The Impact of Morphine or Methadone Administration on the Heart and Cardiovascular System

  • Flavio MoroniEmail author
Living reference work entry


Opium and morphine have been used for centuries to reduce pain in different clinical conditions including acute heart failure with pulmonary edema or hearth ischemia with infarct. It was soon observed that repeated morphine administration gradually leads to a decrease of the analgesic potency (tolerance) and that, after repeated doses, patients may have difficulties in abandoning morphine or opium use (dependence and withdrawal). Other established morphine side effects such as vomiting, hypotension, respiratory depression, and somnolence suggest careful attention in drug use.

In the last few years, most of the literature outline that morphine should not be used in cases of pulmonary edema because of the risk of increased mortality. In patients with infarct, however, morphine is still considered the analgesic of choice, especially when the ischemic pain is not sensitive to nitrates. It has also been suggested that morphine may activate the ischemic tolerance process, thus reducing the ischemic reperfusion damage.

Another opioid with significant analgesic action is methadone. In 1965, it was clearly demonstrated that methadone was useful in reducing the problems associated with morphine or heroin misuse. A significant number of patients are now chronically treated with the drug in the methadone treatment programs. In the last 20 years, it has been observed that methadone may cause an increase of the QT interval of the ECG and possibly an increased risk of sudden death. Since methadone is a mixture of two stereoisomers (R and S) and since R-methadone has high affinity for opioid receptors while S-methadone is possibly the main responsible for QT elongation, it has been proposed that the racemic form of the drug should be abandoned and substituted with the stereoselective active R-methadone form.


Encephalin Endorphin Dynorphin Infarct Ischemic tolerance Long QT Opioid receptors Potassium channels Pulmonary edema Sudden death 


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Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Department of NeurofarbaUniversity of FlorenceFirenzeItaly

Section editors and affiliations

  • Guido Mannaioni
    • 1
  1. 1.Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino (NEUROFARBA), Sezione di Farmacologia e Tossicologia,Università degli Studi di FirenzeFirenzeItaly

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