Dr. Laila M. Matalqah Ph.D. Pharmacology

Classifications Of Diabetes Type 1 diabetes (insulin-dependent diabetes mellitus): TT with insulin injection Type 2 diabetes (non-insulin dependent diabetes mellitus): TT oral glucose-lowering agents. Gestational diabetes: carbohydrate intolerance with onset or first recognition during pregnancy

INSULIN Insulin is a polypeptide hormone Sources of insulin: – Human insulin is produced by recombinant DNA technology using special strains of Escherichia coli or yeast Can not taken orally?? Given I.V or S.C ADR: – hypoglycemia: Vertigo, Diaphoresis, Tachycardia, Confusion, Headache – Lipodystrophy – Hypersensitivity

Insulin Preparations 1.Rapid-acting and short-acting insulin preparations: – regular insulin: I.V or S.C, Pregnancy B – insulin lispro: S.C – insulin aspart: S.C – Insulin glulisine: S.C Administered 15 minutes prior to a meal or immediately following a meal They are administered to increase the prandial (mealtime) release of insulin they are usually used with a longer-acting insulin to ensure proper glucose control

Insulin Preparations 2.Intermediate-acting insulin A.Neutral protamine Hagedorn (NPH) [insulin Isophane] B.Neutral protamine lispro (NPL) NPH is a suspension of crystalline zinc insulin should only be given subcutaneously (never IV) is usually given with rapid- short-acting insulin for mealtime control

Insulin Preparations 3.Long-acting insulin preparations – Insulin glargine – Insulin detemir S.C only 4.Insulin combinations 70%NPH insulin plus 30% regular insulin 50%NPH insulin plus 50% regular insulin 75%NPL insulin plus 25% insulin lispro

Oral hypoglycemic drugs These agents are useful in the treatment of patients who have type 2 diabetes but who cannot be managed by diet alone. 1.Sulfonylureas: E.X: Glyburide, glipizide and glimepiride MOA: 1) they promote insulin release from the β cells of the pancreas. 2) reduction in hepatic glucose production; 3) increase in peripheral insulin sensitivity

Oral hypoglycemic drugs

1.Sulfonylureas: Orally Glyburide is safe for pregnancy The duration of action ranges from 12 to 24 hours. ADR: – weight gain, – hyperinsulinemia, and hypoglycemia

Oral hypoglycemic drugs 2.Glinides repaglinide and nateglinide MOA: same like Sulfonylureas But, have a rapid onset and a short duration of action. Glinides should not be used in combination with sulfonylureas due to overlapping mechanisms of action

INSULIN SENSITIZERS Biguanides: Metformin MOA: reduction of hepatic glucose output, by inhibiting hepatic gluconeogenesis its able to reduce hyperlipidemia: Reduce LDL and VLDL cholesterol and rise HDL the drug of choice for newly diagnosed type 2 diabetics Orally Contraindication: – Diabetic patients with renal and/or hepatic disease. – Patients after MI – Congestive heart failure

α-GLUCOSIDASE INHIBITORS Acarbose Is taken at the beginning of meals. MOA: Inhibit α-glucosidase which hydrolyze carbohydrates to glucose ADR: flatulence, diarrhea, and abdominal cramping. Patients with inflammatory bowel disease, colonic ulceration, or intestinal obstruction should not use these drugs

Endocrine system: adrenal Hormones

Glucocorticoids Adrenal cortex, synthesizes and secretes two major classes of steroid hormones, the adrenocorticosteroids: 1) Glucocorticoids: Cortisol MOA: – Stimulate gluconeogenesis (increase glucose level) protein catabolism and lipolysis – It has Anti-inflammatory action by inhibition of phospholipase A2 – so Cyclooxygenase-2 synthesis is reduced, decrease prostaglandins. the dose must be tapered gradually – to prevent withdrawal effects

Glucocorticoids Therapeutic uses: – Addison disease: caused by adrenal cortex dysfunction: treated by Hydrocortisone with Administration of fludrocortisone (mineralocorticoid) – Relief of inflammatory symptoms: rheumatoid arithritis inflammation, inflammatory conditions of the skin including redness, swelling, heat ADR: Hyperglycemia may cause diabetes mellitus. increase gastric acid and pepsin production and may exacerbate ulcers, Hypokalemia

Adverse effects (long term) Glucose intolerance Acne Hypertension, edema Susceptibility to infection (TB, fungal) Myopathy Behavior & mood changes Cataract Peptic ulcer Skin atrophy, delayed wound healing Growth retardation (children)

Glucocorticoids Cushing disease: is a hypersecretion of glucocorticoids Treated by Ketoconazole: an antifungal agent that strongly inhibits all adrenal steroid hormone synthesis.

Mineralocorticoids 2) Mineralocorticoids: Fludrocortisone MOA: – acts on kidney tubules and collecting ducts, causing a reabsorption of sodium, bicarbonate, and water. – Decreases reabsorption of potassium and H+, is then lost in the urine. ADR: alkalosis and hypokalemia Hyperaldosteronism is treated with spironolactone (Aldosterone antagonist)