PHARMACOLOGY Adrenal Hormones. pptx

Pharmacology

1. University of Juba College of Medicine PHARMACOLOGY LECTURES Adrenal Hormones By Dr. Rita Gabriel Tulba Pharmacy Specialist Dr. Rita Gabriel Tulba

2. The adrenal gland The adrenal gland consists of the cortex and the medulla. -The Adrenal Medulla secretes epinephrine. -T he Adrenal cortex, synthesizes and secretes two major classes of steroid hormones the 1. Adrenocorticosteroids : glucocorticoids and mineralocorticoids 2. A drenal androgens. Dr. Rita Gabriel Tulba

3. The adrenal cortex The adrenal cortex secretes: 1. G lucocorticosteroids , principally cortisol (hydrocortisone); 2. M ineralocorticoids – principally aldosterone; 3. androgens (relatively small amounts). Dr. Rita Gabriel Tulba

4. Glucocorticoids Cortisol (hydrocortisone)is the principal human glucocorticoid. - Normally, its production is diurnal, with a peak early in the morning followed by a decline and then a secondary, smaller peak in the late afternoon. Factors such as stress and levels of the circulating steroid influence secretion. The effects of cortisol are many and diverse. In general, all glucocorticoids: Dr. Rita Gabriel Tulba

5. I. Promote normal intermediary metabolism : 1. Glucocorticoids favor increasing amino acid uptake by the liver and kidney and elevating activities of gluconeogenic enzymes. 2.stimulate protein catabolism and lipolysis, thereby providing the building blocks and energy that are needed for glucose synthesis . Note : Glucocorticoid insufficiency may result in hypoglycemia. 3.Lipolysis results as a consequence of the glucocorticoid augmenting the action of growth hormone on adipocytes , causing an increase in the activity of hormone-sensitive lipase. Dr. Rita Gabriel Tulba

6. II.Increase resistance to stress: By raising plasma glucose levels, glucocorticoids provide the body with the energy it requires to combat stress caused , for example, by trauma, fright , infection , bleeding, III.Alter blood cell levels in plasma: Glucocorticoids cause a decrease in eosinophils , basophils, monocytes, and lymphocytes by redistributing them from the circulation to lymphoid tissue Note : (The decrease in circulating lymphocytes and macrophages compromises the body's ability to fight infections). In contrast to this effect, they increase the blood levels of hemoglobin, erythrocytes, platelets, and polymorphonuclear leukocytes. Dr. Rita Gabriel Tulba

7. IV.Have anti-inflammatory action: The most important therapeutic property of the glucocorticoids is their ability to dramatically reduce the inflammatory response and to suppress immunity. V.Affect other components of the endocrine system: Increase growth hormone production. VI. Can have effects on other systems: High doses of glucocorticoids stimulate gastric acid and pepsin production and may exacerbate ulcers . Effects on the central nervous system that influence mental status have been identified. VII. Replacement therapy for primary adrenocortical insufficiency ( Addison's disease ): This disease is caused by adrenal cortex dysfunction ( as diagnosed by the lack of patient response to corticotropin administration Chronic glucocorticoid therapy can cause severe bone loss. Myopathy leads patients to complain of weakness . Dr. Rita Gabriel Tulba

8. Mechanism of Action: They act as positive transcription factors for proteins involved in inhibition of the production of inflammatory mediators (e.g. lipocortin ) and they inhibit the action of transcription factors for proinflammatory cytokines. Dr. Rita Gabriel Tulba

9. Side effects: 1. Adrenal suppression. 2.Metabolic effects including hyperglycaemia and hypokalaemia occur rapidly, as does insomnia and mood disturbances. 3. Chronic side effects include Cushingoid appearance( redistribution of body fat, puffy face, increased body hair growth, acne, insomnia, and increased appetite ) ,hypertension, osteoporosis and proximal myopathy. 4. Immunosuppression – susceptibility to infections. 5. Patients on chronic steroid treatment require an increased dose for stresses, such as infection or surgery. 6. Acute adrenal insufficiency can result from rapid withdrawal after prolonged glucocorticosteroid administration. 7. Gradual tapered withdrawal is less hazardous. Dr. Rita Gabriel Tulba

10. Glucocorticoids Drugs Glucocorticosteroids are: 1. Cortisol (hydrocortisone) 2. Cortisone 3. Prednisolone and prednisone 4. Methylprednisolone 5. Triamcinolone 6. Dexamethasone 7. Betamethasone Dr. Rita Gabriel Tulba

