Narcan Pharmacology, Pharmacokinetics, Studies, Metabolism - Naloxone

Narcan Pharmacology, Pharmacokinetics, Studies, Metabolism - Naloxone

CLINICAL PHARMACOLOGY

Naloxone prevents or reverses the effects of opioids including respiratory depression, sedation and hypotension. Also, it can reverse the psychotomimetic and dysphoric effects of agonist-antagonists such as pentazocine.

Naloxone hydrochloride is an essentially pure narcotic antagonist, i.e., it does not possess the "agonistic" or morphinelike properties characteristic of other narcotic antagonists; naloxone hydrochloride does not produce respiratory depression, psychotomimetic effects or pupillary constriction. In the absence of narcotics or agonistic effects of other narcotic antagonists, it exhibits essentially no pharmacologic activity.

In the presence of physical dependence on narcotics, naloxone will produce withdrawal symptoms; it has not been shown to produce tolerance nor to cause physical or psychological dependence.

Mechanism of Action

While the mechanism of action of naloxone is not fully understood, the preponderance of evidence suggests that naloxone antagonizes the oploid effects by competing for the same receptor sites.

When Naloxone Hydrochloride Injection is administered intravenously, the onset of action is generally apparent within two minutes; the onset of action is only slightly less rapid when it is administered subcutaneously or intramuscularly. The duration of action is dependent upon the dose and route of administration of naloxone hydrochloride. Intramuscular administration produces a more prolonged effect than intravenous administration. The requirement for repeat doses of naloxone hydrochloride, however, will also be dependent upon the amount, type and route of administration of the narcotic being antagonized.

Following parenteral administration, naloxone hydrochloride is rapidly distributed in the body. It is metabolized in the liver, primarily by glucuronide conjugation and excreted in urine. In one study, the serum half-life in adults ranged from 30 to 81 minutes (mean 64 ±12 minutes). In a neonatal study, the mean plasma half-life was observed to be 3.1 ± 0.5 hours.