Sulfonylurea (UK: Sulphonylurea) derivatives are a class of antidiabetic drugs that are used in the management of diabetes mellitus type 2 ("adult-onset"). Chlorpropamide is an example of a drug class called sulphonylureas used to treat type 2 diabetes mellitus Tolbutamide is a first generation Potassium channel blocker, Sulfonylurea oral hypoglycemic drug sold under the brand name Orinase Tolazamide is an oral Blood glucose lowering drug used for people with Type 2 diabetes. Gliclazide is an oral hypoglycemic ( Anti-diabetic drug) and is classified as a Sulfonylurea. Anti-diabetic drugs treat Diabetes mellitus by lowering Glucose levels in the blood Diabetes mellitus (ˌdaɪəˈbiːtiːz or /ˌdaɪəˈbiːtəs/ /məˈlaɪtəs/ or /ˈmɛlətəs/ often referred to simply as diabetes ( Ancient Greek: grc Diabetes mellitus type 2 or Type 2 Diabetes (formerly called non - Insulin -dependent Diabetes mellitus (NIDDM or adult-onset diabetes is a metabolic They act by increasing insulin release from the beta cells in the pancreas. Insulin is a Hormone with intensive effects on both metabolism and several other body systems (eg vascular compliance Beta cells ( beta-cells, β-cells) are a type of cell in the Pancreas in areas called the Islets of Langerhans. The pancreas is a Gland organ in the digestive and Endocrine system of Vertebrates.
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Drugs in this class
First generation:
Second generation:
- Glipizide
- Gliclazide
- Glibenclamide (glyburide)
- Gliquidone
Third generation:
Chemistry
All sulfonylureas have a central phenyl ring with two branching chains
Pharmacology
Mechanism of action
Sulfonylureas bind to an ATP-dependent K+ (KATP) channel on the cell membrane of pancreatic beta cells. Acetohexamide ( Dymelor) is a first-generation Sulfonylurea Medication used to treat Diabetes mellitus type 2, particularly in people whose diabetes Chlorpropamide is an example of a drug class called sulphonylureas used to treat type 2 diabetes mellitus Tolbutamide is a first generation Potassium channel blocker, Sulfonylurea oral hypoglycemic drug sold under the brand name Orinase Tolazamide is an oral Blood glucose lowering drug used for people with Type 2 diabetes. Glipizide is an oral medium-to-long acting Anti-diabetic drug from the Sulfonylurea class Gliclazide is an oral hypoglycemic ( Anti-diabetic drug) and is classified as a Sulfonylurea. Glibenclamide ( INN) also known as glyburide ( USAN) is an Anti-diabetic drug in a class of medications known as Sulfonylureas used Gliquidone ( INN, sold under the trade name Glurenorm) is an Anti-diabetic drug in the Sulfonylurea class Glimepiride is a medium-to-long acting Sulfonylurea Anti-diabetic drug. In Organic chemistry, the phenyl group or phenyl ring (often abbreviated as -Ph) is the Functional group with the formula - Adenosine-5'-triphosphate ( ATP) is a multifunctional Nucleotide that is most important as a " molecular currency" of intracellular Energy Potassium (pəˈtæsiəm is a Chemical element. It has the symbol K (kalium from qalīy Atomic number 19 and Atomic mass 39 Beta cells ( beta-cells, β-cells) are a type of cell in the Pancreas in areas called the Islets of Langerhans. This inhibits a tonic, hyperpolarizing efflux of potassium, which causes the electric potential over the membrane to become more positive. This depolarization opens voltage-gated Ca2+ channels. In biology depolarization is a decrease in the Absolute value of a cell's Membrane potential. Calcium (ˈkælsiəm is the Chemical element with the symbol Ca and Atomic number 20 The rise in intracellular calcium leads to increased fusion of insulin granulae with the cell membrane, and therefore increased secretion of (pro)insulin. Insulin is a Hormone with intensive effects on both metabolism and several other body systems (eg vascular compliance
There is some evidence that sulfonylureas also sensitize β-cells to glucose, that they limit glucose production in the liver, that they decrease lipolysis (breakdown and release of fatty acids by adipose tissue) and decrease clearance of insulin by the liver. The liver is a vital organ in the human body and is present in Vertebrates and some other animals In Chemistry, especially Biochemistry, a fatty acid is a Carboxylic acid often with a long unbranched Aliphatic tail ( chain) which "Adipose" redirects here For the Doctor Who monster see " Partners in Crime "
The KATP channel in turn is a complex of the inward-rectifier potassium ion channel Kir6. Inwardly rectifing potassium channels ( Kir, IRK) are a specific subset of potassium selective ion channels. 2 and sulfonylurea receptor SUR1 which associate with a stoichiometry of Kir6. In the field of Molecular biology, the sulfonylurea receptors ( SUR) are Membrane proteins which are the molecular targets of the Sulfonylurea Stoichiometry (sometimes called reaction stoichiometry to distinguish it from composition stoichiometry is the Calculation of Quantitative (measurable 24/SUR14.
