Farmakologi Kortikosteroid

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Text of Farmakologi Kortikosteroid

  • Kortikosteroid

  • Kortikosteroid

    Bentuk sintetik dari hormon yang disekresi oleh kortek

    adrenal.

    Esensial:

    Maintenan beberapa sistem terutama sistem

    kardiovaskular

    Berperan pada respon tubuh thd stress

    Mekanisme

    Supresi proses inflamasi, alergi dan sistem imun

    Dapat untuk prevensi dan tx asma dan artritis rematoid

  • Actions of corticosteroids are grouped:

    Glucocorticoid effects, including metabolic changes and anti-inflammatory actions.

    Mineralocorticoid effects, mainly retention of salt and water, together with loss of potassium and hydrogen ions.

  • Classification of Corticosteroids ORAL CORTICOSTEROIDS

    Glucocorticoid Effect Mineralocorticoid Duration of (dose equivalent) effect effect (in hours) SHORT ACTING Cortisone 25mg ++++ 8-12 hours Hydrocortisone 20mg ++++ 8-12 hours

    INTERMEDIATE-ACTING Prednisolone 5mg ++ 18-36 hours Triamcinolone 4mg - 18-36 hours Methylprednisolone 4mg - 18-36 hours Fludrocortisone - ++++ 24-36 hours

    LONG-ACTING Dexamethasone 750 micrograms - 36-54 hours Betamethasone 750 micrograms - 36-54 hours

  • HPA AXIS

  • Pharmacological Actions

    1. Carbohydrate

    2. Protein

    3. Lipid

    4. Electrolyte and H2O

    5. CVS

    6. Skeletal Muscle

    7. CNS

    8. Stomach

    9. Blood

    10. Anti-inflammatory

    11. Immunosuppressant

    12. Respiratory system

    13. Growth and Cell

    Division

    14. Calcium metabolism

  • Indikasi kortikosteroid:

    Kontrol gejala: Asthma, allergic rhinitis, rheumatoid arthritis and related connective

    tissue disorders, temporal arteritis, inflammatory bowel disease, inflammatory skin conditions, emesis following chemotherapy, chronic pain, anaphylactic shock

    Prevensi: Transplant rejection, respiratory distress in the newborn, cerebral

    oedema

    Treatment: Certain tumours, hypercalcaemia, some blood disorders, nephrotic

    syndrome

    Replacement therapy in Addisons disease (under-activity of the adrenal cortex)

  • Efek samping

    Dosis tinggi jangka pendek --- ES < dosis rendah jangka panjang

    Efek samping jangka panjang: Redistribusi lemak

    Hipertensi Intoleransi glukosa Gangguan penyembuhan luka

    Osteoporosis (bisa dicegah dg bifosfonat) Katarak Tukak lambung (Omeprazol, misoprostol) resiko infeksi Efek SSP, psikosis Hambatan pertumbuhan pada anak

    Cushings syndrome

  • Indikasi kortikosteroid:

    Kontrol simtom: Asthma, allergic rhinitis, rheumatoid arthritis and related connective

    tissue disorders, temporal arteritis, inflammatory bowel disease, inflammatory skin conditions, emesis following chemotherapy, chronic pain, anaphylactic shock

    Prevensi: Transplant rejection, respiratory distress in the newborn, cerebral

    oedema

    Treatment: Certain tumours, hypercalcaemia, some blood disorders, nephrotic

    syndrome

    Replacement therapy in Addisons disease (under-activity of the adrenal cortex)

  • Doses and Administration

    Regular medication reviews are needed to ensure doses are kept to the minimum necessary to manage the underlying condition.

    Inhaled beclomethasone, budesonide daily doses >800 mcg (adult)

    >400mcg (child) are associated with systemic (general) side effects. Side effects are seen at half these doses for fluticasone. Some high dose regimens include daily doses up to 2 mg and 1mg

    (fluticasone). Advice to patients should include:

    Keep to the same spacer device. Mouth rinsing may reduce candidiasis and systemic absorption.

    Pre-treatment with bronchodilator may reduce cough.

  • Doses and Administration

    Oral prednisolone. Side effects appear if daily dose >7.5 mg. Maintenance doses usually 2.5-15mg/ day. Severe disease may necessitate much higher doses.

    Administer as a single dose after breakfast, but before 9.00 am., with milk or food plus a full glass of water.

    Topical applications should avoid the face, and be free of occlusive dressings (including disposable nappies).

    Rectal administration may give erratic absorption and cause local pain and bleeding.

    If giving intramuscular injections, use each site only once and document.

  • Managing the Common Adverse Effects

    of Corticosteroids

    Short courses at high dosage for emergencies appear to cause fewer adverse effects than prolonged courses using lower doses.

    Many adverse effects, for example, those related to nutrition, only arise with long-term therapy.

  • INHALED CORTICOSTEROIDS

    (dose equivalent Time in circulation for adverse effects)

    Beclometasone 1000 micrograms - 19.5 hours

    Budesonide 1000 micrograms - 6.9 hours

    Fluticasone 500 micrograms - 43.2 hours

    propionate

    *calculated as 3 times the terminal half life.

