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Diazoxide

Diazoxide
Diazoxide Structural Formula V.1.svg
Clinical data
Trade namesProglycem
AHFS/Drugs.comMonograph
Pregnancy
category
  • AU: C
  • US: C (Risk not ruled out)
Routes of
administration
By mouth, intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding90%
MetabolismLiver oxidation and sulfate conjugation
Elimination half-life21-45 hours
ExcretionKidney
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.006.063 Edit this at Wikidata
Chemical and physical data
FormulaC8H7ClN2O2S
Molar mass230.672 g/mol g·mol−1
3D model (JSmol)
  (verify)

Diazoxide, sold under the brand name Proglycem, is a medication used to treat low blood sugar due to a number of specific causes.[1] This includes islet cell tumors that cannot be removed and leucine sensitivity.[1] It can also be used in refractory cases of sulfonylurea toxicity.[2] It is generally taken by mouth.[1]

Common side effects include high blood sugar, low blood platelets, a fast heart rate, and nausea.[1] It 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.

Diazoxide was approved for medical use in the United States in 1973.[1] It is on the World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system.[3] In the United States as of 2019 it costs about US$1500 per month.[4]

Medical uses

Diazoxide is used as a vasodilator in the treatment of acute hypertension or malignant hypertension.[5]

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)[6] or congenital hyperinsulinism.

Diazoxide acts as a positive allosteric modulator of the AMPA and kainate receptors, suggesting potential application as a cognitive enhancer.[7]

Side effects

Diazoxide interferes with insulin release through its action on potassium channels.[8] 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.[2] 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.[9]

See also

References

  1. ^ a b c d e "Diazoxide Monograph for Professionals". Drugs.com. Retrieved 11 October 2019.
  2. ^ a b 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.
  3. ^ "World Health Organization model list of essential medicines: 21st list 2019". 2019. hdl:10665/325771. Cite journal requires |journal= (help)
  4. ^ "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
  5. ^ 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
  6. ^ 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
  7. ^ 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
  8. ^ 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.
  9. ^ "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.