5 Physiological Functions and Pharmacological Effects: Carbohydrates and Proteins Metabolism:Stimulate glucose formation in the brain.Decrease peripheral utilization of glucose.Promote storage of glucose in the liver.Promote gluconeogenesis.Lipids Metabolism:Redistribution of body fat (Buffalo hump, Moon face).Enhance lipolyses of Triglycerides.Electrolyte and Water balance:Enhance reabsorption of sodium and water into plasma.Increase urinary excretion of potassium.
6 Anti-inflammatory effects: Blood Picture:Increase hemoglobin and Red blood cells.Decrease white blood cells.Anti-inflammatory effects:Suppress inflammations regardless to their cause.Immunosuppressive Effects:Decrease immunity as a result of decrease the WBC’s.Cell Growth:Retardation of cell division and cell growth.
7 Disease States: Addison’s disease: Rare syndrome 1/100,000 due to Hypoadrenalism.Causes:Atrophy of adrenal gland.Tuberculoses.Low level of ACTH.Symptoms:Weakness, fatigue, apathy, depression and irritability.Anemia and low blood pressure.Loss of sodium and dehydration.Hypersensitivity to Insulin.Hyper pigmentation.Nausea and vomiting.
8 Cushing’s disease: Conn’s syndrom: Rare syndrome 2- 5/Million due to Hyperadrenalism.Causes:Tumor of the Adrenal Cortex.Tumor of the Pituitary gland.Symptoms:Alteration of fat distribution.Hypertension.Osteoporosis.Growth retardation.Decrease Immunity.Conn’s syndrom:Inability of adrenal cortex to carry out 17a-hydroxylation of pregnenolone. That leads to low level of Cortisol and high level of Aldosterone.Alkalosis.Polyuria.Edema.
9 Pharmacokinetics: Absorption: Plasma Protein binding: Well absorbed from all sites of administration.Plasma Protein binding:90% to albumin or globulin.Half life (t1/2):hr.Metabolism and Excretion:Excreted in urine after glycosylation with glucuronic acid.
11 Adrenocorticoid Drugs Systemic Corticosteroids:They can be administered by IV, IM injections, oral, topical or by inhalation.They can be short, intermediate or long-acting. Unlike natural corticoids they do not undergo first pass metabolism.Cortisone and Cortisone acetate:Can be given orally or by IM injection.Acetate has longer duration of action.Drug of choice in replacement therapy.
12 Prednisone and Prednisolone: Fludrocortison:9a-fluorocortisone.10 times more active than cortisone as antiinflammatory.times more active as mineralocorticoids.Prednisone and Prednisolone:They are Δ1 corticoids.3, 4 times more active than cortisone and hydrocortisone.Prepared by microbial dehydrogenation (Corynebacterium simplex) or chemically using SeO2.
13 Triamcinolone: Dexamethasone: Betamethasone: 9a-fluoro, 16a-hydroxyprednisolone.Activity equal to prednidolone but with less mineralocorticoid activity.Dexamethasone:9a-fluoro, 16a-methylprednisolone.5- 7 times more active than prednidolone.Betamethasone:9a-fluoro, 16b-methylprednisolone.Slightly more active than Dexamethasone.
14 Topical Corticosteroid: Beclomethasone:9a-fluoro, 16b-methylprednisolone.9a-chloro analog of Betamethasone.Topical activity 500 times more than Betamethasone.
15 Inhaled Corticosteroids: Beclomethasone 17, 21-dipropionate (BDP):Prodrug metabolized to more active 17-BMP.17-BMP is 30 times more active than BDP.Topical activity 500 times more than Betamethasone.Triamcinolone Acetonide:
17 Diagnostic uses: Cause of Hyperadrenalism: Non specific due to obesity or stress.Cushing’s syndrome.2 mg Dexamethasone every 6 hr for 8 doses to diagnose the cause.
18 Side effects: Due to Prolonged use: Withdrawal Symptoms: Fluid and electrolyte disturbances, edema and hypertension.Hyperglycemia and glucosuria.Peptic ulcer.OsteoporosesMyopathyGrowth arrestIncrease susceptibility to infections.Withdrawal Symptoms:Rapid withdrawal after prolonged use leads to sever hypoadrenalism.