Morphine binds to mu opioid receptors and has side effects including sedation, respiratory depression, and nausea. It is metabolized in the liver and kidneys, and renal failure can cause toxic effects from its active metabolite morphine-6-glucoronide. Fentanyl is a potent synthetic opioid analgesic that is metabolized in the liver and excreted by the kidneys, with prolonged effects seen in renal impairment. Remifentanil is an ultra-short acting opioid metabolized by esterases to an inactive metabolite, so renal impairment does not significantly affect its duration of action.

2. 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.

3. 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.

4.  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 remifentanyl
iii. 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

5. 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

7. Naloxone
 Competitive antagonist at mu, delta and
kappa opioid receptors
 Primarily used to reverse opioid induced
respiratory depression

8. 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.