Question 15

Describe the pharmacology of naloxone.

[Click here to toggle visibility of the answers]

College Answer

Naloxone is a commonly used intravenous opioid antagonist, which acts as a competitive antagonist with high affinity for the mu, kappa, delta and sigma opioid receptors. It is used to ameliorate or reverse opioid effects at these sites. It has a shorter effect site and plasma half-life than most opiates so levels will fall before the opioid agonist it is being used to treat, thus a repeat dose maybe required to maintain opioid reversal. Overall candidates 
lacked sufficient depth of information to achieve high marks for this question.


Class Opioid
Chemistry Synthetic phenanthrene opioid
Routes of administration IV, intranasal, IM
Absorption Very poor oral bioavailability: 2% (first pass effect is extensive), which means it may still act on enteric opioid receptors
Solubility pKa 7.9, highly lipid soluble
Distribution VOD = 2.8L/kg; 45% protein-bound
Target receptor mu-opiate receptor (pre-synaptic G-protein coupled receptor)
Metabolism Hepatic metabolism into inactive metabolite, naloxone-3-glucouronide
Elimination The inactive metabolite is renally cleared
Time course of action Half-life is 30-80 minutes, i.e. much shorter than the half-life of most opioids
Mechanism of action By acting as a competitive antagonist, naloxone displaces opioids from their receptors, therefore reversing their effects
Clinical effects Abrupt withdrawal, hyperalgesia, seizures, tachycardia, vomiting, diarrhoea, hypertension and pulmonary oedema
Single best reference for further information TGA PI document