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:

1. Acute Pain Management: Postoperative and severe acute pain.
2. Chronic Pain: Particularly in cancer patients who require long-term opioid therapy.
3. Anesthesia: Used as an adjunct for induction and maintenance of anesthesia.
4. Sedation: For mechanically ventilated patients in the ICU.
5. 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:

1. Hepatic Impairment: Reduce the dose due to decreased metabolism.
2. Renal Impairment: Use with caution; accumulation may occur.
3. Elderly Patients: Start with a lower dose due to increased sensitivity.
4. 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.

References:

• Fentanyl - NCBI StatPearls: https://www.ncbi.nlm.nih.gov/books/NBK459275/
• Stoelting’s Pharmacology and Physiology in Anesthetic Practice, 5th edition.
• Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 13th edition.
• CDC Guidelines for Prescribing Opioids for Pain (2022).
• FDA Safety Communication (2023).