neuro:opioids:fentanyl []

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====== Fentanyl (Duragesic®) ======

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<WRAP infobox>
^ Fentanyl | {{ :neuro:opioids:fentanyl2dcsd.svg?200 |}} |
| Brand Names | Duragesic®, Sublimaze®, Actiq® |
| Drug Class | [[neuro:opioids:start|Opioid]] (Full μ-agonist) |
| Primary Indication | Severe Pain / Anesthesia |
| Relative Potency | ~100× Morphine |
| Histamine Release | Minimal |
| Respiratory Depression | Yes (high potency) |
| Weight Effect | Neutral |
| Elimination | Hepatic metabolism |
| Controlled Substance | Schedule II |
| FDA Approval | 1968 |
</WRAP>
</WRAP>

===== Overview =====

Fentanyl is a highly potent, synthetic full μ-opioid receptor agonist used for severe pain and anesthesia.

It is approximately 100 times more potent than morphine and is highly lipophilic, allowing for rapid CNS penetration.

Unlike morphine, fentanyl causes minimal histamine release and is often preferred in patients with renal impairment or hemodynamic instability.

<WRAP clear></WRAP>

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===== Mechanism of Action =====

**Receptor Activity**
  * Full μ-opioid receptor agonist  
  * High receptor affinity  
  * Gi-protein coupled receptor activation  

**Cellular Effects**
  * ↓ cAMP production  
  * ↑ Potassium efflux → neuronal hyperpolarization  
  * ↓ Calcium influx → ↓ substance P & glutamate release  

**Net Effect**
  * Profound analgesia  
  * CNS and respiratory depression  

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===== Indications =====

  * Severe acute pain  
  * Chronic severe pain (transdermal patch)  
  * Breakthrough cancer pain (transmucosal formulations)  
  * Anesthesia adjunct  
  * Procedural sedation  

Transdermal patch:
  * For opioid-tolerant patients only  

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<WRAP contra>
===== Contraindications =====

Absolute:
  * Significant respiratory depression  
  * Acute severe bronchial asthma  
  * Opioid-naïve patients (for transdermal patch)  

Relative / Caution:
  * Hepatic impairment  
  * Concomitant CNS depressants  
  * Elderly  
  * Obstructive sleep apnea  

</WRAP>

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<WRAP details>
===== Dosing =====

IV (anesthesia/acute pain):
  * Highly titratable based on effect  

Transdermal patch:
  * Applied every 72 hours  
  * Requires opioid tolerance prior to initiation  

Transmucosal (lozenge, buccal):
  * For breakthrough cancer pain  

Equianalgesic:
  * ~100 mcg IV fentanyl ≈ 10 mg IV morphine  

See:
  * [[neuro:opioids:equianalgesic_dosing|Equianalgesic Dosing Guide]]

</WRAP>

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<WRAP details>
===== Pharmacokinetics =====

Absorption:
  * IV, transdermal, transmucosal  

Lipophilicity:
  * Highly lipophilic → rapid CNS penetration  

Metabolism:
  * Hepatic (CYP3A4)  

Half-life:
  * IV: short redistribution phase  
  * Patch: prolonged release over 72 hours  

Elimination:
  * Hepatic metabolism with inactive metabolites  

Preferred in renal failure due to lack of active renally cleared metabolites.

</WRAP>

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<WRAP details>
===== Adverse Effects =====

Common:
  * Sedation  
  * Constipation  
  * Nausea  

Serious:
  * Severe respiratory depression  
  * Chest wall rigidity (rapid IV administration)  
  * Physical dependence  

Minimal histamine release compared to morphine.

</WRAP>

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<WRAP details>
===== Drug Interactions =====

CYP3A4 inhibitors (↑ fentanyl levels):
  * Azole antifungals  
  * Macrolides  
  * Protease inhibitors  

CNS depressants:
  * Benzodiazepines  
  * Alcohol  
  * Other opioids  

Risk:
  * Profound respiratory depression  

</WRAP>

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<WRAP monitoring>
===== Monitoring =====

Clinical:
  * Respiratory rate  
  * Sedation level  
  * Oxygen saturation  

High-risk situations:
  * Patch initiation  
  * Postoperative settings  
  * Concomitant sedatives  

</WRAP>

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<WRAP pearls>
===== Clinical Pearls =====

  * Extremely potent (100× morphine).  
  * Minimal histamine release → less hypotension.  
  * Preferred opioid in renal failure.  
  * Transdermal patch only for opioid-tolerant patients.  
  * Rapid IV administration may cause chest wall rigidity.  
  * CYP3A4 interactions are clinically significant.  

</WRAP>

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===== Toxicity =====

Classic opioid toxidrome:
  * CNS depression  
  * Respiratory depression  
  * Miosis  

Overdose risk is high due to potency.

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

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===== Comparison Within Class =====

Compared to [[neuro:opioids:morphine|Morphine]]:
  * 100× more potent  
  * Less histamine release  
  * Safer in renal failure  

Compared to [[neuro:opioids:hydromorphone|Hydromorphone]]:
  * More potent  
  * More lipophilic  

Compared to [[neuro:opioids:remifentanil|Remifentanil]]:
  * Longer duration  
  * Not metabolized by plasma esterases  

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===== Related =====

  * [[neuro:opioids:start|Opioids]]
  * [[neuro:opioids:morphine|Morphine]]
  * [[neuro:opioids:hydromorphone|Hydromorphone]]
  * [[neuro:opioids:remifentanil|Remifentanil]]
  * [[neuro:opioids:naloxone|Naloxone]]