Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex.
Corticosteroids are involved in a wide range of physiologic systems such as:
Stress response Immune response and regulation of inflammation Carbohydrate metabolism Protein catabolism Blood electrolyte levels, and Behavior
Glucocorticoids such as cortisol control carbohydrate, fat and protein metabolism and are anti-inflammatory by preventing phospholipid release, decreasing eosinophil action and a number of other mechanisms.
Mineralocorticoids such as aldosterone control electrolyte and water levels, mainly by
promoting sodium retention in the kidney.
Common natural hormones: Corticosterone Cortisone Aldosterone
Classification of Corticosteroids:
Group A (short to medium acting glucocorticoids): Hydrocortisone, Hydrocortisone acetate, Cortisone acetate, Tixocortol pivalate, Prednisolone, Methylprednisolone, and Prednisone.
Group B: Triamcinolone acetonide, Mometasone, Amcinonide, Budesonide, Desonide, Fluocinonide, Fluocinolone acetonide, and Halcinonide.
Group C: Betamethasone, Sodium phosphate, Dexamethasone, Dexamethasone sodium phosphate, and Fluocortolone.
Group D: Hydrocortisone-17-butyrate, Betamethasone valerate, Betamethasone dipropionate, Prednicarbate, and Fluprednidene acetate.
Routes of administration of Corticosteroids: 1. Topical steroid for use topically on the skin, eye, and mucous membranes. 2. Inhaled steroids for use to treat the nasal mucosa, sinuses, bronchii, and lungs. 3. Oral forms such as prednisone and prednisolone. 4. Systemic forms available in injectibles for use intravenously and parenteral routes
Glucocorticoids: Are Hydrocortisone, cortisone,corticosterone. Hydrocortisone is the important glucocorticoid secreted in man.
Pharmacological Actions: 1. Carbohydrate metabolism: They promote gluconeogenesis and deposition of glycogen in the liver, but utilization of glucose is inhibited. 2. Protein metabolism: Increase the breakdown of protein. The aminoacids so produced support gluconeogenesis. 3. Fat metabolism: They increase the mobilization of fat from peripheral fat depots. On prolonged administration the produce a redistribution of fat in the body. There is loss of fat from extremities and it is deposited in the neck, face etc. 4. Electrolyte and water metabolism: Hydrocortisone increases sodium retention and potassium excretion. Sodium retention leads to water retention and edema. This may produce rise in blood pressure. 5. Calcium Metabolism: They increase calcium excretion. Absorption of calcium from the gut is decreased. They also stimulate breakdown of the protein matrix of bone. All these effects leads to osteoporosis. 6. Hematological Actions: They decrease the production of eosinophils and lymphocytes, but they stimulate erythropoiesis and the production of polymorphonuclear leucocytes. 7. Muscles: Muscles weakness seen in Addison’s disease is corrected by glucocorticoids. 8. GIT: They stimulate the secretion of pepsin and hydrochloric acid of gastric juice. 9. Anti-inflammatory effects: They inhibit inflammatory response caused by bacterial,chemical and immunological factors. The anti-inflammatory effect is due to a decrease in capillary permeability and stabilization of lysosome membrane. 10.Antiallergic effect: They suppress allergic reactions such as asthma. They also reduce the formation of antibodies and cause shrinkage of lymphatic tissue, 11.CNS: They have an effect on psyche. Large doses can produce elevation of mood, euphoria restlessness. 12.Miscellaneous: They have an uricosuric and non-specific antipyretic effects.
Adverse Reactions: 1. Cushing’s syndrome characterised by rounding of face. 2. Sodium retention and edema. 3. Muscular weakness due to potassium loss. 4. Gain in weight due to fluid retention and fat deposition. 5. Glycosuria and aggravation of diabetes. 6. Hypertension and congestive cardiac failure. 7. Androgenic effects like hirsutism and amenorrhea. 8. Psychological effects like euphoria and excitation. 9. Osteoporosis and spontaneous fracture of bones. 10.Peptic ulcer, perforation and haemorrhage. 11.Increased susceptibility to infections.
Therapeutic uses: 1. Substitution therapy in adrenal insufficiency as in Addison’s disease. 2. Mesenchymal diseases like rheumatoid arthritis and rhematic fever. 3. Anti-inflammatory effect as in case of gout. 4. Allergic diseases like asthma 5. Skin diseases like exfoliative dermatitis, contract dermatitis and psoriasis. 6. Diseases of eye involving inflammatory and exudative phases. 7. Haemopoietic diseases like autoimmune haemolytic anemia, thrombocytopenia, agranulocytosis. 8. Neoplastic diseases like myeloma, lymphoid leukemia and Hodgkin’s disease. 9. Gastointestinal diseases like ulcerative colitis. 10.Hepatic diseases like acute viral hepatitis.
Synthetic Glucocorticoids: The natural glucocorticoids(i.e. hydrocortisone, cortisone and corticosterone) have undesirable effects. The most important of them are salt and water retention. The synthetic glucocoticoids have less salt and water retaining effect and anti- inflammatory effect. The synthetic glucocoticoids are Prednisone, Prednisolone, triamcinolone, paramethasone, dexamethasone and betamethasone. The pharmacological action and toxicities of these compounds are similar to those of natural glucocorticoids, but these compounds do not have a mineralocorticoid action.
Advantages: Effectiveness in smaller doses. Easy diffusion into the tissues. Possibility to prepare esters suitable for topical application and injection into tissues. Mineralocorticoids: The natural mineralocorticoids are aldosterone and desoxycorticosterone. The action of these two compounds are almost similar but aldosterone is thirty times more potent than desoxycorticosterone. Fludrocortisone is a synthetic mineralocorticoid and is commonly used for salt retaining effects.
Pharmacological Actions: Both aldosterone and desoxycorticosterone induce reabsorption of sodium by the renal tubules They increase urinary loss of potassium. They induce sodium reabsorption in the sweat and salivary glands also. Excessive levels of aldosterone(as produced by tumours) leads to hypernatremia, hypokalemia, increased plasma volume and hypertension. In case of aldosterone deficiency there is hyperkalemia, decrease in blood volume and collapse.
Uses: Only in the management of Addison’s disease.