Class

Opioid analgesic

Pharmacodynamics
  • Strong opioid agonist that acts mainly on mu receptor, as well as delta and kappa receptors
  • Reduces presynaptic neurotransmission (especially glutamate)
  • Inhibits post-synaptic neurons (by opening K channels)
  • Central thalamic action and activation of descending inhibitory pain neurons
Pharmacokinetics
  • High first pass metabolism
  • Hepatic metabolism is main mode of inactivation
    • Conjugation primarily to morphine-3-glucuronide (responsible for seizures), 10% to morphine-6-glucuronide (active metabolite)
    • M6G has analgesic potency 4-6x that of morphine, but these polar metabolites have limited ability to cross the blood brain barrier. Therefore don’t contribute to CNS effects of morphine in single dosing, but may contribute in toxicity
  • Half-life 3-4 hours
  • Enterohepatic circulation causes large reabsorption of morphine glucuronides
  • Renal excretion of morphine glucuronides, therefore dose needs to be reduced in renal failure (risk of seizures)
Clinical uses
  • Severe pain
  • Premedication for anaesthesia
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
References
Pharm 101 700

Pharmacology 101

Top 200 drugs

MBBS (UWA) CCPU (RCE, Biliary, DVT, E-FAST, AAA) Emergency Medicine Advanced Trainee in Melbourne, Australia. Special interests in diagnostic and procedural ultrasound, medical education, and ECG interpretation. Editor-in-chief of the LITFL ECG Library. Twitter: @rob_buttner

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