Butorphanol
Encyclopedia
Butorphanol (INN
) is a morphinan
-type synthetic opioid
analgesic
developed by Bristol-Myers. Brand name Stadol was recently discontinued by the manufacturer. It is now only available in its generic formulations, manufactured by Novex, Mylan, Apotex and Ben Venue Laboratories. Butorphanol is most closely structurally related to levorphanol
. Butorphanol is available only as butorphanol tartrate in injectable,tablet, and intranasal spray formulations.
activity at the μ
opioid receptor
and agonist activity at the κ opioid receptor
. Stimulation of these receptors on central nervous system
neuron
s causes an intracellular inhibition
of adenylate cyclase
, closing of influx membrane calcium channels
, and opening of membrane potassium channel
s. This leads to hyperpolarization of the cell membrane potential
and suppression of action potential transmission of ascending pain pathways.
Because of its κ-agonist activity, at analgesic doses butorphanol increases pulmonary arterial pressure and cardiac work. Additionally, κ-agonism can cause dysphoria
at therapeutic or supertherapeutic doses; this gives butorphanol a lower potential for abuse than other opioid drugs.
using the intranasal spray formulation. It may also be used parenteral
ly for management of moderate-to-severe pain, as a supplement for balanced general anesthesia
, and management of pain during labor. Butorphanol is more effective in reducing pain in women than in men.
In veterinary
use, butorphanol ("Torbugesic") is widely used as a sedative
and analgesic in dogs, cats and horses. For sedation, it may be combined with tranquilizers such as alpha-2 agonists (medetomidine
(Domitor)), benzodiazepines, or phenothiazines (acepromazine
) in dogs, cats and exotic animals. It is frequently combined with xylazine
or detomidine
(Domosedan etc.) in horses.
, confusion
, and dizziness
) are considerations with butorphanol. Nausea
and vomiting
are common. Less common are the gastrointestinal effects of other opioids (mostly constipation).
; it is available in various nations under one of any number of trade names, including Moradol and Beforal (Brand name Stadol no longer available in the US); veterinary trade names include Butorphic, Dolorex, Morphasol, Torbugesic, and Torbutrol.
and detomidine
, to make the horse easier to handle during veterinary procedures.
, may be given. Caution should be used if Butorphanol is administered in addition to other narcotics, sedatives, depressants, or antihistamines as it will cause an additive effect.
Butorphanol can cross the placenta, and it will be present in the milk of lactating mares who are given the drug.
The drug is also prohibited for use in competition by most equestrian organizations, including the FEI
, which considers it a class A drug.
In addition to horses, butorphanol with or without acepromazine
is frequently used in veterinary settings for post-operative and accident-related pain in small mammals such as dogs, cats, ferrets, coatis, raccoons, mongooses, various marsupials, some rodents and perhaps some larger birds both in the operating suite and as a regular prescription medication for home use for management of moderate to severe pain. The efficacy of opioids (as well as other drugs that slow down the system like anaesthetics) in treating reptiles is a question about which there is currently not a lot of data.
International Nonproprietary Name
An International Nonproprietary Name is the official nonproprietary or generic name given to a pharmaceutical substance, as designated by the World Health Organization...
) is a morphinan
Morphinan
Morphinan is the base chemical structure of a large chemical class of psychoactive drugs, consisting of opioid analgesics, cough suppressants, and dissociative hallucinogens, among others.- Chemical Derivatives :Immediate derivatives of morphinan include:...
-type synthetic opioid
Opioid
An opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...
analgesic
Analgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....
developed by Bristol-Myers. Brand name Stadol was recently discontinued by the manufacturer. It is now only available in its generic formulations, manufactured by Novex, Mylan, Apotex and Ben Venue Laboratories. Butorphanol is most closely structurally related to levorphanol
Levorphanol
Levorphanol is an opioid medication used to treat severe pain. It is the levorotatory stereoisomer of the synthetic morphinan and a pure opioid agonist, first described in Germany in 1948 as an orally active morphine-like analgesic...
. Butorphanol is available only as butorphanol tartrate in injectable,tablet, and intranasal spray formulations.
