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2. oral hypoglycemic drugs

1. Insulin secretagogues - Sulfonylureas - Other ( Repaglinide & Nateglinide) 2. Biguanides 3. Insulin sensitizers 4. Alpha- Glycosidase inhibitors

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
st

Onset Rapid Intermediate Slow v. rapid Intermediate Slow

Duration Short Intermediate Long Short Intermediate Long

Low Low Low High Intermediate High

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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Other Insulin Secretagogues

Examples: -Repaglinide. -Nateglinide. Action: insulin secretion. Clinical value: -Rapid & short acting (quick on quick off) Adverse effets: -Gastrointestinal : abdominal pain -liver: increase liver enzymes -weight gain.

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.

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