Phenothiazines were originally investigated in the 1870s, although it wasn’t until the 1950s that acepromazine was introduced in human medicine for the treatment of schizophrenia.1 However, the use of acepromazine in humans was quickly abandoned due to it's side effects, but it remains popular in veterinary medicine, and is the only licensed phenothiazine in small animal practice. Acepromazine will be the focus of this article.
Acepromazine is commonly used for premedication prior to general anaesthesia and as a tranquilliser/sedative.
Pharmacology of Acepromazine
Acepromazine acts mainly as dopamine receptor (D1 & D2) antagonist,2 but it also blocks α1 adreno-receptors, and has anticholinergic & antihistamine activity (muscarinic receptor & H1 receptor blockades). There is also evidence that acepromazine has membrane stabilising effects by blocking ion channels.3 Most clinical activity is via depression of the central nervous system.
Acepromazine is more than 90% protein bound and is highly lipophilic, readily crossing the blood-brain barrier and placenta.
Hepatic metabolism is via phase 1 and 2, and some metabolites may be active. Excretion is via the bile and urine.3
Acepromazine is not recommended in patients with compromised liver function, porto-systemic shunts, animals with immature liver function (less than 12 weeks of age) or patients with hepatobiliary disease.2
Acepromazine is not analgesic.
Acepromazine delivers its clinical effects via the antagonistic activity at the dopamine receptors in the basal ganglia, medulla and hypothalamus of the central nervous system. This results in an increased threshold to external stimuli and a reduction in motor activity. Peripherally acepromazine has antagonistic activity at α1 receptors resulting in vasodilation.3
1. Time to onset & duration of clinical effects
Time to onset of action is dependent on the route of administration:
- 10-15 minutes following intravenous administration.2,4
- 30-40 minutes following intramuscular administration.2,4
In healthy animals the duration of action of acepromazine is approximately 6 hours, with the effects starting to wane after 3-4 hours.3 In debilitated or hypothermic patients the duration of action may be extended.
The main clinical effects of acepromazine are:
- Mood altering and calming
- At low doses: Tranquillisation (indifference) and anxiolysis (with minimal hypnosis, narcosis or marked sedation). 2,3,4
- Sedation at higher doses. Initially dose dependent, plateauing at higher doses with no further intensification of sedative activity but with an increase in side-effects and duration of action.2,3,4 Murrell (2007) suggests doses greater than 0.05mg/kg have no additional sedative activity.4
Animals administered acepromazine should be handled quietly and left undisturbed. Sedation may be temporarily overcome by stimulation and animals may rouse or become excitable if handled. For this reason, acepromazine is commonly combined with an opioid (neuroleptanalgasia) to improve the quality and reliability of sedation, and to provide analgesia.2,3
3. Dose sparing
Acepromazine may potentiate the central nervous system depression caused by other sedatives/anaesthetics resulting in a dose sparing effect.3
4. Cardiovascular system
a. Peripheral vasodilation & hypotension
Antagonism of the α1 adrenoceptors and depression of the central & peripheral sympathetic nervous systems results in peripheral vasodilation and hypotension. This is normally well tolerated in healthy animals.2,3 An increase in heart rate is occasionally seen in response to the hypotension, although bradycardia may also occur.3
The use of acepromazine in animals with cardiovascular disease or hypovolaemia should be carefully considered as the vasodilation may result in cardiovascular collapse.2
The management of acepromazine-induced hypotension is problematic. Adrenaline is contraindicated: Following acepromazine administration (α1 receptor antagonism) adrenaline will preferentially activate β2 adrenoceptors and cause additional vasodilation and hypotension. Dugdale (2010) suggests the use of an α1 agonist e.g. phenylephrine and fluid therapy to manage acepromazine induced hypotension, although Sinclair & Dyson (2012) suggest crystalloids may result in further vasodilation.5
Phenothiazines may potentiate the cardiovascular depressive effects of other agents.
