Pharmaniaga Gliclazide Mechanism of Action

Pharmacology: Pharmacodynamics: Gliclazide is a hypoglycaemic sulphonylurea of 2^nd generation which lowers blood glucose by directly stimulating the acute release of insulin from functioning beta cells of pancreatic islet tissue by unknown process that involves a sulphonylurea receptor on the beta cell. Sulphonylureas inhibit the ATP-potassium channels on the beta cell membrane and potassium efflux, which results in depolarisation and calcium influx, calcium-calmodulin binding, kinase activation, and release of insulin-containing granules by exocytosis, an effect similar to that of glucose. Insulin is a hormone that lowers blood glucose and controls the storage and metabolism of carbohydrates, proteins and fats. Therefore, sulphonylureas are effective only in patients whose pancreas are capable of producing insulin.
In addition to the pancreatic action, it has been demonstrated that gliclazide administration improves the metabolic utilisation of glucose at a peripheral level. This extrapancreatic action is not due to a modification in the number of insulin receptors, but may be due to the potentiation of the post-receptor pathways.
Thus, gliclazide restores glycaemic control throughout 24 hours. It normalises fasting and postprandial blood sugar.
In man, apart from having hypoglycaemia effect, gliclazide has been shown to reduce platelet hyperadhesiveness and hyperaggregation and to increase fibrinolytic activity. (These factors are thought to be implicated in the pathogenesis of the long-term complications of diabetes mellitus.) Controlled studies in patients with diabetic retinopathy suggest that these effects of gliclazide are beneficial in slowing down the progression of retinopathy.
Pharmacokinetics: Gliclazide is well absorbed from GI tract and peak plasma concentrations occur 2-4 hours after administration.
Gliclazide is extensively (85%) bound to plasma proteins. Metabolism is extensive and all the metabolites are devoid of hypoglycaemic activity. 60-70% of the dose is excreted in the urine, <5% is excreted unchanged in the urine and 10-20% in the faeces as metabolites. The elimination half-life of gliclazide is 10-12 hours.