Opioids: a review.

Recent discoveries in opioid pharmacology help explain the enormous variability in clinical responses to these powerful analgesics. Although there is only one m opioid receptor gene, splice variants of that gene's expression result in a panoply of different functioning receptors. Other sources of variable response include polymorphisms in the m opioid receptor regulatory region, and pharmacokinetic differences because of cytochrome P-450 mono-oxygenase heterogeneity. Analgesic tolerance is likely the key phenomenon limiting the benefit of opioids. A plethora of intracellular pathways affects this. Among them are the N-methyl-D-aspartate receptor, protein kinase C gamma activity, nitric oxide synthase, and GM1 ganglioside content of the neuronal membrane. Clinical studies undercut the routine use of meperidine in most settings. Other studies have shown better ways to diminish opioid side effects.