Endocrine drugs

Endocrine Drugs, Hormones and Endocrine Drugs, Hormones and Related CompoundsRelated Compounds

OverviewOverview

Endocrine System

- composed of hormone-releasing organs such as the:

hypothalamus thymus

pituitary gland pancreas

thyroid gland gonads

parathyroid -ovaries

adrenal glands -testes

pineal gland

Endocrine SystemEndocrine System


- is controlled by the hypothalamus and the pituitary gland

- along with the Nervous System, it coordinates and directs body function

- maintains homeostasis by releasing chemicals called hormones

Endocrine vs NervousEndocrine vs Nervous

- the nervous system communicates locally by electrical impulses and neurotransmitters directed through neurons to other neurons or to specific target organs such as muscle or glands

- nerve impulses generally act within milliseconds

Nervous SystemNervous System


- the endocrine system releases hormones into the blood stream

- the hormones are then carried by the blood stream into target cells throughout the body

- hormones have broader range of response times (they act from seconds to days or longer)


NOTE: there is close interrelationship between the endocrine and nervous systems


Processes controlled by the endocrine

System:

1. growth & development

2. reproduction

3. body defenses

4. water, electrolyte and nutrient balance

5. regulation of cellular metabolism and energy balance

HormonesHormones

HormonesHormones

- Greek word, “to arouse”

- chemical substances secreted by the cells into the extracellular fluids that stimulate or regulate the metabolic activity of other cells in the body.

- Gen. MOA: binding of the hormone to the target cell or organ elicits response.

Endocrine Drugs Endocrine Drugs

Endocrine DrugsEndocrine Drugs

- Hormones are pharmacologically classified as drugs

- can be natural (from animals), semi-synthetic or synthetic compounds

- Indications:

a. replacement therapy

b. treatment for certain disorders

c. diagnostic purposes

Endocrine DrugsEndocrine Drugs

I. Hypothalamic & Pituitary Hormones

II. Steroid Hormones

A. Gonadal Hormones

1. Estrogens

2. Progestins

3. Androgens

B. Hormones of the Adrenal Cortex

1. Adrenocorticosteroids

2. Adrenal Androgens

III. Thyroid Hormones and Drugs for Thyroid Disorders

IV. Anti-diabetic Agents

Hypothalamic & Pituitary Hypothalamic & Pituitary HormonesHormones

HypothalamusHypothalamus

- master endocrine organ

- secretes releasing/inhibiting hormones

Pituitary GlandPituitary Gland

- weighs 600 mg and rests in the sella turcica under a layer of dura mater in the brain

-composed of 2 lobes:

a. anterior lobe

b. posterior lobe

Hypothalamic & Pituitary HormonesHypothalamic & Pituitary HormonesHypothalamic Hormone Pituitary

HormoneTarget Organ Target Organ

Hormone1. Growth Hormone –

Releasing Hormone(GHRH)

aka: Sermorelin

Growth Hormone (GH)aka: Somatotropin

Liver Somatomedins

2. Growth Hormone –Inhibiting Hormone (GHIH)

aka: Somatostatin

Inhibits Growth Hormone

3. Corticotropin – ReleasingHormone (CRH)

AdrenocorticotropicHormone (ACTH)aka: Corticotropin

Adrenal Cortex GlucocorticoidsMineralocorticoidsAdrenal Androgens

4. Thyrotropin – ReleasingHormone (TRH)

Thyroid – StimulatingHormone (TSH)aka: Thyrotropin

Thyroid Gland T3 (Triiodothyronine)T4 (Thyroxine)

5. Gonadotropin – ReleasingHormone (GnRH) orLuteinizing Hormone –Releasing Hormone(LHRH)

Gonadotropinsa. Follicle Stimulating

Hormone (FSH)b. Luteinizing Hormone

(LH)

Ovaries (Females)Testes (Males)

