Drug-induced arrhythmias and sudden cardiac death: implications for the pharmaceutical industry.
Following a series of high profile withdrawals from the market, the ability of medications to induce potentially fatal arrhythmias is a significant problem facing the pharmaceutical industry. Current preclinical cardiac safety assays are based on the assumption that blockade of a single repolarizing K(+) channel alone precipitates drug-induced arrhythmias, however, current findings point to a range of more complex arrhythmogenic mechanisms. This review begins by exploring clinical findings and potential mechanisms underlying drug-induced sudden cardiac death and then goes on to assess current and explore future strategies to detect cardiotoxicity at the preclinical stage.
Killeen
Matthew J
MJ
Physiological Laboratory, University of Cambridge, Cambridge, UK. mkilleen@cardiacsafety.org.uk
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000517:prevention & control; D002317:Cardiovascular Agents / Q000009:adverse effects*; D016757:Death, Sudden, Cardiac / Q000517:prevention & control; D004345:Drug Industry / Q000379:methods / Q000639:trends*; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced / Q000517:prevention & control; D026902:Potassium Channel Blockers / Q000009:adverse effects
D002317:Cardiovascular Agents; D026902:Potassium Channel Blockers