Pharm 101: Fentanyl

Class

Opioid analgesic

Pharmacodynamics

• Synthetic strong opioid agonist that acts on the mu receptor

Pharmacokinetics

• Many different routes of administration: IV/IM/IN, SC, transdermal patch, epidural
  • Transdermal, mucosal and IM absorption are good
• Highly lipid soluble
• High first pass metabolism (low bioavailability)
• Redistribution half-life 15 minutes, elimination half-life 3 hours
• Duration of action 1-2 hours
• Hepatic metabolism by CYP450 3A4 with no active metabolites
  • Therefore is opioid of choice in renal failure

Clinical uses

• Severe pain
• 0.1mg fentanyl = 10mg morphine (100 times more potent)

Adverse effects with acute use of opioid analgesics

• Respiratory depression
  • Due to inhibition of brainstem respiratory controls allowing less response to hypercapnea
• CNS:
  • Nausea/vomiting
  • Sedation
  • Dysphoria
  • Delirium
  • Seizures
• CVS:
  • Bradycardia
  • Hypotension
• GIT:
  • Urinary retention
  • Constipation
  • Biliary colic
• Skin:
  • Urticaria
  • Pruritus

Adverse effects with chronic use of opioid analgesics

• Endocrine:
  • Hypogonadism
  • Immunosuppression
  • Increased feeding
  • Increased GH secretion
• CNS:
  • Withdrawal effects
  • Dependence,* tolerance**, abuse, addiction
  • Hyperalgesia

Strategies to reduce development of dependence include:

• Smaller doses at longer intervals
• Multi-modal analgesia with non-opioid analgesics
• Use of modified/SR formulations
• Establish goals at start of treatment
• Frequent evaluation of ongoing requirements

Tolerance:

• Does not occur with miosis, constipation and seizures
• There is a moderate degree of tolerance to bradycardia

Precautions/contraindications of opioid analgesics

• Use of pure agonists with weak partial agonists:
  • e.g. buprenorphine with morphine
  • Can reduce analgesia, and induce withdrawal
• Head injury:
  • CO2 retention secondary to respiratory depression causes cerebral vasodilation
• Pregnancy:
  • Chronic use may precipitate dependence in fetus
• Impaired pulmonary function:
  • Risk of acute respiratory failure
• Impaired hepatic or renal function
• Endocrine disease:
  • Patients with Addison’s disease and hypothyroidism (myxedema) may have prolonged and exaggerated responses to opioids
• Drug interactions:
  • Other sedative-hypnotics
  • Antipsychotic agents: increased sedation and accentuation of cardiovascular effects (antimuscarinic and alpha blocking actions)
  • MAOIs: high incidence of hyperpyrexic coma, hypertension

Further reading

• Buttner R. Pharm 101: Morphine. LITFL
• Buttner. Pharm 101: Oxycodone. LITFL

References

• Katzung BG. Basic and Clinical Pharmacology. 14e. 2018: 553-572