticoid drugs Glucocorticoid drugs
Balance the ratio of benefit risk before the use of GCs
AA Glucocorticoid drugsGlucocorticoid drugs
5 Applications
(1) Replacement therapy usually using hydrocortisone
(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone
(3) Long-term therapy oral prednisone or prednisolone
morning single dose
alternate-day therapy
Notes for less severe and less sustained patients
less suppression on hypothalamic-pituitary-adrenal (HPA) axis
(4) Tipical applications skin eye respiratory tract
AA Glucocorticoid drugsGlucocorticoid drugs
bull Aldosterone 醛固酮
bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of
water and electrolytes
BB Mineralocorticoid drugsMineralocorticoid drugs
Action of aldosterone on mineralocorticoid receptor
Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein
AIP
bull 1 Adrenocorticotropic hormone (ACTH)
bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of
adrenocortical hoemones after long-term glucocorticoid drug use
bull Easily inducing allergy to ACTH
CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase
inhibitorsinhibitors
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response
ndash plasma cortisol levels are elevated
bull Abnormal responsendash plasma cortisol level are unchanged
bull 2 Corticosteroid synthetase inhibitors
bull Mitotane 米托坦
bull Metyrapone 美替拉酮
bull Aminoglutethimide 氨鲁米特
bull Used for adrenocortical tumors or hypercorticism
C Adrenocorticotropic hormone and corticosteroid synthetase
inhibitors
Cortisol Suppression Tests
bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
(2) Severe infection and inflammation
a) acute severe infections merely suppressing inflammatory manifestations but at times lifesaving
Causion ①combination with effective anti-microbial drugs ②Large dose ③short term administration
Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms
b) prevention of sequelae ( 后遗症 ) of some types of inflammation such as in brain heart eye joint etc
AA Glucocorticoid drugsGlucocorticoid drugs
(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined
with antimicrobial drugswith antimicrobial drugs
(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc
(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)
(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc
AA Glucocorticoid drugs
4 Adverse effects of glucocorticoid
drugs
Effects resulting from continued used of large doses
AA Glucocorticoid drugs
4 Adverse effects
(1) Effects resulting from continued used of large doses
a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc
b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be
administered with GCs
c) Ingestive system peptic ulcers etc
AA Glucocorticoid drugsGlucocorticoid drugs
d) Cardiovascular system hypertension arteriosclerosis
e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women
f) CNS behavioral disturbances induction of epileptic seizures
g) Inhibition or arrest of growth in children
AA Glucocorticoid drugsGlucocorticoid drugs
Suppression of hypothalamic-pituitary-adrenal axis
and glucocorticoid drugs
‒‒
ACTH
(2) Withdrawal syndrome
a) Suppression of hypothalamic-pituitary-adrenal axis
b) Exacerbation of the underlying diseases (rebound)
(3) Contraindications
psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc
AA Glucocorticoid drugs Glucocorticoid drugs
Balance the ratio of benefit risk before the use of GCs
AA Glucocorticoid drugsGlucocorticoid drugs
5 Applications
(1) Replacement therapy usually using hydrocortisone
(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone
(3) Long-term therapy oral prednisone or prednisolone
morning single dose
alternate-day therapy
Notes for less severe and less sustained patients
less suppression on hypothalamic-pituitary-adrenal (HPA) axis
(4) Tipical applications skin eye respiratory tract
AA Glucocorticoid drugsGlucocorticoid drugs
bull Aldosterone 醛固酮
bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of
water and electrolytes
BB Mineralocorticoid drugsMineralocorticoid drugs
Action of aldosterone on mineralocorticoid receptor
Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein
AIP
bull 1 Adrenocorticotropic hormone (ACTH)
bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of
adrenocortical hoemones after long-term glucocorticoid drug use
bull Easily inducing allergy to ACTH
CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase
inhibitorsinhibitors
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response
ndash plasma cortisol levels are elevated
bull Abnormal responsendash plasma cortisol level are unchanged
bull 2 Corticosteroid synthetase inhibitors
bull Mitotane 米托坦
bull Metyrapone 美替拉酮
bull Aminoglutethimide 氨鲁米特
