Diazoxide

Diazoxide
Names
Trade namesProglycem
IUPAC name
  • 7-Chloro-3-methyl-4H-1,2,4-benzothiadiazine 1,1-dioxide
Clinical data
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
  • AU: C
  • US: C (Risk not ruled out)
    Routes of
    use    		By mouth, intravenous
    Defined daily dose0.3 gram[1]
    External links
    AHFS/Drugs.comMonograph
    Legal
    License data
    Legal status
    Pharmacokinetics
    Protein binding90%
    MetabolismLiver oxidation and sulfate conjugation
    Elimination half-life21-45 hours
    ExcretionKidney
    Chemical and physical data
    FormulaC8H7ClN2O2S
    Molar mass230.67 g·mol−1
    3D model (JSmol)
    Melting point330 to 331 °C (626 to 628 °F)
    SMILES
    • Clc1ccc2c(c1)S(=O)(=O)/N=C(\N2)C
    InChI
    • InChI=1S/C8H7ClN2O2S/c1-5-10-7-3-2-6(9)4-8(7)14(12,13)11-5/h2-4H,1H3,(H,10,11) checkY
    • Key:GDLBFKVLRPITMI-UHFFFAOYSA-N checkY

    Diazoxide, sold under the brand name Proglycem, 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] It is available as a generic medication.[5] In the United States as of 2019 it costs about US$1500 per month.[6] In the United Kingdom this amount costs the NHS about £59.[5]

    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]

    Dosage

    The defined daily dose is 0.3 gram (by injection).[1]

    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]

    See also

    References

    1. 1 2 "WHOCC - ATC/DDD Index". www.whocc.no. Archived from the original on 8 February 2021. Retrieved 11 September 2020.
    2. 1 2 3 4 5 6 7 8 "Diazoxide Monograph for Professionals". Drugs.com. Archived from the original on 3 August 2020. Retrieved 11 October 2019.
    3. 1 2 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.
    4. ↑ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
    5. 1 2 British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 708. ISBN 9780857113382.
    6. ↑ "Proglycem Prices, Coupons & Patient Assistance Programs". Drugs.com. Archived from the original on 11 October 2019. Retrieved 11 October 2019. Typical dose is 3mg/kg * 70 kg * 30 days = 6,300 mg at 11.58 per 50 mg
    7. ↑ 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.closed access
    8. ↑ 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. Archived from the original on 2021-08-28. Retrieved 2009-02-01.open access
    9. ↑ 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.closed access
    10. ↑ 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. PMID 2650685.
    11. ↑ "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. Archived from the original on 2015-07-19. Retrieved 2015-07-19.
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