Acepromazine and Chlorpromazine
Terry Kelley CVT, CPDT
Acepromazine (Promace ®) and Chlorpromazine are two commonly used phenothiazine tranquilizers in veterinary clinics. Their primary method of action is as a Dopamine antagonist, which suppresses both normal and abnormal behavior, including a decrease in coordinated locomotor responsiveness. They are not anti-anxiety drugs and do not provide any analgesia (pain relief).
Ace has a variety of uses (ex: anti-nausea, anti-emetic, decrease itching due to allergies) but is routinely used to sedate fearful or aggressive dogs and cats prior to veterinary visits or as an at-home remedy for noise phobias (thunderstorms, fireworks).
Chlorpromazine (Thorazine ®) is almost identical to Acepromazine and is just as potent. When called Thorazine, it elicits a much stronger reaction from audiences as it was the first antipsychotic to be commonly used in the 1950s and 1960s. Chlorpromazine is used in veterinary medicine as an antiemetic (anti-vomiting and nausea) and a tranquilizer.
Research has shown these drugs functions primarily as chemical restraints without affecting the animal’s emotional behavior. While under the effect of Ace, the animal still has a very strong fear, anxiety, avoidance or arousal response, but it does not physically display these reactions and is less able to react. The dog or cat appears calm and relaxed but mentally is lucid and still having an intense emotional reaction to its surroundings. Ace is a dissociative agent and prevents the patient from understanding his environment in a logical manner. So, the actual fear level of the animal is increased. Compounding the situation, the animal is being restrained and it makes a negative association with the entire experience.
According to veterinary behaviorist Dr. Vint Virga, DVM, ACVB, this is one of the reasons, why clinics are seeing so many animals, who have been previously given Ace, continuing to be fearful during veterinary exams. It becomes a never-ending cycle of chemical restraint and continued fear for the patient. Another potential danger from using Ace, is their fear may intensify to a level, where they override the physiological effects and can physically break through the chemical restraint. The animal seems ‘out of it’, but is having an intense emotional reaction and bites. Dr. Virga has seen serious trauma (typically to faces) to veterinary staff, when trying to restrain an animal on Ace and break-through occurs. He has also observed that clients have an overall negative response to the use of Ace for their pet and speak unfavorably of it. Owners leave with a highly sedated animal, which is ataxic or immobile and the drug effects may require up to 12 hours to disappear.
Ace is appropriate as a tranquilizer for the happy, jubilant, bouncing Laborador, who has no anxiety, stress or fear. These dogs simply need to be slowed down so an examination, ear swab, mouth exam can be performed. Ace is also appropriate when used as a pre-operative agent in a balanced anesthesia, with other drugs (ex: atropine) as it helps to lower the overall amount of anesthesia required and has antidysrhythmic (prevents arrhythmia, erratic heart rhythm) effects.
Side effects of Ace include (but are not limited to): increased noise sensitivity and startle response, decreased respiration, bradycardia leading to cardiovascular collapse (dogs and cats), hypotension, erratic thermoregulation leading to hypothermia or hyperthermia, a decrease in seizure thresholds, muscle spasms, excitation and sudden aggression (break-through response), absent pulse, unconsciousness. The duration of Ace also varies in each individual, thus making the fearful or aggressive patient even more unpredictable. Note: Ace should never be used as a tranquilizer for animals traveling due to the erratic thermoregulation effects (inability to control body temperature in cold or hot conditions).
Veterinary behaviorists now prefer the use of Benzodiazapenes such as Diazepam (Valium) and Alprazolam (Xanax) as alternative drugs which affect the central nervous system and actually reduce anxiety, stress and fear. They have a calming and amnesic effect on the patient and their fast acting effects begin within 30 minutes to 2 hours after oral administration. The dog or cat is sedated, its muscles are relaxed and their fear and anxiety is greatly reduced or eliminated.
Ace, used to sedate fearful animals, is no longer appropriate. Its use should be discontinued. We, as owners, need to advocate for our pets and do what is in their best interest both physically and emotionally. So, if your veterinarian wants to prescribe Acepromazine or Chlorpromazine to ‘calm’ your fearful Fido or Fluffy, politely decline the offer and ask for one of the newer alternative medications.
For veterinarians who want to research the effects of Acepromazine and Chlorpromazine drugs, two very good reference books are "The Handbook of Behavior Problems of the Dog and Cat" by Landsberg, Hunthausen, and Ackerman, and "Veterinary Psychopharmacology" by Sharon Crowell-Davis.
