Fentanyl (Duragesic®)
| Fentanyl |  |
|---|---|
| Brand Names | Duragesic®, Sublimaze®, Actiq® |
| Drug Class | 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 |
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.
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
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
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
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:
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.
Adverse Effects
Common:
- Sedation
- Constipation
- Nausea
Serious:
- Severe respiratory depression
- Chest wall rigidity (rapid IV administration)
- Physical dependence
Minimal histamine release compared to morphine.
Drug Interactions
CYP3A4 inhibitors (↑ fentanyl levels):
- Azole antifungals
- Macrolides
- Protease inhibitors
CNS depressants:
- Benzodiazepines
- Alcohol
- Other opioids
Risk:
- Profound respiratory depression
Monitoring
Clinical:
- Respiratory rate
- Sedation level
- Oxygen saturation
High-risk situations:
- Patch initiation
- Postoperative settings
- Concomitant sedatives
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.
Toxicity
Classic opioid toxidrome:
- CNS depression
- Respiratory depression
- Miosis
Overdose risk is high due to potency.
Treatment:
Comparison Within Class
Compared to Morphine:
- 100× more potent
- Less histamine release
- Safer in renal failure
Compared to Hydromorphone:
- More potent
- More lipophilic
Compared to Remifentanil:
- Longer duration
- Not metabolized by plasma esterases