Pain treatment in multimorbid patients, the older population and other high-risk groups. The clinical challenge of reducing toxicity.

The prevalence of pain is high in multimorbid patients and they can experience a multitude of painful conditions. The changes in physiology and homeostasis associated with multimorbidity and increasing age and the immature metabolism of neonates all increase the risk of toxicity from analgesics. Altered pharmacokinetics and metabolism influence drug pharmacodynamics and therapeutic windows. Imbalances in local homeostatic mechanisms increase local toxicity. The gastrointestinal organs and the kidney have a major role in the absorption, metabolism and excretion of analgesics and changes in their function predispose individuals to adverse effects. Knowledge of such compromise should influence the choice of analgesic, the administration regimen and the mode of application. The mainstay of chronic pain treatment are 3 classes of drugs: nonsteroidal anti-inflammatory drugs (NSAIDs), opioids and a host of so-called adjuvant drugs, which are used to enhance the analgesic action of the classic analgesics. In each class a wide range of drugs are available, that differ in pharmacokinetic and pharmacodynamic characteristics. These differences can be exploited to either increase analgesic efficacy and reduce toxicity, or to minimise the interference of pain therapy with daily life. Clinically important differences in analgesic and toxic effects between drugs in each analgesic class will be discussed in this article from the perspective of reducing adverse effects. New knowledge concerning the mechanism of action of analgesics and their metabolites is making the specific selection of NSAIDs and opioids to reduce adverse effects in multimorbid, chronic pain patients possible.