Acepromazine
Encyclopedia
Acepromazine or acetylpromazine (more commonly known as ACP, Ace, or by the trade names Atravet or Acezine 2 , number depending on mg/ml dose) is a phenothiazine
derivative antipsychotic
drug. It was first used in humans in the 1950s, but is now little used in humans (the closely related analogue, chlorpromazine
, is still used as an antipsychotic in humans). Acepromazine is frequently used in animals as a sedative
and antiemetic
. Its principal value is in quietening and calming anxious animals.
The standard pharmaceutical preparation, acepromazine maleate, is used in veterinary medicine
in dogs, and cats. Its use in horses has fallen out of favor due to the risk of paraphimosis
and persistent priapism
in stallions. Its potential for cardiac effects, namely hypotension
, can be profound and as such is not recommended for use in geriatric or debilitated animals, especially dogs. In these cases it is most often substituted with midazolam
or diazepam
and left out of the preanesthetic medication altogether.
it is commonly administered via the subcutaneous or intramuscular route.
in the UK were implicated for an increased seizure risk when given acepromazine and it was previously recommended to avoid this medication in this breed. For this reason, caution has typically been advised when contemplating acepromazine use in epileptic canine patients although no veterinary studies have been published until quite recently. The two published veterinary studies have failed to show a positive association between use of acepromazine and seizure activity and show a possible role for acepromazine in seizure control: in a retrospective study at University of Tennessee, acepromazine was administered for tranquilization to 36 dogs with a prior history of seizures and to decrease seizure activity in 11 dogs. No seizures were seen within 16 hours of acepromazine administration in the 36 dogs that received the drug for tranquilization during hospitalization. After acepromazine administration, seizures abated for 1.5 to 8 hours (n=6) or did not recur (n=2) in eight of 10 dogs that were actively seizing. Excitement-induced seizure frequency was reduced for 2 months in one dog. A second retrospective study also concluded that administration of acepromazine to dogs with prior or acute seizure history did not potentiate seizures and there was some trend toward seizure reduction. It should be noted that the original seizure cautions reported in the 1950s were in human patients on relatively high anti-psychotic doses of chlorpromazine while the doses of acepromazine used in the only two published veterinary studies cited above are much lower.
Recently a multi-drug resistance gene (MDR1) has been isolated by researchers at Washington State University College of Veterinary Medicine. Mutations in the gene are more common in certain herding breeds and whippets (although Border Collies are underrepresented) as well as many mixed breeds. The mutation causes increased sensitivity to ivermectin and related avermectins, acepromazine, certain opioids and opioid derivatives, as well as vincristine and certain other chemotherapeutics. It is recommended that acepromazine dose be reduced by 25% in heterozyogtes and by 30-50% in dogs homozygous for the mutation. Owners may test their dogs via a kit available from WSU and are strongly encouraged to share those results with their veterinarian.
The Boxer
is reported to have a breed-related sensitivity to acepromazine. In 1996 a warning was placed in the cardiology
section of the Veterinary Information Network (VIN), a US-based network for practicing veterinarians, entitled "Acepromazine and Boxers." It described several adverse reactions to acepromazine in three Boxers at the University of California at Davis veterinary teaching hospital. The reactions included collapse, respiratory arrest, and profound bradycardia
(slow heart rate, less than 60 beats per minute). While there is disagreement among some veterinarians on this point, a number of veterinary publications recommend the drug be avoided in the breed. Individual dogs of any breed can have a profound reaction characterized by hypotension
(low blood pressure), especially if there is an underlying heart problem.
Acepromazine should be used with caution in sighthound
s.
in most horses.
In the UK, acepromazine is not authorised for use in horses intended for human consumption.
In equine surgery
, premedication with acepromazine has been shown to reduce the perianaesthetic mortality rate, although the reasons for this are unclear.
Additionally, acepromazine is used as a vasodilator in the treatment of laminitis
, where an oral dose equivalent to "mild sedation" is commonly used, although the dose used is highly dependent on the treating veterinarian. It is also sometimes used to treat a horse experiencing Equine Exertional Rhabdomyolysis
.
rules, and its use is prohibited or restricted by many other equestrian organizations. It can be detected in the blood for 72–120 hours, although repeated doses may make it remain present for several months.
Side effects are not common, but the use of acepromazine in stallions is usually considered contraindicated due to the risk of paraphimosis
and priapism
.
