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DRUGS USE IN ENDOCRINE SYSTEM DRUGS USE IN DIABETES MELLITUS What is diabetes? • Diabetes mellitus is a group of metabolic diseases characterized by high blood glucose levels (hyperglycemia), that result from defects in insulin secretion, or action, or both • TYPE I DM • TYPE II DM TYPE I DM • In type 1 diabetes (formerly called insulindependent diabetes or juvenile-onset diabetes), more than 90% of the insulinproducing cells of the pancreas are permanently destroyed. • The pancreas, therefore, produces little or no insulin. • Treatment of choice will be insulin TYPE II DM • In type 2 diabetes (formerly called noninsulin-dependent diabetes or adult-onset diabetes), the pancreas continues to produce insulin but body develops resistance to the effects of insulin, so there is not enough insulin to meet the body's needs • Some times with age the production of insulin not enough to meet the demand • In type 2 can use insulin and other antidiabetic drugs INSULINS • People with type 1 diabetes almost always require insulin therapy, and many people with type 2 diabetes also require insulin with time when it becomes difficult to control with oral antidiabetics • Insulin is injected • It currently cannot be taken by mouth because insulin is destroyed in the stomach since it’s a polypeptide hormone • Insulin is injected under the skin into the fat layer, usually in the arm, thigh, buttock or abdominal wall ( subcutaneous) • Small syringes with very thin needles make the injections nearly painless ( usually 28 to 31 gauge needles) • Insulin is available in three basic forms, divided by speed of onset and duration of action Types of insulin • Short acting or rapid acting or regular insulin • Intermediate acting insulin • Long acting insulin Short acting or rapid acting or regular insulin • Rapid-acting insulin, such as regular insulin, is fast and short acting. • Regular insulin reaches its maximum activity in 2 to 4 hours and works for 6 to 8 hours. • Lispro, aspart, and soluble insulins, special types of regular insulin, are the fastest of all, reaching maximum activity in about 1 hour and working for 3 to 5 hours • Rapid-acting insulin is often used by people who take several daily injections and is injected 15 to 20 minutes before meals or just after eating • Soluble insulin is the best insulin for emergencies; it can give IV, IM and SC Intermediate acting insulin • Intermediate-acting insulin (such as zinc suspension, lente, or isophane insulin suspension) starts to work in 1 to 3 hours, reaches its maximum activity in 6 to 10 hours, and works for 18 to 26 hours. • This type of insulin may be used in the morning to provide coverage for the first part of the day or in the evening to provide coverage during the night. Long acting insulin • Long-acting insulin (such as extended zinc suspension, ultra-lente, or glargine) has very little effect in the first few hours but provides coverage for 20 to 36 hours depending on which of these types is used • Generally subcutaneous insulin cause few problems like fat hypertrophy and allergic reactions • Allergic reactions are very rare at present • Fat hypertrophy also minimize by rotating the site Insulin Storage 1. Never freeze. (Frozen insulin should be thrown away.) 2. Never use insulin beyond the expiration date 3. Never expose insulin to direct heat or light 4. Inspect insulin prior to each use. Any insulin that has clumps or solid white particles should not be used. Insulin that is supposed to be clear should not have any cloudy appearance. 5. Check storage guidelines specific to the insulin formulation. This is usually in the product package insert. 6. Insulin should be stored in a refrigerator (not to be freezed) 7. When storing pre-filled insulin syringes, store them with the needle pointing up Oral hypoglycemic agents Biguanides Sulfonylureas Meglitidines Thiazolidinediones Alpha-glucosidase inhibitors SULPHONYLUREAS • Act mainly by augmenting insulin secretion and effective only when residual pancreatic beta cell activity is present • SE include GI disturbances, rarely disturbances of liver functions • CI include severe hepatic and renal impairment, pregnancy and breast feeding • • • • • • • Chlorpropamide Long acting Glibenclamide Gliclazide – short acting Glimepiride Glipizide Gliquidone Tolbutamide – short acting BIGUANIDES • Metformin hydrochloride is the only available biguanide • It exerts its effect mainly by decreasing gluconeogenesis and by increasing peripheral utilisation of glucose • Since it acts only in the presence of endogenous insulin it is effective only if there are some residual functioning pancreatic islet cells • Metformin is the drug of choice in overweight patients since it causes anorexia • Other SE include nausea, vomiting, diarrhea, abdominal pain • CI in renal impairment, pregnancy and breast feeding Hypoglycemic attacks more common with sulphonylureas than with biguanides Oral hypoglycemic agents Meglitidines modulates B cell insulin release by regulating potassium efflux through the potassium channels Oral hypoglycemic agents Thiazolidinediones enhance target tissue insulin sensitivity- rosiglitazone, pioglitazone Their main action is to diminish insulin resistance by increasing glucose uptake and metabolism in muscle and adipose tissues. Can cause oedema as a SE Alpha-glucosidase inhibitors Acarbose and miglitol are competitive inhibitors of the intestinal enzymes and modulate the digestion and absorption of starch THYROID AND ANTITHYROID DRUGS Thyroid hormones • Thyroid hormones are used for the treatment of hypothyroidism • Levothyroxin sodium (thyroxin sodium) is the treatment of choice for maintenance therapy • Taking preferably in the morning • SE-if taken more can cause hyperthyroidism Antithyroid drugs • Antithyroid dugs are use for hyperthyroidism • Carbimazole • Propylthiouracil Carbimazole • Carbimazole is an antithyroid agent that decreases the uptake and concentration