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| neuro:opioids:start [2026/02/15 02:46] – andrew2393cns | neuro:opioids:start [2026/02/15 02:49] (current) – andrew2393cns |
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| Opioids are μ-opioid receptor agonists (or partial/mixed agonists) used for moderate to severe pain, anesthesia, and palliative care. | Opioids are μ-opioid receptor agonists (or partial/mixed agonists) used for moderate to severe pain, anesthesia, and palliative care. |
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| They reduce pain perception at both spinal and supraspinal levels. | They decrease nociceptive transmission at both spinal and supraspinal levels. |
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| ---- | ---- |
| ===== Mechanism of Action ===== | ===== Mechanism of Action ===== |
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| Opioids bind to: | Receptor targets: |
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| * μ (mu) → analgesia, respiratory depression, euphoria, dependence | * μ (mu) → analgesia, respiratory depression, euphoria, dependence |
| * δ (delta) → minor analgesic contribution | * δ (delta) → minor analgesic contribution |
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| Cellular effects: | Cellular effect: |
| * ↑ Potassium efflux → neuronal hyperpolarization | * ↑ Potassium efflux → neuronal hyperpolarization |
| * ↓ Calcium influx → ↓ neurotransmitter release | * ↓ Calcium influx → ↓ neurotransmitter release |
| * ↓ Substance P and glutamate transmission | * ↓ Substance P & glutamate transmission |
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| ---- | ---- |
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| ===== Full μ Agonists (Most Potent → Least Potent) ===== | ===== Opioid Comparison Table (Most Potent → Least Potent) ===== |
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| ^ Drug ^ Brand Examples ^ Relative Potency (vs Morphine) ^ Key Clinical Pearls ^ Major Risks ^ | ^ Drug ^ Brand ^ Mechanism / Receptor Activity ^ Classification ^ Relative Potency (vs Morphine) ^ Key Clinical Pearls ^ |
| | [[neuro:opioids:sufentanil|Sufentanil]] | Sufenta | ~500x | Extremely potent; anesthesia use | Severe respiratory depression | | | [[neuro:opioids:sufentanil|Sufentanil]] | Sufenta | Full μ agonist | Full agonist | ~500x | Extremely potent; anesthesia | |
| | [[neuro:opioids:remifentanil|Remifentanil]] | Ultiva | 100–200x | Ultra-short acting (ester metabolism) | Requires infusion | | | [[neuro:opioids:remifentanil|Remifentanil]] | Ultiva | Full μ agonist | Full agonist | 100–200x | Ultra-short acting (ester metabolism) | |
| | [[neuro:opioids:fentanyl|Fentanyl]] | Duragesic, Sublimaze | ~100x | No histamine release; preferred in renal failure | High overdose risk | | | [[neuro:opioids:fentanyl|Fentanyl]] | Duragesic, Sublimaze | Full μ agonist | Full agonist | ~100x | No histamine release; renal safe | |
| | [[neuro:opioids:alfentanil|Alfentanil]] | Alfenta | 10–20x | Rapid onset IV | Short duration | | | [[neuro:opioids:alfentanil|Alfentanil]] | Alfenta | Full μ agonist | Full agonist | 10–20x | Rapid IV onset | |
| | [[neuro:opioids:hydromorphone|Hydromorphone]] | Dilaudid | 4–7x | Less histamine than morphine | Potent respiratory depression | | | [[neuro:opioids:hydromorphone|Hydromorphone]] | Dilaudid | Full μ agonist | Full agonist | 4–7x | Less histamine than morphine | |
| | [[neuro:opioids:oxymorphone|Oxymorphone]] | Opana | ~3x | Potent oral option | Respiratory depression | | | [[neuro:opioids:oxymorphone|Oxymorphone]] | Opana | Full μ agonist | Full agonist | ~3x | Potent oral agent | |
| | [[neuro:opioids:oxycodone|Oxycodone]] | Roxicodone, OxyContin | ~1.5x | Good oral bioavailability | Misuse potential | | | [[neuro:opioids:oxycodone|Oxycodone]] | Roxicodone, OxyContin | Full μ agonist | Full agonist | ~1.5x | Good oral bioavailability | |
| | [[neuro:opioids:morphine|Morphine]] | MS Contin | 1x (reference) | Histamine release; active metabolites | Hypotension, renal accumulation | | | [[neuro:opioids:morphine|Morphine]] | MS Contin | Full μ agonist | Full agonist | 1x (reference) | Histamine release; active metabolites | |
| | [[neuro:opioids:hydrocodone|Hydrocodone]] | Hysingla ER | ~1x | Often combined with acetaminophen | CYP3A4 interactions | | | [[neuro:opioids:hydrocodone|Hydrocodone]] | Hysingla ER | Full μ agonist | Full agonist | ~1x | Often combined with acetaminophen | |
| | [[neuro:opioids:methadone|Methadone]] | Dolophine | Variable | NMDA antagonism; neuropathic benefit | QT prolongation | | | [[neuro:opioids:methadone|Methadone]] | Dolophine | Full μ agonist + NMDA antagonist | Full agonist | Variable | Long half-life; QT prolongation | |
