OPIOID RECEPTOR AGONISTS

Morphine Bind to mu opioid receptor and to a much lesser

extent, the delta and kappa opioid receptors Side effects include sedation, respiratory

depression, decreased GI motility, nausea and vomiting, histamine release and miosis

Metabolised in liver and kidneys. Active metabolite, morphine-6-glucoronide is

more potent that morphine and is largely excreted via the kidneys.

Renal failure causes accumulation of morphine-6-glucoronide leading to toxic effects even with low doses

Dilates peripheral veins and arteries, making it useful in reducing myocardial workload.

Fentanyl A phenylpiperidine derivative, has a potency 200 times

that of Morphine Has a rapid onset of action and very few adverse effect Peak effect in 6 – 7 minutes after IV administration Prolonged infusion may lead to accumulation of the

drug within the tissue reservoirs resulting in prolonged duration of effect after discontinuation

Metabolised to active metabolite norfentanyl by liver and excreted by kidneys

Prolonged effects in renal impairment and elderly May cause muscle rigidity of the chest wall and may

hamper spontaneous or assisted ventilation.

Sufentanyl is a fentanyl analog and 5 – 10 times more potent as an analgesic than fentanyl.

Alfentanyl has the shortest duration of action and the most rapid onset of this group of drugs.

Remifentanyl i. is an ultra short acting mu opioid receptor agonist. ii. Time to extubation is remarkably short after

discontinuation of remifentanyliii. Metabolised directly by non-specific blood and tissue

esterases to the relatively inactive metabolite remifentanil acid

iv. Renal impairment does not significantly affect time to extubation in patients who were on continuous infusion

v. Bradycardia, hypotension, muscle rigidity and nausea can occur with remifentanyl

FENTANYL ANALOGS

Methadone Synthetic opioid with high oral

bioavailability and a prolonged duration of action

Hepatically metabolised to inactive metabolites that undergo urinary and biliary excretion

Causes less euphoria and less sedation than other opioids

High doses can prolong QT interval and increase the risk of torsades de pointes

OPIOID RECEPTORANTAGONISTS

Naloxone

Competitive antagonist at mu, delta and kappa opioid receptors

Primarily used to reverse opioid induced respiratory depression

METHYLNALTREXONE

Used for the treatment of opioid induced constipation

Peripherally acting mu opioid receptor antagonists

Do not cross blood-brain barrier and therefore do not antagonise the central analgesic effects of opioids.