Endocrine Pharmacology

At the end of this course, students should be able to: 1. explain the role of thyroid hormone in regulating development, metabolism and calorigenesis; 2. identify the steps in synthesis of T4 and T3 and discuss the endocrine regulation of T3 and T4 production and feedback loops, physiological role of T3 and T4 and changes associated with hypo- and hyperthyroidism; 3. enumerate the various thyroid hormone preparations and thyroid hormone antagonists (classes and examples) and describe the pharmacology of thyroid hormone preparations and thyroid hormone antagonists; 4. explain the use of adjunct drugs in treatment of hyperthyroidism; 5. describe the role of ACTH and HPA axis in regulation of corticosteroid synthesis and the principal physiological responses to both glucocorticoids and mineralocorticoids; 6. explain the use of synthetic glucocorticoid and mineralocorticoid drugs in management of the specified endocrine disorders; and 7. describe the pharmacology of adrenocorticosteroids synthetic analogues and inhibitors.

Drugs used in endocrine disorders. Physiology of neuroendocrine hormonal regulation, specifically the regulation and function of the hypothalamus pituitary growth hormone axis. Hypothalamus pituitary reproductive axis. Hypothalamus pituitary prolactin axis. Adenohypophysis hormones and related substances, anterior and posterior pituitary hormones, ACTH, growth hormone, prolactin, thyrotropin, gonadotropic hormones. Use of specific neuroendocrine drugs in the treatment of growth hormone deficiency (recombinant HGH, somatropin, synthetic GHRH, sermorelin, recombinant IGF-1). Growth hormone excess (octreotide, Pegvisomant). Infertility (HCG, menotropins, urofollitropin, follitropin, synthetic GHRH and analogues, Gosselin, GnRH antagonists, ganirelix) and Hyperprolactinaemia (dopamine receptor antagonists, bromocriptine). Indications, mechanism of action, adverse effects, contraindications and therapeutic considerations for the major neuroendocrine hormones and pharmacological drugs. Adrenocortical steroids. Role of ACTH and HPA axis in regulation of corticosteroid synthesis. Principal physiological responses to both glucocorticoids and mineralocorticoids, especially role of cortisol and exogenous glucocorticoids in negative 102 feedback suppression of the HPA axis. Use of synthetic glucocorticoid and mineralocorticoid drugs in treatment of adrenal insufficiency and congenital adrenal hyperplasia; therapeutic uses of adrenocorticosteroid in non-endocrine disease, asthma, rheumatoid arthritis, inflammation and cancer. Pharmacology of adrenocorticosteroids synthetic analogues (hydrocortisone, cortisone, prednisone, prednisolone, dexamethasone) and inhibitors (metyrapone, aminoglutethimide). Diabetes mellitus pathophysiology, type I and II, fundamental differences in types, diagnostic criteria and therapeutic goals. Pharmacological differences between the various insulin formulations, especially in their duration of action (rapid-regular- intermediate- and long-acting insulins), specifically which insulin types are used to control post-prandial glucose levels versus fasting glucose levels. Use and clinical benefits of an intensive insulin therapy regimen in type I diabetes. Indications, mechanism of action, clinical effects, adverse effects and contraindications of drugs used in management of type II diabetes. Sulphonylureas, biguanides, meglitinides, thiazolidinediones, alpha- glucosidase inhibitors, modulators of incretin pathway, pramlintide, glucagon, insulin, understanding which drugs used for treatment of type II primarily affect either post-prandial or fasting glucose levels. Concept of combination therapy with oral drugs, as well as potential use of insulin therapy in type II. Current treatment algorithm approved by the American Diabetes Association for type II diabetes. Effectiveness of tight glycaemic control in prevention of macro- and microvascular complications; treatment of diabetic ketoacidosis. Thyroid and Anti-thyroid Drugs. Role of thyroid hormone in regulating development, metabolism and calorigenesis. Steps in synthesis of tetraiodothyronine (T4) and triiodothyronine (T3), endocrine regulation of T3 and T4 production and feedback loops, physiological role of T3 and T4 and changes associated with hypo- and hyperthyroidism. Thyroid hormone preparations. Thyroid hormone antagonists, thioamides, propylthiouracil, methimazole, carbimazole, thiocyanate, ionic inhibitors, perchlorate, Iodine, other drugs, propranolol and hydrocortisone. Gonadal hormones, oestrogens and progestins, physiological actions, pharmacological effects, clinical uses (contraception and hormonal replacement therapy in menopause), adverse effects and contraindications, pharmacological actions and clinical uses of selective oestrogen receptor modulators (SERMs). Androgens, physiological actions, pharmacological effects, clinical uses, adverse effects and contraindications of androgens (testosterone, dihydrotestosterone, methyltestosterone) and their antagonists (finasteride, flutamide, spironolactone).