Describe the pharmacology of naloxone.
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
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|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|