Sulphonylurea

Sulphonylureas Chlorpropamide, glibenclamideb, gliclazide, glimepiride, glipizide, gliquidone, tolazamide, tolbutamide Stimulate insulin secretion (typically 6-24 h) Oral... 

Although the main therapeutic effect of sulphonylureas is increased insulin secretion, there is evidence that... 

Antidiabetic Drugs other than Insulin. Figure 1 Sulphonylureas stimulate insulin release by pancreatic (3-cells. They bind to the sulphonylurea receptor (SUR-1), which closes Kir6.2 (ATP-sensitive) potassium channels. This promotes depolarisation, voltage-dependent calcium influx, and activation of calcium-sensitive proteins that control exocytotic release of insulin. 

The increase in insulin concentrations produced by sulphonylureas lowers blood glucose concentrations through decreased hepatic glucose output and increased glucose utilisation, mostly by muscle ( insulin, insulin receptor). 

Repaglinide and nateglinide are rapidly absorbed their binding durations to SUR-1 are much shorter than sulphonylurea binding, and their hepatic metabolism... 

Sulphonylureas Severe liver or renal disease0 Hypoglycaemia b... 

Several studies have demonstrated that treatment of diabetic patients with the sulphonylurea, gliclazide, is associated with a fall in lipid peroxidation, protein fluorescence and beneficial effects on platelet function (Florkowski et al., 1988 Jennings et al., 1992). These changes were seen to be independent of changes in giycaemic control. 

UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998 352 837-853. 

Rosiglitazone is a thiazolidinedione that can be used in combination with metformin or a sulphonylurea such as gliclazide. Rosiglitazone should be administered with caution in patients with cardiovascular disease. 

Fluconazole is a triazole antifungal that may be administered in recurrent vaginal candidiasis. Fluconazole interacts with sulphonylureas such as glibenclamide, resulting in increased plasma concentrations of the sulphonylurea. 

Q85 Enalapril may precipitate a hypoglycaemic attack in a diabetic patient. Enalapril may potentiate the effect of sulphonylureas. 

Acetazolamide is a carbonic anhydrase inhibitor that reduces aqueous humour production and is therefore indicated in glaucoma to reduce the intraocular pressure. Salbutamol is a selective, short-acting beta2-agonist used as a bronchodilator in asthma. Tolbutamide is a short-acting sulphonylurea used in type 2 (non-insulin dependent) diabetes mellitus. Chlorpromazine is an aliphatic neuroleptic antipsychotic drug used in schizophrenia. Zafirlukast is a leukotriene-receptor antagonist that is indicated in the prophylaxis of asthma but should not be used to relieve acute severe asthma. 

Gliclazide is a sulphonylurea. In general, diabetic patients are switched over to insulin during pregnancy. Sulphonylureas should be stopped at least 2 days... 

Sitagliptin is a dipeptidylpeptidase-4 inhibitor that increases insulin secretion and lowers glucagon secretion. Sitagliptin is available for oral administration. It is indicated in patients with type 2 diabetes mellitus in combination with either metformin (biguanide) or a sulphonylurea or a thiazolidinedione. 

Avandia (rosiglitazone) as with other thiazolidinediones is used either as monotherapy or in combination with either metformin or a sulphonylurea. A disadvantage of rosiglitazone is the risk of heart failure as a side-effect. This risk is increased when rosiglitazone is used in patients with cardiovascular disease and when used in combination with insulin. Blood-glucose control may deteriorate temporarily when a thiazolidinedione is substituted for an oral antidiabetic agent. 

Glibenclamide is an oral antidiabetic agent (sulphonylurea). It acts by increasing insulin secretion and is therefore indicated in type 2 diabetes (non-insulin dependent) where there is pancreatic activity. 

RendeU M. The role of sulphonylureas in the management of type 2 diabetes melhtus. Drugs 2004 64 1339-58. 

Older patients have predominantly Type 2 diabetes mellitus, which shares with Type 1 the risk for retinopathy, nephropathy and neuropathy, but carries a greater risk for macrovascular complications such as coronary artery disease, stroke and peripheral vascular disease. Many such patients have associated obesity, hypertension and hyperlipidemia, compounding the risk of cardiovascular disease. The goals of treatment of DM in the elderly are to decrease symptoms related to hyperglycaemia and to prevent long-term complications. Treatment of type 2 DM can improve prognosis. In the UKPDS trial, sulphonylureas, insulin, and metformin were all associated with a reduction in diabetes-related... 

Sulphonylureas act by increasing release of insulin from pancreatic cells, reducing serum... 

Non-sulphonylurea insulin 0.5-1.0% Repaglinide 1-16 Taken before meals to reduce... 

Steep dose-response curve Levodopa Sulphonylureas Verapamil... 

Tolbutamide is a short-acting agent. It is rapidly metabolized in the liver with an elimination half-life of 6-10 hours. Protein binding is more than 90%. It has the advantages of causing less frequently and less serious hypoglycemia than the more potent sulphonylureas. 

Rifampicin is a potent inducer of cytochrome P450 enzymes and thus can diminish the activity of a multitude of other agents such as warfarin, gluco-corticosteroids, cyclosporin, oral contraceptives and sulphonylurea-type oral antidiabetic agents. 

The commonest cause of hypoglycaemia is administration of therapeutic doses of insulin or sulphonylureas in patients treated for diabetes. Nondiabetic people may also take or be given hypogly-caemic agents. Hypoglycaemia can occur spontaneously in insulinomas, hypoadrenalism, and other uncommon circumstances. 

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