Opioid Pharmacology — Refresher
Module 1 of 11 · 45 min
Mu-opioid receptor pharmacology, full vs partial agonists, equianalgesic dosing, tolerance + dependence physiology.
Learning objectives
- •Describe the three opioid receptor subtypes + their pharmacologic effects
- •Differentiate full agonists, partial agonists, mixed agonist-antagonists
- •Apply equianalgesic dosing for opioid rotation
- •Explain neuroadaptation underlying tolerance, physical dependence, OUD
Mu, kappa, delta — the receptor map
Endogenous opioid peptides (endorphins, enkephalins, dynorphins) act on G-protein-coupled mu (μ), kappa (κ), and delta (δ) receptors. Mu agonism produces the analgesia, euphoria, respiratory depression, miosis, sedation, and constipation we associate with clinical opioids. Kappa agonism produces dysphoria + diuresis. Delta has limited clinical relevance. Mu-1 mediates supraspinal analgesia; mu-2 mediates respiratory depression + GI effects.
Full vs partial agonists vs antagonists
Full mu agonists (morphine, fentanyl, hydromorphone, oxycodone, methadone): dose-dependent linear analgesia + respiratory depression. Partial agonists (buprenorphine): produce ceiling effect on respiratory depression — safer in overdose. Mixed agonist-antagonists (nalbuphine, butorphanol): mu-antagonist + kappa-agonist — can precipitate withdrawal in mu-dependent patients. Antagonists (naloxone, naltrexone, naloxegol): displace mu agonists, reverse effects.
Equianalgesic dosing + opioid rotation
Standard parenteral morphine 10 mg ≈ hydromorphone 1.5 mg ≈ fentanyl 100 mcg ≈ oxycodone 15 mg PO ≈ oral morphine 30 mg. When rotating opioids (tolerance, side effects, ineffectiveness): convert to morphine equivalent, reduce 25-50% for incomplete cross-tolerance, titrate. Methadone is the exception — non-linear conversion (lower morphine doses convert at lower ratios; higher doses at higher ratios). NIH PEACE charts available.
Tolerance, physical dependence, OUD
Tolerance = need for higher doses to achieve same effect; develops fast for analgesia + respiratory depression, slower for constipation + miosis. Physical dependence = withdrawal on cessation; expected with regular use > 2-3 weeks. OUD = behavioral diagnosis: continued use despite consequences, loss of control, craving — not the same as physical dependence. A patient on chronic opioids for cancer pain has dependence + tolerance but does NOT have OUD. Stigma + conflation drives undertreatment.
References
- · SAMHSA Clinician's Guide
- · Stoelting Pharma 6e Ch 7
- · Miller's 9e Ch 24