Describe the mechanism of action of the analgesic effect of opiates (70% marks). Explain the mechanisms by which morphine causes respiratory depression and constipation (30% marks).

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College Answer

This was a multi-part question, for which many candidates failed to apportion their 
time as indicated by the question. Most patients who enter Intensive Care receive 
opioid analgesia so candidates were expected to have detailed knowledge about the 
mechanics of action of opiates. For a good answer candidates were expected to 
mention that opiate agonists produce analgesia by binding to Mu receptors (which 
are G protein coupled) in the central and peripheral nervous system and spinal cord 
and their cellular mechanism of action eg presynaptic neurone - close voltage gated 
Ca channels and prevent neurotransmitter release and post synaptic neurone -
hyperpolarise and inhibit post synaptic neurone. The fact that opiates also affect 
emotional side of pain and cause euphoria which may help with pain perception was 
often omitted.
Mechanism of respiratory depression is mediated via mu receptor. It occurs at 
normal analgesic doses, and decreases the chemosensitivity of the respiratory 
centre to PaCO2 Mechanism of constipation results from increased tone and decreased motility of the 
GIT via action on visceral smooth muscle mediated by intramural nerve plexus and 
all three opioid receptors.
Many candidates had poor organisation and poor knowledge of all aspects of this 
question.
Syllabus: G2d 2b
Reference: Pharmacology, Rang and Dale pgs 600-601, Basic and Clinical 
Pharmacology, Katzung pg 492