Fentanyl

Fentanyl is a synthetic opioid analgesic that binds predominantly to the mu-opioid receptors in the central nervous system. It is characterized by its rapid onset and short duration of action. Fentanyl is 50-100 times more potent than morphine and is widely used for pain management, anesthesia, and sedation.

Uses:

Acute Pain Management: Postoperative and severe acute pain.
Chronic Pain: Particularly in cancer patients who require long-term opioid therapy.
Anesthesia: Used as an adjunct for induction and maintenance of anesthesia.
Sedation: For mechanically ventilated patients in the ICU.
Procedural Sedation: For diagnostic and therapeutic procedures.

Dosage and Administration:

Acute Pain (IV):

Bolus: 25-100 mcg IV every 30-60 minutes as needed for pain.
Infusion: 0.5-2 mcg/kg/hr IV infusion, titrated to effect.

Chronic Pain (Transdermal):

Patch: 12-100 mcg/hour transdermal patch applied every 72 hours. Adjust based on patient response.

Anesthesia (IV):

Low-dose: 2-20 mcg/kg IV bolus (for general surgery).
High-dose: 50-100 mcg/kg IV (for cardiac surgery).
Maintenance: 0.5-3 mcg/kg/min continuous infusion or additional bolus doses as needed.

Procedural Sedation (IV):

0.5-1 mcg/kg IV, titrated to effect.

Dose Adjustment in Different Diseases:

Hepatic Impairment: Reduce the dose due to decreased metabolism.
Renal Impairment: Use with caution; accumulation may occur.
Elderly Patients: Start with a lower dose due to increased sensitivity.
Respiratory Disorders: Use with caution due to the risk of respiratory depression.

Presentation or Form:

IV Solution: 50 mcg/mL.
Transdermal Patch: 12 mcg/hr, 25 mcg/hr, 50 mcg/hr, 75 mcg/hr, 100 mcg/hr.
Oral Lozenge: 200 mcg to 1600 mcg (for breakthrough cancer pain).
Intranasal Spray: 100-800 mcg/spray for breakthrough cancer pain.

Pharmacokinetics:

Absorption: Rapid with IV and intranasal routes; slower with transdermal patches.
Distribution: Widely distributed with high protein binding (~80%).
Metabolism: Primarily metabolized by the liver via CYP3A4.
Excretion: Predominantly in urine as metabolites.

Pharmacodynamics:

Mechanism of Action: Binds to mu-opioid receptors, inhibiting pain transmission and inducing analgesia, sedation, and respiratory depression.
Onset and Duration:
- IV: Onset 1-2 minutes; Duration 30-60 minutes.
- Transdermal: Onset 12-24 hours; Duration up to 72 hours.

Drug Interactions:

CYP3A4 Inhibitors (e.g., ketoconazole, ritonavir): Increased risk of fentanyl toxicity.
Benzodiazepines: Enhanced risk of sedation, respiratory depression, coma, or death.
MAO Inhibitors: Avoid use within 14 days due to the risk of serotonin syndrome.

Comparison with Other Drugs in the Same Category:

Morphine: Slower onset, longer duration, lower potency.
Hydromorphone: Faster onset than morphine but less potent than fentanyl.
Remifentanil: Ultra-short-acting, used primarily in surgical settings.

Precautions and Special Considerations:

Respiratory Depression: Monitor closely, especially in opioid-naïve patients.
Chest Wall Rigidity: Can occur with rapid IV administration.
Tolerance and Dependence: Long-term use can lead to tolerance and dependence.
Pregnancy: Use only if the benefits outweigh the risks.
Pediatric Use: Dosing requires careful titration.

Side Effects:

Common: Nausea, vomiting, constipation, drowsiness.
Serious: Respiratory depression, bradycardia, chest wall rigidity, hypotension.
Long-Term Use: Risk of tolerance, dependence, and addiction.

Recent Updates and Guidelines:

CDC Guidelines (2022): Emphasis on careful titration and risk assessment for opioid use.
FDA Warning (2023): Reinforced guidance on the risks of fentanyl with benzodiazepines and other CNS depressants.

Naloxone (Antidote for Overdose):

Dose: 0.01 mg/kg (10 mcg/kg) IV/IM/SC, with subsequent doses of 0.1 mg/kg as needed, up to 2 mg IV/IM/SC, repeated every 2-3 minutes. Multiple doses or continuous infusion may be required due to fentanyl’s potency.