Trends in the pharmacology of opioids: implications for the pharmacotherapy of pain

Abstract

Some 25 years ago, it was popular to write a figurative equation for drug treatment:Patient + drug→effect. Clearly, this was too simplistic for the reliable pharmacotherapy of pain. The ‘patient’ with pain is a complex individual and the ‘drug’ is not the same in effect to every patient, regardless of being an opioid analgesic. Besides, the ‘effect’ needs specification: it really means an acceptable balance between therapeutic and side‐effect—to that patient. These days, neural plasticity and neuromodulation associated with nociception are well‐known. Psychological involvement in the physical domain of nociception is similarly well‐known. Given these complexities, it is surprising that the pharmacological control of pain through the application of relatively simple analgesics can be so effective. Opioid analgesics have been administered by every possible route. Because the degree of invasion of the patient differs between routes, the balance between simplicity, aesthetic appeal, and efficacy of the various routes needs to be considered. The effectiveness of opioid analgesics depends in large measure on the application of the right agent, in the right dose, by the right route, at the right time for that patient. To assist in this task, researchers have produced patient‐controlled analgesia and ‘pharmacologically engineered’ analgetic molecules to achieve receptor selectivity and pharmacokinetic predictability. Also, much relevant data concerning the time courses of analgetic drug (± metabolite) concentrations in the body and in the ways in which these properties are modified by different normal and pathophysiological variations have been gathered, and the philosophy of ‘opioid rotation’ has arisen to maintain therapeutic benefits when tolerance or metabolite‐induced side‐effects prevail. This essay discusses some of the trends in opioid pharmacotherapy over the past 25 years.