Acepromazine should not be used in horses dewormed with piperazine. It lowers blood pressure, and should therefore be used with caution in horses that are experiencing anemia
, dehydration
, shock, or colic
.
What role do cell enzymes (CYP3A) play? In addition to having proteins on the membrane that remove drugs from the cell, most cells have enzymes that break down drugs and inactivate them. Cytochrome P 450 (CYP 450) is a family of enzymes that inactivates about 60% of drugs used in pets. One of the CYP 450 family—CYP3A—can be blocked or inactivated by ketoconazole and by grapefruit juice. With CYP3A inactivated, drugs reach toxic concentrations within cells.
Dogs can have both the defective MDR1 gene and have inactivated CYP3A enzymes. These dogs are very likely to develop toxicity with certain drugs.
Which dogs have the MDR1 gene?
Herding dogs:Australian Shepherd, Border Collie, Collie, English Shepherd, German Shepherd, Old English Sheepdog and Sighthounds
Which drugs become toxic if not pumped out by P-glycoproteins?
Many different drugs are normally pumped from cells by P-glycoproteins: anticancer drugs, antiparasitics, antibiotics, cardiac drugs, immunosuppressants, opioids, steroid hormones, and miscellaneous drugs. Acepromazine can become toxic in dogs with the MDR1 mutation.
The anxiolytic drugs like Acepromazine can lead to hearing loss and other serious side effects.
Phenothiazine
Phenothiazine is an organic compound that occurs in various antipsychotic and antihistaminic drugs. It has the formula S2NH. This yellow tricyclic compound is soluble in acetic acid, benzene, and ether. The compound is related to the thiazine-class of heterocyclic compounds...
derivative antipsychotic
Antipsychotic
An antipsychotic is a tranquilizing psychiatric medication primarily used to manage psychosis , particularly in schizophrenia and bipolar disorder. A first generation of antipsychotics, known as typical antipsychotics, was discovered in the 1950s...
drug. It was first used in humans in the 1950s, but is now little used in humans (the closely related analogue, chlorpromazine
Chlorpromazine
Chlorpromazine is a typical antipsychotic...
, is still used as an antipsychotic in humans). Acepromazine is frequently used in animals as a sedative
Sedative
A sedative or tranquilizer is a substance that induces sedation by reducing irritability or excitement....
and antiemetic
Antiemetic
An antiemetic is a drug that is effective against vomiting and nausea. Antiemetics are typically used to treat motion sickness and the side effects of opioid analgesics, general anaesthetics, and chemotherapy directed against cancer....
. Its principal value is in quietening and calming anxious animals.
The standard pharmaceutical preparation, acepromazine maleate, is used in veterinary medicine
Veterinary medicine
Veterinary Medicine is the branch of science that deals with the prevention, diagnosis and treatment of disease, disorder and injury in non-human animals...
in dogs, and cats. Its use in horses has fallen out of favor due to the risk of paraphimosis
Paraphimosis
Paraphimosis is an uncommon medical condition where the foreskin becomes trapped behind the glans penis, and cannot be reduced...
and persistent priapism
Priapism
Priapism is a potentially harmful and painful medical condition in which the erect penis or clitoris does not return to its flaccid state, despite the absence of both physical and psychological stimulation, within four hours. There are two types of priapism: low-flow and high-flow. Low-flow...
in stallions. Its potential for cardiac effects, namely hypotension
Hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
, can be profound and as such is not recommended for use in geriatric or debilitated animals, especially dogs. In these cases it is most often substituted with midazolam
Midazolam
Midazolam is a short-acting drug in the benzodiazepine class developed by Hoffmann-La Roche in the 1970s. The drug is used for treatment of acute seizures, moderate to severe insomnia, and for inducing sedation and amnesia before medical procedures. It possesses profoundly potent anxiolytic,...
or diazepam
Diazepam
Diazepam , first marketed as Valium by Hoffmann-La Roche is a benzodiazepine drug. Diazepam is also marketed in Australia as Antenex. It is commonly used for treating anxiety, insomnia, seizures including status epilepticus, muscle spasms , restless legs syndrome, alcohol withdrawal,...
and left out of the preanesthetic medication altogether.
Canine
When used as a premedicationPremedication
Premedication refer to a drug treatment given to a patient before a medical procedure. These drugs are typically sedative or analgesic....
it is commonly administered via the subcutaneous or intramuscular route.
