Usage
Fentanyl, a synthetic opioid analgesic, is prescribed for the management of moderate to severe acute and chronic pain, particularly in opioid-tolerant patients. It is also used as an anesthetic adjunct in surgical procedures and for sedation in intubated or mechanically ventilated patients.
Pharmacological Classification: Opioid analgesic, narcotic.
Mechanism of Action: Fentanyl binds to mu-opioid receptors in the central nervous system, inhibiting ascending pain pathways, altering pain perception, and producing analgesia. It also affects other opioid receptors (kappa, delta) to a lesser extent.
Alternate Names
Fentanyl citrate, Sublimaze, Duragesic, Actiq, Fentora, Abstral. Numerous generic and brand name variations exist internationally.
How It Works
Pharmacodynamics: Fentanyl exerts its primary effects on the central nervous system, producing analgesia, sedation, euphoria, and respiratory depression. It also impacts the gastrointestinal tract, causing constipation due to decreased motility. Cardiovascular effects can include bradycardia and hypotension.
Pharmacokinetics:
- Absorption: Rapidly absorbed following intravenous, intramuscular, intranasal, and transmucosal administration. Absorption is slower with transdermal patches.
- Metabolism: Primarily metabolized in the liver by CYP3A4 enzyme to norfentanyl (an active metabolite) and other inactive metabolites.
- Elimination: Primarily eliminated via renal excretion of metabolites. Hepatic elimination plays a lesser role. Elimination half-life varies depending on the route of administration but generally ranges from 2 to 4 hours for intravenous administration.
Mode of Action: Fentanyl binds with high affinity to mu-opioid receptors located in the brain, spinal cord, and peripheral tissues. This binding triggers intracellular signaling cascades, leading to:
- Inhibition of neurotransmitter release: Reduces the release of excitatory neurotransmitters like substance P, glutamate, and acetylcholine involved in pain transmission.
- Activation of inhibitory pathways: Increases the release of inhibitory neurotransmitters like GABA and dopamine, further suppressing pain signals.
- Ion channel modulation: Alters ion channel activity (potassium and calcium channels) in neurons, reducing neuronal excitability and pain signal propagation.
Dosage
Detailed dosage guidelines vary considerably based on the patient’s age, weight, medical condition, opioid tolerance, and route of administration. Always consult the latest prescribing information and tailor dosages to individual patient needs.
Standard Dosage
Adults: Highly variable. IV: Analgesia: 1-2 mcg/kg; Anesthesia adjunct: 2-50 mcg/kg. Transdermal: 12-100 mcg/hour.
Children: Pediatric dosing requires careful titration based on weight and clinical response. IV: Analgesia: 1-3 mcg/kg; Sedation: 0.5-1 mcg/kg. Intranasal: 1-2 mcg/kg.
Special Cases:
- Elderly Patients: Reduced initial dose recommended due to age-related decline in organ function and increased sensitivity to opioids.
- Patients with Renal Impairment: Dose adjustment needed in severe renal dysfunction.
- Patients with Hepatic Dysfunction: Dose reduction indicated in moderate to severe hepatic impairment due to reduced metabolism.
- Patients with Comorbid Conditions: Careful monitoring required in patients with respiratory disorders, cardiovascular disease, and other relevant conditions.
Clinical Use Cases:
- Intubation: 2-4 mcg/kg IV.
- Surgical Procedures: 2-50 mcg/kg IV, depending on the extent of surgery.
- Mechanical Ventilation: 25-250 mcg/hour IV infusion, titrated to effect.
- Intensive Care Unit (ICU) Use: Continuous IV infusion, titrated for analgesia and sedation.
- Emergency Situations: Rapid IV administration as needed for pain control.
Dosage Adjustments:
Dose adjustments based on patient response, renal/hepatic function, drug interactions, and other factors are crucial to optimize therapy and minimize adverse events.
Side Effects
Common Side Effects:
Drowsiness, nausea, vomiting, constipation, dizziness, headache, confusion, sweating.
Rare but Serious Side Effects:
Respiratory depression, apnea, hypotension, bradycardia, seizures, serotonin syndrome, ileus.
