Sulfonylurea is an oral anti-diabetic drug (OAD). This group of medicines is commonly used to treat type 2 diabetes, an illness that affects close to 350 million persons worldwide. Genetic and non-genetic factors may influence how a person responds to these drugs. Persons with type 2 diabetes have chronically high blood sugar levels and sulfonylureas make the body free up more insulin (a hormone that activates the cells to absorb the sugar in the blood).
Sulfonylurea drugs are metabolized in the body using an enzyme called CYP2C9, which breaks up the drugs so that they can be filtered and eliminated from the body. The variations in the gene that encodes the CYP2C9 enzyme is associated with a reduced capacity to eliminate sulfonylurea from the body, leading to problems.
Sulfonylureas should not be administered to pregnant women, women who are breastfeeding, to diabetes mellitus type 1 patients, to children, to patients with diabetic ketoacidosis, with hyperosmolar nonketotic coma, with intercurrent diseases such as acute myocardial infarction, or cerebral vascular illnesses (stroke), nor whenever possible to patients who have advanced hepatic or renal insufficiency or who have porphyria.
Side effects caused by sulfonylureas tend to be slight and infrequent, consisting of gastrointestinal disorders such as nausea, vomiting, diarrhea and constipation. Nearly 4% of the first-generation sulfonylureas produce unfavorable reactions which are less frequent in the second-generation drugs. The most adverse side effect is hypoglycemia which can produce coma, a neurologic urgency especially frequent in patients with alterations of hepatic or renal functions.
First-generation chlorpropamide can cause jaundice, cholestasis, dilutional hyponatremia and side effects caused by alcohol consumption such as nausea, vomiting, aplastic anemia, neutropenia, skin rashes and thrombocytopenia. It may also cause facial redness after alcohol consumption, an effect which does not usually happen with other sulfonylureas.
First-generation tolbutamide increases the risk of cardiovascular death in certain risk patients. On occasion, there may be hypersensitivity reactions, almost always in the first 6 - 8 weeks of treatment which basically consist of allergic skin reactions that exceptionally develop into erythema multiforme and exfoliative dermatitis, fever and jaundice. Photosensitivity is a rare side effect affecting some patients treated with chlorpropamide and glipizide. Hematologic disorders are also rare as well hyponatremia with glimepiride and glipizide (both second generation).
Sulfonylureas should not be administered to pregnant patients, during lactation, in type 1 diabetes mellitus, in children, in patients with diabetic ketoacidosis, hyperosmolar non-ketotic coma, intercurrent diseases such as acute myocardial infarction or CVD, or in patients with advanced liver and kidney failure.
Sulfonylureas should be avoided as far as possible in severe liver and kidney failure and porphyria.
Gene or region studied