11. I. HYDROCORTISONE (CORTISOL): Hydrocortisone has predominantly glucocorticoid effects, but also has significant mineralocorticoid activity. Uses; 1. Hydrocortisone is given with fludrocortisone to replace mineralocorticoid as replacement therapy in patients with adrenocortical insufficiency. 2. High-dose intravenous hydrocortisone is used short term to treat acute severe asthma (usually followed by oral prednisolone ) 3. Autoimmune inflammatory diseases (e.g. acute inflammatory bowel disease). Dr. Rita Gabriel Tulba

12. 4. Hydrocortisone acetate is an insoluble suspension which can be injected into joints to provide a localized anti-inflammatory effect. 5. Hydrocortisone cream is relatively low in potency and is of particular use on the face where more potent steroids are Contraindicated . Dr. Rita Gabriel Tulba

13. II.PREDNISOLONE: Prednisolone is an analogue of hydrocortisone that is approximately four times more potent than the natural hormone with regard to anti-inflammatory metabolic actions. Uses: 1.The anti-inflammatory effect of prednisolone can improve inflammatory symptoms of connective tissue and vasculitic diseases. 2. Prednisolone is considered in progressive rheumatoid arthritis when other forms of treatment have failed. Dr. Rita Gabriel Tulba

14. 3.Short-term management of patients with severe articular symptoms from systemic lupus Erythematosus . 4. Prednisolone may be indicated for severe asthma and some interstitial lung diseases, e.g. fibrosing alveolitis . 5. Acute hepatitis and chronic active hepatitis. 6.Acute and chronic inflammatory bowel disease ( where suppositories or enemas are used). 7. The immunosuppressant effect of prednisolone is further utilized in transplantation in order to prevent rejection Dr. Rita Gabriel Tulba

15. III. DEXAMETHASONE Uses 1. Dexamethasone is used as a diagnostic agent in the investigation of suspected Cushing’s syndrome 2. In the symptomatic treatment of cerebral oedema associated with brain tumours ; 3. Used to prevent respiratory distress syndrome in premature babies by administration to pregnant mothers; 4. Used in combination with other anti-emetics to prevent cytotoxic chemotherapy- induced nausea and vomiting. Dr. Rita Gabriel Tulba

16. Mineralocorticoids -Mineralocorticoids help to control the body's water volume and concentration of electrolytes, especially sodium and potassium. -Aldosterone acts on kidney tubules and collecting ducts, causing a reabsorption of sodium , bicarbonate , and water . - Aldosterone decreases reabsorption of potassium , which, with H + , is then lost in the urine. Note : -Elevated aldosterone levels may cause alkalosis and hypokalemia. -whereas retention of sodium and water leads to an increase in blood volume and blood pressure. Dr. Rita Gabriel Tulba

17. Mineralocorticoids Drugs Mineralocorticosteroids 1. Aldosterone 2. Fludrocortisone Dr. Rita Gabriel Tulba

18. I.ALDOSTERONE Aldosterone is the main mineralocorticoid secreted by the adrenal cortex. -It has no glucocorticoid as a mineralocorticoid. -Its release is controlled by are plasma sodium, plasma potassium and angiotensin II. -Aldosterone acts on the distal nephron, promoting Na/K exchange, causing sodium retention and urinary loss of potassium and hydrogen ions. Dr. Rita Gabriel Tulba

19. II.FLUDROCORTISONE Fludrocortisone is a potent synthetic mineralocorticoid, which is more powerful than hydrocortisone. - It binds to the mineralocorticoid steroid receptor and mimics the action of aldosterone . -It is active by mouth. Uses: 1. It is used as replacement therapy in patients with adrenocortical insufficiency. 2. It is sometimes used to treat patients with symptomatic postural hypotension. Dr. Rita Gabriel Tulba

20. The Adrenal Medulla Adrenaline ( epinephrine ) Is the main hormone produced by the adrenal medulla. Uses : 1. In emergency situations, such as cardiac arrest 2. Anaphylactic shock. 3. other life-threatening disorders that require combined potent α - and β - agonist activity (e.g. shock, beta-blocker overdose). 4. Used to prolong the action of local anaesthetics (via its vasoconstrictor action). 5. Dipivefrine is a prodrug eye-drop formulation of adrenaline used to treat chronic open angle Glaucoma . Dr. Rita Gabriel Tulba

21. THANK YOU DR. RITA GABRIEL TULBA Email: [email protected] Tel:[phone] Dr. Rita Gabriel Tulba