3. Old stuff
          3.1. Old pharm stuff (pre 2009)
              3.1.3. Pharmacology
                  3.1.3.5. Opioids
                      3.1.3.5.5. Opioid antagonists
 3.1.3.5.5.1. Naloxone 

Naloxone

[SH4:p120-121]

Structure

  • Naloxone is the N-alkyl derivative of oxymorphone
  • Nonselective antagonist at all 3 classic opioid receptors
  • Compared with morphine, naloxone has
    * Oxygen (instead of hydroxyl group) at carbon 6
    * Single bond (instead of double) between carbon 7 and 8
    * Hydroxyl group (instead of hydrogen) at carbon 14
    * Two more carbon (an ethene) attached to the methyl group at the N at position 17

NB:

  • Antagonist action is due to substitution at N at position 17 [???]

 

Pharmacodynamics

Effects

  • Antagonism at the opioid receptors
  • Reversal of general anesthesia
    * Could be due to activation of cholinergic arousal system in the brain, independent of any interaction with opioid receptors

NB:

  • When administered in doses >1mg/kg IV
    --> Improvement in myocardial contractility
    * Probably not opioid receptor mediated

Side effects

  • Reversal of analgesia
  • N&V
    * Related to dose and speed of injection
    * Large dose and fast injection increases incidence of N&V
    * Awakening often occurs before or simultaneously with vomiting
  • Increased sympathetic activity
    --> CVS stimulation
    * Probably due to sudden preception of pain
    * Manifest as tachycardia, hypertension, pulmonary oedema, and cardiac dysrhythmias

 

Pharmacokinetics

Absorption

  • PO --> Bioavailability = 20%
  • IV

Metabolism

  • Metabolised primarily in the liver by conjugation with glucuronic acid
    --> Naloxone-3-glucuronide

Action profile

  • Duration of action = 30-45 min
    * Due to rapid removal from brain
  • Elimination half-time = 60-90 min

Clinical

Administration

  • Naloxone 1-4 microgram/kg IV
    --> Reverses opioid-induced analgesia and depression of ventilation
  • Continuous infusion of naloxone 5 microgram/kg/hour
    --> Prevents respiratory depression without altering analgesia produced by neuraxial opioids

 

Special considerations

Maternal-foetal

Naloxone easily crosses placenta
--> Potentially could cause acute withdrawal in the neonate