acepromazine

アセプロマジン

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/08/20 21:47:49」(JST)

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Acepromazine

Systematic (IUPAC) name
1-{10-[3-(dimethylamino)propyl]-10H-phenothiazin-2-yl}ethanone
Clinical data
AHFS/Drugs.com	International Drug Names
Pregnancy cat.	?
Legal status	not approved for use in cattle
Routes	IV, IM, oral
Pharmacokinetic data
Bioavailability	6.6L/kg, high volume of distribution
Half-life	3 hours in horses
Excretion	found in equine urine up to 96 hours after dosage
Identifiers
CAS number	61-00-7 Y
ATC code	N05AA04
PubChem	CID 6077
DrugBank	DB01614
ChemSpider	5852 Y
UNII	54EJ303F0R Y
KEGG	D07065 Y
ChEBI	CHEBI:44932 Y
ChEMBL	CHEMBL39560 Y
Chemical data
Formula	C19H22N2OS
Mol. mass	326.456 g/mol
SMILES O=C(c2cc1N(c3c(Sc1cc2)cccc3)CCCN(C)C)C
InChI InChI=1S/C19H22N2OS/c1-14(22)15-9-10-19-17(13-15)21(12-6-11-20(2)3)16-7-4-5-8-18(16)23-19/h4-5,7-10,13H,6,11-12H2,1-3H3 Y Key:NOSIYYJFMPDDSA-UHFFFAOYSA-N Y
Y (what is this?)  (verify)

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. It is used widely in horses as a pre-anaesthetic sedative and has been shown to reduce anaesthesia related death. However, is contraindicated in stallions due to the risk of paraphimosis and persistent priapism. Its potential for cardiac effects, namely hypotension due to peripheral vasodilation, 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.

Administration

Canine

When used as a premedication 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 Boxer 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 sighthounds.

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 sedation 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. While it is shown to elicit vasodilation in the distal limb, evidence showing its efficacy at increasing perfusion in the laminae is lacking. It is also sometimes used to treat a horse experiencing Equine Exertional Rhabdomyolysis.

Precautions when using in horses

Acepromazine is a prohibited class A drug under FEI 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.

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

For over 20 years herding dogs have died from negative reactions to acepromazine that were rooted in genetic mutations (citation needed). This reveals a lack of understanding about Acepromazine, and other drugs with potentially toxic side effects. Scientists isolated 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.

Cell enzymes (CYP3A), 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.

Breeds with MDR1 gene

Herding dogs:Australian Shepherd, Border Collie, Collie, English Shepherd, German Shepherd, Old English Sheepdog and Sighthounds

Drugs that 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.

References

English Journal

• Deformation of the rodent optic nerve head and peripapillary structures during acute intraocular pressure elevation.

• Fortune B, Choe TE, Reynaud J, Hardin C, Cull GA, Burgoyne CF, Wang L.SourceDiscoveries in Sight Research Laboratories, Devers Eye Institute, Legacy Health, Portland, OR, USA.
• Investigative ophthalmology & visual science.Invest Ophthalmol Vis Sci.2011 Jul 5. [Epub ahead of print]
• Purpose: To evaluate the effect of acutely elevated intraocular pressure (IOP) on retinal thickness and optic nerve head (ONH) structure in the rat eye by spectral domain optical coherence tomography (SDOCT). Methods: Fourteen adult male Brown-Norway rats were studied under anesthesia (ketamine, xyl
• PMID 21730343

• Reduction of the minimum alveolar concentration of isoflurane in dogs using a constant rate of infusion of lidocaine-ketamine in combination with either morphine or fentanyl.

• Aguado D, Benito J, Gomez de Segura IA.SourceDepartment of Animal Medicine and Surgery, Veterinary Faculty, Complutense University of Madrid, Madrid, Spain.
• Veterinary journal (London, England : 1997).Vet J.2011 Jul;189(1):63-6. Epub 2010 Jul 1.
• The objective of this study was to determine the effects of a constant rate of infusion of lidocaine and ketamine in combination with either morphine or fentanyl on the minimum alveolar concentration of isoflurane (MAC(ISO)) during ovariohysterectomy in dogs. Female dogs (n=44) were premedicated wit
• PMID 20594878

Japanese Journal

• 犬におけるプロポフォール全静脈麻酔とイソフルレン吸入麻酔の覚醒に関する臨床的比較(外科学)

• TSAI Yi-Chin,WANG Liang-Yi,YEH Lih-Seng
• The journal of veterinary medical science 69(11), 1179-1182, 2007-11-25
• 手術や診断のための検査で麻酔をかけた149頭の飼育犬について,プロポフォールによる全静脈麻酔(TIVA)とイソフルレンによる吸入麻酔の覚醒時の特性を臨床的に比較した.すべての犬はアセプロマジンもしくはジアゼパムの前投与後,プロポフォールの静脈内投与により導入された.その結果,58頭のプロポフォール-TIVA麻酔群は91頭のイソフルレン吸入麻酔群よりも覚醒は遅延したが,円滑な覚醒を示した.麻酔終了後 …
• NAID 110006452657

• 犬におけるプロポフォールの全身麻酔導入必要量および薬物相互作用に及ぼすミタゾラム-ブトルファノール,アセプロマジン-ブトルファノールおよびメデトミジンの影響(短報)(外科学)

• 佐野 忠士,西村 亮平,望月 学,佐々木 伸雄
• The journal of veterinary medical science 65(10), 1141-1143, 2003-10-25
• 犬80症例に対しプロポフォールによる麻酔導入時におけるミダゾラム-ブトルファノール,アセプロマジン-ブトルファノールおよびメデトミジンの影響について検討した.全ての麻酔前投与薬により症例を良好に鎮静でき,麻酔導入必要量を明らかに減少する事ができた.前投与薬との相互作用による無呼吸の発生および心血管系への作用に注意すれば,プロポフォールと前投与薬との併用は安全な臨床使用が可能であると思われた.
• NAID 110003886143

Related Links

• Acepromazine - Wikipedia, the free 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, ...

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