Opioid agonists produce analgesia via peripheral, spinal, and supraspinal actions. The analgesic actions of opioid drugs can be viewed as an activation of the brain's own feedback mechanisms for modulating perception of pain. Opioid agonists also produce a range of other therapeutically useful (e.g. antitussive and antidiarhoeal) and unwanted effects. Major unwanted effects of opioids include drowsiness, nausea and vomiting, constipation, miosis (pinpoint pupils), hypotension and bradycardia, and immunosuppression. Through a non-opioid mechanism, morphine can also release histamine from mast cells leading to urticaria, hypotension, and bronchoconstriction. Although usually only seen with overdose, respiratory depression is the most dangerous of the adverse effects of the opioid agonists. The potential for tolerance, physical dependence and addiction are major influences on the usage of opioid agonists. Development of addiction and tolerance can increase the likelihood that accidental overdose will occur.
There are 3 major types of opioid receptor (mu, delta, and kappa) which contribute to both desirable and undesirable effects of the opioid agonists. It is therefore difficult to pharmacologically separate the therapeutic and adverse effects. All of the opioid analagesics have dose-dependent adverse effects. The strong opioid agonsits (e.g. morphine) are strong analgesics but also have greater potential for addiction/abuse and respiratory depression. The weaker opioid agonists (e.g codeine) have less potential for addiction/abuse but are not devoid of risk and have weaker analgesic actions. Various mixed agonists and antagonists or partial agonists may offer minor improvements in the risk-benefit ratio.
Due to the risk of respiratory depression, opioid overdose can be lethal. Opioid antagonists are used to counteract opioid overdose. Naloxone is a short-acting opioid antagonist, while naltrexone is a long-acting opioid antagonist. Antagonists should be used with caution in addicts as they may precipitate catastrophic and potentially fatal withdrawal.