Pharmacokinetics
Various sulfonylureas have different pharmacokinetics. The choice depends on the propensity of the patient to develop hypoglycemia - long-acting sulfonylureas with active metabolites can induce hypoglycemia. Hypoglycemia or hypoglycaemia is the medical term for a pathologic state produced by a lower than normal level of Glucose ( sugar) in the blood They can, however, help achieve glycemic control when tolerated by the patient. The shorter-acting agents may not control blood sugar levels adequately.
Due to varying half-life, some drugs have to be taken twice (e. g. tolbutamide) or three times a day rather than once (e. g. glimepiride). The short-acting agents may have to be taken about 30 minutes before the meal, to ascertain maximum efficacy when the food leads to increased blood glucose levels.
Some sulfonylureas are metabolised by liver metabolic enzymes (cytochrome P450) and inducers of this enzyme system (such as the antibiotic rifampicin) can therefore increase the clearance of sulfonylureas. Cytochrome P450 (abbreviated CYP, P450, infrequently CYP450) is a very large and diverse superfamily of Hemoproteins found in all Domains Rifampicin ( INN) (rɪˈfæmpəsɪn or rifampin ( USAN) is a Bactericidal Antibiotic drug of the Rifamycin group In addition, because some sulfonylureas are bound to plasma proteins, use of drugs that also bind to plasma proteins can release the sulfonylureas from their binding places, leading to increased clearance.
Uses
Sulfonylureas are used almost exclusively in diabetes mellitus type 2. Diabetes mellitus (ˌdaɪəˈbiːtiːz or /ˌdaɪəˈbiːtəs/ /məˈlaɪtəs/ or /ˈmɛlətəs/ often referred to simply as diabetes ( Ancient Greek: grc Sulfonylureas are ineffective where there is absolute deficiency of insulin production such as in type 1 diabetes or post-pancreatectomy.
Although for many years sulfonylureas were the first drugs to be used in new cases of diabetes, in the 1990s it was discovered that obese patients might benefit more from metformin. The 1990s collectively refers to the years between and including 1990 and 1999 Obesity is a condition in which excess Body fat has accumulated to such an extent that health may be negatively affected Metformin ( INN; trade names Glucophage, Riomet, Fortamet, Glumetza, Obimet, Dianben, Diabex,
In about 10% of patients, sulfonylureas alone are ineffective in controlling blood glucose levels. Addition of metformin or a thiazolidinedione may be necessary, or (ultimately) insulin. The Medication class of thiazolidinedione (also called glitazones) was introduced in the late 1990s as an adjunctive therapy for Diabetes mellitus (type Triple therapy of sulfonylureas, a biguanide (metformin) and a thiazolidinedione is generally discouraged, but some doctors prefer this combination over resorting to insulin.
More recently, a pharmaceutical startup, Remedy Pharmaceuticals, Inc. has begun developing intravenous glyburide[1] as a treatment for acute stroke, traumatic brain injury and spinal cord injury based on the identification of a non-selective ATP-gated cation channel which is upregulated in neurovascular tissue during these conditions and closed by sulfonylurea agents. [2][3]
Some diabetes experts feel that sulfonylureas accelerate the loss of beta cells from the pancreas, and should be avoided.
Side-effects and cautions
Sulfonylureas, as opposed to metformin, the thiazolidinediones, exenatide, symlin and other newer treatment agents induce hypoglycemia as a result of intermittent excesses in insulin production and release. Metformin ( INN; trade names Glucophage, Riomet, Fortamet, Glumetza, Obimet, Dianben, Diabex, The Medication class of thiazolidinedione (also called glitazones) was introduced in the late 1990s as an adjunctive therapy for Diabetes mellitus (type Exenatide ( INN, marketed as Byetta) is one of a new class of medications ( Incretin mimetics approved for the treatment of Diabetes mellitus type 2 Pramlintide acetate (Symlin is a relatively new adjunct treatment for diabetes (both type 1 and 2 developed by Amylin Pharmaceuticals. Hypoglycemia or hypoglycaemia is the medical term for a pathologic state produced by a lower than normal level of Glucose ( sugar) in the blood Thus use of these agents, as with extra insulin from ouside the body, typically prevents achieving good glucose control; people usually keep their blood glucose elevated above optimal in order to reduce the frequency and severity of hypoglycemia. Hypoglycemia is treated with increasing sugar in take by mouth or injection, or (in the case of hypoglycemic coma) with parenteral (injected into the skin or muscle) glucagon and intravenous dextrose. Hypoglycemia or hypoglycaemia is the medical term for a pathologic state produced by a lower than normal level of Glucose ( sugar) in the blood In Pharmacology and Toxicology, a route Glucagon is an important Hormone involved in Carbohydrate metabolism. Intravenous therapy or IV therapy is the giving of Liquid substances directly into a Vein. Glucose (Glc a Monosaccharide (or simple Sugar) also known as grape sugar, is an important Carbohydrate in Biology.