b. Syncope, giant breeds and Boxer dogs
The hypotension and possible bradycardia following the administration of acepromazine can lead to cardiovascular collapse and fainting, particularly in brachycephalics and some Boxer dogs.2,3
Giant breeds are often considered to be more sensitive to the cardiovascular effects of acepromazine, possibly due to allometric scaling, and therefore metabolic body size may be a more suitable determinant for dose selection.3
Acepromazine has long-lasting effects which are not antagonisable, and its administration should therefore be avoided if hypotension or cardiovascular compromise are present or anticipated.2
c. Anti-arrhythmic effects
Acepromazine is considered to impart an anti-arrhythmic action via three suggested mechanisms: Antagonism of the α1 adrenoceptors in the heart; a reduction in overall sympathetic activity; reduced conduction velocity in cardiac muscle cells via membrane stabilisation.2,3 The antiarrhythmic effects of ACP are of unknown relevance in small animal practice.2
5. Body temperature
Following Acepromazine administration animals should be vigilantly monitored for the changes in body temperature that may occur as a consequence of peripheral vasodilation and depression of the thermoregulatory centre. Hypothermia may reduce drug metabolism, increase anaesthetic recovery time and affect immune and cardiovascular function. Therefore, careful measures to prevent or reduce heat loss should be taken.2,3,4
6. Respiratory effects
Popovic et al (1972) reported that clinical doses of acepromazine administered to dogs and cats had little or no influence on respiratory function and had a calming influence on patients with airway disease or dysfunction.6 However, the effects of acepromazine are long-lasting, may cause relaxation of the pharyngeal muscles compromising airway function and, in laterally recumbent patients experiencing excessive sedation, may result in an inability to maintain a patent airway.2
Phenothiazines reduce the sensitivity of the respiratory centre to the stimulatory effects of carbon dioxide resulting in a slight reduction in respiratory rate. However, in healthy animals, the tidal volume remains relatively stable (or slightly reduced) and there is little change to blood gases and minute volume.3
At clinical doses in healthy animals ACP has little overall effect on the pulmonary system. Nevertheless, at higher doses respiratory depression can occur.2
Acepromazine may potentiate the respiratory depressive effects of some opioids2,3 and other sedative/anaesthetic agents.
7. Anti-emetic effects
Dopamine activity in the chemoreceptor trigger zone of the medulla oblongata is inhibited by phenothiazines resulting in depression of the vomiting centre.7 This produces a mild anti-emetic effect which is particularly useful for reducing the nausea and vomiting associated with some opioids (and possible α2-agonists).3 In a study reported by Valverde et al (2004), when ACP was administered at least 15 minutes prior to an opioid known to induce emesis (morphine) there was a reduction in the incidence of vomiting from 75% to 25%.8
Although Acepromazine has anti-emetic properties, it is not effective for directly treating motion sickness (caused by stimulation of the vestibular system), although the anxiolytic action may reduce the incidence of nausea/vomiting.3
8. Acepromazine and anti-histamine effects
The H1 receptor depressive action of acepromazine causes a mild anti-histamine effect.3 Acepromazine administration is therefore not recommended prior to intradermal skin allergy testing.2,3
9. Seizure threshold
There is no current clinical data to suggest acepromazine has a detrimental effect on animals with a history of seizures, or that it is contraindicated in animals undergoing myelography.2,3 Indeed, acepromazine was historically used as an anticonvulsant for the treatment of metaldehyde poisoning. In a series of canine myelograms reported by Drynan et al (2012) there was no difference in the incidence of seizures in animals that received acepromazine + methadone premedication when compared to a group that received methadone alone.9
10. Spleen, PCV and haemoglobin
Splenic enlargement, via relaxation of the capsule, results in sequestration of erythrocytes and platelets. Consequently, a decreased packed cell volume (PCV) and haemoglobin concentration are commonly observed following the administration of acepromazine.10 In a study performed by Sutil et al (2017) PCV, red blood cell count and haemoglobin concentrations started to decrease 15 minutes after acepromazine administration and had not returned to baseline levels by the conclusion of the study period (12 hours). An 18% reduction in PCV was reported in this study. 11
11. MDR1 mutants
In a 2016 paper by Deshpande et al, intravenously administered acepromazine resulted in more profound sedation with a longer duration of action in MDR1 mutant animals when compared to normal controls.12 In such animals the dose of acepromazine should be reduced or an alternative product considered.
Summary of Acepromazine
• Depression of the CNS via antagonism of D1, D2, α1, muscarinic & H1 receptors.
• Readily crosses the blood-brain barrier & placenta.
• Liver metabolism. Excretion via bile & urine.
• Tranquillisation & anxiolysis at low doses.
• Sedation at higher doses. Sedation plateaus/increased side effects/increased duration of action at higher doses.
Following administration handle patients quietly and minimise stimulation to reduce the possibility of arousal/excitement.
• Onset: 10-15 minutes (intravenous); 30-40 minutes (intramuscular)
• Long duration of action. Approximately 6 hours in healthy patients. Clinical effects begin to wane after 3-4 hours.
• Not analgesic.
• Combine with opioid to improve quality & reliability of sedation & provide analgesia.
• Dose sparing effects on other CNS depressants.
• Minimal respiratory effects in healthy animals although higher doses may cause respiratory depression.
