Butorphanol is somewhat unusual among opiate drugs, because it is both an agonist and antagonist of the brain's Mu opioid receptor, and also an agonist of the Kappa opioid receptor; most opiates primarily agonize the Mu receptor, the one most responsible for the profound relaxation of the central nervous system commonly associated with such drugs. By antagonizing (attenuating) the Mu receptor as well as agonizing (activating) it, butorphanol behaves inherently differently from other opiates such as morphine. Morphine is the prototypical Mu receptor agonist, while naloxone (used to counteract opiates in cases of overdose) is the most powerful Mu receptor antagonist. Butorphanol derives much of its analgesic effect from its influence on the Kappa receptor, which also relaxes the central nervous system, but can also cause other largely negative psychological side effects. Agonizing the Kappa receptor can sometimes lead to a condition called dysphoria characterized by agitation, depression, and anxiety.
Despite its unusual mechanism of action compared to other opiate drugs, clinical trials indicate that butorphanol is remarkably effective as an aid to anesthesia, and for treating acute or postoperative pain.
Clinical comparisons have found butorphanol to be a better complement to general anesthesia than another potent opiate, fentanyl; while considerably less fentanyl is needed to sedate a patient, those who were given butorphanol reported feeling more satisfied with their anesthetic experience, though the trial's authors note that neither is an ideal addition to anesthesia. Neither drug is itself used to induce general anesthesia, but rather to sedate patients while an anesthetic is administered.
Butorphanol is extremely effective for treating acute pain, such as following an injury or while awaiting treatment for an internal problem. A trial interviewing patients who had received butorphanol on ambulance rides found that while 70% of the patients experienced some negative side effects, 80% reported satisfactory pain relief, and 90% would request it for pain relief in the future.
Butorphanol has also been used to manage chronic pain, but it is now rarely prescribed for this purpose. Clinical trials describing its utility as compared with similar drugs for chronic pain are outdated, and intravenous drugs are not typically prescribed for chronic pain, since pills or other methods of ingestion are easier to use, more affordable, and equally or more effective.
Butorphanol was developed by Bristol-Meyers and sold until recently under the brand name Stadol. However, Bristol-Meyers has discontinued its production, and it is now available only as a generic, manufactured by several companies including Mylan, Apotex, and Novex. Preparations of butorphanol are sold under a variety of trade names, including Beforal and Moradol. Butorphanol is classified as a Schedule IV drug in the United States, meaning it has some potential for abuse and there are legal controls regarding its possession and distribution, but far less than other drugs with lower schedules, including many other opiates.
Butorphanol's side effects are similar to those of other opioid drugs:
The most common side effects of butorphanol are drowsiness, dizziness, and nausea; a clinical trial of butorphanol examining 2446 patients, about half of whom received the drug intravenously, found that about 43% reported feeling sleepy, 19% felt dizzy, and 13% felt at least mildly nauseous. While it is typically very safe if used in a medical setting and administered by nurses or doctors, butorphanol can also cause the most dangerous side effects of opiates if used irresponsibly, including respiratory depression, dependence or addiction, and potentially fatal overdose.
Opiate drugs can lead to physical or emotional dependence; this is less likely when they are used under medical supervision for legitimate pain relief, but it remains a risk nonetheless. After prolonged use, patients may need to gradually reduce their dose before stopping in order to avoid withdrawal symptoms, which can be extremely unpleasant but are rarely dangerous for adults.
Some clinical trials have found that butorphanol can cause mild cardiovascular side effects, including increased blood pressure and cardiac index, but its effects on the heart seem to be negligible.
Excessive doses of opiates can also cause serious side effects, including loss of consciousness, seizure, difficulty breathing, and death; opiate overdoses can be terminated with the drug naloxone, a potent opiate antagonist. Repeat doses of naloxone may be required in cases of an overdose, because butorphanol's duration of action exceeds that of naloxone. In cases of overdose, patients will need emergency medical treatment to maintain body temperature, heart rate, and breathing.
Respiratory depression may take place at even moderate doses of butorphanol. While severe respiratory depression is virtually always present in cases of overdose, slowed breathing may not be acutely dangerous, but should always be very closely monitored. Medical attention should be sought immediately if a patient's breathing becomes too slow or shallow; hypoxia (low blood oxygen levels) is the direct cause of death in many cases of opiate overdose.
Like other opiates, butorphanol can cause severe constipation if used over a long period of time. Patients may need to use laxatives, increase the amount of fiber in their diet, or drink far more than fluids than usual to alleviate these side effects. If constipation persists for an unusually long period of time, doesn't improve following diet and lifestyle changes, or begins to cause pain, patients should seek immediate medical attention; prolonged constipation can lead to serious problems if waste is not removed from the body as usual.
Butorphanol can cause unpleasant psychological agitation in some individuals, because it is an agonist of the kappa opioid receptor; exciting this receptor is known to cause an unpleasant condition, known as dysphoria. Because of this side effect, butorphanol likely has a lower potential for abuse than other opiate drugs, but its risks remain nonetheless.
