Acarbose 56180-94-0

Mechanism of action

Acarbose inhibits enzymes needed to digest carbohydrates, to be specific, alpha-glucosidase enzymes in the brush border of the small intestines and pancreatic alpha-amylase. Pancreatic alpha-amylase hydrolyzes complex starches to oligosaccharides in the lumen of the small intestine, whereas the membrane-bound intestinal alpha-glucosidases hydrolyze oligosaccharides, trisaccharides, and disaccharides to glucose and other monosaccharides in the small intestine. Inhibition of these enzyme systems reduces the rate of digestion of complex carbohydrates. Less glucose is absorbed because the carbohydrates are not broken down into glucose molecules. In diabetic patients, the short-term effect of these drugs therapies is to decrease current blood glucose levels; the long-term effect is a small reduction in Hb_A1c level.

Dosing

Since acarbose prevents the digestion of complex carbohydrates, the drug should be taken at the start of main meals (taken with first bite of meal). Moreover, the amount of complex carbohydrates in the meal will determine the effectiveness of acarbose in decreasing postprandial hyperglycemia. Adults are to take doses of 25 mg 3 times daily.

Side-effects

Since acarbose prevents the degradation of complex carbohydrates into glucose, the carbohydrates will remain in the intestine. In the colon, bacteria will digest the complex carbohydrates, thereby causing gastrointestinal side-effects such as flatulence (78% of patients) and diarrhea (14% of patients). Since these effects are dose-related, in general it is advised to start with a low dose and gradually increase the dose to the desired amount. If a patient using acarbose suffers from a bout of hypoglycemia, the patient should eat something containing monosaccharides, such as fruit juice or glucose tablets. Since acarbose will prevent the digestion of complex carbohydrates, starchy foods will not effectively reverse a hypoglycemic episode in a patient taking acarbose. Hepatitis has been reported with acarbose use. It usually goes away when the medicine is stopped. Therefore, liver enzymes should be checked before and during use of this medicine.

Relationship to etiology of Type 2 diabetes mellitus

Type 2 diabetes mellitus is currently of unknown etiology, but medication with acarbose clearly suggests that the primary stimulus leading to development of Type 2 diabetes mellitus may be repeated "carbohydrate overload" - eating monosaccharides and disaccharides in large amounts in one portion and/or eating carbohydrate or protein meals so that the time between the last bite of an evening meal and the first bite of a breakfast of the next day is shorter than 12 hours. This is exactly what is observed in the US population and may be the reason of the high incidence of diabetes mellitus type 2 in the US population (see also Type 2 diabetes mellitus). In this respect, following habits may be contributing to developing Type 2 diabetes mellitus:1. Consuming fruit homogenates (=juices) instead of raw fruit. 2. Consuming refined grains instead of whole grains. 3. Consuming food containing refined sugar .