The mechanism of action of opioids and clinically relevant differences among the opioid analgesics are described. Both endorphins (endogenous morphine-like substances) and exogenous opioids (opium alkaloids and their derivatives) bind to opioid receptors in the human central nervous system to provide analgesia and other effects. Some drugs, such as morphine, are true agonists, i.e., they bind to and activate receptors. Some are partial agonists, binding to part of the receptor and causing effects that are similar to, but perhaps less pronounced than, the effects produced by agonists. Others are antagonist, i.e., they bind to the receptor but do not cause the associated effects. Some drugs, termed agonist-antagonist opioids, act as antagonists at one type of receptor and agonists at another type of receptor. True agonists tend to have relatively straight-line dose-response curves; in other words, their effect increases with increasing doses over a broad dosage range. Partial agonists and agonist-antagonists tend to have ceiling effects; that is, they do not have the broad dosage range of drugs such as morphine, methadone, hydromorphone, and other "strong" opioids. This fact mediates against the use of partial agonists and agonist-antagonists in cancer patients who have chronic pain that may increase as the disease progresses. Three major factors that should be considered when a drug is selected for clinical use are (1) relative affinities for the different opioid receptor types, (2) pharmacokinetic characteristics that influence onset and duration of action, and (3) whether the opioids are strong or weak. For treatment of cancer pain, drugs with long durations of action are preferable.(ABSTRACT TRUNCATED AT 250 WORDS)

 

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