| | [[neuro:opioids:tapentadol|Tapentadol]] | Nucynta | ~0.4x | μ agonist + NRI | CNS depression | | | [[neuro:opioids:tapentadol|Tapentadol]] | Nucynta | Weak μ agonist + Norepinephrine reuptake inhibition | Dual mechanism | ~0.4x | Less serotonergic than tramadol | |
| | [[neuro:opioids:tramadol|Tramadol]] | Ultram | ~0.1x | μ agonist + SNRI; serotonin risk | Seizures, serotonin syndrome | | | [[neuro:opioids:tramadol|Tramadol]] | Ultram | Weak μ agonist + SNRI | Weak agonist | ~0.1x | Serotonin syndrome risk. Lowers seizure threshold | |
| | [[neuro:opioids:codeine|Codeine]] | — | ~0.1x | Prodrug (CYP2D6 activation required) | Variable metabolism | | | [[neuro:opioids:codeine|Codeine]] | — | Weak μ agonist (CYP2D6 prodrug) | Weak agonist | ~0.1x | Variable metabolism | |
| | [[neuro:opioids:meperidine|Meperidine]] | Demerol | ~0.1x | Normeperidine metabolite → seizures | Neurotoxicity; avoid in renal failure | | | [[neuro:opioids:meperidine|Meperidine]] | Demerol | Full μ agonist | Full agonist | ~0.1x | Normeperidine → seizures | |
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| ---- | ---- |
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| ===== Partial / Mixed Agonists ===== | ===== Partial / Mixed Agonists (Lower Maximal Efficacy) ===== |
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| ^ Drug ^ Receptor Activity ^ Key Feature ^ Clinical Risk ^ | ^ Drug ^ Mechanism ^ Classification ^ Key Feature ^ |
| | [[neuro:opioids:buprenorphine|Buprenorphine]] | Partial μ agonist | High receptor affinity; ceiling effect | Precipitated withdrawal | | | [[neuro:opioids:buprenorphine|Buprenorphine]] | Partial μ agonist (high affinity) | Partial agonist | Ceiling effect; MOUD | |
| | [[neuro:opioids:butorphanol|Butorphanol]] | κ agonist / μ antagonist | Ceiling effect | Withdrawal in dependent patients | | | [[neuro:opioids:butorphanol|Butorphanol]] | κ agonist / μ antagonist | Mixed agonist | Ceiling effect | |
| | [[neuro:opioids:nalbuphine|Nalbuphine]] | κ agonist / μ antagonist | Ceiling effect | Dysphoria | | | [[neuro:opioids:nalbuphine|Nalbuphine]] | κ agonist / μ antagonist | Mixed agonist | Dysphoria | |
| | [[neuro:opioids:pentazocine|Pentazocine]] | κ agonist / weak μ antagonist | Psychotomimetic effects | Hypertension, dysphoria | | | [[neuro:opioids:pentazocine|Pentazocine]] | κ agonist / weak μ antagonist | Mixed agonist | Psychotomimetic effects | |
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| | Partial and mixed agonists: |
| | * Have ceiling effect on respiratory depression |
| | * Can precipitate withdrawal in opioid-dependent patients |
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| ---- | ---- |
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| ===== Core Clinical Effects ===== | ===== Clinical Effect Summary ===== |
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| * Analgesia | * Analgesia |
| * Sedation / euphoria | * Sedation / euphoria |
| * Respiratory depression (dose-limiting toxicity) | * Respiratory depression |
| * Constipation (NO tolerance develops) | * Constipation (no tolerance) |
| * Miosis | * Miosis |
| * Nausea / vomiting | * Nausea / vomiting |
| * Pruritus (histamine-mediated) | * Pruritus (histamine mediated) |
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| ---- | ---- |
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| ===== High-Yield Clinical Pearls ===== | ===== High-Yield Exam Pearls ===== |
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| * Tolerance develops to analgesia and respiratory depression. | * Full μ agonists → no ceiling effect. |
| * Tolerance does NOT develop to constipation. | * Partial agonists → ceiling effect. |
| * Renal failure → avoid morphine and meperidine. | * Renal failure → avoid morphine and meperidine. |
| * Methadone prolongs QT interval. | * Methadone → QT prolongation. |
| * Codeine and tramadol require CYP2D6 activation. | * Tramadol → seizure + serotonin risk. |
| * Tramadol increases serotonin → serotonin syndrome risk. | * Codeine → CYP2D6 dependent. |
| * Fentanyl preferred in renal failure. | * Fentanyl → safest in renal failure. |
| * Avoid opioids with benzodiazepines or alcohol. | * Constipation persists despite tolerance. |
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| ---- | ---- |
| ===== Related Sections ===== | ===== Related Sections ===== |
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| * [[eicosanoids:start|Eicosanoids (NSAIDs, COX inhibitors)]] | * [[eicosanoids:start|Eicosanoids (NSAIDs)]] |
| * [[neuro:cns_depressants:start|CNS Depressants]] | * [[neuro:cns_depressants:start|CNS Depressants]] |
| * [[neuro:pain_modulation:start|Pain Pathways]] | * [[neuro:pain_modulation:start|Pain Pathways]] |