Like insulin, sulfonylureas can induce weight gain, mainly as a result of edema and reduction of the osmotic diuresis caused by hyperglycemia. Insulin is a Hormone with intensive effects on both metabolism and several other body systems (eg vascular compliance Oedema (or Edema in American English formerly known as dropsy or hydropsy, is the increase of Interstitial fluid in any organ &mdash swelling Osmotic diuresis is increased Urination caused by the presence of certain substances in the small tubes of the Kidneys. Hyperglycemia, hyperglycaemia, or high blood sugar is a condition in which an excessive amount of Glucose circulates in the Blood plasma Other side-effects are: abdominal upset, headache and hypersensitivity reactions. A headache ( cephalalgia in medical terminology is a condition of pain in the Head; sometimes Neck or upper back pain may also be interpreted Hypersensitivity (also called hypersensitivity reaction refers to undesirable (damaging discomfort-producing and sometimes fatal reactions produced by the normal immune system
Sulfonylureas are potentially teratogenic and cannot be used in pregnancy or in patients who may become pregnant. Teratology stems from the Greek ( Genitive) meaning monster, or marvel and, meaning word, speech. Impairment of liver or kidney function increase the risk of hypoglycemia, and are contraindications. As other anti-diabetic drugs cannot be used either under these circumstances, insulin therapy is typically recommended during pregnancy and in hepatic and renal failure, although some of the newer agents offer potentially better options.
Second-generation sulfonylureas have increased potency by weight, compared to first-generation sulfonylureas. They have decreased side effects but are more expensive.
History
Sulfonylureas were discovered by the chemist Marcel Janbon and co-workers,[4] who were studying sulfonamide antibiotics and discovered that the compound sulfonylurea induced hypoglycemia in animals. There are several sulfonamide-based groups of drugs The original antibacterial sulfonamides (sometimes called simply sulfa drugs are synthetic antimicrobial agents that contain the sulfonamide In modern usage an antibiotic is a Chemotherapeutic agent with activity against Microorganisms such as Bacteria, fungi or Protozoa Hypoglycemia or hypoglycaemia is the medical term for a pathologic state produced by a lower than normal level of Glucose ( sugar) in the blood [5]
See also
References
- ^ Breakthrough Discovery Offers Hope to Stroke Victims. Diabetes mellitus (ˌdaɪəˈbiːtiːz or /ˌdaɪəˈbiːtəs/ /məˈlaɪtəs/ or /ˈmɛlətəs/ often referred to simply as diabetes ( Ancient Greek: grc Metformin ( INN; trade names Glucophage, Riomet, Fortamet, Glumetza, Obimet, Dianben, Diabex, The Medication class of thiazolidinedione (also called glitazones) was introduced in the late 1990s as an adjunctive therapy for Diabetes mellitus (type Carrot Capital. Retrieved on 2008-01-06. 2008 ( MMVIII) is the current year in accordance with the Gregorian calendar, a Leap year that started on Tuesday of the Common Events 1066 - Harold Godwinson is crowned King of England. 1205 - Philip of Swabia becomes King
- ^ Kunte H, Schmidt S, Eliasziw M, del Zoppo GJ, Simard JM, Masuhr F, Weih M, Dirnagl U (2007). "Sulfonylureas improve outcome in patients with type 2 diabetes and acute ischemic stroke". Stroke 38 (9): 2526–30. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 17673715.
- ^ Simard JM, Woo SK, Bhatta S, Gerzanich V (2007). "Drugs acting on SUR1 to treat CNS ischemia and trauma". Curr Opin Pharmacol: 42. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 18032110.
- ^ Janbon M, Chaptal J, Vedel A, Schaap J (1942). "Accidents hypoglycémiques graves par un sulfamidothiodiazol (le VK 57 ou 2254 RP)". Montpellier Med. 441: 21-22.
- ^ Patlak M (2002). "New weapons to combat an ancient disease: treating diabetes". FASEB J. 16 (14): 1853. PMID 12468446.
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