bull Used for adrenocortical tumors or hypercorticism
C Adrenocorticotropic hormone and corticosteroid synthetase
inhibitors
Cortisol Suppression Tests
bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
(3) Septic shock (3) Septic shock CausionCausion larger dose short-term and combined larger dose short-term and combined
with antimicrobial drugswith antimicrobial drugs
(4) Hemological diseases (4) Hemological diseases acute lymphocytic acute lymphocytic leukemia lymphomas aplastic anemia leukemia lymphomas aplastic anemia (( 再生障碍性贫再生障碍性贫血血 )) hemolytic anemia leukocytopenia hemolytic anemia leukocytopenia thrombocytopenia thrombocytopenia etetcc
(5) Topical applications (5) Topical applications skin eye respiratory skin eye respiratory tract joint (local injection)tract joint (local injection)
(6) Some types of tumors(6) Some types of tumors breast and prostatic breast and prostatic cancers acute lymphocytic leukemia cancers acute lymphocytic leukemia etcetc
AA Glucocorticoid drugs
4 Adverse effects of glucocorticoid
drugs
Effects resulting from continued used of large doses
AA Glucocorticoid drugs
4 Adverse effects
(1) Effects resulting from continued used of large doses
a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc
b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be
administered with GCs
c) Ingestive system peptic ulcers etc
AA Glucocorticoid drugsGlucocorticoid drugs
d) Cardiovascular system hypertension arteriosclerosis
e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women
f) CNS behavioral disturbances induction of epileptic seizures
g) Inhibition or arrest of growth in children
AA Glucocorticoid drugsGlucocorticoid drugs
Suppression of hypothalamic-pituitary-adrenal axis
and glucocorticoid drugs
‒‒
ACTH
(2) Withdrawal syndrome
a) Suppression of hypothalamic-pituitary-adrenal axis
b) Exacerbation of the underlying diseases (rebound)
(3) Contraindications
psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc
AA Glucocorticoid drugs Glucocorticoid drugs
Balance the ratio of benefit risk before the use of GCs
AA Glucocorticoid drugsGlucocorticoid drugs
5 Applications
(1) Replacement therapy usually using hydrocortisone
(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone
(3) Long-term therapy oral prednisone or prednisolone
morning single dose
alternate-day therapy
Notes for less severe and less sustained patients
less suppression on hypothalamic-pituitary-adrenal (HPA) axis
(4) Tipical applications skin eye respiratory tract
AA Glucocorticoid drugsGlucocorticoid drugs
bull Aldosterone 醛固酮
bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of
water and electrolytes
BB Mineralocorticoid drugsMineralocorticoid drugs
Action of aldosterone on mineralocorticoid receptor
Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein
AIP
bull 1 Adrenocorticotropic hormone (ACTH)
bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of
adrenocortical hoemones after long-term glucocorticoid drug use
bull Easily inducing allergy to ACTH
CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase
inhibitorsinhibitors
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response
ndash plasma cortisol levels are elevated
bull Abnormal responsendash plasma cortisol level are unchanged
bull 2 Corticosteroid synthetase inhibitors
bull Mitotane 米托坦
bull Metyrapone 美替拉酮
bull Aminoglutethimide 氨鲁米特
bull Used for adrenocortical tumors or hypercorticism
C Adrenocorticotropic hormone and corticosteroid synthetase
inhibitors
Cortisol Suppression Tests
bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
4 Adverse effects of glucocorticoid
drugs
Effects resulting from continued used of large doses
AA Glucocorticoid drugs
4 Adverse effects
(1) Effects resulting from continued used of large doses
a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc
b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be
administered with GCs
c) Ingestive system peptic ulcers etc
AA Glucocorticoid drugsGlucocorticoid drugs
d) Cardiovascular system hypertension arteriosclerosis
e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women
f) CNS behavioral disturbances induction of epileptic seizures
g) Inhibition or arrest of growth in children
AA Glucocorticoid drugsGlucocorticoid drugs
Suppression of hypothalamic-pituitary-adrenal axis
and glucocorticoid drugs
‒‒
ACTH
(2) Withdrawal syndrome
a) Suppression of hypothalamic-pituitary-adrenal axis
b) Exacerbation of the underlying diseases (rebound)
(3) Contraindications
psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc
AA Glucocorticoid drugs Glucocorticoid drugs
Balance the ratio of benefit risk before the use of GCs
AA Glucocorticoid drugsGlucocorticoid drugs
5 Applications
(1) Replacement therapy usually using hydrocortisone