Mechanism of action
Butorphanol exhibits partial agonist and antagonistOpioid antagonist
An opioid antagonist is a receptor antagonist that acts on opioid receptors.Naloxone and naltrexone are commonly used opioid antagonist drugs which are competitive antagonists that bind to the opioid receptors with higher affinity than agonists but do not activate the receptors...
activity at the μ
Mu Opioid receptor
The μ-opioid receptors are a class of opioid receptors with high affinity for enkephalins and beta-endorphin but low affinity for dynorphins. They are also referred to as μ opioid peptide receptors. The prototypical μ receptor agonist is the opium alkaloid morphine; μ refers to morphine...
opioid receptor
Opioid receptor
Opioid receptors are a group of G protein-coupled receptors with opioids as ligands. The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins and nociceptin. The opioid receptors are ~40% identical to somatostatin receptors...
and agonist activity at the κ opioid receptor
Kappa Opioid receptor
The κ-opioid receptor is a protein that in humans is encoded by the OPRK1 gene. The κ-opioid receptor is one of five related receptors that bind opium-like compounds in the brain and are responsible for mediating the effects of these compounds...
. Stimulation of these receptors on central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
s causes an intracellular inhibition
Enzyme inhibitor
An enzyme inhibitor is a molecule that binds to enzymes and decreases their activity. Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. They are also used as herbicides and pesticides...
of adenylate cyclase
Adenylate cyclase
Adenylate cyclase is part of the G protein signalling cascade, which transmits chemical signals from outside the cell across the membrane to the inside of the cell ....
, closing of influx membrane calcium channels
Voltage-dependent calcium channel
Voltage-dependent calcium channels are a group of voltage-gated ion channels found in excitable cells with a permeability to the ion Ca2+...
, and opening of membrane potassium channel
Potassium channel
In the field of cell biology, potassium channels are the most widely distributed type of ion channel and are found in virtually all living organisms. They form potassium-selective pores that span cell membranes...
s. This leads to hyperpolarization of the cell membrane potential
Membrane potential
Membrane potential is the difference in electrical potential between the interior and exterior of a biological cell. All animal cells are surrounded by a plasma membrane composed of a lipid bilayer with a variety of types of proteins embedded in it...
and suppression of action potential transmission of ascending pain pathways.
Because of its κ-agonist activity, at analgesic doses butorphanol increases pulmonary arterial pressure and cardiac work. Additionally, κ-agonism can cause dysphoria
Dysphoria
Dysphoria is medically recognized as a mental and emotional condition in which a person experiences intense feelings of depression, discontent and indifference to the world around them.Mood disorders can induce dysphoria, often with a heightened risk of suicide, especially in...
at therapeutic or supertherapeutic doses; this gives butorphanol a lower potential for abuse than other opioid drugs.
Place in therapy
The most common indication for butorphanol is management of migraineMigraine
Migraine is a chronic neurological disorder characterized by moderate to severe headaches, and nausea...
using the intranasal spray formulation. It may also be used parenteral
Parenteral
Parenteral is a route of administration that involves piercing the skin or mucous membrane. Parenteral nutrition refers to providing nutrition via the veins.-Etymology:...
ly for management of moderate-to-severe pain, as a supplement for balanced general anesthesia
Anesthesia
Anesthesia, or anaesthesia , traditionally meant the condition of having sensation blocked or temporarily taken away...
, and management of pain during labor. Butorphanol is more effective in reducing pain in women than in men.
In veterinary
Veterinary anesthesia
Veterinary anesthesia is anesthesia performed on animals by a veterinarian. Anesthesia is used for a wider range of circumstances in animals than in people, due to animals' unwillingness to cooperate with certain diagnostic or therapeutic procedures...
use, butorphanol ("Torbugesic") is widely used as a sedative
Sedative
A sedative or tranquilizer is a substance that induces sedation by reducing irritability or excitement....
and analgesic in dogs, cats and horses. For sedation, it may be combined with tranquilizers such as alpha-2 agonists (medetomidine
Medetomidine
Medetomidine is a synthetic drug used as both a surgical anesthetic and analgesic often used as the hydrochloride salt medetomidine hydrochloride. It is a crystalline white alpha-two adrenergic agonist that can be administered as an intravenous drug solution with sterile water...
(Domitor)), benzodiazepines, or phenothiazines (acepromazine
Acepromazine
Acepromazine or acetylpromazine is a phenothiazine derivative antipsychotic drug. It was first used in humans in the 1950s, but is now little used in humans...