Long-Term Effects:
Tolerance, dependence, opioid use disorder, adrenal insufficiency, hormonal imbalances.
Adverse Drug Reactions (ADR):
Anaphylaxis, angioedema, severe respiratory depression, cardiac arrest.
Contraindications
Absolute contraindications: Known hypersensitivity to fentanyl, severe respiratory depression, acute or severe bronchial asthma, upper airway obstruction, paralytic ileus.
Relative contraindications: Increased intracranial pressure, head injury, hepatic or renal impairment, pregnancy (unless benefits outweigh risks).
Drug Interactions
Fentanyl interacts with numerous medications, including:
- CYP3A4 Inhibitors: (e.g., macrolide antibiotics, azole antifungals, protease inhibitors) can increase fentanyl levels, leading to increased risk of respiratory depression and other adverse effects.
- CYP3A4 Inducers: (e.g., rifampin, carbamazepine, phenytoin) can decrease fentanyl levels, reducing analgesic efficacy.
- CNS Depressants: (e.g., benzodiazepines, alcohol, sedatives) can potentiate respiratory depression and sedation.
- Serotonergic Drugs: (e.g., SSRIs, SNRIs, MAOIs) can increase the risk of serotonin syndrome.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C. Fentanyl can cross the placenta and may cause neonatal respiratory depression if used near term. Use with caution during pregnancy only if benefits outweigh risks.
- Breastfeeding: Fentanyl is excreted in breast milk. While generally considered compatible with breastfeeding in low doses and short durations, infant monitoring for sedation and respiratory depression is essential.
Drug Profile Summary
- Mechanism of Action: Binds to mu-opioid receptors, inhibiting pain pathways and producing analgesia.
- Side Effects: Drowsiness, nausea, constipation, respiratory depression.
- Contraindications: Hypersensitivity, severe respiratory depression, acute asthma.
- Drug Interactions: CYP3A4 inhibitors, CNS depressants, serotonergic drugs.
- Pregnancy & Breastfeeding: Use with caution; monitor infant.
- Dosage: Highly variable; adjust based on patient and route.
- Monitoring Parameters: Respiratory rate, oxygen saturation, pain scores, sedation level.
Popular Combinations
Fentanyl is often combined with local anesthetics for regional anesthesia or with benzodiazepines for procedural sedation. However, caution is warranted due to increased risk of respiratory depression.
Precautions
Careful patient selection and monitoring are essential to ensure safe and effective use of fentanyl. Baseline assessment of respiratory function, hepatic and renal function, and concomitant medications is necessary.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Fentanyl?
A: Fentanyl dosing is highly individualized. See above sections for adult, pediatric, and special population dosing guidelines.
Q2: How is fentanyl administered?
A: Fentanyl can be administered intravenously, intramuscularly, intranasally, transdermally (patch), transmucosally (lozenges, buccal tablets, sublingual sprays), and epidurally.
Q3: What are the key monitoring parameters for fentanyl?
A: Monitor respiratory rate, oxygen saturation, heart rate, blood pressure, pain scores, and level of sedation.
Q4: Can fentanyl be used in patients with renal impairment?
A: Use with caution in renal impairment. Dose adjustment may be needed in severe renal dysfunction.
Q5: What are the signs of a fentanyl overdose?
A: Pinpoint pupils, respiratory depression (slow or shallow breathing), loss of consciousness, unresponsiveness.
Q6: What is the antidote for a fentanyl overdose?
A: Naloxone (Narcan) is an opioid antagonist that can reverse the effects of a fentanyl overdose.
Q7: Can fentanyl be used during pregnancy?
A: Use with caution during pregnancy only if clearly needed. Chronic use can lead to neonatal abstinence syndrome.
Q8: What are the drug interactions to be aware of with fentanyl?
A: CYP3A4 inhibitors and inducers, CNS depressants (alcohol, benzodiazepines), serotonergic drugs. See the “Drug Interactions” section for details.
Q9: What are the long-term risks of fentanyl use?
A: Tolerance, dependence, opioid use disorder, hormonal imbalances, adrenal insufficiency.
Q10: What are the common side effects of fentanyl?
A: Nausea, vomiting, constipation, dizziness, drowsiness, headache, confusion.