*The author would like to thank Dr. Virga for providing detailed information on Acepromazine and Chlorpromazine. Dr. Virga is a board-certified Diplomate of the American College of Veterinary Behaviorists. He is currently the president of Behavioral Medicine for AnimalsSM. Dr. Virga currently attends companion animal cases East Greenwich and zoo animal cases on site at zoological gardens and wild animal parks. His special interests include stereotypic behaviors, self-directed behaviors, and environmental and social enrichment for captive wildlife.
Of course, obtaining another pet is not something one should jump into hastily, and, depending on your anxious dog's history, a fellow canine companion may not be able to help. Other solutions are available, however.
Separation anxiety is rapidly becoming the most treatable canine behavioral disorder, probably in part due to the introduction of Clomicalm, a brand name for the drug clomipramine hydrochloride, manufactured by Novartis Animal Health U.S. Inc., of Greensboro, N.C. Clomicalm is the first such medication approved for canine use by the U.S. Food and Drug Administration; it is engineered specifically for the treatment of separation anxiety.
Prior to clomipramine's approval, other drugs had been used to treat separation anxiety. The following. as explained by Patricia Cahill, D.V.M., outlines some of those drugs and how they worked:
Acetyl promazine (acepromazine) is a tranquilizer that commonly is prescribed to blunt the behavior, but it doesn't actually change the anxiety; the dog still feels stress, but the drug reduces its ability to respond to the stress actively. Acepromazine would be inappropriate for treating separation anxiety because it does nothing to enhance learning or reduce the actual anxiety. It is fine for use in the treatment of short-term anxiety, such as a stressful visit to the groomer, unless you hope to recondition your dog to learn better self-control in such situations. Basically it works as a psychological crutch rather than a lifeline to treat the underlying problem; i.e., it is restraining rather than retraining. It can be effective, however, in reducing the symptoms of anxiety that might otherwise lead some owners to give up on their out-of-control pets.
Alprazolam (Xanax®) is a benzodiazepine tranquilizer typically prescribed to humans suffering from anxiety, and diazepam (Valium®) is another drug from this family. Both have been used effectively to help control canine anxiety. The downside in using these drugs is while they do decrease anxiety they do not enhance learning; therefore, once the dog stops taking the drugs any changes made in handling and environment may not have helped it gain better, independent, drug-free control.
Amitriptyline (Elavil®), an anti-depressant, is in the same family as clomipramine; it has been used effectively in the treatment of many separation anxiety cases. It is comparatively inexpensive and relatively free from side effects when used properly. It is a human drug, however, and is not specifically approved for animal use; as long as owners know this drug has not been clinically tested for animals, it can be used with the owners' consent. Anti-depressants, in addition to having a calming effect, increase the brain chemicals associated with learning. While on the drug, the dog can learn new behaviors that are retained once the drug no longer is used.
Fluoxetine (Prozac®) is another anti-depressant that has been used to treat separation anxiety. People have become very aware of this drug in recent years due to its effectiveness in treating a broad spectrum of human psychiatric conditions. Its effective use in the treatment of both canine compulsive disorders and anxiety disorders makes it another prescribed medication for the treatment of separation anxiety. It is not label-approved for use in dogs, however, and can be very expensive, especially with large-breed dogs.
Clomipramine, or Clomicalm, effectively relieves anxiety and doesn't dull the dog's personality or memory. In fact, it actually may enhance the dog's ability to learn more positive behaviors and responses to stressful stimuli. During FDA testing, 47 percent of the dogs treated with Clomicalm improved compared with 29 percent given a placebo during the first three weeks of treatment. By the end of two months, 65 percent of dogs receiving both the drug and behavioral therapy had improved, while 55 percent of dogs receiving behavioral therapy alone improved. Drugs certainly are not the only or even the most important tool in treating separation anxiety, but Clomicalm seems to make an important difference when combined with behavioral therapy, especially in the early stages of treatment. Clomicalm perhaps is the most exciting new drug on the market because it offers hope to desperate owners who have been held hostage by their dog's condition. Clomicalm is not a wonder drug, however, and the problem will not be resolved without behavioral modification for both the anxious dog and its family. The one possible negative side effect of the recent publicity Clomicalm has received is that people might view it as a "magic pill" offering a "miracle cure" for separation anxiety. People might look to the medication for immediate relief from their dogs' stressful behavioral symptoms, but once the acute problem has been resolved, they might not go the distance by following through with behavioral therapy.
