Diazoxide

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Diazoxide
Diazoxide Structural Formula V.1.svg
Names
Trade namesProglycem
Clinical data
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)
  (verify)

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, the safest and most effective medicines needed in a health system.[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 (parenteral)[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. 1.0 1.1 "WHOCC - ATC/DDD Index". www.whocc.no. Retrieved 11 September 2020.
  2. 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 "Diazoxide Monograph for Professionals". Drugs.com. Retrieved 11 October 2019.
  3. 3.0 3.1 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. 5.0 5.1 British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 708. ISBN 9780857113382.
  6. "Proglycem Prices, Coupons & Patient Assistance Programs". Drugs.com. 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.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. Retrieved 2015-07-19.

External links

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