PainPharm – Opiates

Master answer

Mechanism of Action and Effects

• Opiates act on MOP, DOP, KOP and NOP receptors
• MOP are distributed widely:
  • Cortex
  • Basal ganglia
  • Spinal cord – dorsal horn
  • Periaqueductal grey – descending inhibition
• DOP, KOP and NOP less affected by commonly used opiates
  • Produce analgesia, with different levels of other opiate effects
• Opioid receptors are G_iPCR
  • Inhibit Ca²⁺ channels
    • Prevent neurotransmitter release at pre-synaptic nerve terminals
  • Open K⁺ channels
    • Hyperpolarise post-synaptic nerves, preventing signal transmission

Analgesia

• Analgesia induced by inhibition of ascending pain transmission
• Sites of action
  • Primary afferents
  • Dorsal horn interneurons
  • Descending modulatory neurons
    • Inhibition of GABA-releasing inhibitory neurons
  • Supraspinally
• Analgesia enhanced by centrally mediated euphoria and sedation

Respiratory depression

• MOP-mediated
• Action on medullary chemoreceptors
  • Blunted increase in respiratory drive with increasing CO₂
• Effect is antagonised by painful stimulus

Constipation

• Mediated by MOP, KOP and DOP receptors
  • Expressed in high density throughout GIT nerve plexus
• Increased GIT tone, with subsequent loss of rhythmic peristaltic movements

Mooney 2016

Answer by Mooney