indication

For the relief of moderate to severe pain.

pharmacology

Nalbuphine is a synthetic opioid agonist-antagonist analgesic of the phenanthrene series. Nalbuphine's analgesic potency is essentially equivalent to that of morphine on a milligram basis. The opioid antagonist activity of nalbuphine is one-fourth as potent as nalorphine and 10 times that of pentazocine. Nalbuphine by itself has potent opioid antagonist activity at doses equal to or lower than its analgesic dose. When administered following or concurrent with mu agonist opioid analgesics (e.g., morphine, oxymorphone, fentanyl), nalbuphine may partially reverse or block opioid-induced respiratory depression from the mu agonist analgesic. Nalbuphine may precipitate withdrawal in patients dependent on opioid drugs. Nalbuphine should be used with caution in patients who have been receiving mu opioid analgesics on a regular basis.

mechanism of action

The exact mechanism of action is unknown, but is believed to interact with an opiate receptor site in the CNS (probably in or associated with the limbic system). The opiate antagonistic effect may result from competitive inhibition at the opiate receptor, but may also be a result of other mechanisms. Nalbuphine is thought primarily to be a kappa agonist. It is also a partial mu antagonist analgesic, with some binding to the delta receptor and minimal agonist activity at the sigma receptor.

toxicity

Oral, acute LD50 is 1100 mg/kg in dog. Symptoms of overdose include primarily sleepiness and mild dysphoria.

absorption

The mean absolute bioavailability was 81% and 83% for the 10 and 20 mg intramuscular doses, respectively, and 79% and 76% following 10 and 20 mg of subcutaneous nalbuphine.

half life

The plasma half-life of nalbuphine is 5 hours, and in clinical studies the duration of analgesic activity has been reported to range from 3 to 6 hours.

drug interactions

Cimetidine: Increases the effect of the narcotic

Triprolidine: The CNS depressants, Triprolidine and Nalbuphine, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.