PainPharm – Opiates

Master answer

Pharmacokinetic Effects

• D: Dependent on degree of lipid solubility.  Fentanyl has > systemic absorption than Morphine.  More likely to cause systemic opoid effects
• M: Minimal metabolic effects occur in the intrathecal space
• E:  Clearance from the intrathecal space is via the arachnoid villi.

Pharmacodynamic Effects and Side-effects
Secondary to:

• Local Effects
  • Analgesia
    • MOP in spinal cord → ↓pain transmission primary afferent neurons
  • Orthostatic hypotension
    • 2° direct SNS blockade at sympathetic chain → vasodilation → venous pooling
  • ↓ temperature
    • Inhibition of shivering
• Cephalic migration:
  • Depends primarily on the lipid solubility of the drug
  • Sedation
    • Direct effect on μ-receptors in reticular formation
  • Confusion
    • Anticholinergic (pre-synaptic blockade of ACh release)
  • Pruritis
    • Interaction with μ-receptors in trigeminal nucleus
  • CNS Excitation
    • In overdose → myoclonic jerks
    • Due to bulk flow to brainstem/basal ganglia
  • ↓MV
    • Direct opioid effect depressing ventilatory centre of brainstem
    • ↑PaCO2 due to right-shift in ventilation v PaCO2 curve
  • N&V
• Systemic Absorption
  • ↓gastric emptying, ↓gut motility
  • ↓MAP
    • Mast cell degranulation → histamine release → vasodilation (rare with fentanyl, ↑with morphine)

Gladwin 2016

Answer by Gladwin