Pharm 101: Oxycodone

Class

Opioid analgesic

Pharmacodynamics

• Moderate opioid agonist that acts mainly on mu receptors in brain and spinal cord, but also outside of CNS

Pharmacokinetics

• PO administration, IR/SR formulations
• Good oral absorption
• High Vd
• Low first pass metabolism (compared with morphine)
• Duration of action 3-4 hours, longer if controlled released formulation
• Hepatic metabolism by P450 to oxymorphone and noroxycodone
• Renal excretion of metabolites

Clinical uses

• Treatment of moderate to severe pain
• 10 mg morphine = 4.5 mg oxycodone

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 R. Pharm 101: Fentanyl. LITFL

References

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