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By Vahe Hovasapyan and U.S. Rao

Vahe Hovasapyan-finalU.S. Rao-finalA recent report by National Public Radio about the botched execution of a prison inmate requiring 15 times the normal dose of one of the lethal injection drugs caught our attention as members of the pharmacy education community. This prompted us to look into the details of lethal injections and the role of pharmacists as the professionals with the background necessary to tackle the issues surrounding lethal injection complications.

As discussed by Owen Dyer in The Slow Death of Lethal Injection, the approach used to carry out lethal injections by most U.S. states for several decades has been a combination of sodium thiopental and pancuronium bromide for sedation and induction of paralysis, followed by injection of potassium chloride for stopping the heart. But for more than four years, sodium thiopental has been unavailable due to manufacturer concerns over their product’s use for executions in the USA, forcing a switch to compounded pentobarbital as a substitute. But the fear of bad publicity and lawsuits has contributed to the decline in the availability of that drug as well. Thus, the states turned to midazolam—a benzodiazepine sedative—as a substitute for the thiopental; however, midazolam has demonstrated widely varied effects in individuals, as portrayed by the unexpected turn of events in the executions of Clayton Lockett and Joseph R. Wood III in 2014. Both executions involved a much longer than usual time to death as well as reports of patient discomfort, raising concerns over the efficacy of the new injection formulation. The dosing of midazolam for lethal injections varies widely among states; Ohio uses 50 mg, while Florida uses 500 mg in their executions.

We suggest that prior enzymatic assays in prison inmates scheduled for lethal injection can be helpful in avoiding complications like the ones experienced by the above prisoners. CYP 3A4 is a well-known enzyme found in the liver and is involved in the metabolism of many of the current drugs found on the market, including midazolam. The enzyme is known for its high inducibility and slow turnover, both of which contribute to the interpersonal variability seen in patients; thus, it is advantageous to evaluate the CYP 3A4 activity or the status of CYP 3A4 polymorphisms in prison inmates prior to lethal injection. The current lack of focus on pharmacogenomic data and enzymatic testing can present a concern for the inmates scheduled for lethal injections, as well as the individuals tasked with insuring proper efficacy of the procedure, as they do so without the proper information to account for individual metabolic differences.

The discussion of the ethics of the highly controversial lethal injections is beyond our scope here, but as members of the pharmacy education community, we have the goal to underline a right approach toward improving medication use in individuals to avoid unnecessary complications such as those mentioned above.

Vahe Hovasapyan is a Pharm.D. candidate at the Appalachian College of Pharmacy, class of 2016.
U.S. Rao, Ph.D., is a professor and director of research at the Appalachian College of Pharmacy.