Estrogen (by FSH)Progesterone (by LH

in females)Testosterone (by LH

in males)6. Prolactin – Releasing

Hormone (PRH)Prolactin Breasts

7. Prolactin – InhibitingHormone (PIH)

Inhibits Prolactin

8. Oxytocin Stored in the PosteriorPituitary Gland

9. Vasopressin Stored in the PosteriorPituitary Gland

Growth HormoneGrowth Hormone

Growth Hormone (GH)Growth Hormone (GH)

- aka: Somatotropin, Asellacrin- a large polypeptide: about 191 amino

acids (MW: 21,500)

- released by the anterior pituitary in response to GHRH (Sermorelin) produced by the hypothalamus

- produced synthetically by recombinant DNA technology


- animal source is ineffective in humans

- induces the release of somatomedins in the liver

- promotion of cell proliferation and bone growth at open epiphyses

- boosts cartilage synthesis


Indications:

- for long term treatment in growth hormone deficiency in children (Dwarfism)

- for non-GH deficient short children (can grow up to 2 cm per year)

DwarfismDwarfism

SomatremSomatrem

- a therapeutically equivalent drug of GH

- contains an extra terminal methionyl group

Growth Hormone Inhibiting Growth Hormone Inhibiting HormoneHormone

Growth Hormone Inhibiting Growth Hormone Inhibiting Hormone (GHIH)Hormone (GHIH)

- aka: Somatostatin

- inhibits Growth Hormone

- Indications:

Pituitary Gigantism (pre-pubertal)

Acromegaly (post-pubertal)

Pituitary GigantismPituitary Gigantism

AcromegalyAcromegaly

macrognathia (large jaw)

wide-spaced teeth

macroglossia

thickened lips

broad nose

enlarged joints

cardiomegaly

organomegaly

OctreotideOctreotide

- synthetic octapeptide analog of somatostatin

- 45x more potent than GHIH

Adrenocorticotropic HormoneAdrenocorticotropic Hormone

Adrenocorticotropic Hormone (ACTH)Adrenocorticotropic Hormone (ACTH)

- aka: Corticotropin, Acthar- single-chain polypeptide containing 39

amino acids

- precursor: pro-opiomelanocortin

- released by the anterior pituitary in response to CRH produced by the hypothalamus

Adrenocorticotropic Hormone (ACTH)Adrenocorticotropic Hormone (ACTH)

- stimulates the adrenal cortex to produce adrenocorticosteroids & androgens

- is used primarily for the diagnosis and differentiation of primary & secondary adrenal insufficiency

- Primary: Addison’s Disease associated with adrenal atrophy

- Secondary: caused by inadequate secretion of ACTH by the pituitary

Addison’s DiseaseAddison’s Disease

• hyposecretion of adrenocorticosteroids

• characterized by:– anorexia– dehydration– weakness and lethargy– hyperpigmentation (bronze-colored skin)

Cushing’s SyndromeCushing’s Syndrome

• hypersecretion of adrenocorticosteroids

• characterized by:– moon face– buffalo hump– pendulous abdomen– hypertension

Cushing's SyndromeCushing's Syndrome

CosyntropinCosyntropin

- synthetic human ACTH

- more preferred since animal ACTH can cause allergic reactions

Thyrotropin Stimulating Thyrotropin Stimulating HormoneHormone

Thyrotropin Stimulating Hormone (TSH)Thyrotropin Stimulating Hormone (TSH)

- aka: Thyrotropin

- released by the anterior pituitary in response to TRH (aka: Protirelin) produced by the hypothalamus

- stimulates the thyroid to produce T3 and T4

- T3: triiodothyronine (most active)

- T4: thyroxine

(converted to T3 in the body)

Thyrotropin Stimulating Hormone (TSH)Thyrotropin Stimulating Hormone (TSH)

- the thyroid hormones T3 and T4 are essential for the normal growth and maturation of the body

- Conditions:

hypothyroidism

hyperthyroidism

HypothyroidismHypothyroidism

- inability of the thyroid gland to supply sufficient thyroid hormone to the body