of inorganic iodine by thyroid, reducing the formation of thyroxine • SE includes GI disturbances, rash, arthralgia, alopecia, bone marrow suppression ( if patient develop sore throat it’s a sign of agranulocytosis which immediately should report to the clinician) • Propylthiouracil also same as carbimazole CORTICOSTEROIDS Corticosteroids • Produced by the adrenal cortex • Involved in stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte levels and behavior. Uses of Corticosteroids • Use to treat a number of different disorders especially inflammatory or immunologic disorders • Arthritis • Dermatitis • Allergic reactions • Asthma • Hepatitis • Lupus erythematosus • Inflammatory bowel disease: ulcerative colitis and Crohn’s disease • Uveitis – inflammation of eye Replacement therapy • Indicated when the adrenal gland not functioning properly or when the gland is removed • Usually use a combination of hydrocortisone (glucocorticoid) and fludrocortisone (mineralocortocoid) for complete replacement • Usually larger dose in the morning and smaller dose in the evening • Use as oral drugs on regular basis; but in acute adrenal insufficiency hydrocortisone is given intravenously Side Effects • Moon face, buffalo hump, obese trunk (love handles), acne, hirsutism, weight gain • Impaired healing or bruising • CNS: nervousness, insomnia, depression, aggravation of pre-existing mental disorders • Musculoskeletal: long term use can cause osteoporosis, muscle weakness and atrophy • GI: peptic ulcer, increased appetite • Cardiovascular: fluid retention • Ocular: increased intraocular pressure, glaucoma, cataracts Moon Face High-dose corticosteroid therapy produces a characteristic “moon face” appearance. Glucocorticoid therapy • Mostly as antiinflammatory agents in inflammation and allergies • Prednisolone • Betamethasone • Cortisone acetate • Deflazacort • Dexamethazone • Hydrocortisone • Methylprednisolone • Triamcinolone • All these drugs contraindicated in systemic infections • Avoid live virus vaccines those who are receiving immunosuppressive doses SEX HORMONES Female sex hormones Male sex hormones Female sex hormones • Main indication is hormone replacement therapy • If long therapy of estrogen is required a progesteron also should be added to reduce the risk of hyperplasia of the endometrium and possible transformation to cancer Hormone Replacement Therapy • Helps to relive symptoms of menopause such as such as hot flashes, vaginal dryness, mood swings, sleep disorders, and decreased sexual desire. • Specially improve the conditions such as osteoporosis and urinary incontinence Complications • Increase risk of deep vein thrombosis and pulmonary embolism • Increase risk of breast cancer when using for more than 5 years • Increase risk of endometrial cancer when using estrogen alone • Increase risk of stroke • Does not prevent coronary heart disease Estrogens Side effects • GI disturbances, weight changes, breast enlargement and tenderness, premenstrual like syndrome, sodium and fliud retention, altered blood lipids, cholestatic jaundice, rashes, changes in libido, depression, headache, migraine, dizziness, leg cramps Contra indications • • • • • • • • • • Pregnancy Oestrogen dependent cancer History of breast cancer Active thrombophlebitis Angina, MI Venous thromboembolism Liver disease Undiagnosed vaginal bleeding Breast feeding Untreated endometrial hyperplasia Progestogens • Other than hormone replacement therapy use in oral contraception, to treat endometriosis, recurrent miscarriages, infertility, dysfunctional menstrual bleeding Side effects • • • • • • • • • Menstrual disturbances Premenstrual like syndrome Weight gain Nausea Headache, dizziness Insomnia Drowsiness Depression Fluid retention • Urticaria, pruritus, rash and acne • Hirsutism and alopecia Contraindications • • • • • Liver diseases Arterial diseases Genital or breast cancers Undiagnosed vaginal bleeding Porphyria • Dydrogesterone • Medroxyprogesterone acetate • Norethisterone – use for postponement of menstruation, 5mg tds starting 3 days before anticipated onset (menstruation occurs 2 to 3 days after stopping) • Progesterone Male Sex Hormones • Use to treat androgen deficiency • Testosterone and esters • SE include prostate abnormalities, prostate cancer, headache, depression, GI bleeding, nausea, cholestatic jaundice, hypertension, oedema, hypercalcaemia, increase bone growth, • Androgenic effects such as hirsutism, male pattern baldness, acne, excessive frequency and duration of penile erection, precocious sexual development, virilism in women • CI in breast cancer in men, prostate cancer, liver tumors, hypercalcaemia, nephrosis, pregnancy and breast feeding HYPOTHALAMIC AND PITUITARY HORMONES Anterior pituitary hormones • ACTH • Gonadotrophins Chorionic gonadotrophin, HCG Chorionic gonadotrophin • In females, chorionic gonadotropin is used to help conception occur • Use in many women being treated with clomiphene and other drugs such as follitrophin and have not been able to conceive yet. • Chorionic gonadotropin is also used in in vitro fertilization (IVF) programs. • In males, LH and chorionic gonadotropin stimulate the testes to produce male hormones such as testosterone. • Testosterone causes the enlargement of the penis and testes and the growth of pubic and underarm hair. • It also increases the production of sperm • SE include edema, headache, tiredness, mood changes, gynaecomastia, local reactions • CI in androgen dependent tumors • Use as SC or IM injections Growth hormone • Somatrophin – synthetic human GH • Indicated in GH deficiency, Turner syndrome, Prader – Willi syndrome • SE include headache, papilloedema, visual problems, nausea and vomiting • CI in any evidence of tumor • vasopressin and desmopressin – Used in the treatment of diabetes insipidus – Used in the treatment of various types of bleeding, especially GI bleeding – desmopressin is useful for: • Hemophilia A • Type I von Willebrand’s disease Thank you…