dr. laila m. matalqah ph.d. pharmacology. classifications of diabetes type 1 diabetes...
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Endocrine system: Diabetes MellitusGeneral Pharmacology
M212
Dr. Laila M. MatalqahPh.D. Pharmacology
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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
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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
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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
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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
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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
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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
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Oral hypoglycemic drugs
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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
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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
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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
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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
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Endocrine system: adrenal Hormones
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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
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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
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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)
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Glucocorticoids
• Cushing disease: is a hypersecretion of glucocorticoids
• Treated by Ketoconazole: an antifungal agent that strongly inhibits all adrenal steroid hormone synthesis.
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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)