- manifestations:

Cretinism (infant-state)

Myxedema (adult-state)

CretinismCretinism

- infant-state hypothyroidism- characterized by physical and mental

retardation

MyxedemaMyxedema

- adult-state hypothyroidism- characterized by:

• bradycardia• weakness and lethargy• dry skin and hair• coldness• goiter

HyperthyroidismHyperthyroidism

- overabundance of thyroid hormone in the body

- thyrotoxicosis

- Forms:

Graves’ Disease - most common

Plummer’s Disease - less common

- with cardiac abnormalities

Graves' DiseaseGraves' Disease

GonadotropinsGonadotropins

GonadotropinsGonadotropins- include:

Follicle-Stimulating Hormone (FSH)

Luteinizing Hormone (LH)

- released by the anterior pituitary gland in response to GnRH / LHRH

- stimulates the gonads (ovaries & testes) to produce sex hormones

- Females: FSH estrogen

LH progesterone

- Males: LH testosterone

GonadotropinsGonadotropins

NOTE: Pituitary gonadotropins (FSH, LH) are not available for therapeutic use, however, there are non-pituitary gonadotropins that have FSH-like or LH-like activity and are the ones used therapeutically

Non-Pituitary GonadotropinsNon-Pituitary Gonadotropins

1. Menotropins

2. Urofollitropin

3. Human Chorionic Gonadotropin

Non-Pituitary GonadotropinsNon-Pituitary Gonadotropins

- Indications:

women: to induce ovulation & pregnancy

men: to induce spermatogenesis

- Adverse effects:

ovarian enlargement

multiple births

gynecomastia in men

MenotropinMenotropin

- aka:

Human Menopausal Gonadotropin (hMG)

Pergonal®

- obtained from the urine of post-menopausal women

- partially broken down into FSH and LH in the body

UrofollitropinUrofollitropin

- Metrodin®

- obtained from the urine of post-menopausal women

- high in FSH-like activity

Human Chorionic GonadotropinHuman Chorionic Gonadotropin

- aka: hCG, Follutein®

- a placental hormone

- LH agonist effect

-obtained from the urine of pregnant women

Hormones of the Posterior Hormones of the Posterior Pituitary GlandPituitary Gland

Hormones of the PosteriorHormones of the PosteriorPituitary GlandPituitary Gland

1. Oxytocin

2. Vasopressin

OxytocinOxytocin- stimulates uterine contraction and plays an

important role in the induction of labor

- also promotes breast milk ejection

- Indications:

to induce contraction during labor

to control postpartum bleeding

- Contraindications:

abnormal fetal presentation

fetal distress

premature births

OxytocinOxytocin

VasopressinVasopressin

- aka: Antidiuretic Hormone (ADH)

- has both antidiuretic and vasopressor activity

-acts by binding to its receptor in the kidneys promoting the reabsorption of water in the collecting tubules

-Indications:

Diabetes Insipidus

Postoperative Abdominal Distention

Diabetes Insipidus (DI)Diabetes Insipidus (DI)

- a disorder due to the deficiency or lack of response to Antidiuretic Hormone (ADH)

- 2 Types:

a. Central DI - deficiency in ADH

b. Nephrogenic DI - sufficient ADH

but body does not respond to the hormone

DesmopressinDesmopressin

- modified analog of vasopressin

- more preferred for DI and nocturnal enuresis because it is largely free of pressor effects and is longer-acting

Steroid HormonesSteroid Hormones


- contain the steroid nucleus, CPPP

cyclopentanoperhydrophenanthrene


• Carbon 3 & Carbon 17

• -OH (sterol)

• =O (sterone)

Gonadal / Sex HormonesGonadal / Sex Hormones

Steroid HormonesSteroid HormonesA. Gonadal / Sex Hormones

1. Estrogens

2. Progestins

3. Androgens

B. Hormones of the Adrenal Cortex

1. Adrenocoticosteroids

a. Glucocorticoids

b. Mineralocorticoids


Gonadal / Sex HormonesGonadal / Sex Hormones

EstrogensEstrogens

EstrogensEstrogens

- basic nucleus: estrane

Estradiol

EstrogensEstrogens

- Effects:

