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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)