Potential adverse effects in dogs
Literature from the 1950s raised concerns about phenothiazine-induced seizures in human patients. A family of BoxerBoxer (dog)
Developed in Germany, the Boxer is a breed of stocky, medium-sized, short-haired dog. The coat is smooth and fawn or brindled, with or without white markings. Boxers are brachycephalic , and have a square muzzle, mandibular prognathism , very strong jaws and a powerful bite ideal for hanging on to...
in the UK were implicated for an increased seizure risk when given acepromazine and it was previously recommended to avoid this medication in this breed. For this reason, caution has typically been advised when contemplating acepromazine use in epileptic canine patients although no veterinary studies have been published until quite recently. The two published veterinary studies have failed to show a positive association between use of acepromazine and seizure activity and show a possible role for acepromazine in seizure control: in a retrospective study at University of Tennessee, acepromazine was administered for tranquilization to 36 dogs with a prior history of seizures and to decrease seizure activity in 11 dogs. No seizures were seen within 16 hours of acepromazine administration in the 36 dogs that received the drug for tranquilization during hospitalization. After acepromazine administration, seizures abated for 1.5 to 8 hours (n=6) or did not recur (n=2) in eight of 10 dogs that were actively seizing. Excitement-induced seizure frequency was reduced for 2 months in one dog. A second retrospective study also concluded that administration of acepromazine to dogs with prior or acute seizure history did not potentiate seizures and there was some trend toward seizure reduction. It should be noted that the original seizure cautions reported in the 1950s were in human patients on relatively high anti-psychotic doses of chlorpromazine while the doses of acepromazine used in the only two published veterinary studies cited above are much lower.
Recently a multi-drug resistance gene (MDR1) has been isolated by researchers at Washington State University College of Veterinary Medicine. Mutations in the gene are more common in certain herding breeds and whippets (although Border Collies are underrepresented) as well as many mixed breeds. The mutation causes increased sensitivity to ivermectin and related avermectins, acepromazine, certain opioids and opioid derivatives, as well as vincristine and certain other chemotherapeutics. It is recommended that acepromazine dose be reduced by 25% in heterozyogtes and by 30-50% in dogs homozygous for the mutation. Owners may test their dogs via a kit available from WSU and are strongly encouraged to share those results with their veterinarian.
The Boxer
Boxer (dog)
Developed in Germany, the Boxer is a breed of stocky, medium-sized, short-haired dog. The coat is smooth and fawn or brindled, with or without white markings. Boxers are brachycephalic , and have a square muzzle, mandibular prognathism , very strong jaws and a powerful bite ideal for hanging on to...
is reported to have a breed-related sensitivity to acepromazine. In 1996 a warning was placed in the cardiology
Cardiology
Cardiology is a medical specialty dealing with disorders of the heart . The field includes diagnosis and treatment of congenital heart defects, coronary artery disease, heart failure, valvular heart disease and electrophysiology...
section of the Veterinary Information Network (VIN), a US-based network for practicing veterinarians, entitled "Acepromazine and Boxers." It described several adverse reactions to acepromazine in three Boxers at the University of California at Davis veterinary teaching hospital. The reactions included collapse, respiratory arrest, and profound bradycardia
Bradycardia
Bradycardia , in the context of adult medicine, is the resting heart rate of under 60 beats per minute, though it is seldom symptomatic until the rate drops below 50 beat/min. It may cause cardiac arrest in some patients, because those with bradycardia may not be pumping enough oxygen to their heart...
(slow heart rate, less than 60 beats per minute). While there is disagreement among some veterinarians on this point, a number of veterinary publications recommend the drug be avoided in the breed. Individual dogs of any breed can have a profound reaction characterized by hypotension
Hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
(low blood pressure), especially if there is an underlying heart problem.
Acepromazine should be used with caution in sighthound
Sighthound
Sighthounds, also called gazehounds, are hounds that primarily hunt by speed and sight, instead of by scent and endurance as scent hounds do.-Appearance:...
s.
Equine
Acepromazine can be administered by the intramuscular route, taking effect within 30–45 minutes, or may be given intravenously, taking effect within 15 minutes. Sedation usually lasts for 1–4 hours, although some horses may feel the effects for up to 24 hours. The standard dose is highly variable, depending upon the desired effect following administration. An oral gel formulation is also available (Sedalin gel). The dosage by this route is also highly variable, but it is generally accepted that the recommended dose will give moderate sedationSedation
Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure...
in most horses.