1. normal female maturation and development

2. inhibit bone resorption

3. increase HDL, decrease LDL

4. decrease platelet adhesiveness

EstrogensEstrogens

- Indications:

contraception

postmenopausal hormone therapy

primary hypogonadism

osteoporosis

Natural Steroidal EstrogensNatural Steroidal Estrogens

Estradiol - most potent estrogen produced by women

Estrone, Estriol - have about one tenth the potency of estradiol

* Premarin - a preparation of conjugated estrogens (sulfate esters of estrone & equilin)

- obtained from pregnant mare’s urine

PremarinPremarin

Synthetic Steroidal EstrogensSynthetic Steroidal Estrogens

Ethinyl estradiol

Mestranol

Quinestrol

Synthetic Nonsteroidal EstrogensSynthetic Nonsteroidal Estrogens

Diethylstilbestrol - possible cause of a rare, clear cell cervical or vaginal adenocarcinoma among daughters of women who took the drug during early pregnancy

Estrogen Antagonists / Estrogen Antagonists / AntiestrogensAntiestrogens

Clomiphene - fertility drug; it induces ovulation by negative feedback mechanism

Tamoxifen & Toremifene - palliative treatment of advanced breast cancer in postmenopausal women

Estrogen Related DrugsEstrogen Related Drugs

Aromatase Inhibitors

Selective Estrogen Receptor Modulators

Aromatase InhibitorsAromatase Inhibitors

- are potent and selective non-steroidal inhibitors of aromatase, an enzyme reponsible for the conversion of androgens to estrogens

- used to treat advanced breast cancer

- Anastrozole, Letrozole

SERMsSERMs

- Selective Estrogen Receptor Modulators

- reduce bone resorption and decrease bone turnover

- used for the prevention of osteoporosis

- Raloxifene

ProgestinsProgestins


- basic nucleus: pregnane


- Effects:

1. endometrial changes

2. alveolobular development of secretory apparatus in breasts

3. hepatic glycogenesis &ketogenesis

4. increase lipoprotein lipase activity and fat deposition


- Indications:

contraception

for menstrual disorders

-dysfunctional uterine bleeding

-dysmenorrhea

endometriosis

Natural ProgestinNatural Progestin

Progesterone

- endogenous progestin produced in response to luteinizing hormone (LH)

- also synthesized by the adrenal cortex

- in females, it promotes the development of a secretory endometrium that can accommodate implantation of a newly forming embryo

Synthetic ProgestinsSynthetic Progestins

- more stable to first-pass metabolism, allowing for lower doses when administered orally

- medroxyprogesterone

hydroxyprogesterone

megestrol

norethindrone

norgestrel

Progestin Antagonist / Progestin Antagonist / AntiprogestinAntiprogestin

Mifepristone

- aka: RU 486

- progestin antagonist with partial agonist activity

- can cause abortion of the fetus due to the interference with progesterone and the decline in hCG

Oral & Implantable Oral & Implantable ContraceptivesContraceptives

Major ClassesMajor Classes

1. Combination Pills

2. Progestin Only Contraceptives

3. Postcoital Contraceptives

Combination PillsCombination Pills

- contain both estrogen and progestin

- provided as 21 day or 28 day-packs

- most common type of oral contraceptives

- estrogen: suppresses ovulation

ethinyl estradiol - most common

mestranol

Combination PillsCombination Pills

- progestin: prevents implantation in the endometrium and makes the cervical mucus impenetrable to the sperm

norethynodrel

norethindrone

norgestrel

Progestin Only ContraceptivesProgestin Only Contraceptives- less effective than combination pills

