====== 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.

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===== 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

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===== Opioid Comparison Table (Most Potent → Least Potent) =====

^ Drug ^ Brand ^ Mechanism / Receptor Activity ^ Classification ^ Relative Potency (vs Morphine) ^ Key Clinical Pearls ^
| [[neuro:opioids:sufentanil|Sufentanil]] | Sufenta | Full μ agonist | Full agonist | ~500x | Extremely potent; anesthesia |
| [[neuro:opioids:remifentanil|Remifentanil]] | Ultiva | Full μ agonist | Full agonist | 100–200x | Ultra-short acting (ester metabolism) |
| [[neuro:opioids:fentanyl|Fentanyl]] | Duragesic, Sublimaze | Full μ agonist | Full agonist | ~100x | No histamine release; renal safe |
| [[neuro:opioids:alfentanil|Alfentanil]] | Alfenta | Full μ agonist | Full agonist | 10–20x | Rapid IV onset |
| [[neuro:opioids:hydromorphone|Hydromorphone]] | Dilaudid | Full μ agonist | Full agonist | 4–7x | Less histamine than morphine |
| [[neuro:opioids:oxymorphone|Oxymorphone]] | Opana | Full μ agonist | Full agonist | ~3x | Potent oral agent |
| [[neuro:opioids:oxycodone|Oxycodone]] | Roxicodone, OxyContin | Full μ agonist | Full agonist | ~1.5x | Good oral bioavailability |
| [[neuro:opioids:morphine|Morphine]] | MS Contin | Full μ agonist | Full agonist | 1x (reference) | Histamine release; active metabolites |
| [[neuro:opioids:hydrocodone|Hydrocodone]] | Hysingla ER | Full μ agonist | Full agonist | ~1x | Often combined with acetaminophen |
| [[neuro:opioids:methadone|Methadone]] | Dolophine | Full μ agonist + NMDA antagonist | Full agonist | Variable | Long half-life; QT prolongation |
| [[neuro:opioids:tapentadol|Tapentadol]] | Nucynta | Weak μ agonist + Norepinephrine reuptake inhibition | Dual mechanism | ~0.4x | Less serotonergic than tramadol |
| [[neuro:opioids:tramadol|Tramadol]] | Ultram | Weak μ agonist + SNRI | Weak agonist | ~0.1x | Serotonin syndrome risk. Lowers seizure threshold |
| [[neuro:opioids:codeine|Codeine]] | — | Weak μ agonist (CYP2D6 prodrug) | Weak agonist | ~0.1x | Variable metabolism |
| [[neuro:opioids:meperidine|Meperidine]] | Demerol | Full μ agonist | Full agonist | ~0.1x | Normeperidine → seizures |

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===== Partial / Mixed Agonists (Lower Maximal Efficacy) =====

^ Drug ^ Mechanism ^ Classification ^ Key Feature ^
| [[neuro:opioids:buprenorphine|Buprenorphine]] | Partial μ agonist (high affinity) | Partial agonist | Ceiling effect; MOUD |
| [[neuro:opioids:butorphanol|Butorphanol]] | κ agonist / μ antagonist | Mixed agonist | Ceiling effect |
| [[neuro:opioids:nalbuphine|Nalbuphine]] | κ agonist / μ antagonist | Mixed agonist | Dysphoria |
| [[neuro:opioids:pentazocine|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

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===== Clinical Effect Summary =====

  * Analgesia
  * Sedation / euphoria
  * Respiratory depression
  * Constipation (no tolerance)
  * Miosis
  * Nausea / vomiting
  * Pruritus (histamine mediated)

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===== 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.

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===== Classic Opioid Toxidrome =====

  * CNS depression
  * Respiratory depression
  * Miosis
  * Decreased bowel sounds

Treatment:
  * [[neuro:opioids:naloxone|Naloxone]]

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===== Related Sections =====

  * [[eicosanoids:start|Eicosanoids (NSAIDs)]]
  * [[neuro:cns_depressants:start|CNS Depressants]]
  * [[neuro:pain_modulation:start|Pain Pathways]]