Endocrine system: Diabetes MellitusGeneral Pharmacology

M212

Dr. Laila M. MatalqahPh.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 Preparations1. 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 Preparations2. Intermediate-acting insulinA. 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

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 nateglinideMOA: same like SulfonylureasBut, 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 SENSITIZERSBiguanides: 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: FludrocortisoneMOA: – 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)