Diazoxide

Diazoxide
Clinical data
Trade names Proglycem
AHFS/Drugs.com Monograph
Pregnancy
category
  • AU: C
  • US: C (Risk not ruled out)
    Routes of
    administration
    Oral, intravenous
    ATC code
    Legal status
    Legal status
    Pharmacokinetic data
    Protein binding 90%
    Metabolism Hepatic oxidation and sulfate conjugation
    Elimination half-life 21-45 hours
    Excretion Renal
    Identifiers
    CAS Number
    PubChem CID
    IUPHAR/BPS
    DrugBank
    ChemSpider
    UNII
    KEGG
    ChEBI
    ChEMBL
    ECHA InfoCard 100.006.063
    Chemical and physical data
    Formula C8H7ClN2O2S
    Molar mass 230.672 g/mol
    3D model (JSmol)
      (verify)

    Diazoxide (INN; brand name Proglycem[1]) is a potassium channel activator, which causes local relaxation in smooth muscle by increasing membrane permeability to potassium ions. This switches off voltage-gated calcium ion channels, preventing calcium flux across the sarcolemma and activation of the contractile apparatus.

    In the United States, this agent is only available in the oral form and is typically given in hospital settings.[2]

    Medical uses

    Diazoxide is used as a vasodilator in the treatment of acute hypertension or malignant hypertension.[3]

    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)[4] or congenital hyperinsulinism.

    Diazoxide acts as a positive allosteric modulator of the AMPA and kainate receptors, suggesting potential application as a cognitive enhancer.[5]

    Side effects

    Diazoxide interferes with insulin release through its action on potassium channels.[6] 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.[7] 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.[2]

    See also

    References

    1. Diazoxide, drugs.com
    2. 1 2 "FDA Drug Safety Communication: FDA warns about a serious lung condition in infants and newborns treated with Proglycem (diazoxide)" (Press release). Food and Drug Administration. July 16, 2015. Retrieved 2015-07-19.
    3. van Hamersvelt HW, Kloke HJ, de Jong DJ, Koene RA, Huysmans FT (August 1996). "Oedema formation with the vasodilators nifedipine and diazoxide: direct local effect or sodium retention?". Journal of Hypertension. 14 (8): 1041–5. doi:10.1097/00004872-199608000-00016. PMID 8884561.
    4. Huang Q, Bu S, Yu Y, et al. (January 2007). "Diazoxide prevents diabetes through inhibiting pancreatic beta-cells from apoptosis via Bcl-2/Bax rate and p38-beta mitogen-activated protein kinase". Endocrinology. 148 (1): 81–91. doi:10.1210/en.2006-0738. PMID 17053028.
    5. Randle, John C.R.; Biton, Catherine; Lepagnol, Jean M. (15 November 1993). "Allosteric potentiation by diazoxide of AMPA receptor currents and synaptic potentials". European Journal of Pharmacology. 247 (3): 257–65. doi:10.1016/0922-4106(93)90193-D. PMID 8307099.
    6. Panten, Uwe; Burgfeld, Johanna; Goerke, Frank; Rennicke, Michael; Schwanstecher, Mathias; Wallasch, Andreas; Zünkler, Bernd J.; Lenzen, Sigurd (1989-04-15). "Control of insulin secretion by sulfonylureas, meglitinide and diazoxide in relation to their binding to the sulfonylurea receptor in pancreatic islets". Biochemical Pharmacology. 38 (8): 1217–1229. doi:10.1016/0006-2952(89)90327-4.
    7. Doyle, Máire E.; Egan, Josephine M. (2003-03-01). "Pharmacological Agents That Directly Modulate Insulin Secretion". Pharmacological Reviews. 55 (1): 105–131. doi:10.1124/pr.55.1.7. ISSN 1521-0081. PMID 12615955.

    [Category:AMPA receptor positive allosteric modulators]

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