indication

For the relief of moderate to severe pain.

pharmacology

Butorphanol is a synthetic opioid agonist-antagonist analgesic with a pharmacological and therapeutic profile that has been well established since its launch as a parenteral formulation in 1978. The introduction of a transnasal formulation of butorphanol represents a new and noninvasive presentation of an analgesic for moderate to severe pain. This route of administration bypasses the gastrointestinal tract, and this is an advantage for a drug such as butorphanol that undergoes significant first-pass metabolism after oral administration. The onset of action and systemic bioavailability of butorphanol following transnasal delivery are similar to those after parenteral administration. Butorphanol blocks pain impulses at specific sites in the brain and spinal cord.

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. Butorphanol is a mixed agonist-antagonist that exerts antagonistic or partially antagonistic effects at mu opiate receptor sites, but is thought to exert its agonistic effects principally at the kappa and sigma opiate receptors.

toxicity

The clinical manifestations of butorphanol overdose are those of opioid drugs in general. The most serious symptoms are hypoventilation, cardiovascular insufficiency, coma, and death.

biotransformation

Extensively metabolized in the liver. The pharmacological activity of butorphanol metabolites has not been studied in humans; in animal studies, butorphanol metabolites have demonstrated some analgesic activity.

absorption

Rapidly absorbed after intramuscular injection and peak plasma levels are reached in 20-40 minutes. The absolute bioavailability is 60-70% and is unchanged in patients with allergic rhinitis. In patients using a nasal vasoconstrictor (oxymetazoline) the fraction of the dose absorbed was unchanged, but the rate of absorption was slowed. Oral bioavailability is only 5-17% because of extensive first-pass metabolism.

half life

The elimination half-life of butorphanol is about 18 hours. In renally impaired patients with creatinine clearances <30 mL/min the elimination half-life is approximately doubled. After intravenous administration to patients with hepatic impairment, the elimination half-life of butorphanol was approximately tripled.

route of elimination

Butorphanol is extensively metabolized in the liver. Elimination occurs by urine and fecal excretion.

drug interactions

Alvimopan: Opioid analgesics such as butorphanol may enhance the adverse/toxic effect of alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. According to alvimopan prescribing information, alvimopan is contraindicated in patients receiving therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan initiation. Monitor for increased alvimopan adverse effects in patients using opioids prior to alvimopan.

Droperidol: Droperidol may enhance the CNS depressant effect of butorphanol. Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use.

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