Toward a broader view of mechanisms of drug cardiotoxicity

Cell Rep Med. 2021 Mar 16;2(3):100216. doi: 10.1016/j.xcrm.2021.100216.

Abstract

Cardiotoxicity, defined as toxicity that affects the heart, is one of the most common adverse drug effects. Numerous drugs have been shown to have the potential to induce lethal arrhythmias by affecting cardiac electrophysiology, which is the focus of current preclinical testing. However, a substantial number of drugs can also affect cardiac function beyond electrophysiology. Within this broader sense of cardiotoxicity, this review discusses the key drug-protein interactions known to be involved in cardiotoxic drug response. We cover adverse effects of anticancer, central nervous system, genitourinary system, gastrointestinal, antihistaminic, anti-inflammatory, and anti-infective agents, illustrating that many share mechanisms of cardiotoxicity, including contractility, mitochondrial function, and cellular signaling.

Keywords: adverse reactions; cardiotoxicity; cell signaling; mechanisms of toxicity; side effects.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-Infective Agents / adverse effects
  • Anti-Inflammatory Agents / adverse effects
  • Antineoplastic Agents / adverse effects
  • Arrhythmias, Cardiac / chemically induced*
  • Arrhythmias, Cardiac / metabolism
  • Arrhythmias, Cardiac / pathology
  • Arrhythmias, Cardiac / prevention & control
  • Cardiotoxicity / etiology*
  • Cardiotoxicity / metabolism
  • Cardiotoxicity / pathology
  • Cardiotoxicity / prevention & control
  • Cardiovascular Agents / adverse effects*
  • Drug Development
  • Gastrointestinal Agents / adverse effects
  • Genitourinary Agents / adverse effects
  • Histamine Antagonists / adverse effects
  • Humans
  • Mitochondria, Heart / drug effects
  • Mitochondria, Heart / metabolism
  • Myocardial Contraction / drug effects
  • Myocardium / metabolism
  • Myocardium / pathology*
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology
  • Neuroprotective Agents / adverse effects
  • Safety-Based Drug Withdrawals / statistics & numerical data*
  • Signal Transduction

Substances

  • Anti-Infective Agents
  • Anti-Inflammatory Agents
  • Antineoplastic Agents
  • Cardiovascular Agents
  • Gastrointestinal Agents
  • Genitourinary Agents
  • Histamine Antagonists
  • Neuroprotective Agents