Opioids

The opioid drugs include morphine and its synthetic derivatives. They are powerful analgesics, and have dose-dependent sedative properties.

Opioids have additional recognised effects. They:

• Decrease the sensitivity of the respiratory centres of the brain to carbon dioxide.
• Give potent cough suppression.
• Cause emesis.
• Constrict the pupils (miosis).
• Reduce gastro-intestinal motility.
• Lead to histamine release.

Mechanism of Action

Opiods act on opioid (OP) receptors. OP receptors are G-protein coupled: activation of the receptors causes inhibition of adenylate cyclase, decreasing cAMP levels within the cell. Thus, receptor-ligand interaction promotes the opening of K⁺ channels within the plasma membrane, and also inhibits that of voltage-gated calcium channels. There are three types of opioid receptors:

• OP1: These are located spinally and supraspinally. The primary effect of receptor engagement is sedation.
• OP2: Located spinally, the main effect of OP2 activation is sedation.
• OP3: OP3 receptor interaction gives rise to analgesia, on a spinal and supraspinal level.

Following interaction with the receptor and the subsequent cascade of events, opiods exert their effects by a variety of mechanisms. Neuronal excitability is decreased, along with reductions in the release of the neurotransmitters glutamate and substance P. In this manner, transmission of nociceptive impulses is inhibited and the actions detailed above are elicited.

Pharmacokinetic Considerations

Opioids can be administered intramuscularly, intravenously, subcutanously, intrathecally or orally. Absorption following oral administration is variable with the drug used, but first-pass metabolism decreases the efficacy of the drug when given this way.

The half-life of opioids is around 3-6 hours.

Opioid Antagonists

Naloxone is an antagonist to endogenous opioids. It is frequently used in human medicine to antagonise opioid narcotics in the incidence of overdose. Naloxone may be administered intravenously, intramuscularly, intrathecally or subcutaneously. It has a short duration of action (1-2 hours) and so repeated administrations may be necessary.