In the UK, acepromazine is not authorised for use in horses intended for human consumption.
In equine surgery
Surgery
Surgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...
, premedication with acepromazine has been shown to reduce the perianaesthetic mortality rate, although the reasons for this are unclear.
Additionally, acepromazine is used as a vasodilator in the treatment of laminitis
Laminitis
Laminitis is a disease that affects the feet of ungulates. It is best known in horses and cattle. Symptoms include lameness, and increased temperature in the hooves...
, where an oral dose equivalent to "mild sedation" is commonly used, although the dose used is highly dependent on the treating veterinarian. It is also sometimes used to treat a horse experiencing Equine Exertional Rhabdomyolysis
Equine Exertional Rhabdomyolysis
Equine exertional rhabdomyolysis is a syndrome that damages the muscle tissue in horses...
.
Precautions when using in horses
Acepromazine is a prohibited class A drug under FEIInternational 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...
rules, and its use is prohibited or restricted by many other equestrian organizations. It can be detected in the blood for 72–120 hours, although repeated doses may make it remain present for several months.
Side effects are not common, but the use of acepromazine in stallions is usually considered contraindicated due to the risk of paraphimosis
Paraphimosis
Paraphimosis is an uncommon medical condition where the foreskin becomes trapped behind the glans penis, and cannot be reduced...
and priapism
Priapism
Priapism is a potentially harmful and painful medical condition in which the erect penis or clitoris does not return to its flaccid state, despite the absence of both physical and psychological stimulation, within four hours. There are two types of priapism: low-flow and high-flow. Low-flow...
.
Acepromazine should not be used in horses dewormed with piperazine. It lowers blood pressure, and should therefore be used with caution in horses that are experiencing anemia
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
, dehydration
Dehydration
In physiology and medicine, dehydration is defined as the excessive loss of body fluid. It is literally the removal of water from an object; however, in physiological terms, it entails a deficiency of fluid within an organism...
, shock, or colic
Horse colic
Colic in horses is defined as abdominal pain, but it is a clinical sign rather than a diagnosis. The term colic can encompass all forms of gastrointestinal conditions which cause pain as well as other causes of abdominal pain not involving the gastrointestinal tract. The most common forms of colic...
.
Feline
Acepromazine is sometimes recommended or prescribed in tiny oral doses to the pet cats of allergy sufferers. This is a homeopathic remedy that has been demonstrated to be ineffective.Drug reaction in herding dogs
In the past 20 years, many herding dogs have died because we did not understand a genetic mutation that caused normal doses of some drugs to have toxic effects, Acepromazine being one of these. Scientists have found the problem: the Multi Drug Resistant 1 (MDR1) gene. In addition, more than 30 potentially toxic drugs have been identified, and a lab test has been developed to identify dogs with the abnormal MDR1 gene. We now recognize 3 different factors that contribute to drug toxicity especially common in herding dogs: a genetic mutation, drugs that inactivate normal cell pumps, and substances that inactivate cell enzymes so they cannot break down drugs.What role do cell enzymes (CYP3A) play? In addition to having proteins on the membrane that remove drugs from the cell, most cells have enzymes that break down drugs and inactivate them. Cytochrome P 450 (CYP 450) is a family of enzymes that inactivates about 60% of drugs used in pets. One of the CYP 450 family—CYP3A—can be blocked or inactivated by ketoconazole and by grapefruit juice. With CYP3A inactivated, drugs reach toxic concentrations within cells.
Dogs can have both the defective MDR1 gene and have inactivated CYP3A enzymes. These dogs are very likely to develop toxicity with certain drugs.
Which dogs have the MDR1 gene?
Herding dogs:Australian Shepherd, Border Collie, Collie, English Shepherd, German Shepherd, Old English Sheepdog and Sighthounds
Which drugs become toxic if not pumped out by P-glycoproteins?
Many different drugs are normally pumped from cells by P-glycoproteins: anticancer drugs, antiparasitics, antibiotics, cardiac drugs, immunosuppressants, opioids, steroid hormones, and miscellaneous drugs. Acepromazine can become toxic in dogs with the MDR1 mutation.
The anxiolytic drugs like Acepromazine can lead to hearing loss and other serious side effects.