Describe the mechanism of action of the analgesic effect of opiates. (70% of marks) Explain the mechanism by which morphine causes respiratory depression and constipation. (30% of marks)
This question was poorly answered with a low pass rate; which was unexpected for this core topic. In general, completed answers demonstrated good understanding of the analgesic mechanisms of opiates, but only superficial understanding of respiratory depression and constipation. Better answers explained the decreased responsiveness of the respiratory centre to CO2, and the effects of opiates on the enteric nervous system and peristalsis.
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:
Bernards, Christopher M. "Understanding the physiology and pharmacology of epidural and intrathecal opioids." Best Practice & Research Clinical Anaesthesiology 16.4 (2002): 489-505.
Waldhoer, Maria, Selena E. Bartlett, and Jennifer L. Whistler. "Opioid receptors." Annual review of biochemistry 73.1 (2004): 953-990.
Pasternak, Gavril W. "Molecular biology of opioid analgesia." Journal of pain and symptom management 29.5 (2005): 2-9.
Chahl, Loris A. "Opioids-mechanisms of action." (1996).
Manzke, Till, et al. "5-HT4 (a) receptors avert opioid-induced breathing depression without loss of analgesia." Science 301.5630 (2003): 226-229.
Townsend, DeWayne, Philip S. Portoghese, and David R. Brown. "Characterization of specific opioid binding sites in neural membranes from the myenteric plexus of porcine small intestine." Journal of Pharmacology and Experimental Therapeutics 308.1 (2004): 385-393.