- dosage forms/ delivery systems:

a. “mini-pill” - low dose progestins

350 g norethindrone or

75 g norgestrel

b. progestin implants - subdermal implant of 216 mg of norgestrel (Norplant®) effective for 5 years

Progestin Only ContraceptivesProgestin Only Contraceptives

c. intramuscular - given every 3 months

150 mg of medroxyprogesterone acetate (Depo-Provera®)

Progestin Only ContraceptivesProgestin Only Contraceptives

d. intrauterine device (IUD) - for yearly insertion; Progestasert®

Postcoital Contraceptives Postcoital Contraceptives

- called, “morning-after pills”

- high dose estrogen administered within 72 hours after coitus and continued 2x for 5 days

- ethinyl estradiol

diethylstilbestrol

conjugated estrogens

estrone

AndrogensAndrogens

AndrogensAndrogens

- basic nucleus: androstane

Testosterone

AndrogensAndrogens

- group of steroids that have anabolic and/or masculinizing effects in both males and females

Endogenous AndrogenEndogenous Androgen

Testosterone

- primary natural endogenous androgen

- synthesized by Leydig cells in the testes of males and in smaller amounts by the cells in the ovary of females, and in the adrenal gland

-produced in response to LH

Synthetic AndrogensSynthetic Androgens

Methyltestosterone

Danazol

Stanozolol

Nandrolone

Therapeutic UsesTherapeutic Uses

1. Androgenic Effects

- in hypogonadism in males

2. Anabolic Effects

- in senile osteoporosis, severe burns, speedy recovery from surgery or from chronic debilitating diseases

3. Endometriosis (Danazol)

Unapproved UseUnapproved Use

Used to increase lean body mass, muscle strength and aggressiveness in athletes and body builders (Nandrolone & Stanozolol)

AntiandrogensAntiandrogens

- inhibit the action of androgens by interfering with androgen synthesis or by blocking their receptors

a. Finasteride - used in Benign Prostatic Hypertrophy (BPH)

AntiandrogensAntiandrogens

b. Flutamide - for prostatic carcinoma

c. Cyproterone acetate - for hirsutism in females

Hormones of the Adrenal Hormones of the Adrenal CortexCortex

Hormones of the Adrenal CortexHormones of the Adrenal Cortex

1. Adrenocorticosteroids

a. Mineralocorticoids

b. Glucocorticoids


Adrenal CortexAdrenal Cortex

3 Zones:

1. Zona glomerulosa

- produces mineralocorticoids

2. Zona fasciculata

- produces glucocorticoids

3. Zona reticularis

- produces adrenal androgens

Adrenal CortexAdrenal Cortex

Zona glomerulosa

Zona fasciculata

Zona reticularis

Kidney

MineralocorticoidsMineralocorticoids

- possess sodium-retaining and potassium-secreting effects

- essential for fluid and electrolyte balance

- endogenous: aldosterone

desoxycorticosterone

- synthetic: fludrocortisone

GlucocorticoidsGlucocorticoids

- Endogenous: Cortisol

Cortisone

Corticosterone

Hydrocortisone

- essential for the metabolism of carbohydrates, fats and proteins

- they enhance response of the vascular and bronchial smooth muscles to catecholamines


Other Preparations:

Prednisone Betamethasone

Methylprednisolone Dexamethasone

Triamcinolone

- anti-inflammatory, anti-allergy and immunosuppressant effects

- inhibit cell growth and division

- catabolic effects on protein and bones


Therapeutic Uses:

Allergy

Inflammation of joints and bones

Skin diseases

Organ transplant immunosuppression

Pulmonary Diseases: Bronchial Asthma

COPD


Adverse effects:

Cushing’s syndrome

Adrenal suppression

osteoporosis

PUD

impaired wound healing

increased susceptibility to infection

hyperglycemia/DM

cataract

Addison’s DiseaseAddison’s Disease

• hyposecretion of adrenocorticosteroids

• characterized by:– anorexia– dehydration– weakness and lethargy– hyperpigmentation (bronze-colored skin)