• Hypotension via peripheral vasodilation and depression of SNS. Usually well tolerated in healthy animals.
• Syncope in some Boxer dogs and brachycephalics.
• Hypothermia via peripheral vasodilation and depression of thermoregulatory centre. Monitor regularly and manage accordingly.
• Potentiation of cardiovascular and respiratory effects of the other CNS depressants
• Mild anti-emetic.
• Mild anti-histamine. Avoid administration prior to intradermal skin testing.
• Splenomegally & reduced PCV & Hb.
• Giant breeds “more sensitive”. Select dose based on metabolic body size. Reduce dose.
• MDR1 mutants. Reduce the dose or administer an alternative product.
• Not antagonisable.
Originally published: Thursday, 11th October 2018
1. Collard JF & Maggs R (1958). Clinical trial of acepromazine maleate in chronic schizophrenia. BMJ, 1452-1454
2. BSAVA Manual of Canine & Feline Anaesthesia & Analgesia. 3rd Edition. (2016)
3. Dugdale A (2010). Veterinary Anaesthesia: Principles to Practice.
4. Murrell J (2007). Choice of premedicants in cats and dogs. In Practice 29, 100-106
5. Sinclair MD & Dyson DH (2012). The impact of acepromazine on the efficacy of crystalloid, dextran and ephedrine treatment in hypotensive dogs under isoflurane anesthesia. Veterinary Anaesthesia and Analgesia 39, 563-573
6. Popovic NA, Mullane JF & Yhap EO (1972). Effects of acetylpromazine maleate on certain cardiorespiratory responses in dogs. American Journal of Veterinary Research 33, 1819-1824
7. Lorenzutti AM, Martin-Flores M, Litterio NJ, Himelfarb MA & Zarazaga MP (2015). Evaluation of the antiemetic efficacy of maropitant in dogs medicated with morphine and acepromazine. Veterinary Anaesthesia and Analgesia 43, 195-198
8. Valverde A, Cantwell S, Hernandez J, Brotherson C (2004). Effects of acepromazine on the incidence of vomiting associated with opioid administration in dogs. Veterinary Anaesthesia and Analgesia 31, 40-45
9. Drynan EA, Gray P & Raisis (2012). Incidence of seizures associated with the use of acepromazine in dogs undergoing myelography. Journal of Veterinary Emergency and Critical Care 22, 262-266
10. Dyson DH, Maxie MG & Schnurr D (1998). Morbidity and mortality associated with anesthetic management in small animal veterinary practice in Ontario. J Am Anim Hosp Assoc 34, 325-335
11. Sutil DV, Mattoso CRS, Volpato J et al (2017). Hematological and splenic Doppler ultrasonographic changes in dogs sedated with acepromazine or xylazine. Veterinary Anaesthesia & Analgesia 44, 746-754
12. Deshpande D, Hill KE, Mealey KL, Chambers JP & Gieseg MA (2016). The effect of the canine ABCB1-1 mutation on sedation after intravenous administration of acepromazine. Journal of Veterinary Internal Medicine 30, 636-641
Paper summary: Heated intravenous fluids alone fail to prevent hypothermia in cats under general anaesthesia.
In this summary of a paper by Jourdan et al (2017) we examine the common practice of warming intravenous fluids and the effect on patient temperature.Read On...
This summary of a publication by Panti et al., examines the effect of orally administered omeprazole on gastro-oesophageal reflux in the anaesthetised dog.Read On...
In this paper we explore perceptions and opinions of Canadian pet owners about anaesthesia, pain and surgery in small animals.Read On...
How can a Veterinary version of the ASA Physical Status Classification help you achieve safer anaesthesia? To find out how watch our webinar.Read On...
This scientific paper assessed whether the American Society of Anesthesiologists (ASA) Physical Status Classification correlated with the risk of anaesthetic death in dogs and cats.Read On...
This is our third product launch this year, and the latest addition to our anaesthesia and analgesia portfolio, Methadyne, contains 10mg/ml methadone as its active ingredient. It can be administered for analgesia of moderate to severe pain in dogs and cats, to provide neuroleptanalgesia, and as part of a patient’s premedication protocol prior to general anaesthesia.Read On...
A retrospective comparison of two analgesic strategies after uncomplicated tibial plateau levelling osteotomy in dogs.
In this review we summarise a publication by Bini (2018) examining two protocols for the administration of methadone following TPLO surgery in dogs.Read On...
In this article we have identified the key clinical peer reviewed papers to support the use of Alfaxan for maintenance of Anaesthesia in Cats and Dogs.Read On...