Butorphanol typically causes sedation at doses of 0.5 mg, but most patients requiring the drug to be injected use two to four times that per dose, depending on the severity of their pain, their body weight, and whether it is administered intravenously or intramuscularly. Doses of 10 to 12 mg administered intravenously over 10 to 15 minutes will cause narcosis (anesthetized unconsciousness) in most patients, but this is far beyond butorphanol's typical therapeutic dosage, and would put many patients at risk of overdose.
For treating acute or postoperative pain, most patients initially require only one milligram of intravenous butorphanol, or two milligrams administered intramuscularly. The timing of maintenance doses should be decided based on the patient's response, instead of some fixed interval, but only very rarely will patients need a second dose before six hours.
When used to supplement general anesthesia prior to or during surgery, patients are typically initially given two mg; the dose is the same whether delivered intravenously or intramuscularly, but intramuscular injections should take place 60 to 90 minutes before the surgery, whereas intravenous doses should be administered immediately before the surgery. During the course of the anesthesia, patients will usually require maintenance doses, typically half to a full milligram intravenously, but perhaps up to 0.06 mg per kg of their body weight (4 mg per 70 kg), depending on the anesthestetic being used. The total dosage of butorphanol used throughout a procedure will vary depending on the patient's age, weight, the duration of the procedure, and the anesthetic in use, but patients rarely require less than 4 mg or more than 12.5 mg.
Women going into labor usually need 1 or 2 mg of intravenous butorphanol. It is given as a single dose, but may be repeated in four hours if necessary. It may be administered intravenously, or epidurally (directly into the spinal cord). Using butorphanol or other opiates to relieve pain during childbirth is typically not dangerous for the baby, but mothers may need to delay breast feeding for several days while the drug clears out of their system.
Intravenous butorphanol is typically not prescribed for long-term pain management at home, but is rather used in medical settings for serious acute pain. Patients who need chronic pain management typically use pills or other formulations that are easier to properly use.
Determining the proper dosage for patients with kidney or liver impairment, geriatric patients, or mothers going into labor requires special caution. For pain relief, these patients typically need only half the normal dose (half a milligram intravenously, or one intramuscularly).
Like all opiate drugs, butorphanol should never be used alongside alcohol or other central nervous system depressants, because this could amplify those drugs' depressant effects and lead to dangerously excessive intoxication. Many drugs, both prescription and over-the-counter, depress the central nervous system, including antihistamines, cold medicines, sedatives such as barbiturates, and sleep aids. Other opiates, including prescription painkillers, are particularly dangerous to use with butorphanol.
Opiates such as butorphanol should be used with caution alongside aprepitant, an antiemetic drug prescribed to prevent postoperative nausea; aprepitant can increase the absorption and worsen the side effects of opiates.
Certain antibiotics and antiretrovirals, such as clarithromycin and atazanavir, have been known to increase opiates' absorption rate in the blood, and can increase the likelihood of an overdose. Always tell your doctor about all the drugs you're using to avoid the possibility of such an interaction.
Butorphanol carries many of the same warnings as other opiate drugs:
Opiate drugs such as butorphanol are addictive, can cause unpleasant or dangerous withdrawal symptoms, and are responsible for thousands of life-threatening overdoses annually. They should be prescribed with extreme caution, and administered at the lowest dose possible, and patients should be monitored for signs of dependence or abuse, especially those with a history of drug abuse. Patients who have used butorphanol for a long period of time may need to gradually reduce their dosage before stopping, in order to avoid unpleasant or dangerous withdrawal symptoms.
Like all opiates, butorphanol should never be used while pregnant or nursing, because this could cause potentially fatal dependence and withdrawal symptoms for the baby. If it used to relieve pain during childbirth, the mother may need to wait for several days before breast feeding while the drug passes out of her system.
As a central nervous system depressant, butorphanol leaves many patients feeling dizzy, lightheaded, or drowsy; thus, patients should avoid driving or operating machinery until they thoroughly understand how they react to the drug.
Butorphanol should be stored at room temperature (68 to 77 degrees Fahrenheit, or 20 to 25 Celsius). It should be protected from light.
Butorphanol must be kept away from children and pets; accidental ingestion could be potentially fatal.
Storing opiate drugs properly is critically important to keep them out of the hands of those who may misuse them; butorphanol, like other opiates, should be stored in a secure and, if necessary, locked container.
Unused supplies of butorphanol should be immediately disposed of at proper drug drop-off locations, such as at a police or fire station.
Butorphanol is an opiate with a somewhat unusual mechanism of action, agonizing the Kappa receptors and both agonizing and antagonizing the Mu receptors. It is a potent sedative, effective in treating patients in acute pain and in preparation for general anesthesia.
Like all opiate drugs, butorphanol has a potential for abuse, dependence, and fatal overdose. It should always be administered at the lowest effective dosage and used for the shortest possible amount of time, and stored and disposed of carefully. Patients should be closely monitored for signs of overdose, including respiratory depression, unresponsiveness, and low body temperature.
For many patients and physicians, the benefits of opiate drugs often far outweigh the risks; millions of patients in extreme pain have found relief from opiates, helping not only them but the doctors working to examine and heal them.