Adrenal steroids Dr Sanjeewani Fonseka Department of Pharmacology

Adrenal steroids Dr Sanjeewani Fonseka Department of Pharmacology

Objectives • Recall the physiological effect of adrenocortical steroids • Describe the anti- inflammatory and immunosuppressive effects of glucocorticoids • Compare the relative potency, glucocorticoid/mineralocorticoid activity and duration of action of commonly available steroid drugs • List clinical uses and adverse effects of glucocorticoid drugs • Explain the principles underling replacement therapy in adrenocortical insufficiency • Describe the precautions that can be taken to minimize the adverse effects of long-term steroid therapy

Endogenous Glucocorticoids Hydrocortisone Corticosterone

Corticosteroids are Gene-Active

Glucocorticoids Kinetics: • Well absorbed orally • Bound to corticosteroid-binding globulin and albumin • Distributed all over the body & passes the BBB • In the liver, cortisol is reversibly converted to cortisone & conjugated with glucuronic & sulfuric acid • Excreted in urine as 17 -hydroxy corticosteroids

Action of glucocorticoids • Metabolic • Anti-inflammatory • Immunosuppressive

Actions 1. Carbohydrate 8. Stomach 2. Protein 9. Blood 3. Lipid 10. Anti-inflammatory 4. Electrolyte and H 2 O 11. Immunosuppressant 5. CVS 12. Growth and Cell Division 6. Skeletal Muscle 13. Calcium metabolism 7. CNS

Carbohydrate metabolism • Gluconeogenesis – Peripheral actions (mobilize – Hepatic actions glucose and glycogen) • Peripheral utilization of glucose • Glycogen deposition in liver (activation of hepatic glycogen synthase) hyperglycemia

protein metabolism Negative nitrogen balance • Decreased protein synthesis • Increased protein breakdown

Skeletal Muscles Needed for maintaining the normal function of Skeletal muscle Addison's disease: weakness and fatigue is due to inadequacy of circulatory system Prolonged use: Steroid myopathy

Lipid metabolism • Redistribution of Fat

Electrolyte and water balance Act on DT and CD of kidney – Na+ reabsorption – Urinary excretion of K+ and H+

CNS • Direct – Mood – Behavior – Brain excitability • Indirect – maintain glucose, circulation and electrolyte balance

Stomach – Acid and pepsin secretion – immune response to H. Pylori

Blood RBC: Hb and RBC content (erythrophagocytosis) WBC: Lymphocytes, eosinophils, monocytes, basophils Polymorphonucleocytes

Actions on inflammatory cells • Recruitment of N, monocytes, macrophage into affected area • Action of fibroblasts • T helper action • Osteoblast • osteoclast

Inflammatory mediators • Reduced cytokines • Reduced complement • Reduced histamine

Anti-inflammatory actions of corticosteroids Corticosteroid inhibitory effect

Growth and Cell division • Inhibit cell division or synthesis of DNA • Delay the process of healing • Retard the growth of children

Calcium metabolism • Intestinal absorption • Renal excretion • Excessive loss of calcium from bones (e. g. , vertebrae, ribs, etc) • Osteoporosis

Pharmacological Actions • synthetic glucocorticoids are used because they have a higher affinity for the receptor • have little or no salt-retaining properties.

Clinical uses • Replacement therapy • Immunosuppressive / anti-inflammatory therapy • Neoplastic disease

Types of Steroids Replacement Therapy • glucocorticoid (hydrocortisone) • mineralocorticoid (fludrocortisone)

Anti-inflammatory Therapy • Short acting: hydrocortisone • Intermediate acting: prednisolone, methylprednisolone, triamcinolone • Long acting: dexamethasone

Preparations Drug Cortisol Anti-inflam. Salt retaining Topical 1 1. 0 1 0. 8 0 Prednisone 4 0. 8 0 Prednisolone 5 0. 3 4 Methylprednisolone 5 0 5 Paramethasone 10 0 - Fluprednisolone 15 0 7 Cortisone Intermediate acting Triamcinolone

Preparations Drug Anti-inflam. Salt retaining Topical Long acting Betamethasone 25 -40 Dexamethasone 30 Mineralocorticoids Fludrocortisone 10 DOCA 0 0 0 10 10 250 20 10 0

Side effects • Not seen in replacement therapy • Seen if used for anti-inflammatory property • Excess of physiological actions

Iatrogenic Cushing’s syndrome

Adverse effects (long term) • • • Glucose intolerance Acne Hypertension, edema Susceptibility to infection (TB, fungal) Myopathy Behavior & mood changes

Adverse effects (long term) • • • Avascular necrosis of bone Cataract Peptic ulcer Skin atrophy, delayed wound healing Growth retardation (children) Suppression of HPA axis

Drug interactions • Estrogens - decrease prednisone clearance • Phenobarbital, phenytoin, and rifampicin increase metabolism of glucocorticoids • May cause digitalis toxicity secondary to hypokalemia • Monitor for hypokalemia with co-administration of diuretics

Read Monitoring while on steroids Pregnancy and steroids Infections and long term steroid Surgery and steroids

Summary

long term steroids • Monitor BP, electrolyte and blood sugar • Advise moderate exercise • Bone protection measures • Gastric protection if needed

• Give morning dose • Every other day • Minimum effective dose • Steroid sparing agents

Read • Mineralocorticoids – action, side effects, clinical uses