    (Karch 2000, BNF 2002, Cave et al. 1999, Lipworth 1999)

  • Corticosteroids may affect:

    inflammatory and immune responses metabolic pathways:

    the starvation response + redistribution skin gastrointestinal tract bones muscles

    cardiovascular system central nervous system eyes reproductive system adrenal glands

  • POTENTIAL PROBLEM

    SUGGESTED PREVENTION

    Increased risk of

    infections

    Teach good hand washing

    techniques

    Monitor body temperature at 5-6 p.m.

    daily

    Avoid exposure to infectious disease

    Contact doctor on exposure to

    chickenpox or measles.

    Caution with immunisations: avoid live

    vaccines (also for 6 months after

    discontinuation).

    SE

  • POTENTIAL PROBLEM

    SUGGESTED PREVENTION

    Nutrition

    Increase in appetite

    Encourage a well balanced, low calorie

    diet. Ask dietician to provide diet plan

    Monitor intake by asking patient to

    record intake for 24-hour periods.

    Weigh patient weekly

    Measure waist circumference

    regularly

    Potensi masalah

  • POTENTIAL PROBLEM

    SUGGESTED PREVENTION

    Nutrition

    Risk of dental caries

    Encourage scrupulous dental

    hygiene

    & low-sugar diet.

    Arrange 6 monthly dental

    inspections

    Consider using a mouthwash

  • POTENTIAL PROBLEM

    SUGGESTED PREVENTION

    Nutrition

    Risk of hypertension

    Foods rich in salt should be avoided,

    except with replacement regimens.

    Condiments and processed foods are

    high in sodium. Avoid salt-containing

    medicines e.g. some antacids. Avoid

    liquorice.

    Monitor blood pressure regularly.

  • POTENTIAL PROBLEM

    SUGGESTED PREVENTION

    Nutrition

    Risk of osteoporosis

    Encourage patient to eat foods high in

    calcium. Low fat dairy products are

    suggested.

    Suggest vitamin D supplementation,

    together with monitoring for vitamin D

    intoxication.

  • POTENTIAL PROBLEM

    SUGGESTED PREVENTION

    Nutrition

    Loss of potassium, causing

    muscle weakness,

    depression, constipation,

    cardiac complications.

    Venous blood samples to monitor

    electrolytes

    Encourage foods that are high in

    potassium e.g. raisins, bananas,

    meat.

  • POTENTIAL PROBLEM

    SUGGESTED PREVENTION

    Nutrition

    Salt and water retention

    Limit salt intake.

    Fluid balance records and daily

    weighing are important during

    initiation of therapy

  • POTENTIAL PROBLEM

    SUGGESTED PREVENTION

    Cardiovascular disease

    Hyperglycaemia / diabetes

    Increased cholesterol and

    triglycerides

    Congestive heart failure

    ? increased risks of

    thrombosis

    Monitor blood glucose concentrations

    regularly and if thrush appears on the

    skin

    Monitor lipid profile

    Observe for breathlessness. Monitor

    fluid retention. Minimise salt intake.

    Monitor full blood count

  • POTENTIAL PROBLEM

    SUGGESTED PREVENTION

    Skin

    (particularly topical

    preparations)

    Increase in body hair and

    acne

    Poor wound healing

    Provide advice on managing acne

    Consult podiatrist regarding foot-care.

    Anticipate poor healing and contact

    wound care specialists promptly.

    Take swabs if healing delayed.

  • POTENTIAL PROBLEM

    SUGGESTED PREVENTION

    Skin

    (particularly topical

    preparations)

    Thinning of the skin

    Increased vigilance of pressure areas.

    Evaluate pressure damage risk score

    regularly

    Avoid friction and shearing forces on

    the skin, for example, teach patients in

    the correct use of moving and handling

    aids (glide sheets) when moving along

    the bed/chair.

  • POTENTIAL PROBLEM

    SUGGESTED PREVENTION

    Skin

    (particularly topical

    preparations)

    Thinning of the skin

    Allow extra time for procedures

    involving tissue handling, such as

    transfer to hoist, care of infusion sites.

    Ensure good communication within

    the multidisciplinary team: for example,

    orthopaedic surgeons, and plaster

    technicians, or nurses applying plaster

    casts, need to be aware that the patient

    is prescribed corticosteroids, and adjust

    treatment, if possible.

  • POTENTIAL PROBLEM

    SUGGESTED PREVENTION

    Gastrointestinal Tract

    Irritation of stomach and

    oesophagus

    Take oral corticosteroids with food or

    milk

    Observe and test stools for blood loss

  • POTENTIAL PROBLEM

    SUGGESTED PREVENTION

    Bones

    Osteoporosis

    (see nutrition above)

    Growth

    Encourage moderate exercise

    Bone densiometry assessments

    Consider HRT

    Plot height and weight on centile

    charts at regular intervals.