(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone
(3) Long-term therapy oral prednisone or prednisolone
morning single dose
alternate-day therapy
Notes for less severe and less sustained patients
less suppression on hypothalamic-pituitary-adrenal (HPA) axis
(4) Tipical applications skin eye respiratory tract
AA Glucocorticoid drugsGlucocorticoid drugs
bull Aldosterone 醛固酮
bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of
water and electrolytes
BB Mineralocorticoid drugsMineralocorticoid drugs
Action of aldosterone on mineralocorticoid receptor
Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein
AIP
bull 1 Adrenocorticotropic hormone (ACTH)
bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of
adrenocortical hoemones after long-term glucocorticoid drug use
bull Easily inducing allergy to ACTH
CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase
inhibitorsinhibitors
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response
ndash plasma cortisol levels are elevated
bull Abnormal responsendash plasma cortisol level are unchanged
bull 2 Corticosteroid synthetase inhibitors
bull Mitotane 米托坦
bull Metyrapone 美替拉酮
bull Aminoglutethimide 氨鲁米特
bull Used for adrenocortical tumors or hypercorticism
C Adrenocorticotropic hormone and corticosteroid synthetase
inhibitors
Cortisol Suppression Tests
bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
4 Adverse effects
(1) Effects resulting from continued used of large doses
a) Hypercorticism-like syndrome central obesity (moon face buffalo hump etc) hypertension glycosuria hypokalemia etc
b) Increasing susceptibility to infections Causion specfic antimicrobial drugs should be
administered with GCs
c) Ingestive system peptic ulcers etc
AA Glucocorticoid drugsGlucocorticoid drugs
d) Cardiovascular system hypertension arteriosclerosis
e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women
f) CNS behavioral disturbances induction of epileptic seizures
g) Inhibition or arrest of growth in children
AA Glucocorticoid drugsGlucocorticoid drugs
Suppression of hypothalamic-pituitary-adrenal axis
and glucocorticoid drugs
‒‒
ACTH
(2) Withdrawal syndrome
a) Suppression of hypothalamic-pituitary-adrenal axis
b) Exacerbation of the underlying diseases (rebound)
(3) Contraindications
psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc
AA Glucocorticoid drugs Glucocorticoid drugs
Balance the ratio of benefit risk before the use of GCs
AA Glucocorticoid drugsGlucocorticoid drugs
5 Applications
(1) Replacement therapy usually using hydrocortisone
(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone
(3) Long-term therapy oral prednisone or prednisolone
morning single dose
alternate-day therapy
Notes for less severe and less sustained patients
less suppression on hypothalamic-pituitary-adrenal (HPA) axis
(4) Tipical applications skin eye respiratory tract
AA Glucocorticoid drugsGlucocorticoid drugs
bull Aldosterone 醛固酮
bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of
water and electrolytes
BB Mineralocorticoid drugsMineralocorticoid drugs
Action of aldosterone on mineralocorticoid receptor
Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein
AIP
bull 1 Adrenocorticotropic hormone (ACTH)
bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of
adrenocortical hoemones after long-term glucocorticoid drug use
bull Easily inducing allergy to ACTH
CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase
inhibitorsinhibitors
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response
ndash plasma cortisol levels are elevated
bull Abnormal responsendash plasma cortisol level are unchanged
bull 2 Corticosteroid synthetase inhibitors
bull Mitotane 米托坦
bull Metyrapone 美替拉酮
bull Aminoglutethimide 氨鲁米特
bull Used for adrenocortical tumors or hypercorticism
C Adrenocorticotropic hormone and corticosteroid synthetase
inhibitors
Cortisol Suppression Tests
bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
d) Cardiovascular system hypertension arteriosclerosis
e) Myopathy and osteoporosis vertebral compression fractures spontaneous fractures especially in postmenopausal women
f) CNS behavioral disturbances induction of epileptic seizures
g) Inhibition or arrest of growth in children
AA Glucocorticoid drugsGlucocorticoid drugs
Suppression of hypothalamic-pituitary-adrenal axis
and glucocorticoid drugs
‒‒
ACTH
(2) Withdrawal syndrome
a) Suppression of hypothalamic-pituitary-adrenal axis
b) Exacerbation of the underlying diseases (rebound)
(3) Contraindications
psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc
AA Glucocorticoid drugs Glucocorticoid drugs
Balance the ratio of benefit risk before the use of GCs
AA Glucocorticoid drugsGlucocorticoid drugs
