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).
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
Mechanism of opioid-induced analgesia is by two main effects:
Mechanism of opioid-induced respiratory depression is mediated by two main mechanisms:
Mechanism of opioid-induced constipation:
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