) in dogs, cats and exotic animals. It is frequently combined with xylazine
Xylazine
Xylazine is a drug that is used for sedation, anesthesia, muscle relaxation, and analgesia in animals such as horses, cattle and other non-human mammals. An analogue of clonidine, it is an agonist at the α2 class of adrenergic receptor....
or detomidine
Detomidine
Detomidine is an imidazole derivative and α2-adrenergic agonist, used as a large animal sedative, primarily used in horses. It is usually available as the salt detomidine hydrochloride...
(Domosedan etc.) in horses.
Adverse effects
As with other opioid analgesics, central nervous system effects (such as sedationSedation
Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure...
, confusion
Mental confusion
Confusion of a pathological degree usually refers to loss of orientation sometimes accompanied by disordered consciousness and often memory Confusion (from Latin confusĭo, -ōnis, noun of action from confundere "to pour together", also "to confuse") of a pathological degree usually refers to loss...
, and dizziness
Dizziness
Dizziness refers to an impairment in spatial perception and stability. The term is somewhat imprecise. It can be used to mean vertigo, presyncope, disequilibrium, or a non-specific feeling such as giddiness or foolishness....
) are considerations with butorphanol. Nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
and vomiting
Vomiting
Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...
are common. Less common are the gastrointestinal effects of other opioids (mostly constipation).
Proprietary preparations
Butorphanol is available in the U.S. as a generic drugGeneric drug
A generic drug is a drug defined as "a drug product that is comparable to brand/reference listed drug product in dosage form, strength, route of administration, quality and performance characteristics, and intended use." It has also been defined as a term referring to any drug marketed under its...
; it is available in various nations under one of any number of trade names, including Moradol and Beforal (Brand name Stadol no longer available in the US); veterinary trade names include Butorphic, Dolorex, Morphasol, Torbugesic, and Torbutrol.
Use in horses
Butorphanol is a commonly used narcotic for pain relief in horses. It is administered either IM or IV, with its analgestic properties beginning to take effect about 15 minutes after injection and lasting 4 hours. It is also commonly paired with sedatives, such as xylazineXylazine
Xylazine is a drug that is used for sedation, anesthesia, muscle relaxation, and analgesia in animals such as horses, cattle and other non-human mammals. An analogue of clonidine, it is an agonist at the α2 class of adrenergic receptor....
and detomidine
Detomidine
Detomidine is an imidazole derivative and α2-adrenergic agonist, used as a large animal sedative, primarily used in horses. It is usually available as the salt detomidine hydrochloride...
, to make the horse easier to handle during veterinary procedures.
Side effects, overdose, and precautions
Side effects specific to horses include sedation, CNS excitement (displayed by head pressing or tossing). Overdosing may result in seizures, falling, salivation, constipation, and muscle twitching. If an overdose occurs, a narcotic antagonist, such as naloxoneNaloxone
Naloxone is an opioid antagonist drug developed by Sankyo in the 1960s. Naloxone is a drug used to counter the effects of opiate overdose, for example heroin or morphine overdose. Naloxone is specifically used to counteract life-threatening depression of the central nervous system and respiratory...
, may be given. Caution should be used if Butorphanol is administered in addition to other narcotics, sedatives, depressants, or antihistamines as it will cause an additive effect.
Butorphanol can cross the placenta, and it will be present in the milk of lactating mares who are given the drug.
The drug is also prohibited for use in competition by most equestrian organizations, including the FEI
International Federation for Equestrian Sports
The Fédération Équestre Internationale or in English, the International Federation for Equestrian Sports, is the international governing body of equestrian sports. It recognizes ten international disciplines...
, which considers it a class A drug.
In addition to horses, butorphanol with or without acepromazine
Acepromazine
Acepromazine or acetylpromazine is a phenothiazine derivative antipsychotic drug. It was first used in humans in the 1950s, but is now little used in humans...
is frequently used in veterinary settings for post-operative and accident-related pain in small mammals such as dogs, cats, ferrets, coatis, raccoons, mongooses, various marsupials, some rodents and perhaps some larger birds both in the operating suite and as a regular prescription medication for home use for management of moderate to severe pain. The efficacy of opioids (as well as other drugs that slow down the system like anaesthetics) in treating reptiles is a question about which there is currently not a lot of data.