ADVERSE-EFFECTS OF OPIOID AGONISTS AND AGONIST-ANTAGONISTS IN ANESTHESIA

The traditional view of opioids held that the individual opioid agonis ts shared the same mechanism of action, differing only in their potenc y and pharmacokinetic properties. However, recent advances in opioid r eceptor pharmacology have made this view obsolete. Distinguishing feat ures of the synthetic opioid agonists are related, at least in part, t o variation in affinity and intrinsic efficacy at multiple opioid rece ptors. Respiratory depression is the opioid adverse effect most feared by anaesthesiologists. Specific Ic-receptor agonists produce analgesi a with little or no respiratory depression. There are a number of comm ercially available K-receptor partial agonist drugs, the so-called ago nist-antagonist or nalorphine-like opioids, which appear to have a lim ited effect on breathing. Within the series of fentanyl analogues ther e are differences in behaviour towards particular opioid receptors and there is evidence for subtle differences in respiratory depressant ef fects. Pethidine (meperidine) causes histamine release and myocardial depression, while the fentanyl analogues do not. Pethidine has atropin e-like effects on heart rate, while fentanyl analogues reduce heart ra te by a vagomimetic action. Severe bradycardia or even asystole is pos sible with fentanyl analogues, especially in conjunction with the vaga l stimulating effects of laryngoscopy. Fentanyl analogues often produc e minor reductions in blood pressure, and occasionally severe hypotens ion by centrally mediated reduction in systemic vascular resistance. M uscle rigidity and myoclonic movement occurs frequently during inducti on of anaesthesia with larger doses of opioids. Fentanyl and alfentani l have been reported to produce localised temporal lobe electrical sei zure activity in patients with complex partial epilepsy. There are pro bably fewer biliary effects with agonist-antagonist opioids than the a gonist opioids. The mechanism of adverse effects after spinal administ ration is distinctly different for morphine, which is very water solub le, compared with more lipid-soluble opioids. The systemic absorption of morphine after intrathecal or epidural administration is very slow, resulting in long duration of analgesia and low plasma concentrations , while lipid-soluble opioids are rapidly absorbed into the circulatio n and redistributed to the brain. The serotonin syndrome may result fr om coadministration of pethidine, dextromethorphan, pentazocine or tra madol with monoamine oxidase inhibitors (MAOIs) or selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs). There are cl inically important interactions between opioids and hypnosedatives, re sulting in synergistic effects on sedation, breathing and blood pressu re.