Adverse Effects of Systemic Opioid Analgesics

Abstract

Adverse effects of opioids are multiple. They are most often receptor-mediated and inseparable from their desired effects. The most severe mishaps with opioids are related to their respiratory depressant effect, which is widely influenced by factors such as pain, previous opioid experience and awareness. Other relevant central nervous system effects of opioids include cough suppression, nausea and vomiting, rigidity, pruritus and miosis. The cardiovascular adverse effects of opioids are mainly related to histamine release and differ widely between agonists and agonist-antagonists. Gastrointestinal effects such as constipation, reflux and spasms of the bile duct are well described. Adverse effects on endocrine, immunological and haematological functions are possible, while allergic reactions are extremely rare. The adverse effects of long term use are overestimated. Systemic toxicity is negligible and development of tolerance is minimal while treating pain. In the clinical setting of pain control, addiction and withdrawal do not pose significant problems. Nevertheless, the possible effects of opioids on the unborn child should always be considered. Overall, opioids show a good record of safety. Their use should not be unduly limited by unfounded fears of adverse effects, but these effects should be avoided by anticipation and prevention.

Antinociceptive effect of a genomic herpes simplex virus-based vector expressing human proenkephalin in rat dorsal root ganglion

“…One potential advantage of gene transfer to primary sensory neurons is that continuous local release of an opiate peptide in the spinal cord may avoid some of the problems that result from the central actions of systemic or intrathecal administration of opiate drugs. 35 Is it possible that the biological effect of released vector-encoded enkephalin is mediated through actions at peripheral, rather than the central terminal of the sensory neuron? 36 Mu, delta and kappa opioid receptors have been demonstrated on the peripheral terminals of sensory axons, 37,38 and the peripheral injection of opioid drugs relieves inflammatory pain in animal models.…”

Abolition of morphine-immunosuppression in mice lacking the μ-opioid receptor gene

“…3). Morphine remains one of the most valuable drugs for the treatment of severe pain, despite a large number of adverse side effects, which include respirator depression, constipation, tolerance, and dependence (4). Another potential drawback is the inhibitory action of morphine on immune responses.…”

Clonidine attenuates morphine withdrawal and subsequent drug sensitization in rhesus monkeys

“…Many investigators are convinced that the cardiovascular changes are mediated by changes in catecholamines levels at the periphery [72] , but this interpretation is debatable. Opiates are mainly known to reduce heart rate and blood pressure [73] . However, an initial cardiovascular stimulating effect of opiate has been noted in cats [74] , dogs [75] , and humans [76] .…”

“…However, an initial cardiovascular stimulating effect of opiate has been noted in cats [74] , dogs [75] , and humans [76] . These effects may also involve catecholamine and histamine release [73] . Here, we extended these findings to rhesus monkeys, since we had found significant cardiovascular activation 1 h following morphine and cocaine administration.…”