PHARMACOLOGY

Pharmacotherapeutic Group:  Alpha glucosidase inhibitor

Pharmacodynamic properties:  Acarbose is an inhibitor of alpha glucosidase, an enteric enzyme that releases glucose from larger carbohydrates. It competitively and reversibly inhibits pancreatic alpha-amylase and membrane-bound intestinal alpha-glucoside hydrolase enzymes. Pancreatic alpha-amylase hydrolyzes complex starches to oligosaccharides in the lumen of the small intestine, while the membrane-bound intestinal alpha-glucosidases hydrolyze oligosaccharides, trisaccharides, and disaccharides to glucose and other monosaccharides in the brush border of the small intestine. In diabetic patients, this enzyme inhibition results in a delayed glucose absorption and a lowering of postprandial hyperglycemia.

Pharmacokinetic properties: Half life: 2.8 hrs ; Absorption: 35% absorbed from the GI tract (oral).; Distribution: Volume of distribution is found to be 0.32 l/kg and plasma protein binding is 13-18%.; Metabolism: In Intestines by microbial flora and intestinal enzymes.; Excretion: Via urine and faeces.

INDICATIONS Management of Type 2 Diabetes Mellitus, Impaired Glucose Tolerance.

DOSE Initial dose: 25 mg orally 3 times a day with first bite of every meal. Maintenance dose: 50 to 100 mg orally 3 times a day. The maximum dose for patients less than 60 kg is 50 mg orally 3 times a day. The maximum dose for patients greater than 60 kg is 100 mg orally 3 times a day.

CONTRAINDICATIONS :  Contraindicated in patients with diabetic ketoacidosis, cirrhosis, inflammatory bowel disease, colonic ulceration, chronic intestinal diseases, andhypersensitivity.

SPECIAL PRECAUTIONS  Monitor LFT every 3 months for 1st year and periodically thereafter especially for doses >50 mg tid. Reduce dose or withdraw therapy if transaminases elevations persist. If hypoglycaemia occurs, give glucose orally as a 1st aid measure. Adhere strictly to the prescribed diabetic diet to avoid intensification of GI symptoms.

ADVERSE DRUG REACTIONS  Flatulence, abdominal pain, distension, diarrhoea, nausea, vomiting. Elevation of transaminases, hepatitis, jaundice. Rarely, skin reactions. Potentially Fatal: Hepatotoxicity.

DRUG INTERACTIONS  Drugs that may increase blood glucose levels e.g. thiazides and loop diuretics, steroids, chlorpromazine, atypical antipsychotics, may antagonise the action of acarbose. GI adsorbents and digestive enzyme preparations may reduce acarbose effects; avoid concomitant administration. Cholestyramine may enhance effects of acarbose. Effects of other hypoglycaemics may be potentiated by acarbose. Neomycin may enhance reduction of postprandial blood-glucose and intensify GI symptoms. Acarbose may reduce digoxin bioavailability. May interact with warfarin and affect INR (International Normalised Ratio). Increased risk of hypoglycaemia with disopyramide.May decrese absorption of digoxin.

 PRESENTATION