Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.20 (alpha-glucosidase)
 4,237 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The drugs used to treat diabetes mellitus are diverse and involve several classes. However, these drugs can be roughly separated into hypoglycaemic agents, such as insulin and the sulphonylureas, and antihyperglycaemic agents, such as the biguanides, the alpha-glucosidase inhibitors and troglitazone. Reports of insulin overdose are rare. The major effects of insulin overdose are secondary to the insult to the CNS produced by hypoglycaemia. The mainstay of insulin overdose management is glucose replacement therapy. Sulphonylureas are the most commonly used oral antihyperglycaemic agents in the management of type 2 (non-insulin-dependent; NIDDM) diabetes mellitus. Sulphonylureas primarily cause serum glucose reduction by stimulating the release of preformed insulin from the pancreatic islets. The mainstay of sulphonylurea overdose management is glucose replacement therapy, and in severe cases, reduction of insulin release. In the large majority of patients intravenous glucose supplementation will be sufficient to maintain euglycaemia. Repaglinide, a meglitinide analogue, is a new nonsulphonylurea oral hypoglycaemic agent. In overdose, this drug may produce prolonged hypoglycaemia similar to the sulphonylureas. The primary problem with biguanide overdose is the potential for lactic acidosis. The management of biguanide overdose is largely supportive and directed at correcting the metabolic acidosis along with associated complications. The alpha-glucosidase inhibitors, acarbose, voglibose and miglitol competitively and reversibly inhibit the alpha-glucosidase enzymes (glucoamylase, sucrase, maltase and isomaltase) in the brush border in the small intestine, which delays the hydrolysis of complex carbohydrates. They appear unlikely to produce hypoglycaemia in overdose, but abdominal discomfort and diarrhoea may occur. Troglitazone is the first thiazolidinedione antidiabetic drug available. There are no data on overdose, probably because of its very recent introduction. Overdoses with antidiabetic drugs produce major morbidity, with many cases requiring intensive care medicine and prolonged hospital stays. However, fatalities are rare when treatment is initiated early. The management of the hypoglycaemic drugs (insulin and sulphonylureas) is based primarily on restoring and maintaining euglycaemia via intravenous dextrose supplementation. In the case of the sulphonylureas, reduction of insulin secretion via pharmacological intervention may also be necessary. With biguanides the main risk appears to be cardiovascular collapse secondary to profound acidosis. The management focus is on restoring acid-base balance with hyperventilation and the use of insulin to shift the utilisation of glucose from the nonoxidative pathway to the oxidative pathway. Use of haemodialysis has shown equivocal results but may be valuable in metformin overdose.
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PMID:Management of antidiabetic medications in overdose. 982 53

It is widely accepted that the most challenging goal in the management of patients with diabetes mellitus is to achieve blood glucose levels as close to normal as possible. In general, normalising postprandial blood glucose levels is more difficult than normalising fasting hyperglycaemia. In addition, some epidemiological studies suggest that postprandial hyperglycaemia (PPHG) or hyperinsulinaemia are independent risk factors for the development of macrovascular complications of diabetes mellitus. Recently, several drugs with differing pharmacodynamic profiles have been developed which target PPHG. These include insulin lispro, amylin analogues, alpha-glucosidase inhibitors and meglitinide analogues. Insulin lispro has a more rapid onset of action and shorter duration of efficacy compared with regular human insulin. In clinical trials, the use of insulin lispro was associated with improved control of PPHG and a reduced incidence of hypoglycaemic episodes. Repaglinide, a meglitinide analogue, is a short-acting insulinotropic agent which. when given before meals, stimulates endogenous insulin secretions and lowers postprandial hyperglycaemic excursions. Both insulin lispro and repaglinide are associated with postprandial hyperinsulinaemia. In contrast, amylin analogues reduce PPHG by slowing gastric emptying and delivery of nutrients to the absorbing surface of the gut. Alpha-Glucosidase inhibitors such as acarbose, miglitol and voglibose also reduce PPHG primarily by interfering with the carbohydrate-digesting enzymes and delaying glucose absorption. With the availability of agents which preferentially reduce postprandial blood glucose excursions, it is now possible to achieve glycaemic goals in a larger proportion of individuals with diabetes mellitus.
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PMID:Drug therapy of postprandial hyperglycaemia. 995 49

