Kidney disease not only alters the renal elimination but also the non-renal disposition of drugs that are metabolized by the liver. Indeed, modifications in the expression and activity of intestinal and hepatic drug metabolism enzymes and uptake and efflux transporters have been reported. Accumulated uremic toxins, inflammatory cytokines, and parathyroid hormones may modulate these proteins either directly or by inhibiting gene expression. This can lead to important unintended variations in exposure and response when drugs are administered without dose adjustment for reduced renal function. This review summarizes our current understanding of non-renal clearance in circumstances of chronic and acute renal failure with experimental but also clinical studies. It also evaluates the clinical impact on drug disposition. Predicting the extent of the drug disposition modification is difficult first because of the complex interplay between metabolic enzymes and transport proteins but also because of the differential effects in the different organs (liver, intestines). Recommendations of the US FDA are presented as they may be potentially helpful tools to predict these modifications when no specific pharmacokinetic studies are available.
A continuous quality programme conducted by psychiatrists and pharmacists showed positive impact in reducing doses of benzodiazepine prescribed to prisoner patients and contributing to reduce risk of benzodiazepine-related problems.
In a French prison, most inmates reported not being satisfied with their sleep. Life habits between good and bad sleepers were not significantly different except for television and smoking. The most frequently reported symptom of insomnia was several awakenings at night, and the most frequently cited etiologies were rumination of thoughts and noise. Most patients reported that their sleeping problems began or worsened after incarceration. A quarter of the inmates were following a hypnotic treatment, and most of these treatments began in prison. Only 42% of patients were satisfied with its effectiveness. These observations enabled us to make recommendations for healthy sleep patterns such as respecting normal night-and-day cycles, encouraging to stop smoking, and promoting appropriate use of hypnotic treatments.
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