Analgesia: μ-receptor agonism in brain (periaquaductal gray matter) and spinal cord (substantia gelatinosa). Opioids bind to G-Protein-coupled opioid receptor and inhibit adenylate cyclase and voltage gated Calcium channels. This reduces excitability and interferes with pain transmission.

Side effects:

μ-receptor agonism:

• Constipation due to ↓GI Transit.
• Pruritis
• Urinary Retention
• Biliary Spasm

μ1 receptor agonism:

• Prolactin release.

μ2 receptor agonism:

• Respiratory depression
• Bradycardia
• Hypotension
• Constipation due to ↓GI Transit.

K receptor agonism:

• Sedation
• ↓ADH Release

δ receptor agonism:

• Respiratory depression
• Constipation due to ↓GI Transit.
• Growth hormone relase
• Urinary retention.

δ2 receptor agonism:

• Pupillary constriction, nausea, vomiting.

• Side Effects of Neuraxial Opioids:
  • Hypotension (abrupt pain relief → decreases adrenaline)
  • Pruritis (unclear etiology)
  • Urinary Retention (inhibition of sacral parasympathetic flow → Detrusor Relaxation)
  • Early Respiratory Depression (systemic absorption)
  • Late Respiratory Depression (migration to medulla).
  • Nausea/Vomiting (rostral migration to chemoreceptor trigger zone)

• Morphine

  • Relatively low potency
  • Active Metabolite, morphine-6-glucuronide has analgesic properties and is renally extreted.
  • Can cause histamine release (Pruritis and Vasodilation)

• Hydromorphone (Dilaudid)

  • 8x more potent than morphine.
  • No active metabolites, no histamine release.

• Fentanyl

  • 100x more potent than morphine.
  • Fast onset and short duration of action.
  • Unlike morphine, no histamine release, so does not cause vasodilation and hypotension.
  • Causes more intense respiratory depression compared to morphine.
  • Causes less nausea compared to moprhine.

• Remifentanil

  • 200x more potent than morphine
  • Extremely rapid offset (~90 sec) as it is metabolized by plasma esterases (as opposed to the liver).

Naloxone (Narcan) can be used to reverse the effects of opioids. It is a competitive antagonist for central opioid receptors.

• Dosing: 0.40mg – 2mg IV q2 minutes. (Can dilute to give in 0.04mg increments)

• If no response after 10 mg, reconsider narcotic overdose as cause of delayed emergence.

• Narcan's effects last for ~45 min. It should be given with caution, as pain control becomes difficult to achieve after narcan is administered.