Although diet and exercise remain the cornerstones of type 2 diabetes therapy, attempts at lifestyle changes seldom result in the achievement of glycaemic control. As a result, the addition of pharmacological agents is usually necessary. Currently available treatment options improve glycaemic control in the short term; however, maintaining long-term glycaemic control, halting disease progression, and preventing the complications of type 2 diabetes have all proven to be elusive therapeutic goals. For more than 30 years, sulphonylureas (SUs) have been first-line therapy for the management of type 2 diabetes. These compounds control hyperglycaemia by stimulating insulin release from pancreatic beta cells, and thus their benefits are limited to patients with preserved beta-cell function. Despite historic reliance on these agents to treat type 2 diabetes, long-term use of SUs may desensitize beta cells. The meglitinides (e.g. repaglinide) are a new class of non-sulphonylurea secretagogues that bind to a different receptor on the beta cell. Repaglinide has a short duration of action and may be useful for the treatment of postprandial hyperglycaemia. The biguanides (e.g. metformin) represent another class of antidiabetic agents and improve glycaemic control primarily by decreasing hepatic glucose output. Metformin and SUs provide similar glucose-lowering effects, and, in combination, may provide additional benefits in some patients. Reducing the rate of glucose absorption with alpha-glucosidase inhibitors (e.g. acarbose) has been explored as an alternative approach to the management of postprandial hyperglycaemia, but these agents do not address the primary defect in type 2 diabetes. Eventually, prolonged overproduction of insulin to compensate for hyperglycaemia leads to dramatically reduced beta-cell function, and exogenous insulin therapy is required.
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PMID:Effects of current therapeutic interventions on insulin resistance. 1122 Feb 86

Numerous drugs with different mechanisms of action and different pharmacologic profiles are being used with the aim of improving glycemic control in patients with type 2 diabetes. Therapeutic options for patients with type 2 diabetes and chronic kidney disease (CKD) are limited because a reduced glomerular filtration rate results in the accumulation of certain drugs and/or their metabolites. Conventional oral hypoglycemic agents, such as sulfonylurea (SU), are not suitable due to the risk of prolonged hypoglycemia; furthermore, metformin is contraindicated for moderate to advanced CKD. Therefore, in order to achieve good glycemic control, insulin injection therapy remains the mainstay of treatment in diabetic patients with moderate to advanced CKD, particularly in those receiving dialysis therapy. However, some agents have been used even in patients with CKD. Repaglinide and mitiglinide are rapid- and short-acting insulinotropic SU receptor ligands. They are rarely accompanied by hypoglycemia, and are attractive therapeutic options even in the dialysis population. In addition, alpha-glucosidase inhibitors are rarely accompanied by hypoglycemia and are administered without dose adjustments in dialysis patients. However, the National Kidney Foundation Kidney Disease Outcomes Quality Initiative guidelines recommended that alpha-glucosidase inhibitors should be avoided in patients with advanced stage CKD and on dialysis. Furthermore, mitiglinide is not currently used in the US. Thus, recommended oral antidiabetic agents differ between countries. Moreover, dipeptidyl peptidase-4 inhibitors and incretin mimetics are new antihyperglycemic agents, which may be used more frequently in the future in patients with type 2 diabetes and CKD. Here, we describe the pharmacokinetics, metabolism, clinical efficacy, and safety of oral Antidiabetic agents for patients with CKD, including those receiving dialysis.
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PMID:Antidiabetic agents in patients with chronic kidney disease and end-stage renal disease on dialysis: metabolism and clinical practice. 2130 32