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Research Article Open access CC BY 4.0

Torsades De Pointes Induced by Methadone and Clonazepam Use

Anthony G. Ashkar, Tamara Goldberg, Ilir Maraj, Alina Masters, Samy I. McFarlane

International Journal of Medical and Pharmaceutical Case Reports · pp. 81–85 · Published 5 Nov 2014

10.9734/IJMPCR/2015/13517

Abstract

Background: While recent data showed that illicit drug use rates at six months of treatment with either methadone or buprenorphine were comparable among patients [1] and that slow-release oral morphine was not inferior to methadone as detoxification treatment [2], methadone continues to be commonly prescribed in drug addiction centers [3]. The compound was developed in Germany in 1937, by scientists who sought to solve Germany's longstanding opioid shortage and derive a synthetic opium from readily available precursors [4]. According to the most recent CDC statistics, between the period of 1999 to 2006, the number of deaths from opioid pain relievers more than tripled in the U.S., from 4,000 to 13,800. Of these, deaths from methadone overdose increased from 790 to 5,420 individuals. Methadone was involved in approximately one in three opioid-related overdose deaths [5]. This medication has been implicated in prolongation of the QT interval which may predispose to Torsades de Pointes, a fatal cardiac arrhythmia. The mechanism of QT prolongation by methadone, is thought to be the result of inhibition of the hERG K+ channel [6]. Additionally, methadone blocks Na+ channels, and this blockade compensates for hERG K+ inhibition by methadone resulting in diminished risk of Torsades by this agent. Benzodiazepines have been shown to reverse the methadone induced Na+ channel blockade, thus resulting in action potential prolongation by intensifying methadone-induced hERG K+ channel inhibition and potentiating methadone’s ability to induce Torsades De Pointes [7]. In addition, evidence exists that QT prolongation was greater among patients on methadone who also had a positive urine test for benzodiazepines [8,9].

Torsades de pointes methadone benzodiazepines QT prolongation drug dependence.

References (10)

  1. 1 Drug induced QT prolongation and torsades de pointes [DOI]
  2. 2 Torsade de Pointes Associated with Very-High-Dose Methadone [DOI]
  3. 3 Influence of Opioid Agonists on Cardiac Human Ether-a-go-go-related Gene K+ Currents [DOI]
  4. 4 Impact of methadone treatment on cardiac repolarization and conduction in opioid users [DOI]
  5. 5 Effects of Methadone on QT‐Interval Dispersion [DOI]
  6. 6 Trends in Reporting Methadone-Associated Cardiac Arrhythmia, 1997–2011 [DOI]
  7. 7 Increased Cardiac Risk in Concomitant Methadone and Diazepam Treatment: Pharmacodynamic Interactions in Cardiac Ion Channels [DOI]
  8. 8 A double‐blind, randomized, parallel group study to compare the efficacy, safety and tolerability of slow‐release oral morphine versus methadone in opioid‐dependent in‐patients willing to undergo detoxification [DOI]
  9. 9 Prospective Study of QTc Changes Among Former Opiate Addicts Since Admission to Methadone Maintenance Treatment [DOI]
  10. 10 A naturalistic comparison of the effectiveness of methadone and two sublingual formulations of buprenorphine on maintenance treatment outcomes: Findings from a retrospective multisite study. [DOI]

Cited by 1

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