Adrenal Glucocorticoids 7 أ. م. د. وحدة بشير اليوزبكي Head of Department of Pharmacology- College of Medicine- University of Mosul-2014

Objectives: At the end of this lecture, students should be able to: 1- State the difference between physiological and pharmacological effect of adrenal corticosteroid. 2- State the mechanism of action and therapeutic uses of adrenal corticosteroid. 3- Discuss the adverse effects & drug interactions of adrenal corticosteroid. - At a level accepted to the quality assurance standards for the College of Medicine/ University of Mosul.

The adrenal gland Medulla which secrete Adrenaline (epinephrine) Cortex which produces: 1-Corticosteroids a- Glucocorticoids (Cortisol) b-Mineralocorticoids (Aldosterone) 2- Androgens (Estrogen, Progesterone & Testosterone)

Mechanism of Action of Steroid hormones

Type of steroids The Naturally Occurring Glucocorticoids; Cortisol (Hydrocortisone) Synthetic Corticosteroids 1- Short acting glucocorticoids : Prednisone, Prednisolone, Methylprednisolone 2- Intermediate-acting glucocorticoids : Triamcinolone, Fluprednisolone 3- Long-acting glucocorticoids : Betamethasone, dexthamethasone - Mineralocorticoids: Deoxycorticosterone (DOCA), Fludrocorti sone

Clinical Pharmacology of Glucocorticoid A- On adrenal disorders 1- Adrenocortical Insufficiency: a- Replacement therapy of acute adrenocortical insufficiency (adrenal or Addisonian crisis) which is duo to: - Failure to provide patient receiving replacement therapy with adequate doses - Abrupt withdrawal from chronic, high dose glucocorticoid Therapy consists of: - Seek and correct cause of crisis (often an infection). - Correction of fluid and electrolyte abnormalities by IV fluid and salts. - Hydrocortisone in doses of 100 mg IV every 8 hours until the patient is stable. The dose is then gradually reduced, achieving maintenance dosage within 5 days.

A- On adrenal disorders b- Replacement therapy of chronic adrenocortical insufficiency (Addison's disease) - In primary adrenal insufficiency, About 20–30 mg of hydrocortisone must be given daily orally. This must be supplemented by a salt-retaining hormone such as fludrocortisone. - Secondary (decrease secretion of ACTH by pituitary) & tertiary (decrease secretion of CRH by hypothalamus) adrenocortical insufficiency The treatment similar to that in primary.

A- On adrenal disorders 2- Congenital Adrenal Hyperplasia This is suppressed by Prednisolone or Dexamethasone which inhibit pituitary ACTH release. 3- Cushing's Syndrome Treatment is by surgical removal of the tumor producing ACTH or cortisol or resection of adrenals. - Doses of up to 300 mg of hydrocortisone may be given on the day of surgery. The dose must be reduced slowly to normal replacement levels.

A- On adrenal disorders 4- Aldosteronism - Primary aldosteronism usually results from the excessive production of aldosterone by an adrenal adenoma. - Patients generally improve when treated with spironolactone, which is an aldosterone receptor-blocking agent. 5- Use of Glucocorticoids for Diagnostic Purposes: (Dexamethasone suppression test) 6- Corticosteroids and stimulation of lung maturation in the fetus. IM betamethasone, 12 mg, followed by 12 mg 18–24 hours later, is commonly used.

B- On nonadrenal disorders Allergic reactions Systemic inflammation Inflammatory conditions of bones and joints Organ transplants Renal disorder Skin disease Hematological disorder Pulmonary disease Neurologic disorders Eye disease GIT diseases Hematological disorder

Adverse Effects of Corticosteroid 1.Endocrine Iatrogenic Cushing's syndrome result in moon face, deposition of fat on the body, oedema, hypertension, striae, acne, hirsutism. Hypothalamic/pituitary' /adrenal (HPA) suppression

Adverse Effects of Corticosteroid 2.Musculoskeletal: myopathy, Osteoporosis fractures of vertebrae, ribs 3.Immune: Suppression of the inflammatory response to infection and immunosuppression 4.Gastrointestinal: Peptic ulcer and hemorrhage 5.Central nervous system: Depression and psychosis Euphoria insomnia, aggravation of schizophrenia and epilepsy

Adverse Effects of Corticosteroid 6.Ophthalmic effects: cataracts and glaucoma (related to age, dosage) 7.Hypertension, edema, hypokalemia 8.Growth retardation in children. 9. In Pregnancy: Adrenal steroids are teratogenic in animals, cleft palate and other fetal abnormalities may occur. Dosage during pregnancy should be low and fluorinated steroids are avoided because they are more teratogenic.

Precautions during chronic adrenal steroid therapy Patients must always 1- Carry a card giving details of therapy 2- Be impressed with the importance of compliance 3- Know what to do if they develop an intercurrent illness or other severe stress: double their next dose and to tell their doctor. 4- If a patient forget a dose then it should be taken as soon as possible so that the total daily intake is maintained, because every patient should be taking the minimum dose necessary to control the disease.

Contraindications of Corticosteroid Infections (demands that effective chemotherapy be begun before the steroid). Tuberculosis Hypertension with CHF A history of mental disorder or epilepsy Peptic ulcer Diabetes mellitus Osteoporosis Glaucoma Pregnancy

Withdrawal of adrenal steroid therapy - Withdrawal from these drugs can be a serious problem, because if the patient has experienced HPA suppression, abrupt removal of the corticosteroids causes an acute adrenal insufficiency syndrome that can be lethal and withdrawal might cause an exacerbation of the disease, - The dose must be tapered according to duration of therapy,the longer the duration of therapy the slower must be the withdrawn.