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Anti-diabetic drug From Wikipedia, the free encyclopedia Jump to: navigation, search An anti-diabetic drug or oral hypoglycemic agent is used to treat diabetes mellitus. They usually work by lowering the glucose levels in the blood. There are different types of anti-diabetic drugs, and their use depends on the nature of the diabetes, age and situation of the person, as well as other factors.

Insulin, exenatide, and pramlintide are the only non-oral antidiabetic drugs. Insulin is the mainstay of treatment in Type I diabetes, in which insulin production is impaired. In Type II diabetes, Insulin is used when oral medication has become ineffective. Exenatide and pramlintide are new injectable medications approved in 2005 in the US by the FDA to treat Diabetes mellitus type 2.

Diabetes mellitus

Types of Diabetes Diabetes mellitus type 1 Diabetes mellitus type 2 Gestational diabetes Pre-diabetes: Impaired fasting glycaemia Impaired glucose tolerance Disease Management Diabetes management: •Diabetic diet •Anti-diabetic drugs •Conventional insulinotherapy •Intensive insulinotherapy Other Concerns Cardiovascular disease Diabetic comas: •Diabetic hypoglycemia •Diabetic ketoacidosis •Nonketotic hyperosmolar

Diabetic myonecrosis Diabetic nephropathy Diabetic neuropathy Diabetic retinopathy

Diabetes and pregnancy Blood tests Fructosamine Glucose tolerance test Glycosylated hemoglobin Contents [hide] 1 Sulfonylureas 2 Meglitinides 3 Biguanides 4 Thiazolidinediones 5 Alpha glucosidase inhibitors 6 Incretin mimetic 7 DPP-4 inhibitors 8 Amylin analogue 9 Experimental agents 10 Insulin by mouth 11 Herbal extracts 12 References 13 Footnotes

[edit] Sulfonylureas Sulfonylureas were the first widely used oral hypoglycemic medications. They are insulin secretagogues, triggering insulin release by direct action on the KATP channel of the pancreatic beta cells. Eight types of these pills have been marketed in North America, but not all remain available. The "second-generation" drugs are now more commonly used. They are more effective than first-generation drugs and have fewer side effects.

Sulfonylureas bind strongly to plasma proteins. Sulfonylureas are only useful in Type II diabetes, as they work by stimulating endogenous release of insulin. They work best with patients over 40 years old, who have had diabetes mellitus for under ten years. They can not be used with type I diabetes, or diabetes of pregnancy. They can be safely used with metformin or -glitazones. The primary side effect is hypoglycemia.

First-generation agents tolbutamide (Orinase) acetohexamide (Dymelor) tolazamide (Tolinase) chlorpropamide (Diabinese) Second-generation agents glipizide (Glucotrol) glyburide (Diabeta, Micronase, Glynase) glimepiride (Amaryl) gliclazide (Diamicron)

[edit] Meglitinides Meglitinides are related to sulfonylureas and are often called "short-acting secretagogues." The amplification of insulin release is shorter and more intense, and they are taken with meals to boost the insulin response to each meal.

repaglinide (Prandin) - The max dosage is 16 mg/day. Take this drug 0 to 30 minutes prior before eating a meal. If a meal is skipped, then the medication should also be skipped. nateglinide (Starlix) - The max dosage is 360 mg/day, usually 120 mg three times a day (TID). It also follows the same recommendations as repaglinide. Adverse reactions include weight gain and hypoglycemia.

[edit] Biguanides Biguanides reduce hepatic glucose output and increase uptake of glucose by the periphery, including skeletal muscle. Although it must be used with caution in patients with impaired liver or kidney function, metformin has become the most commonly used agent for type 2 diabetes in children and teenagers.

metformin (Glucophage) Phenformin (DBI): used in 1960-1980s, withdrawn due to lactic acidosis risk. Metformin should be temporarily discontinued before any radiographic procedure involving intravenous iodinated contrast as patients are at an increased risk of lactic acidosis.

[edit] Thiazolidinediones Thiazolidinediones, also known as "glitazones," bind to PPARγ, a type of nuclear regulatory protein involved in transcription of numerous genes regulating glucose and fat metabolism. They act as "insulin sensitizers" without increasing insulin secretion.

rosiglitazone (Avandia) pioglitazone (Actos) troglitazone (Rezulin): used in 1990s, withdrawn due to hepatitis and liver damage risk.

[edit] Alpha glucosidase inhibitors Alpha glucosidase inhibitors are "diabetes pills" but not technically hypoglycemic agents because they do not have a direct effect on insulin secretion or sensitivity. These agents slow the digestion of starch in the small intestine, so that glucose from the starch of a meal enters the bloodstream more slowly, and can be matched more effectively by an impaired insulin response or sensitivity. These agents are effective by themselves only in the earliest stages of impaired glucose tolerance, but can be helpful in combination with other agents in type 2 diabetes.

miglitol (Glyset) acarbose (Precose/Glucobay) These medications are rarely used in the United States because of the severity of their side effects (flatulence and bloating). They are more commonly prescribed in Europe.

[edit] Incretin mimetic Exenatide (also Exendin-4, marketed as Byetta) is the first of a new class of medications approved for the treatment of type 2 diabetes. It is to be used in conjunction with oral medications such as metformin and/or a sulfonylurea to improve glucose control. The medication is injected twice per day using a specially designed pen. The typical human response is both an improvement of the release of internal insulin by the pancreas and suppression of pancreas glucagon release, behaviors more typical of individuals without blood sugar control problems. In the presence of exenatide, these responses are greater when the blood sugar is elevated.

