| Indication |
For the relief of moderate to severe pain. |
| Pharmacodynamics |
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. |
| 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. |
| Volume of distribution |
|
| Protein binding |
Serum protein binding is approximately 80%. |
| Metabolism |
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. |
| Route of elimination |
Butorphanol is extensively metabolized in the liver. Elimination occurs by urine and fecal excretion. |
| 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. |
| Clearance |
- 99 +/- 23 L/h [Young with IV 2 mg]
- 82 +/- 21 [Eldery with IV 2 mg]
|
| 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. |
