The opioid oxycodone inhibits the sodium channel of cardiomyocytes

Opioids are often the last resort for pain relief in patients that suffer from severe acute or chronic pain. Unfortunately, opioids can cause addiction and they have recently become notorious for causing what is now being called the opioid epidemic in the US: In 2016 alone, over 14,000 people died in the US from overdoses involving opioids. Accordingly, the US Centers for Disease Control and Prevention has issued a wake-up call to address the epidemic in March 2018 (<link https: www.cdc.gov media releases p0306-vs-opioids-overdoses.html _blank external-link-new-window external link in new>www.cdc.gov/media/releases/2018/p0306-vs-opioids-overdoses.html). One of the most commonly used opioids is oxycodone, a semi-synthetic compound that is more effective than morphine and causes fewer side effects. However, oxycodone has been implicated in cardiac arrhythmias and could potentially lead to sudden cardiac arrest when taken in high doses. In our recent publication in the British Journal of Pharmacology (<link https: bpspubs.onlinelibrary.wiley.com doi abs bph.14348 _blank external-link-new-window external link in new>bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.14348), we show that oxycodone concentration-dependently and use-dependently inhibits the cardiac voltage-gated sodium channel Nav1.5. In addition, the drug slows the recovery of Nav1.5 from fast inactivation and increases slow inactivation of the channel. Using stem cell-derived human cardiomyocytes, we show that these effects of oxycodone lead to a reduced beat rate and to arrhythmia. The concentrations needed to elicit cardiac arrhythmia in vitro are comparably high. Some patients under long-term treatment with high doses of oxycodone as well as drug abusers and addicts might suffer from cardiac side effects induced by the slow effects of oxycodone on Nav1.5.