Hypokalemia, cardiac failure, and reporting NXY-059 safety for acute stroke

Victor L. Serebruany

Research output: Contribution to journalArticle

Abstract

NXY-059, an alpha-phenyl-N-tert-butyl nitrone derivative, is a free radical-trapping agent presently in late clinical trials as a potential neuroprotectant limiting reperfusion injury following acute stroke. Two recent trials suggest that NXY-059 causes hypokalemia and associated cardiac disturbances. With regard to the mechanism of such association, most investigators agree that potent trapping of free radicals leads to the 11 beta-hydroxysteroid dehydrogenase blockade in kidneys, diminishing renal hydrocortisone oxidation and increasing K+ ion urine excretion. Importantly, potassium deficiency represents the major avoidable cause of the array of serious cardiac adverse reactions: QT-prolongation, Torsades de pointes and other life-threatening arrhythmias, and higher risks for perioperative cardiopulmonary resuscitation and cardiac death. Because a prime target for NXY-059 use will likely be acute strokes in the emergency room environment, the potential combination of the drug with intensive therapy including fluid infusions, particularly with diuretics, might be especially harmful because of the synergic depletion of potassium, which might also jeopardize the fate of the novel nitrone neuroprotectant.

Original languageEnglish (US)
Pages (from-to)229-231
Number of pages3
JournalJournal of Cardiovascular Pharmacology and Therapeutics
Volume11
Issue number4
DOIs
StatePublished - Dec 2006

Fingerprint

Hypokalemia
Heart Failure
Stroke
Neuroprotective Agents
Safety
Free Radicals
Potassium Deficiency
11-beta-Hydroxysteroid Dehydrogenases
Kidney
Torsades de Pointes
Fluid Therapy
Cardiopulmonary Resuscitation
Drug Combinations
Reperfusion Injury
Diuretics
Hydrocortisone
Hospital Emergency Service
Cardiac Arrhythmias
Potassium
Research Personnel

Keywords

  • Cardiac failures
  • Clinical trials
  • Hypokalemia
  • NXY-059
  • Safety
  • Serious adverse events

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

Hypokalemia, cardiac failure, and reporting NXY-059 safety for acute stroke. / Serebruany, Victor L.

In: Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 11, No. 4, 12.2006, p. 229-231.

Research output: Contribution to journalArticle

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