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 decrease nociceptive transmission at both spinal and supraspinal levels.
Mechanism of Action
Receptor targets:
- μ (mu) → analgesia, respiratory depression, euphoria, dependence
- κ (kappa) → analgesia, dysphoria
- δ (delta) → minor analgesic contribution
Cellular effect:
- ↑ Potassium efflux → neuronal hyperpolarization
- ↓ Calcium influx → ↓ neurotransmitter release
- ↓ Substance P & glutamate transmission
Opioid Comparison Table (Most Potent → Least Potent)
| Drug | Brand | Mechanism / Receptor Activity | Classification | Relative Potency (vs Morphine) | Key Clinical Pearls |
|---|---|---|---|---|---|
| Sufentanil | Sufenta | Full μ agonist | Full agonist | ~500x | Extremely potent; anesthesia |
| Remifentanil | Ultiva | Full μ agonist | Full agonist | 100–200x | Ultra-short acting (ester metabolism) |
| Fentanyl | Duragesic, Sublimaze | Full μ agonist | Full agonist | ~100x | No histamine release; renal safe |
| Alfentanil | Alfenta | Full μ agonist | Full agonist | 10–20x | Rapid IV onset |
| Hydromorphone | Dilaudid | Full μ agonist | Full agonist | 4–7x | Less histamine than morphine |
| Oxymorphone | Opana | Full μ agonist | Full agonist | ~3x | Potent oral agent |
| Oxycodone | Roxicodone, OxyContin | Full μ agonist | Full agonist | ~1.5x | Good oral bioavailability |
| Morphine | MS Contin | Full μ agonist | Full agonist | 1x (reference) | Histamine release; active metabolites |
| Hydrocodone | Hysingla ER | Full μ agonist | Full agonist | ~1x | Often combined with acetaminophen |
| Methadone | Dolophine | Full μ agonist + NMDA antagonist | Full agonist | Variable | Long half-life; QT prolongation |
| Tapentadol | Nucynta | μ agonist + Norepinephrine reuptake inhibition | Dual mechanism | ~0.4x | Less serotonergic than tramadol |
| Tramadol | Ultram | Weak μ agonist + SNRI | Weak agonist | ~0.1x | Serotonin syndrome risk |
| Codeine | — | Weak μ agonist (CYP2D6 prodrug) | Weak agonist | ~0.1x | Variable metabolism |
| Meperidine | Demerol | Full μ agonist | Full agonist | ~0.1x | Normeperidine → seizures |
Partial / Mixed Agonists (Lower Maximal Efficacy)
| Drug | Mechanism | Classification | Key Feature |
|---|---|---|---|
| Buprenorphine | Partial μ agonist (high affinity) | Partial agonist | Ceiling effect; MOUD |
| Butorphanol | κ agonist / μ antagonist | Mixed agonist | Ceiling effect |
| Nalbuphine | κ agonist / μ antagonist | Mixed agonist | Dysphoria |
| Pentazocine | κ agonist / weak μ antagonist | Mixed agonist | Psychotomimetic effects |
Partial and mixed agonists:
- Have ceiling effect on respiratory depression
- Can precipitate withdrawal in opioid-dependent patients
Clinical Effect Summary
- Analgesia
- Sedation / euphoria
- Respiratory depression
- Constipation (no tolerance)
- Miosis
- Nausea / vomiting
- Pruritus (histamine mediated)
High-Yield Exam Pearls
- Full μ agonists → no ceiling effect.
- Partial agonists → ceiling effect.
- Renal failure → avoid morphine and meperidine.
- Methadone → QT prolongation.
- Tramadol → seizure + serotonin risk.
- Codeine → CYP2D6 dependent.
- Fentanyl → safest in renal failure.
- Constipation persists despite tolerance.
Classic Opioid Toxidrome
Related Sections
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