Opioids

Mechanism of Action

• Receptors: Act as agonists at opioid receptors (μ, δ, κ), which are Gi protein-coupled receptors. The μ-receptor is the most important for analgesia and the primary mediator of most clinical and adverse effects.
• Cellular Effect: Activation leads to closing of presynaptic voltage-gated Ca²⁺ channels (↓ neurotransmitter release, e.g., substance P, ACh, NE, glutamate) and opening of postsynaptic K⁺ channels (→ hyperpolarization, ↓ neuronal excitability).
• Overall Effect: Produces analgesia, sedation, and euphoria.

Classification

• Full agonists
  • Morphine, heroin
  • Methadone
  • Meperidine
  • Codeine
  • Fentanyl
• Partial agonist: buprenorphine
• Mixed agonist/antagonists
  • Butorphanol
  • Nalbuphine
  • Pentazocine
• Full antagonists
  • Naloxone
  • Naltrexone
  • Methylnaltrexone

Strategies for safe opioid prescribing

• Optimize non-opioid interventions
  • Use acetaminophen/NSAIDs, supportive care (eg, heat/ice) for mild/moderate pain
  • Avoid routine opioid use for chronic pain
• Optimize opioid dose and duration
  • Limit therapy to <5 days for acute pain
  • Use lowest dose resulting in adequate pain control
  • Avoid long-acting opioids
• Optimize monitoring
  • Counsel patients on safe use; arrange close follow-up
  • Educate patients on safe disposal of unused opioids

Adverse effects

• Constipation (not affected by tolerance, most common and persistent opioid side effect.)