neuro:opioids:start
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Opioids
Opioids are μ-opioid receptor agonists (or partial/mixed agonists) used for moderate to severe pain, anesthesia, and palliative care.
They reduce pain perception at both spinal and supraspinal levels.
Mechanism of Action
Opioids bind to:
- μ (mu) → analgesia, respiratory depression, euphoria, dependence
- κ (kappa) → analgesia, dysphoria
- δ (delta) → minor analgesic contribution
Cellular effects:
- ↑ Potassium efflux → neuronal hyperpolarization
- ↓ Calcium influx → ↓ neurotransmitter release
- ↓ Substance P and glutamate transmission
Full μ Agonists (Most Potent → Least Potent)
| Drug | Brand Examples | Relative Potency (vs Morphine) | Key Clinical Pearls | Major Risks |
|---|---|---|---|---|
| Sufentanil | Sufenta | ~500x | Extremely potent; anesthesia use | Severe respiratory depression |
| Remifentanil | Ultiva | 100–200x | Ultra-short acting (ester metabolism) | Requires infusion |
| Fentanyl | Duragesic, Sublimaze | ~100x | No histamine release; preferred in renal failure | High overdose risk |
| Alfentanil | Alfenta | 10–20x | Rapid onset IV | Short duration |
| Hydromorphone | Dilaudid | 4–7x | Less histamine than morphine | Potent respiratory depression |
| Oxymorphone | Opana | ~3x | Potent oral option | Respiratory depression |
| Oxycodone | Roxicodone, OxyContin | ~1.5x | Good oral bioavailability | Misuse potential |
| Morphine | MS Contin | 1x (reference) | Histamine release; active metabolites | Hypotension, renal accumulation |
| Hydrocodone | Hysingla ER | ~1x | Often combined with acetaminophen | CYP3A4 interactions |
| Methadone | Dolophine | Variable | NMDA antagonism; neuropathic benefit | QT prolongation |
| Tapentadol | Nucynta | ~0.4x | μ agonist + NRI | CNS depression |
| Tramadol | Ultram | ~0.1x | μ agonist + SNRI; serotonin risk | Seizures, serotonin syndrome |
| Codeine | — | ~0.1x | Prodrug (CYP2D6 activation required) | Variable metabolism |
| Meperidine | Demerol | ~0.1x | Normeperidine metabolite → seizures | Neurotoxicity; avoid in renal failure |
Partial / Mixed Agonists
| Drug | Receptor Activity | Key Feature | Clinical Risk |
|---|---|---|---|
| Buprenorphine | Partial μ agonist | High receptor affinity; ceiling effect | Precipitated withdrawal |
| Butorphanol | κ agonist / μ antagonist | Ceiling effect | Withdrawal in dependent patients |
| Nalbuphine | κ agonist / μ antagonist | Ceiling effect | Dysphoria |
| Pentazocine | κ agonist / weak μ antagonist | Psychotomimetic effects | Hypertension, dysphoria |
Core Clinical Effects
- Analgesia
- Sedation / euphoria
- Respiratory depression (dose-limiting toxicity)
- Constipation (NO tolerance develops)
- Miosis
- Nausea / vomiting
- Pruritus (histamine-mediated)
High-Yield Clinical Pearls
- Tolerance develops to analgesia and respiratory depression.
- Tolerance does NOT develop to constipation.
- Renal failure → avoid morphine and meperidine.
- Methadone prolongs QT interval.
- Codeine and tramadol require CYP2D6 activation.
- Tramadol increases serotonin → serotonin syndrome risk.
- Fentanyl preferred in renal failure.
- Avoid opioids with benzodiazepines or alcohol.
Classic Opioid Toxidrome
Related Sections
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