Diazoxide

Pregnancy
categoryRoutes of
administrationBy mouth, intravenousATC codeLegal statusLegal status Pharmacokinetic dataProtein binding90%MetabolismLiver oxidation and sulfate conjugationElimination half-life21-45 hoursExcretionKidneyIdentifiersCAS NumberPubChem CIDIUPHAR/BPSDrugBankChemSpiderUNIIKEGGChEBIChEMBLCompTox Dashboard (EPA)ECHA InfoCard100.006.063 Chemical and physical dataFormulaC₈H₇ClN₂O₂SMolar mass230.67 g·mol⁻¹3D model (JSmol)Melting point330 to 331 °C (626 to 628 °F)  (verify)

Diazoxide, sold under the brand name Proglycem and others, is a medication used to treat low blood sugar due to a number of specific causes.^[2] This includes islet cell tumors that cannot be removed and leucine sensitivity.^[2] It can also be used in refractory cases of sulfonylurea toxicity.^[3] It is generally taken by mouth.^[2]

Common side effects include high blood sugar, fluid retention, low blood platelets, a fast heart rate, increased hair growth, and nausea.^[2] Other severe side effects include pulmonary hypertension and heart failure.^[2] It is chemically similar to thiazide diuretics.^[2] It works by decreasing insulin release from the pancreas and increasing glucose release by the liver.^[2]

Diazoxide was approved for medical use in the United States in 1973.^[2] It is on the World Health Organization's List of Essential Medicines.^[4][5] It is available as a generic medication.^[6]

Medical uses

Diazoxide is used as a vasodilator in the treatment of acute hypertension or malignant hypertension.^[7]

Diazoxide also inhibits the secretion of insulin by opening ATP-sensitive potassium channel of beta cells of the pancreas; thus, it is used to counter hypoglycemia in disease states such as insulinoma (a tumor producing insulin)^[8] or congenital hyperinsulinism.

Diazoxide acts as a positive allosteric modulator of the AMPA and kainate receptors, suggesting potential application as a cognitive enhancer.^[9]

Side effects

Diazoxide interferes with insulin release through its action on potassium channels.^[10] Diazoxide is one of the most potent openers of the K+ ATP channels present on the insulin producing beta cells of the pancreas. Opening these channels leads to hyperpolarization of cell membrane, a decrease in calcium influx, and a subsequently reduced release of insulin.^[3] This mechanism of action is the mirror opposite of that of sulfonylureas, a class of medications used to increase insulin release in type 2 diabetics. Therefore, this medicine is not given to non-insulin dependent diabetic patients.

The Food and Drug Administration published a safety announcement in July 2015 highlighting the potential for development of pulmonary hypertension in newborns and infants treated with this drug.^[11]

Research

Diazoxide, formulated as its choline salt diazoxide choline, is an experimental antiobesity drug being tested in people with Prader-Willi syndrome^[12][13][14] and monogenic obesity caused by mutations in the SH2B1, PCSK1, or SIM1 genes.^[15]

References