5 Applications
(1) Replacement therapy usually using hydrocortisone
(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone
(3) Long-term therapy oral prednisone or prednisolone
morning single dose
alternate-day therapy
Notes for less severe and less sustained patients
less suppression on hypothalamic-pituitary-adrenal (HPA) axis
(4) Tipical applications skin eye respiratory tract
AA Glucocorticoid drugsGlucocorticoid drugs
bull Aldosterone 醛固酮
bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of
water and electrolytes
BB Mineralocorticoid drugsMineralocorticoid drugs
Action of aldosterone on mineralocorticoid receptor
Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein
AIP
bull 1 Adrenocorticotropic hormone (ACTH)
bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of
adrenocortical hoemones after long-term glucocorticoid drug use
bull Easily inducing allergy to ACTH
CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase
inhibitorsinhibitors
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response
ndash plasma cortisol levels are elevated
bull Abnormal responsendash plasma cortisol level are unchanged
bull 2 Corticosteroid synthetase inhibitors
bull Mitotane 米托坦
bull Metyrapone 美替拉酮
bull Aminoglutethimide 氨鲁米特
bull Used for adrenocortical tumors or hypercorticism
C Adrenocorticotropic hormone and corticosteroid synthetase
inhibitors
Cortisol Suppression Tests
bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
Suppression of hypothalamic-pituitary-adrenal axis
and glucocorticoid drugs
‒‒
ACTH
(2) Withdrawal syndrome
a) Suppression of hypothalamic-pituitary-adrenal axis
b) Exacerbation of the underlying diseases (rebound)
(3) Contraindications
psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc
AA Glucocorticoid drugs Glucocorticoid drugs
Balance the ratio of benefit risk before the use of GCs
AA Glucocorticoid drugsGlucocorticoid drugs
5 Applications
(1) Replacement therapy usually using hydrocortisone
(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone
(3) Long-term therapy oral prednisone or prednisolone
morning single dose
alternate-day therapy
Notes for less severe and less sustained patients
less suppression on hypothalamic-pituitary-adrenal (HPA) axis
(4) Tipical applications skin eye respiratory tract
AA Glucocorticoid drugsGlucocorticoid drugs
bull Aldosterone 醛固酮
bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of
water and electrolytes
BB Mineralocorticoid drugsMineralocorticoid drugs
Action of aldosterone on mineralocorticoid receptor
Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein
AIP
bull 1 Adrenocorticotropic hormone (ACTH)
bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of
adrenocortical hoemones after long-term glucocorticoid drug use
bull Easily inducing allergy to ACTH
CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase
inhibitorsinhibitors
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response
ndash plasma cortisol levels are elevated
bull Abnormal responsendash plasma cortisol level are unchanged
bull 2 Corticosteroid synthetase inhibitors
bull Mitotane 米托坦
bull Metyrapone 美替拉酮
bull Aminoglutethimide 氨鲁米特
bull Used for adrenocortical tumors or hypercorticism
C Adrenocorticotropic hormone and corticosteroid synthetase
inhibitors
Cortisol Suppression Tests
bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
(2) Withdrawal syndrome
a) Suppression of hypothalamic-pituitary-adrenal axis
b) Exacerbation of the underlying diseases (rebound)
(3) Contraindications
psychiatric disorders epilepsy active peptic ulcers fractures hypercorticism severe hypertension diabetes mellitus viral or fungal infections etc
AA Glucocorticoid drugs Glucocorticoid drugs
Balance the ratio of benefit risk before the use of GCs
AA Glucocorticoid drugsGlucocorticoid drugs
5 Applications
(1) Replacement therapy usually using hydrocortisone
(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone
(3) Long-term therapy oral prednisone or prednisolone
morning single dose
alternate-day therapy
Notes for less severe and less sustained patients
less suppression on hypothalamic-pituitary-adrenal (HPA) axis
(4) Tipical applications skin eye respiratory tract
AA Glucocorticoid drugsGlucocorticoid drugs
bull Aldosterone 醛固酮
bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of
water and electrolytes
BB Mineralocorticoid drugsMineralocorticoid drugs
Action of aldosterone on mineralocorticoid receptor
Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein
AIP
bull 1 Adrenocorticotropic hormone (ACTH)
bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of
adrenocortical hoemones after long-term glucocorticoid drug use
bull Easily inducing allergy to ACTH
CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase
inhibitorsinhibitors
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response
ndash plasma cortisol levels are elevated
bull Abnormal responsendash plasma cortisol level are unchanged
bull 2 Corticosteroid synthetase inhibitors
bull Mitotane 米托坦
bull Metyrapone 美替拉酮
bull Aminoglutethimide 氨鲁米特
bull Used for adrenocortical tumors or hypercorticism
C Adrenocorticotropic hormone and corticosteroid synthetase
inhibitors
Cortisol Suppression Tests
bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
Balance the ratio of benefit risk before the use of GCs
AA Glucocorticoid drugsGlucocorticoid drugs
5 Applications
(1) Replacement therapy usually using hydrocortisone
(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone
(3) Long-term therapy oral prednisone or prednisolone
morning single dose
alternate-day therapy
Notes for less severe and less sustained patients
less suppression on hypothalamic-pituitary-adrenal (HPA) axis
(4) Tipical applications skin eye respiratory tract
AA Glucocorticoid drugsGlucocorticoid drugs
bull Aldosterone 醛固酮
bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of
water and electrolytes
BB Mineralocorticoid drugsMineralocorticoid drugs
Action of aldosterone on mineralocorticoid receptor
Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein
AIP
bull 1 Adrenocorticotropic hormone (ACTH)
bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of
adrenocortical hoemones after long-term glucocorticoid drug use
bull Easily inducing allergy to ACTH
CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase
inhibitorsinhibitors
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response
ndash plasma cortisol levels are elevated
bull Abnormal responsendash plasma cortisol level are unchanged
bull 2 Corticosteroid synthetase inhibitors
bull Mitotane 米托坦
bull Metyrapone 美替拉酮
bull Aminoglutethimide 氨鲁米特
bull Used for adrenocortical tumors or hypercorticism
C Adrenocorticotropic hormone and corticosteroid synthetase
inhibitors
Cortisol Suppression Tests
bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
5 Applications
(1) Replacement therapy usually using hydrocortisone
(2) Prompt intensive treatment iv gtt hydrocortisone dexamethasone
(3) Long-term therapy oral prednisone or prednisolone
morning single dose
alternate-day therapy
Notes for less severe and less sustained patients
less suppression on hypothalamic-pituitary-adrenal (HPA) axis
(4) Tipical applications skin eye respiratory tract
AA Glucocorticoid drugsGlucocorticoid drugs
bull Aldosterone 醛固酮
bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of
water and electrolytes
BB Mineralocorticoid drugsMineralocorticoid drugs
Action of aldosterone on mineralocorticoid receptor
Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein
AIP
bull 1 Adrenocorticotropic hormone (ACTH)
bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of
adrenocortical hoemones after long-term glucocorticoid drug use
bull Easily inducing allergy to ACTH
CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase
inhibitorsinhibitors
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response
ndash plasma cortisol levels are elevated
bull Abnormal responsendash plasma cortisol level are unchanged
bull 2 Corticosteroid synthetase inhibitors
bull Mitotane 米托坦
bull Metyrapone 美替拉酮
bull Aminoglutethimide 氨鲁米特
bull Used for adrenocortical tumors or hypercorticism
C Adrenocorticotropic hormone and corticosteroid synthetase
inhibitors
Cortisol Suppression Tests
bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
bull Aldosterone 醛固酮
bull Na+ excretion K+ excretion edema hypertension hypokalemia etc used for adrenocortical dysfunction with imbalance of
water and electrolytes
BB Mineralocorticoid drugsMineralocorticoid drugs
Action of aldosterone on mineralocorticoid receptor
Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein
AIP
bull 1 Adrenocorticotropic hormone (ACTH)
bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of
adrenocortical hoemones after long-term glucocorticoid drug use
bull Easily inducing allergy to ACTH
CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase
inhibitorsinhibitors
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response
ndash plasma cortisol levels are elevated
bull Abnormal responsendash plasma cortisol level are unchanged
bull 2 Corticosteroid synthetase inhibitors
bull Mitotane 米托坦
bull Metyrapone 美替拉酮
bull Aminoglutethimide 氨鲁米特
bull Used for adrenocortical tumors or hypercorticism
C Adrenocorticotropic hormone and corticosteroid synthetase
inhibitors
Cortisol Suppression Tests
bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
Action of aldosterone on mineralocorticoid receptor
Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein
AIP
bull 1 Adrenocorticotropic hormone (ACTH)
bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of
adrenocortical hoemones after long-term glucocorticoid drug use
bull Easily inducing allergy to ACTH
CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase
inhibitorsinhibitors
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response
ndash plasma cortisol levels are elevated
bull Abnormal responsendash plasma cortisol level are unchanged
bull 2 Corticosteroid synthetase inhibitors
bull Mitotane 米托坦
bull Metyrapone 美替拉酮
bull Aminoglutethimide 氨鲁米特
bull Used for adrenocortical tumors or hypercorticism
C Adrenocorticotropic hormone and corticosteroid synthetase
inhibitors
Cortisol Suppression Tests
bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
Mineralocorticoid receptor signal transduction bull MR mineralocorticoid receptorbull HRE hormone responsive elementbull AIP Aldosterone induced protein
AIP
bull 1 Adrenocorticotropic hormone (ACTH)
bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of
adrenocortical hoemones after long-term glucocorticoid drug use
bull Easily inducing allergy to ACTH
CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase
inhibitorsinhibitors
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response
ndash plasma cortisol levels are elevated
bull Abnormal responsendash plasma cortisol level are unchanged
bull 2 Corticosteroid synthetase inhibitors
bull Mitotane 米托坦
bull Metyrapone 美替拉酮
bull Aminoglutethimide 氨鲁米特
bull Used for adrenocortical tumors or hypercorticism
C Adrenocorticotropic hormone and corticosteroid synthetase
inhibitors
Cortisol Suppression Tests
bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
bull 1 Adrenocorticotropic hormone (ACTH)
bull Used for diagnosis of adrenocortical functionbull inhibition of secretion of
adrenocortical hoemones after long-term glucocorticoid drug use
bull Easily inducing allergy to ACTH
CC Adrenocorticotropic hormone Adrenocorticotropic hormone and corticosteroid synthetase and corticosteroid synthetase
inhibitorsinhibitors
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response
ndash plasma cortisol levels are elevated
bull Abnormal responsendash plasma cortisol level are unchanged
bull 2 Corticosteroid synthetase inhibitors
bull Mitotane 米托坦
bull Metyrapone 美替拉酮
bull Aminoglutethimide 氨鲁米特
bull Used for adrenocortical tumors or hypercorticism
C Adrenocorticotropic hormone and corticosteroid synthetase
inhibitors
Cortisol Suppression Tests
bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull synthetic ACTH used as adrenal cortical stimulantbull Normal response
ndash plasma cortisol levels are elevated
bull Abnormal responsendash plasma cortisol level are unchanged
bull 2 Corticosteroid synthetase inhibitors
bull Mitotane 米托坦
bull Metyrapone 美替拉酮
bull Aminoglutethimide 氨鲁米特
bull Used for adrenocortical tumors or hypercorticism
C Adrenocorticotropic hormone and corticosteroid synthetase
inhibitors
Cortisol Suppression Tests
bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
bull 2 Corticosteroid synthetase inhibitors
bull Mitotane 米托坦
bull Metyrapone 美替拉酮
bull Aminoglutethimide 氨鲁米特
bull Used for adrenocortical tumors or hypercorticism
C Adrenocorticotropic hormone and corticosteroid synthetase
inhibitors
Cortisol Suppression Tests
bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
Cortisol Suppression Tests
bull 1048708 Principlebull 1048708 Based on the ability of exogenous cortisol to exert (-)bull feedback on hypothalamus-pituitary release of ACTHbull 1048708 Canrsquot measure with cortisol itself (exogenous would justbull replace endogenous)bull 1048708 Must use a more potent glucocorticoid derivativebull 1048708 usually dexamethasone
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
Diagnosis of H-P-A Axis statusH-P suppression test
bull Dexamethasonebull 1048708 used to evaluate the basis for elevated cortisolbull levels in individuals with suspected pituitarybull adenoma (Cushingrsquos disease)bull 1048708 Normal response in Cushingrsquos diseasebull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are reducedbull 1048708 Abnormal response in cortisol-producing adrenal tumorbull (low ACTH) or ectopic ACTH-producing tumors (highbull ACTH)bull 1048708 plasma ACTH and cortisol urine 17-OH corticosteroidbull levels are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged
Diagnosis of H-P-A Axis statusAdrenocortical function test
bull Cosyntropinbull 1048708 synthetic ACTH used as adrenal cortical stimulantbull 1048708 Normal responsebull 1048708 plasma cortisol levels are elevatedbull 1048708 Abnormal responsebull 1048708 plasma cortisol level are unchanged