Drug

Dosage

MOA

ADR

USES

Sulphonylureas

• Tolbutamide-

0.5-1 gm TDS

• Glibenclamide- 5-20 mg OD or BD

• Block the Sulfonylurea receptor (SUR1) which constitutes a subunit of the inwardly rectifying ATP-sensitive K+ channel (K_ATP) in the

membrane of pancreatic β cells.

• The inward flow of K+ ions is thereby restricted, intracellular K+ concentration falls and the membrane is partially depolarized augmenting Ca2+ channel opening as well as release of Ca2+ from intracellular stores.
• The Ca2+ ions promote fusion of insulin containing intracellular granules with the

plasma membrane and exocytotic release of insulin.

• Hypoglycemia
• Weight gain
• Hypersensitivity– Rash, photosensitivity, purpura, rarely agranulocytosis
• Disulfiram like action
• Dilutional hyponatremia- chlorpropamide due to ADH like action
• Non- specific side effects– N, V, D, constipation, flatulence, headache, paresthesia

• DM
• Diabetes insipidus (Chlorpropamide)
• Diagnosis of insulinomas and diabetes

Metformin

• 500 mg tablet up to 8 tablet per day
• 850 mg BD

• Biguanides do not cause insulin release, but presence of insulin is essential for their action.
• Though the details are not clear, recent studies have recognized activation of AMP dependent protein kinase (AMPK) to play a crucial role in mediating the actions of metformin, the key features of which are:
  1. Suppresses hepatic gluconeogenesis and glucose output from liver. This is the major action responsible for lowering of blood glucose in diabetics.
  2. Enhances insulin-mediated glucose uptake and disposal in skeletal muscle and fat. Insulin resistance exhibited by type-2 diabetics is thus overcome. This translates into— • glycogen storage in skeletal muscle reduced lipogenesis in adipose tissue and enhanced fatty acid oxidation.
  3. Interferes with mitochondrial respiratory chain and promotes peripheral glucose utilization through anaerobic glycolysis

• GI Side effect- Abdominal pain, anorexia, bloating, nausea, metallic taste, mild diarrhea
• Tiredness
• Metformin does not cause hypoglycemia except in overdose.
• Lactic acidosis
• Vit. B12 deficiency due to interference with its absorption can occur with high dose of metformin.

• DOC for all Type II DM except when not tolerated or contraindicated
• PCOS– improve ovulation and fertility