Toward a broader view of mechanisms of drug cardiotoxicity

Area of Science:

• Pharmacology
• Cardiology
• Toxicology

Background:

• Cardiotoxicity is a frequent adverse drug effect impacting cardiac function.
• Current preclinical testing primarily focuses on drug effects on cardiac electrophysiology.
• However, many drugs also induce cardiotoxicity through mechanisms independent of electrophysiology.

Purpose of the Study:

• To review key drug-protein interactions implicated in cardiotoxicity.
• To discuss cardiotoxic mechanisms beyond electrophysiology.
• To examine cardiotoxicity across various therapeutic drug classes.

Main Methods:

• Literature review of drug-protein interactions and cardiotoxicity.
• Analysis of adverse effects of anticancer, CNS, genitourinary, gastrointestinal, antihistaminic, anti-inflammatory, and anti-infective agents.
• Identification of shared cardiotoxic mechanisms.

Main Results:

• Numerous drugs can induce lethal arrhythmias by affecting cardiac electrophysiology.
• A significant number of drugs impact cardiac function through non-electrophysiological pathways.
• Shared mechanisms of cardiotoxicity include effects on contractility, mitochondrial function, and cellular signaling.

Conclusions:

• Cardiotoxicity encompasses a broad range of cardiac dysfunctions induced by drugs.
• Understanding drug-protein interactions is crucial for identifying and mitigating cardiotoxicity.
• Diverse drug classes share common mechanisms of cardiotoxicity, necessitating comprehensive preclinical evaluation.