The traditional view of
opioids held that the individual
opioid agonists shared the same mechanism of action, differing only in their potency and pharmacokinetic properties. However, recent advances in
opioid receptor pharmacology have made this view obsolete. Distinguishing features of the synthetic
opioid agonists are related, at least in part, to variation in affinity and intrinsic efficacy at multiple
opioid receptors.
Respiratory depression is the
opioid adverse effect most feared by anaesthesiologists. Specific
kappa-receptor agonists produce
analgesia with little or no
respiratory depression. There are a number of commercially available
kappa-receptor partial agonist drugs, the so-called agonist-antagonist or
nalorphine-like
opioids, which appear to have a limited effect on breathing. Within the series of
fentanyl analogues there are differences in behaviour towards particular
opioid receptors and there is evidence for subtle differences in respiratory depressant effects.
Pethidine (
meperidine) causes histamine release and myocardial depression, while the
fentanyl analogues do not.
Pethidine has
atropine-like effects on heart rate, while
fentanyl analogues reduce heart rate by a vagomimetic action. Severe
bradycardia or even
asystole is possible with
fentanyl analogues, especially in conjunction with the vagal stimulating effects of laryngoscopy.
Fentanyl analogues often produce minor reductions in blood pressure, and occasionally severe
hypotension by centrally mediated reduction in systemic vascular resistance.
Muscle rigidity and myoclonic movement occurs frequently during induction of anaesthesia with larger doses of
opioids.
Fentanyl and
alfentanil have been reported to produce localised temporal lobe electrical seizure activity in patients with
complex partial epilepsy. There are probably fewer biliary effects with agonist-antagonist
opioids than the agonist
opioids. The mechanism of adverse effects after spinal administration is distinctly different for
morphine, which is very water soluble, 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 circulation and redistributed to the brain. The
serotonin syndrome may result from coadministration of
pethidine,
dextromethorphan,
pentazocine or
tramadol with
monoamine oxidase inhibitors (MAOIs) or selective
serotonin (
5-hydroxytryptamine; 5-HT) reuptake inhibitors (
SSRIs). There are clinically important interactions between
opioids and hypnosedatives, resulting in synergistic effects on sedation, breathing and blood pressure.