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من طرف **Shamsology** السبت أغسطس 21, 2010 3:55 am

Oral Hypoglycemic drugs "insulin stimulant secretions"
- used in treatment of patient with type II diabetes
- should not be given to patient with type I diabetes.

A. Sulfonylureas:
- they promote insulin release form beta-cells
- drugs that used:

Tolbutamide

Chloropropamide

2nd generations, including: glyubride, glipizide, & glimerpiride

Mechanism of action:
1) stimulation of insulin release from beta-cells
2) reduction in serum glucagon levels
3) increasing insulin binding to target tissues & receptors

Pharmacokinetics:
- orally
- binds serum protein
- metabolized by liver
- excreted by liver or kidney
- Tolbutamide have the shortest duration of action (6 -12 hours)
- Chloropropamide, longest acting
- 2nd generation ---- action up to 24 hours

adverse effects:
weight gain
hyperinsulinemia
contraindicated in patient with hepatic or renal insufficiency; delayed
excretion resulting in its accumulation (drug) may cause hypoglycemia
do not given in pregnancy (pregnant treated with insulin only)

1) Tolbutamide:
- shortest duration of action (6-12 hours); rapidly metabolized in the liver; given 3 times
- safe in renal faliure & elderly patient
- well absorbed
- adverse effects:
hypoglycemia
GIT upset
alcohol intolerance (ethanol)
skin rashes
rarely blood disorders (anemia, thrombocytopenia)

2) Chloropropamide:
- longest action; slowly metabolized & slowly excreted from the body

3) Glibenclamide (glyburide):
- also called danoil
- very commonly used
- half-life = 4-6 hours
- long duration of action; 24 hours result in hypoglycemia
- interact with other drugs (resulting in palpitations & arrhythmias), hypoglycemia
2nd generation drugs:

4) Glimepiride:
- 100% absorption
- peak in plasma in 2-3 hours
- once daily
- half-life: 5-7 hours
- metabolized by CYP2C9
- Adverse effects:
hypoglycemia (rare), headache, dizziness, nausea
abnormality in liver enzymes
hematological problems
blurred vision

5) Glipizide:
- short acting; do not reach 24 hours (although second generation)
- metabolized in liver
- 10% excreted in kidney
- adverse effects in liver & kidney impairment
Meglitinide analogus
- rapid onset & short duration of action
- same mechanism of action as sulfonylureas

1- Repaglinide
- post prandial regulators (after meal
- combined with other oral hypoglycemic
- cause hypoglycemia( severe hypoglycemia in patient taking gemfibrozil ( lipid lowering drugs

Insulin Sensitizers:
- improve insulin action; by improving target cells response without increasing pancreatic insulin secretion

1) Biguanides:
- includes metformin & phenoformin
- phenoformin rarely used because of severe lactic acidosis

Metformin:
- decreasing insulin resistance; by increase glucose uptake & utilization
- requires insulin for action; as with Sulfonylureas (but dose not promote insulin secretion)
- low risk of hypoglycemia (no hyperinsulinemia)
- absorbed orally, not metabolized & not bound to plasma protein
- combined with insulin or Sulphanylureas "additive effects"
- mechanism of action:

inhibit gluconeogensis; reducing hepatic glucose output

slow intestinal absorption of sugars

reduce plasma glucagon levels

stimulation of glycolysis in peripheral tissue

increase insulin binding to its receptors on target tissues

inhibition of LDL & Cholesterol with increasing HDL; decreased cardiovascular mortality

used alone or in combination (with insulin)

- contraindicated in:
renal & liver failure
severe infection
Cardio-respiratory failure
interfering with alcohol (ethanol)

- adverse effectrs:
GIT upset
interfers with vitamin B12 absorption
causes lactic acidosis