Cushing’s SyndromeCushing’s Syndrome

• hypersecretion of adrenocorticosteroids

• characterized by:– moon face– buffalo hump– pendulous abdomen– hypertension

Cushing's SyndromeCushing's Syndrome

Thyroid Hormones and Thyroid Hormones and Drugs for Thyroid DisordersDrugs for Thyroid Disorders

Thyroid GlandThyroid Gland

Thyroid Hormone SynthesisThyroid Hormone Synthesis

1. Iodide uptake

2. Peroxidation of iodide to iodine

3. Organification of iodine

4. Coupling reaction: DIT + DIT T4

MIT + DIT T3

5. Proteolysis

6. Peripheral conversion of T4 to T3

Thyroid HormonesThyroid Hormones

- the thyroid hormones T3 and T4 are essential for the normal growth and maturation of the body

T4T4

- thyroxine

- converted to T3 by the action of the enzyme deiodinase

- 99.98% protein bound to thyroxine-binding globulin

- 0.02% is in free form

- half-life: 7 days

T3T3- triiodothyronine

- most active form

- 3-4x more potent than T4

- responsible for most of the effects of the thyroid hormones

- has 10-fold greater affinity for the receptors

- 99.8 % protein bound

- 0.2% is in free form

- half-life: 1.5 days

HypothyroidismHypothyroidism

- inability of the thyroid gland to supply sufficient thyroid hormone to the body

- manifestations:

Cretinism (infant-state)

Myxedema (adult-state)

CretinismCretinism

- infant-state hypothyroidism- characterized by physical and mental

retardation

MyxedemaMyxedema

- adult-state hypothyroidism- characterized by:

• bradycardia• weakness and lethargy• dry skin and hair• coldness• goiter

Thyroid Hormone PreparationsThyroid Hormone Preparations

Preparation T4:T3 ratio

Thyroid, USP

Beef 4:1

Pork 2-3:1

Thyroglobulin 2:1

Levothyroxine Pure T4

Levothyronine Pure T3

Liotrix 4:1

HyperthyroidismHyperthyroidism

- overabundance of thyroid hormone in the body

- thyrotoxicosis

- Forms:

Graves’ Disease - most common

Plummer’s Disease - less common

- with cardiac abnormalities

Graves' DiseaseGraves' Disease

Antithyroid DrugsAntithyroid Drugs

1. Thioamides

2. Inorganic Anions/Anionic Inhibitors

3. Iodides

4. Radiocontrast dyes

5. Beta-blocker

6. Dexamethasone

7. Radioactive Iodine

ThioamidesThioamides

- MOA: inhibit iodine organification and coupling

- examples:

Propylthiouracil (PTU)

Methimazole

Carbimazole

- S/E:

pruritic maculopapular rash

agranulocytosis

Inorganic AnionsInorganic Anions

- aka: Anionic Inhibitors

- MOA: interfere with the uptake of iodine and cause the discharge of intra-thyroidal iodine

- examples:

Potassium perchlorate

Potassium thiocyanate

- S/E:

aplastic anemia, nephrotic syndrome

IodidesIodides

- MOA: inhibit organification and hormone release

- they decrease the size and vascularity of goiter

- examples:

KISS - Potassium iodide saturated solution

Lugol’s solution - strong iodine solution

Radiocontrast DyesRadiocontrast Dyes

- MOA: inhibit peripheral conversion of T4 to T3; also inhibit proteolysis

- examples:

Ipodate

Iopanoic acid

Beta-blockerBeta-blocker

- MOA: symptomatic relief of the sympathetic manifestations of hyperthyroidism; may also inhibit peripheral conversion of T4 to T3

