Methadone, synthetic opioids and torsades de pointes

Mori J. Krantz, Mark C.P. Haigney

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review


Opioids are the most potent of all analgesics. Currently available agents are classified as natural, semisynthetic, and synthetic. Opioids have traditionally been used solely for acute self-limited conditions such as fracture or postoperatively, as well as for chronic palliation of cancer-associated pain. However, within the United States, a movement to promote subjective pain (scale, 0 to 10) to the status of a fifth vital-sign led to widespread prescribing of extended-release opioids for managing chronic, noncancer pain. This, coupled with rising opioid misuse, initiated a surge in unintentional deaths. Natural opioids via “on-target” μ-receptor agonism result in cardiovascular and respiratory consequences including hypotension and ventilatory depression but are devoid of electrophysiologic properties. By contrast, synthetic agents can be proarrhythmic via “off-target” effects. Herein, we explore conduction and repolarization effects of opioids using methadone as a prototype. We also examine the potential contribution of these electrophysiologic properties to opioid-associated mortality and provide practical cardiac safety recommendations for clinicians.

Original languageEnglish
Title of host publicationTorsades de Pointes
Number of pages18
ISBN (Electronic)9780128214466
ISBN (Print)9780128214619
StatePublished - 1 Jan 2022
Externally publishedYes


  • Dextromethorphan
  • Levacetylmethadol
  • Loperamide
  • Methadone
  • Mortality
  • Opioids
  • Propoxyphene
  • QT interval prolongation
  • Torsades de pointes
  • hERG


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