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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| 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 |