[edit] DPP-4 inhibitors Dipeptidyl peptidase-4 (DPP-4) inhibitors (vildagliptin, sitagliptin) increase blood concentration of GLP-1 (glucagon-like peptide-1).

[edit] Amylin analogue Pramlintide.

[edit] Experimental agents Many other potential drugs are currently in investigation by pharmaceutical companies. Some of these are simply newer members of one of the above classes, but some work by novel mechanisms. For example, at least one compound that enhances the sensitivity of glucokinase to rising glucose is in the stage of animal research. Others are undergoing phase I/II studies.

PPARα/γ ligands (muraglitazar and tesaglitazar) - development stopped due to adverse risk profile SGLT (sodium-dependent glucose transporter 1) inhibitors increase urinary glucose. FBPase (fructose 1,6-bisphosphatase) inhibitors decrease gluconeogenesis in liver.

[edit] Insulin by mouth The basic appeal of oral hypoglycemic agents is that most people would prefer a pill to an injection. Unlike all the oral drugs described in this article, insulin is a protein. Protein hormones, like meat proteins, are digested in the stomach and gut. One alternative delivery method is by inhalation. In 2006 the U.S. Food and Drug Administration approved the use of Exubera, the first inhalable insulin.

However, the potential market for an oral form of insulin is enormous and many laboratories have attempted to devise ways of moving enough intact insulin from the gut to the portal vein to have a measurable effect on blood sugar. One can find several research reports over the years describing promising approaches or limited success in animals, and limited human testing, but as of 2004, no products appear to be successful enough to bring to market.[1]

[edit] Herbal extracts The first registred use of anti-diabetic drugs was as herbal extracts used by Indians in the Amazon Basin for the treatment of type 2 diabetes, and today promoted as vegetable insulin although not formally an insulin analog.[1] The major recent development was done in Brazil around Myrcia sphaerocarpa and other Myrcia species.

"Many countries, especially in the developing world, have a long history of the use of herbal remedies in diabetes (...) STZ diabetic rats were also used to test Myrcia Uniflora extracts (...) ".[2]

The usual treatment is with concentrated (root) Myrcia extracts, commercialized in a 4 US dollar per kilogram packed rocks (~100 times cheaper than equivalent artificial drugs), named "Pedra hume de kaá". Phytochemical analysis of the Myrcia extracts reported kinds of flavanone glucosides (myrciacitrins) and acetophenone glucosides (myrciaphenones), and inhibitory activities on aldose reductase and alpha-glucosidase.[3]

A recent review article presents the profiles of plants with hypoglycaemic properties, reported in the literature from 1990 to 2000 and states that "Medical plants play an important role in the management of diabetes mellitus especially in developing countries where resources are meager."[4]

[edit] References Lebovitz HE. Therapy for Diabetes Mellitus and Related Disorders. 4th edition. Alexandria: American Diabetes Association, 2004. Holland, Norman & Adams, Michael Patrick. Core Concepts in Pharmacology. Pearson Education, Inc. New Jersey. 2003.

[edit] Footnotes ^ Soumyanath, Amala(ed.) (2005-11-01). Traditional Medicines for Modern Times, 1st Edition (in english), Taylor & Francis. ISBN 0-415-33464-0. ^ McNeill, John H. (1999-02-01). Experimental Models of Diabetes, 1st Edition (in english), CRC Press, 208. ISBN 0-8493-1667-7. ^ Matsuda, H; Nishida N, Yoshikawa M. (Mar 2002). "Antidiabetic principles of natural medicines. V. Aldose reductase inhibitors from Myrcia multiflora DC. (2): Structures of myrciacitrins III, IV, and V.". Chem Pharm Bull (Tokyo) 50(3): 429-31. ^ Bnouham M et al (2006). "Medicinal plants with potential antidiabetic activity - A review of ten years of herbal medicine research (1990-2000)". Int J Diabetes & Metabolism 14: 1-25. [hide]v • d • eOral antidiabetic drugs (A10B) Biguanides Metformin Sulfonylureas Chlorpropamide, glibenclamide (Glyburide), Gliclazide, Glimepiride, Glipizide, Gliquidone, Tolazamide, Tolbutamide Alpha-glucosidase inhibitors Acarbose, Miglitol Thiazolidinediones (TZD) Pioglitazone, Rosiglitazone, Troglitazone Meglitinides Nateglinide, Repaglinide, Mitiglinide Dipeptidyl peptidase-4 (DPP-4) inhibitors Saxagliptin, Sitagliptin, Vildagliptin [show]v • d • eMajor Drug Groups Brain and Nervous system Analgesics, Anesthetics, Anxiolytics, Antidepressants, Antipsychotics, Anticonvulsants, Nervous system stimulants, Antiemetics, Hallucinogens, Mood stabilizers Respiratory system Bronchodilators, Decongestants Heart and Circulation Angiotensin converting enzyme inhibitors, Antiarrhythmics, Antianginals, Antihypertensives, Antihyperlipidemics, Anticoagulants, Antiplatelets, Beta blockers, Diuretics, Thrombolytics, Vasodilators Gastrointestinal tract Antacids, Antidiarrhoeals, H2-receptor antagonists, Proton pump inhibitors, Laxatives Muscles, Bones, and Joints Anti-inflammatories, Antirheumatics, Corticosteroids, Muscle relaxants Allergy Antihistamines Infections and Infestations Antibiotics, Antivirals, Vaccines, Antiprotozoals, Antifungals, Anthelmintics Endocrine system Corticosteroids, Anti-diabetics Malignant and Immune disease Anticancer agents, Immunosuppressants Reproductive system Hormonal contraception, Fertility agents, Selective estrogen receptor modulators Skin Antipruritics

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