Paper summary: Effect of benzodiazepines on the dose of alfaxalone needed for endotracheal intubation in healthy dogs
This paper examined whether a benzodiazepine, administered as a co-induction agent with alfaxalone, improved endotracheal intubation, and reduced the dose of alfaxalone, in the dogRead On...
In this article we examine why methadone could be considered the analgesic of choice for many of our patients and understand its importance in modern veterinary medicine. The article includes a link to a downloadable summary sheet.Read On...
This study looks at the effects of three methadone doses combined with acepromazine on sedation and some cardiopulmonary variables in dogs.Read On...
We have extended our anaesthesia and analgesia portfolio with the launch of AceSedate®. Containing the tried and trusted, long-acting sedative agent acepromazine as its active ingredient, AceSedate can be used for the premedication, sedation and tranquilisation of cats and dogs.Read On...
Caesarean Section Survival Guide. Part 2: Anaesthetic Protocol Selection & Peri-operative Considerations.
In this second instalment of the 2-part article, we explore premedication, induction, maintenance & monitoring, recovery and analgesia for the Caesarean section patient.Read On...
In the first instalment of this 2-part review Karen examines the physiological changes that occur during pregnancy and how those adjustments can affect the selection of anaesthetic protocols for the increasingly common Caesarean section.Read On...
No leeway for the spay: A comparison between methadone and buprenorphine for perioperative analgesia in dogs undergoing ovariohysterectomy.
This recent paper compares post-operative pain scores and requirement for rescue analgesia following premedication with methadone or buprenorphine, in combination with acepromazine or medetomidine, in 80 bitches undergoing ovariohysterectomy.Read On...
Cardiac arrest in dogs and cats is, thankfully, relatively rare. However, when it does happen it can have devastating consequences for the animal, owner and the veterinary team. This study examined the common causalities leading up to a cardiac arrest with the aim of changing protocols to improve outcomes.Read On...
In this article, Carl focuses on the benefits of introducing a safety checklist in practice to reduce patient morbidity, mortality and to improve communication between members of the veterinary team. The article contains links to the AVA safety checklist as well as a link to a customisable list that you can adapt to your practice needs.Read On...
The effects of hypothermia are very far reaching throughout the peri-anaesthetic process. In this article, James takes us through the interesting mechanisms of body cooling and warming, the clinical relevance of hypothermia and what we can do to prevent it.Read On...
All patients are exposed to the risks associated with general anaesthesia. Continuously monitoring anaesthetised patients maximises patients safety and wellbeing. In this article, Dan takes us through the common monitoring techniques that provide information about the cardiovascular status of your patient.Read On...
Despite being widely recognized in humans, postoperative nausea and vomiting (PONV), and the role of maropitant in reducing inhalational anaesthetic requirements have been poorly documented in dogs. This recent study evaluates PONV and isoflurane requirements after maropitant administration during routine ovariectomy in bitches.Read On...
Little information is available about the effect that different doses of medetomidine and butorphanol may have when using sevoflurane for maintenance of anaesthesia in dogs. This recent study evaluates heart rate and median sevoflurane concentration required at different dose rates.Read On...
In this second article of the capnography series, James provides a guide to a few of the most common traces that you will encounter during surgery. Scroll to the end of the article to download a printable capnography cheatsheet.Read On...
Pain, what a Pain! (Part 2) – Practical Tips On How To Perform Dental Nerve Blocks In Companion Animal Practice
In this second article of the Pain, what a Pain! series, Dan takes us through the LRA techniques associated with dental and oral surgery. In this article, you will find practical tips and pictures on common dental nerve blocks as well as safety concerns to consider.Read On...
This recent retrospective study looks at the cases of 185 pet rabbits admitted for sedation or general anaesthetic and evaluates the incidence and risk factors contributing to peri-anaesthetic mortality and gastrointestinal complications.Read On...
Pain, what a Pain! How Locoregional Anaesthesia can Improve the Outcome and Welfare of Veterinary Patients (Part 1)
In this first article out of a series of two, Dan takes us through an introduction and practical tips for appropriate local anaesthesia delivery. Find out why these anaesthesia techniques, that are well recognised in human medicine, have seen an increase in popularity in veterinary medicine over the recent yearsRead On...
Read the highlights of a recently published research paper that evaluates cardiorespiratory, sedative and antinociceptive effects of dexmedetomidine alone and in combination with morphine, methadone, meperidine, butorphanol, nalbuphine and tramadol.Read On...
This study evaluates the effectiveness of two methods of preoxygenation in healthy yet sedated dogs and the impact of these methods on time taken to reach a predetermined haemoglobin desaturation point (haemoglobin saturation (SpO2) of 90%) during an experimentally induced period of apnoea.Read On...