  • POTENTIAL PROBLEM

    SUGGESTED PREVENTION

    Muscles

    Muscle weakness

    Cramps

    Routine exercise may help to prevent or

    decrease muscle weakness.

    Assess activities such as rising from a

    chair

    Monitor respiratory function

    Check electrolytes if cramps occur

  • POTENTIAL PROBLEM

    SUGGESTED PREVENTION

    Mental health

    Emotional changes such as

    moodiness, depression,

    euphoria or hallucinations

    Steroid abuse/ dependence

    Monitor behaviour.

    Consider the possibility of steroid

    psychosis and refer as necessary.

    Refer patients who resist dose

    reductions.

  • POTENTIAL PROBLEM

    SUGGESTED PREVENTION

    Eyes

    (particularly eye drops or if

    creams applied close to

    eyes)

    Increased intraocular

    pressure and glaucoma

    Cataracts or clouding of

    vision

    Infections

    Regular eye examinations are

    important to detect changes before

    permanent eye damage occurs.

    Arrange appointments on initiation

    of therapy, after 6 months, then at

    least yearly.

  • POTENTIAL PROBLEM

    SUGGESTED PREVENTION

    Reproductive system

    Delayed puberty

    Changes in menstrual cycle

    Impotence

    Offer reassurance

    Advise clients of potential problems

  • POTENTIAL PROBLEM

    SUGGESTED PREVENTION

    Adrenal suppression/

    insufficiency:

    Persists 3 months- years

    after discontinuation

    Administer medication before 9.00 am.

    Monitor pulse, blood pressure,

    electrolytes and glucose regularly.

    Repeat checks if bruises appear.

    After 1 weeks use, advise against sudden discontinuation of therapy.

    Advise wearing a medical-alert bracelet

    to inform emergency workers of

    medication

  • Control of Glucocorticoid Secretion (The hypothalamic/pituitary/adrenal (HPA) axis)

    Corticosteroids administered as medications constantly inhibit CRH & ACTH secretion.

    The adrenal cortex eventually shrinks and may fail to synthesise any hormones,

    even in response to extreme stress, such as surgery or infection.

    In health, when there is not stress, cortisol suppresses secretion of

    CRH and ACTH by a negative feedback mechanism

  • POTENTIAL PROBLEM

    SUGGESTED PREVENTION

    Withdrawal of therapy

    Supervise gradual withdrawal of therapy

    Supervise transition from oral to inhaled

    administration and conversion to

    alternate day therapy.

    Continue to monitor patients for possible

    adrenal insufficiency for a year after

    discontinuation.

    Ensure that patient always carries a

    'steroid card'

  • Cautions and contra-indications

    When administering corticosteroids, caution is needed in some circumstances:

    Presence of infections. Infections may 'flare up', including HIV/AIDS,

    previous TB, wound infection, Herpes simplex.

    Conditions which will be exacerbated: hypertension, diabetes, heart failure, osteoporosis, glaucoma, epilepsy, mood disorders, pressure sores.

    Conditions where potassium loss will prove dangerous: liver failure.

    Situations where muscle weakening could be problematic: Recent myocardial infarction, muscle wasting, elderly, bedridden.

  • Cautions and contra-indications

    Masking of serious symptoms: peptic ulcer,

    inflammatory bowel disease, pneumonia

    Corticosteroids worsen cardiovascular risk factors. Their long-term use should be carefully evaluated in patients already at high risk of stroke or heart attack.

    Lower doses are needed in patients unable to eliminate drugs at the normal rate: hypothyroidism, liver failure, renal failure, elderly.

  • Cautions and contra-indications

    Pregnancy. The risks of intrauterine growth retardation

    with repeated courses of intra-muscular corticosteroids are administered to prevent respiratory distress of the new-born are currently under investigation. When cortIcosteroids are administered for severe maternal disease, the benefits are likely to outweigh any risks. Most prednisolone (unlike dexamethasone) is inactivated by the placenta.

    Breastfeeding: avoid if >40mg prednisolone /day (or equivalent) administered. Doses below those causing systemic side effects are considered safe.

  • Interactions (Not a complete list)

    Corticosteroids interact with many other drugs.

    Some drugs intensify the adverse reactions of corticosteroids:

    Increased risk of gastro-intestinal bleeding: alcohol, anticoagulants, aspirin, NSAIDs

    Increased fluid retention and hypertension: beta2 agonists, NSAIDs, sodium-containing preparations, oestrogens, liquorice, ginseng, some Asian herbal mixtures

    Increased potassium depletion: beta2 agonists, diuretics, digoxin, laxatives

  • Interactions (Not a complete list)

    The effects of some drugs and appliances are antagonised: anti- epileptics, anti-diabetics, anti-hypertensives, growth hormone, intra- uterine contraceptive devices.

    The dose of corticosteroids is effectively reduced by:

    co-administration with antacids, within 2 hours carbamazepine, phenytoin, rifampicin, theophylline

    The dose of corticosteroids is effectively increased by:

    erythromycin, ketoconazole, itraconazole, ciclosporin, some anti-virals