Sulfonylurée 334367 31798393 2008-07-22T18:42:36Z 62.224.84.74 +interwiki ([[de:Benutzer:Omphalos]]) [[Image:Chlorpropamide.svg|thumb|[[Chlorpropamide]]]] [[Image:Tolbutamide.svg|thumb|[[Tolbutamide]]]] [[Image:Tolazamide.svg|thumb|[[Tolazamide]]]] [[Image:Gliclazide.svg|thumb|[[Gliclazide]]]] Les '''sulfonylurées''' sont une classe d'[[antidiabétique]]s utilisés dans le suivi du [[Diabète de type 2|diabète sucré de type 2]]. Ils agissent par accroissement de la libération d'[[insuline]] par les [[cellule beta|cellules beta]] du [[pancréas]]. ==Médicaments de cette classe== Première génération: * [[Chlorpropamide]] * [[Tolbutamide]] * [[Tolazamide]] Seconde génération: * [[Glipizide]] * [[Gliclazide]] * [[Glibenclamide]] * [[Glimepiride]] * [[Gliquidone]] ==Chimie== ''En ce qui concerne la structure chimique, voir chacun des membres de cette classe pharmaceutique'' Toutes les sulfonylurées ont un noyau [[phényl]] central portant deux chaînes. ==Pharmacologie== ===Mécanisme d'action=== <!--Sulfonylureas bind to an [[adenosine triphosphate|ATP]]-dependent [[potassium|K]]<sup>+</sup> channel on the cell membrane of pancreatic [[beta cell]]s. This inhibits a tonic, hyperpolarizing outflux of potassium, which causes the electric potential over the membrane to become more positive. This [[depolarization]] opens voltage-gated [[calcium|Ca]]<sup>2+</sup> channels. The rise in intracellular calcium leads to increased fusion of [[insulin]] granulae with the cell membrane, and therefore increased secretion of (pro)insulin. 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 acid]]s by [[adipose tissue]]) and decrease clearance of insulin by the liver.--> ===Pharmacocinétique=== <!--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. 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 (tolbutamide) or three times a day rather than once (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. 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.--> ==Utilisations== <!--Sulfonylureas are used almost exclusively in [[diabetes mellitus]] type 2. Other types of diabetes generally do not respond to sulfonylurea therapy, or (in [[diabetes of pregnancy]]) there are other contraindications. Although for many years sulfonylureas were the first drugs to be used in new cases of diabetes, in the [[1990s]] it was discovered that [[obesity|obese]] patients might benefit more from [[metformin]]. 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. Triple therapy of sulfonylureas, a biguanide (metformin) and a thiazolidinedione is generally discouraged, but some doctors prefer this combination over resorting to insulin.--> ==Effets secondaires et précautions== <!--Sulfonylureas, as opposed to [[metformin]] and the [[thiazolidinedione]]s, can induce [[hypoglycemia]] when insulin production overshoots. It is treated with sugary food, or (in the case of hypoglycemic coma) with [[intravenous]] [[dextrose]]. The best way to prevent this side-effect is to choose the lowest possible dose that adequately controls glucose levels. Like [[insulin]], sulfonylureas can induce weight gain, mainly as a result of [[fluid retention]] and improvement of [[osmotic diuresis]]. Other side-effects are: abdominal upset, [[headache]] and hypersensitivy reactions. Sulfonylureas are potentially [[teratogenic]] and cannot be used in pregnancy or in patients who intend to get pregnant. 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 the only option in pregnancy and hepatic and renal failure.--> *[[Hypoglycémie]], favorisée par la consommation d'alcool, le jeûne ou un exercice physique inhabituel. ==Historique== <!--Sulfonylureas were discovered by the chemist Marcel Janbon and co-workers, who were studying [[sulfonamide]] [[antibiotic]]s and discovered that the compound sulfonylurea induced [[hypoglycemia]] in animals (see also Patlak 2002). It was reported in: Janbon M, Chaptal J, Vedel A, Schaap J. ''Accidents hypoglycémiques graves par un sulfamidothiodiazol (le VK 57 ou 2254 RP)''. Montpellier Med. 1942;441:21-22.--> ==Voir aussi== * [[diabète sucré]] * [[metformine]] * [[thiazolidinedione]]s ==Références== * {{en}} Patlak M. New Weapons to Combat an Ancient Disease: Treating Diabetes. FASEB J 2002;16:1853E [http://www.fasebj.org/cgi/content/full/16/14/1853e full text]. {{portail médecine}} [[Catégorie:Sulfonylurée]] [[en:Sulfonylurea]] [[de:Sulfonylharnstoffe]]