Oral Hypoglycemic
Oral Hypoglycemic
Oral Hypoglycemic
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1. Sulfonylureas
Pharmacological actions Decrease blood glucose: 1- increase insulin secretion 2- increase uptake of glucose by target cells 3- decrease glucagon secretion 4- increase the process of glycolysis(break down of glucose) Potency 1 generation Tolbutamide Acetohexamide Chlorpropamide 2nd generation Glipizide Cliclazide Glibenclamide
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first generation >> low potency >> is used for mild hyperglycemia second generation >> high potency >> is used for severe DM why do we need fast acting drugs ? to treat postprandial hyperglycemia Glibenclamide is the most commonly used although it is contraindicated for elderly patients BCZ of its long duration of action
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Adverse effects of sulfonylaureas -Gastrointestinal: pain & abdominal discomfort -Hematological : Granulocytosis & Anemia -Liver : increase in liver enzymes (GOT & AST) -Syndrome of inappropriate ADH (Hyponatremia) -Hypoglycemia -Weight gain
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2- BIGUANIDES
Actions : - decrease plasma glucose by : 1- glucose uptake into cells increase its metabolism 2- potenciate effect of insulin on tissue receptors Advantages : - No weight gain BCz they produce anorexia - No hypoglycemia ( Euoglaycemia = normal glucose level) - Suitable for obese patients Clinical value of BIGUANIDES - initial therapy in diabetes with obesity - in combination with SULFONYLUREAS in whom sulfonylureas alone are inadequate. Examples of BIGUANIDES : - Metformin ( is the most commonly used ) - Phenformin - Buformin 2
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Adverse Effects : - GI (most common : anorexia & abdominal pain & diarrhea) - Vit B12 malabsorption - Lactic Acidosis ( Phenformin)
3- Insulin Sensetizers
Examples : - Rosiglitazone - Pioglitazone Actions : ( increase receptor sensitivity ) They diminish insulin resistance by : - Increase glucose uptake into cells - Increase cell glucose metabolism Clinical value of Insulin-sensitizers In combination with other oral hypoglycemics or insulin to overcome insulin resistance. Features: Good for insulin resistance. Cause weight gain. Slow onset. Used in combination. Most of type 2 diabetics use sulphonamide combined with insulin sensitizers. Adverse effects: Edema, fluid retention Anemia, due to effect on bone marrow Weight gain Abdominal pain Elevation of liver enzymes, BCZ all these agents are metabolized in liver.
4. -Glycosidase Inhibitors
This enzyme is found in the stomach & intestine Used to increase absorption of glucose by binding monosacharides into polysaccharides Example: Acarbose 3
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Used in obese patients for weight control, also in postprandial hyperglycemia It has no effect on FBS (Fasting Blood Sugar) Action: Decrease CHO absorption. Clinical Value: Combined with diet control in mild postprancial hyperglycemia. Adverse effects: GI (most common): Abdominal pain, flatulence and diarrhea.
Hypoglycemia
Symptoms: Central : dizziness , confusion Peripheral : tremors , sweating , hunger, palpitation ( sypathatic ) Some drugs may mask these symptoms associated with hypoglycemia, such as blockers. Hence diabetic patients suffering from \hypertension should not be given -blockers. If given , the patient may go into severe hypoglycemia, which may proceed into coma, without manifestations. Death might occur. in DM 1- over dose of insulin 2- fasting 3- skipped meal 4- insulinoma Two types of hypoglycemia : 1- acute hypoglycemia seen in diabetic patients 2- chronic hypoglycemia seen in insulinoma patients Treatment: Glucose (Oral,IV). Glucagon. (1mg I.M. in unconsciousness) Diazoxide (chronic hypoglycemia).
Drug-Drug interaction :
1- drug reduce the efficacy of antidiabetics ( treatment failure ) - -adrenergic agonist - diazoxide 4
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corticosteroids phenytoin diuretics ( thiazide, furosemide) oral contraceptives thyroid hormones
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2- drugs increase th efficacy of antdiabetics ( hypoglycemia ) - sulphonamides - salicylates - coumarins - microsomal enzyme inhibitors N.B. 1st 3 drugs displace the oral hypoglycemic agents in plasma. N.B. 4th one increase in the level of oral hypoglycemic in plasma.