- Propranolol

DexamethasoneDexamethasone

- MOA: inhibits peripheral conversion of T4 to T3

Radioactive iodineRadioactive iodine

- 131I

- MOA: destruction of thyroid cells by emission of high-energy beta radiation

- can offer cure

- Contraindicated to pregnant women or women who will become pregnant

Anti-diabetic AgentsAnti-diabetic Agents

PancreasPancreas

- is a mixed gland

- Exocrine portion

-releases pancrealipase & chymotrypsin

- Endocrine portion

-1million islets of Langerhan

-have at least 4 hormone-producing cells

Endocrine PancreasEndocrine Pancreas

Cell Type % islet Hormone

A (alpha) 20 glucagon

proglucagon

B (beta) 75 insulin

pro-insulin

D (delta) 3-5 somatostatin

F (PP cell) <2 pancreatic

polypeptide (PP)

Diabetes Mellitus (DM)Diabetes Mellitus (DM)

- diabetes = Greek “siphon”

mel = honey

- “something sweet is passing through or siphoning from the body”

- a metabolic disorder in which glucose levels in the blood are too high and begins to spill in the urine because the kidney tubule cells cannot reabsorb it fast enough

Types of DMTypes of DM

Type 1

Type 2

Gestational DM

Secondary DM

Type 1Type 1

- insulin-dependent DM (IDDM)

- juvenile-onset DM

- ketosis-prone diabetes

- most common in children

- insulin secretion is destroyed

- dependent upon exogenous insulin to sustain life

Type 2Type 2

- non-insulin-dependent DM (NIDDM)

- adult-onset DM

- not insulin dependent

- endogenous insulin levels may appear normal or increased but beta-cell dysfunction is manifested by a relative insulin insufficiency

Gestational DMGestational DM

- defined as any degree of glucose intolerance that has its onset during pregnancy

Secondary DMSecondary DM

- broad term used to classify patients who have unusual causes of DM due to certain diseases of the pancreas, endocrinopathies or drugs

3 Cardinal Signs of DM3 Cardinal Signs of DM

1. Polyuria - excessive urination to flush out the glucose and ketones

2. Polydipsia - excessive thirst resulting from water loss

3. Polyphagia - excessive hunger due to inability to use sugars and the loss of fats and proteins from the body

InsulinInsulin

- is the storage and anabolic hormone of the body

- produced by the Beta-cells of the pancreas

- principal hormone required for proper glucose use in normal metabolic processes

- previously extracted from beef/pork pancreas

- now is produced via recombinant DNA technology

Insulin - EffectsInsulin - Effects

1. It facilitates transport of glucose across cell membrane

2. In the liver, it promotes glycogenesis and gluconeogenesis

3. In the muscles, it increases amino acid transport, protein synthesis and glycogenesis

4. In adipose tissues, it increases triglyceride storage

Insulin - IndicationsInsulin - Indications

• Diabetes Mellitus Type 1

• Diabetes Mellitus Type 2 that cannot be controlled by diet, exercise and oral hypoglycemic agents (OHAs)

• Ketoacidosis

• Diabetic coma

Insulin PreparationsInsulin PreparationsActivity in hoursPharmakokinetic

TypeSpecies Type

Peak DurationUltra rapid-acting

Insulin LisproHuman

(Modified) 0.25 – 0.50 3 – 4

Rapid actingInsulin injection, USP(Regular, Crystalline)

Human, Pork 0.50 – 3 5 – 7

Intermediate actingNPH Insulin(Isophane)

Lente Insulin(Insulin zinc susp)

Human, Pork

Human, Pork

8 – 12

8 – 12

18 – 24

18 – 24

Long actingUltralente Insulin(Insulin zinc susp

extended)

Human 8 – 16 18 – 28

Ultra long actingInsulin glargine Human

(Modified)No peak > 24

Oral Hypoglycemic DrugsOral Hypoglycemic Drugs

• Insulin secretagogues

• Biguanides

• Alpha-glucosidase inhibitors

• Thiazolidinedione derivatives

Insulin SecretagoguesInsulin Secretagogues

• Sulfonylureas

• Meglitinides

SulfonylureasSulfonylureas

MOA:

