Fentanyl
Fentanyl
Generic Name
Fentanyl
Mechanism
- Potent μ‑opioid receptor agonist – binds with 100–1000× higher affinity than morphine.
- Activates G‑protein‑coupled receptors → inhibits adenylate cyclase, reduces cAMP, opens K⁺ channels, closes Ca²⁺ channels → hyperpolarization of neurons.
- Results in analgesia, sedation, analgesic tolerance, and respiratory depression.
- The drug’s high lipophilicity allows rapid crossing of the blood‑brain barrier, producing a fast onset (minutes via transdermal or buccal, <1 min IV).
Pharmacokinetics
- Absorption: Rapid transdermal/ buccal absorption; IV route gives 100 % bioavailability.
- Distribution: Highly protein‑bound (~90 % to α‑1‑acid glycoprotein); large volume of distribution (~2–6 L/kg).
- Metabolism: O‑desmethyl‑fentanyl via CYP3A4 and CYP3A5; O‑2‑malonyl‑fentanyl by UGT2B7.
- Excretion: Mainly renal (≈35 % unchanged), rest as metabolites in bile/feces.
- Half‑life: IV 3–5 h; transdermal patch 12–24 h (steady state ~24 h).
Indications
- Severe chronic pain – malignant or non‑malignant, refractory to other opioids.
- Perioperative analgesia – adjunct or alternative to morphine in high‑dose settings.
- Anesthesia maintenance – rapid onset for short procedures or critical care sedation.
- Palliative care – breakthrough pain in cancer patients.
- Epidural/ spinal – for thoracic/lumbar surgeries (rare, specialized).
Contraindications
- Contraindications:
- Known hypersensitivity to fentanyl or any excipient.
- Acute severe bronchial asthma or severe COPD.
- Undesired severe respiratory depression.
- Warnings:
- Respiratory depression—especially with CNS depressants, alcohol, or other opioids.
- Drug interactions: ↑↑ risk with CYP3A4 inhibitors (ketoconazole, clarithromycin) or potentiators of opioids.
- Pregnancy: Category C—use if benefits outweigh risks.
- Liver dysfunction: Dose adjustment may be necessary.
- Elderly & debilitated: increased sensitivity; start low.
Dosing
| Form | Initial dose | Titration | Common adjustments |
| IV | 25–50 µg (bolus) or 50–100 µg/h continuous infusion | Increase by 25–50 µg bolus or 10 µg/h every 5–10 min | Reduce ∼50 % in hepatic impairment |
| Transdermal patch | 25 µg/24 h (step‑up: 50 µg/24 h) | Up to 100 µg/24 h (max 200 µg/24 h) | Patch reposition each 72 h or earlier if skin irritation |
| Buccal tablet | 200 µg | 400 µg if inadequate; 50 µg increments at 5 min intervals | Avoid in patients with severe mucositis |
| Sublingual film | 50 µg | 100 µg if pain persists; 25 µg increments | Prevent aspiration in vomiting patients |
• Titration: Begin at the lowest effective dose; titrate by 25–50 µg IV or 25 µg transdermal patch per 30 min until analgesia achieved.
• "PE" (Patient‑Elicited) dosing: Allow scheduled “rescue” doses with clear monitoring to avoid accumulation.
Adverse Effects
- Common: nausea, vomiting, pruritus, constipation, dizziness, hypotension, dry mouth.
- Serious: respiratory depression, bradycardia, paradoxical agitation, rhabdomyolysis (high doses), chest wall rigidity (IV).
Monitoring
- Respiratory: SpO₂ > 92 %, respiratory rate ≥12/min, capnography if available.
- Hemodynamic: BP, HR, ECG (especially in patients on QT‑prolonging drugs).
- Pain score: Numerical Rating Scale (0‑10) every 30 min during titration.
- Drug levels: Consider plasma fentanyl measurement in overdose or atypical response.
Clinical Pearls
- “Fentanyl One‑Minute Rule”: If a patient has a 2 µg/kg IV dose and demonstrates adequate analgesia within 1 min, consider dose escalation carefully.
- Patch “Dosing Conversion”: 25 µg/24 h patch ≈ 60 µg IV over 24 h; thus, add 0.6 µg/kg/h IV equivalent for bridging.
- Avoid “Weaning the Patch”: Abrupt removal can precipitate withdrawal; taper by reducing patch dosage in 25 µg increments every 72 h.
- Rhabdomyolysis Alert: In ICU patients on high‑dose fentanyl (>200 µg/h IV), monitor CK and myoglobin; treat fluidly to preserve renal function.
- Co‑administration with benzodiazepines: Use lowest possible doses and monitor respiratory depression closely; complex interactions may occur.
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• Key take‑away: Fentanyl’s lipophilicity yields rapid, potent analgesia but demands vigilant dosing and respiratory monitoring. Use patient‑tailored titration, avoid high‑risk combinations, and always follow a clear protocol for induction, maintenance, and tapering.