Core pharmacology

Class Group

Antidote

Legacy Cicm Level

Level 3

Indications Uses

- the reversal of respiratory depression due to opioids
- the diagnosis of suspected opioid overdose and has been used in the
treatment of.
- clonidine overdose

Chemical Pharmaceutics

substituted oxymorphone derivative.
pKa = 8.0

Presentation

clear solution for injection containing 0.02/0.4 mg/ml of naloxone hydrochloride

Main Action

competitive antagonist at mu-, delta-,
kappa-, and sigma-opioid receptors

Mechanism of action

Reversal of MoP receptor effects such as sedation, hypotension, respiratory depression, and the dysphoric effects of partial agonists
Will precipitate acute withdrawal symptoms in opiate addicts

Onset Peak Duration

Onset: 1-3 mins
Peak effect: 15 mins
Duration: 30 mins
> Less than the effect site time of most opioids → requirement for repeat dosing or infusion.

Physiological effects

- CVS: > 0.3 mg/kg → ↑MAP
- RESP: nil
- CNS: Drowsiness at high dose, Decreased pain tolerance
- OTHER: Sphincter of oddi spasm

Adverse Effects Toxicity

Rapid onset of withdrawal symptoms in opioid drug addiction
At High Doses:
- Hypertension
- Tachycardia
- Arrhythmias

Absorption

91% absorption but Oral BA 2% due to extensive first-pass metabolism

Protein binding

46%

Volume of distribution

2 L/kg
Highly lipid soluble

Metabolism

Liver
via glucuronidation to naloxone-3-glucouronide

Clearance

25 ml/min/kg

Half-life

0.5-1.5 hrs

Special Points

effective in alleviating the pruritus, nausea,
and respiratory depression associated with the epidural or spinal administration of opioids.

Route And Dose

IV/IM

- Reversal of post-operative respiratory depression and coma: 20-40mcg IV PRN
- For opioid overdose reversal 0.4-2 mg IM/IV → Via infusion a 5mcg/kg/hr
- Reversal of S/Es of opioids: 1-4 mcg/kg
- Increased cardiac contractility in septic shock at doses 1mg/kg IV