Naloxone

Pharmacokinetics

- Absorption: rapid - Distribution: 50% plasma protein binding, predominantly to albumin. Very lipophilic and easily crosses the BBB. - Metabolism: glucuronidation in the liver to form the main metabolite naloxone-3-glucorinide. There are no significant effects from liver impairment on acute administration. - Excretion: 25-40% of the drug is excreted in the urine as metabolites. Half-life: 30-80mins. The duration of action of naloxone may be shorter than the duration of action of the opiate it is being used to antagonise, therefore naloxone may need to be repeated.

Obstetrics

- Category B - During pregnancy: crosses the placental barrier. Safety has not been demonstrated but naloxone should be administered if indicated. - Whilst breast feeding: unknown is naloxone is excreted into breastmilk, but may be administered if indicated. Advise the patient to stop breast feeding and seek further advice from their LMC

Additional notes

- Do not administer naloxone during cardiac arrest secondary to opiate poisoning because in this setting cardiac arrest is secondary to respiratory arrest and once cardiac arrest occurs it has no useful effect. If ROSC occurs, naloxone should still not be administered because it may be associated with HTN, flash pulmonary oedema, severe agitation, and/or seizures. - There is no evidence to support the commonly held view that adequate oxygenation prior to naloxone administration reduces the severity of naloxone induced agitation. However, treatment of severe hypoxia takes precedence over the administration of naloxone - Acute opiate withdrawal can cause agitation and/or aggression following naloxone administration, particularly when there has also been a period of hypoxia. Ensure a planned team approach to maintain safety to both the patient and personnel.

Adverse effects

- Flash pulmonary oedema (associated with rapid reversal of opiate poisoning) - in opiate dependent patients, high dose of rapidly infused naloxone to rapidly reverse opiate OD may cause non-cardiogenic PO. Mu-opioid receptor antagonism mediates changes in central sympathetic outflow, and stimulates an increase in catecholamines (particularly adrenaline). This increase in catecholamines results in increased CO and pulmonary-capillary hydrostatic pressure. Furthermore, rapid reversal of opiate OD results in increased capillary permeability (causing leakage of histamine and protein into the lung tissue and vasculature), and negative pulmonary pressure (causing negative pressure PO). - Seizures (associated with rapid reversal of opiate poisoning) - Severe agitation (associated with rapid reversal of opiate poisoning) - HTN (associated with rapid reversal of opiate poisoning) - Tachycardia - Sweating - Nausea - Vomiting Most adverse effects can be prevented, as they are related to opiate withdrawal and the rapid reversal of opiate poisoning, which is particularly the case if the patient takes opiates regularly (this may be minimised by giving the minimum amount of naloxone required just to reverse the adverse effect of the opiate).

Onset

- IV: 1-2mins - IM: 5-10mins.

Cautions

1). Chronic opiate use (due to the high risk of adverse physiological effects associated with opiate withdrawal).

Indications

1). Excess adverse effects from administration of opiates. 2). Opiate poisoning is suspected and the patient has a significantly impaired LOC or breathing.

Contraindications

1). Known severe allergy

Duration

30-60mins. The duration of action of naloxone may be shorter than the duration of action of the opiate it is being used to antagonise, therefore naloxone may need to be repeated.

Administration: - Adult IV - Paediatric IV - IM.

Adult and paediatric IV: - Dilute 0.4mg/1ml to a total of 4ml using NaCl IM: - Undiluted.

Preparation

Ampoule containing 0.4mg/1ml

Dose

IV: - Adults: 0.1-0.4mg repeated every 5mins as required - 5kg: 0.05mg - 10kg: 0.1mg - 20kg: 0.1-0.2mg - 30kg: 0.1-0.3mg - 40kg: 0.1-0.4mg. IM: - Adults: 0.8mg repeated every 20mins as required - Paediatrics: 0.02mg/kg. Notes: - Naloxone should only be repeated if there are clinical signs that is has been effective. - Administer the minimum dose required to produce improvement. Rapid reversal of opiate overdose increases the risk of seizures, HTN, pulmonary oedema, or severe agitation, particularly if the patient takes opiates regularly.

Pharmacodynamics

Naloxone is a competitive opioid receptor antagonist, with the highest affinity for the mu opioid receptors, but has some effect at the kappa receptors. Naloxone prevents or reverses the effects of opioids.

Class

Opiate antidote/antagonist