- stimulate pancreatic release of insulin - inhibit pancreatic release of glucagons

- increase insulin receptor binding

- decrease hepatic extraction of insulin


Ist Generation

Chlorpropamide Acetohexamide

Tolbutamide Tolazamide

2nd Generation

Glibenclamide Glipizide

Gliclazide Glimepiride


Side-effects:

hypoglycemia

blood dyscrasias

disulfiram-like reactions with 1st Gen and glipizide

weight gain

MeglitinidesMeglitinides

- MOA: increase pancreatic insulin secretion

- short duration of action: 1 to 3 hours

- examples: Repaglinide

Nateglinide

- S/E:

hypoglycemia

weight gain

BiguanidesBiguanides- unknown MOA

- reduce blood glucose level even in the absence of beta cell function

- proven as a useful initial therapy among DM Type 2 patients, especially among obese patients

- not associated with hypoglycemia

- ex. Metformin (most proven)

Phenformin ( no longer available)

- S/E: lactic acidosis, megaloblastic anemia

Alpha-glucosidase inhibitorsAlpha-glucosidase inhibitors

- MOA: competitive inhibition of intestinal alpha-glucosidase enzyme, preventing digestion of dextrins and disaccharides into absorbable monosaccharides

- examples: Acarbose

Voglibose

Miglitol

- S/E: flatulence, potential hepatotoxicity of acarbose

Thiazolidinedione derivativesThiazolidinedione derivatives

- MOA: insulin sensitizers - increase skeletal muscle sensitivity to insulin; they also decrease hepatic gluconeogenesis

- examples: Rosiglitazone

Pioglitazone

- S/E: Hepatic failure (reason for the withdrawal of Troglitazone), edema and mild anemia

Let’s see how much Let’s see how much you can recall… :)you can recall… :)

Question 1:Question 1:

Which of the following is generally true of hormones?

A. Exocrine glands produce them.B. They travel throughout the body in the

blood.C. They affect only non-hormone

producing organs.D. All steroid hormones produce very

similar physiologic effects in the body.

B


All of the following substances are endogenous tropic hormones secreted by the pituitary gland EXCEPT:

A. SomatotropinB. hCGC. FSHD. TSHE. Corticotropin

B


Which of the following is secreted by the posterior pituitary gland?

A. Luteinizing HormoneB. ACTHC. OxytocinD. ThyrotropinE. Growth Hormone

C

Question 4:Question 4:ACTH or Adrenocorticotropic Hormone is

released by the anterior pituitary gland in response to which hypothalamic hormone?

A. GnRHB. TRHC. GHIHD. CRHE. PRH

D


All of the following are steroidal hormones except:

A. testosteroneB. levothyroxineC. cortisoneD. dexamethasoneE. estradiol

B


Which of the following insulins can be administered IV?

A. Lente insulinB. Isophane insulinC. Protamine Zinc InsulinD. Ultralente insulinE. Regular insulin

E


It is a fertility drug. It induces ovulation by negative feedback mechanism.

A. TamoxifenB. Ethinyl estradiolC. ClomipheneD. FinasterideE. Prednisone

C


Which of the following is not properly paired with its indication?

A. testosterone - hypergonadismB. finasteride - BPHC. cyproterone - hirsutismD. PTU - hyperthyroidismE. Tamoxifen - estrogen-dependent

breast cancer

A


Which of the following drugs can be used for rheumatoid disorders?

A. diethylstilbestrolB. triiodothyronineC. methimazoleD. betamethasoneE. metformin

D


Which of the following is a sulfonylurea?A. metforminB. repaglinideC. acarboseD. rosiglitazoneE. glibenclamide

E

““Success is to be measured not so much by the Success is to be measured not so much by the position that one has reached in life, but by the position that one has reached in life, but by the

obstacles which he has overcome.”obstacles which he has overcome.”

- - Booker T. WashingtonBooker T. Washington

Thank You for Listening!Thank You for Listening!

Health & Medicine

Endocrine drugs