Pharmacology Notes

Opioids interact with one or more subtypes of opioid receptors (eg mu, kappa, delta) at supraspinal, spinal and peripheral sites to produce analgesia and a multitude of other effects. Current potent opioid analgesics are mu agonists, although specific delta and kappa agonists may also produce analgesia. Evidence suggests that these opioid receptors exist as heterodimers, which respond in complex ways to combinations of drugs. This may ultimately provide a rationale for using more than one opioid at a time.

Opioids act by causing presynaptic inhibition of neurotransmitter release from C-fibre terminals, postsynaptic inhibition of evoked activity in nociceptive pathways, or disinhibition of other circuits regulating nociceptive transmission. Supraspinal opioids increase descending inhibition of spinal nociceptive transmission.

Opioid analgesics may be pure agonists of specific opioid receptors (notably the mu receptor), mixed agonist–antagonist drugs with opposing effects at distinct receptor subtypes, or partial mu agonists. No ceiling effect to analgesia is found with the pure agonists, in contrast to the partial agonist and mixed agonist–antagonist opioids.