What are the physiologic effects of fentanyl?

Physiologic Effects of Fentanyl

Fentanyl produces multiple physiologic effects primarily on the central nervous system and respiratory system, including analgesia, respiratory depression, sedation, and cardiovascular effects. 1, 2

Primary Pharmacologic Effects

• Central Nervous System Effects:

  • Interacts predominantly with opioid mu-receptors 2
  • Produces analgesia (primary therapeutic effect)
  • Causes alterations in mood, euphoria, dysphoria, and drowsiness
  • Depresses the cough reflex
  • Causes pupillary constriction (miosis)

• Respiratory System:

  • Causes dose-dependent respiratory depression 1, 2
  • Depresses central ventilatory response to hypoxia and hypercapnia 1
  • May induce chest wall rigidity and generalized skeletal muscle hypertonicity with large doses 1
  • Respiratory depression may last longer than the analgesic effect 1

• Gastrointestinal System:

  • Increases tone and decreases propulsive contractions of GI smooth muscle 2
  • Prolongs gastrointestinal transit time, contributing to constipation 2
  • May cause nausea and vomiting by direct stimulation of the chemoreceptor trigger zone 2
  • Nausea and vomiting are more common in ambulatory than recumbent patients 2

• Cardiovascular System:

  • At therapeutic doses, generally does not exert major cardiovascular effects 2
  • Some patients may exhibit orthostatic hypotension and fainting 2
  • May cause vasodilation and hypotension due to ablation of sympathetic tone 1

Pharmacokinetics

• Onset of action: 1-2 minutes (intravenous) 1, 3
• Peak effect: 3-4 minutes 3
• Duration of action: 30-60 minutes 1, 3
• Accumulation: With repeated dosing or continuous infusion, fentanyl accumulates in skeletal muscle and fat, potentially prolonging its duration of effect 1

Special Considerations

Histamine Release

• Unlike some other opioids, fentanyl rarely causes clinically significant histamine release 2
• Clinical assays show no significant histamine release in dosages up to 50 mcg/kg 2

Biliary and Urinary Effects

• May increase biliary tract pressure, potentially worsening biliary colic in some patients 2
• Variable effects on urinary tract smooth muscle, sometimes producing urinary urgency, in other cases difficulty urinating 2

Synergistic Effects

• When combined with benzodiazepines or other CNS depressants, has synergistic effect on respiratory depression 1
• Requires dose reduction when used with other sedatives due to this synergistic interaction 1

Clinical Implications and Cautions

• Respiratory Monitoring:

  • Respiratory depression is the most serious adverse effect 1, 2
  • Careful monitoring is essential, especially when combined with other CNS depressants
  • Naloxone should be readily available for emergency reversal 3

• Dosage Considerations:

  • Initial IV dose is usually 50-100 μg with supplemental doses of 25 μg every 2-5 minutes until adequate sedation is achieved 1
  • Elderly patients require dose reduction of 50% or more 1, 3
  • Patients with renal insufficiency may benefit from fentanyl over meperidine due to lack of neurotoxic metabolites 1

• Chest Wall Rigidity:

  • With large doses, may cause chest wall rigidity that can interfere with ventilation 1
  • This effect is more common with rapid IV administration of higher doses

By understanding these physiologic effects, clinicians can optimize fentanyl's therapeutic benefits while minimizing potential adverse effects through appropriate dosing, monitoring, and patient selection.