Drug therapy is not always necessary or even appropriate in treating every separation anxiety case, many dogs suffering from this condition will respond to behavioral therapy alone, without needing drugs. But for some dogs, medication can provide the scaffolding they require to help keep them glued together until changes in their environment and social relationships enable them to stand more securely on their own four paws. For dogs that harm themselves due to separation anxiety, drug therapy can make the difference between life and death. And in some cases drug therapy calms the owners as much as the anxious dog, although the owners don't actually take the medicine themselves. Just knowing their dog has been given help to decrease anxiety and resulting outbursts allows some owners to leave home without feeling over-whelming anxiety of their own. With the help of anti-anxiety medication, many dogs that otherwise might have been given away or put down get a second chance and some bought time to begin behavioral therapy.
In the News: Tails of Marin
By Carrie Harrington
Fireworks are no fun for pets, so plan ahead
Fireworks displays will illuminate the skies during Fourth of July celebrations. As we enjoy these holiday festivities, it’s important to remember that this can be a very traumatic time for our pets. Loud noises can frighten animals, causing them to panic and even run away from home. In fact, animal shelters across the country report an increased number of lost animal companions after fireworks displays, and Marin County is no exception.
“Every year, dogs and cats bolt from their yards or homes in fear during the holiday festivities,” says MHS animal services director Cindy Machado. “In an attempt to find refuge, some pets become lost or wind up at the Humane Society.” Fortunately, there are steps you can take to ensure a safe and enjoyable holiday for you and your pet. Just follow these simple guidelines.
Keep your pets indoors during fireworks displays. A quiet, sheltered area is best. Close windows and curtains and turn on the TV or radio to help drown out some of the noise. Some animals can become destructive when frightened, so be sure to remove any items that your pet could destroy or that would be harmful if chewed. You’ll find that some dogs will prefer to lay in the bathroom as the small space will buffer the sound better.
Make sure your pets are wearing current identification and tags so that if they do become lost, they can be returned to you promptly. Keep current photos of your pets handy — and make sure the photos show any unique markings.
Never take your dog to a fireworks display. It’s usually hot. There are always large crowds. And the dogs really don’t enjoy it.
Never leave pets outside unattended, even in a fenced yard or on a tether. Pets who normally wouldn’t try to leave the yard may panic and try to escape. Dogs may become entangled in their tethers or hang themselves if they try to leap over a fence. To avoid injury, keep your pets indoors.
Other ways to help your pets
If you know that your pet is seriously distressed by the sounds of fireworks, consult with your veterinarian in advance. Your vet may recommend a fast-acting anti-anxiety medication, such as alprazolam and diazepam (the canine versions of Xanax and Valium), which generally take effect within 20 minutes and last for only a few hours. The key is to give the medications before the noise starts — they are less effective if you wait until the dog is already stressed. You may also need to give an additional dose later, depending on the duration of the noise. Note that, used routinely, these drugs can be addictive.
While the tranquilizer Acepromazine is commonly recommended, according to Whole Dog Journal, it does nothing to decrease the anxiety, but makes a dog unable to react — which can actually make your pet feel worse.
If, despite your best efforts, your pet does become lost, don’t panic. Check inside garages, yards, storage sheds, basements, closets, under cars and in the shrubbery at your home and throughout the neighborhood. The Marin Humane Society can assist you in finding a lost pet. Last year, we received a dozen lost dogs the evening of July 4th. Come to the shelter the next day to check the kennels, fill out a lost pet report and look over the “Found” reports. Download lost animal flyers from our Web site (http://www.marinhumanesociety.org). And check our 24-hour lost animal hotline at (415) 883-4621.
Carrie Harrington is the public relations associate at the Marin Humane Society.
Sep 1, 2004
By: Karen L. Overall, VMD, PhD, Dipl. ACVB
Storm phobias: No other problem is as widespread, as devastating for the animal, and as frustrating for the veterinarian in practice as is the issue of managing animals experience seasonal terror.
The issue of noise and storm phobias and their tendency to be associated with other anxiety disorders was an issue much discussed by me and others at the recent AVMA meetings and the associated behavior meetings. Ironically, as these meetings were wrapping up, a dog I loved very much was dying - because of her terror of storms.
About nine years ago, I obtained a retired show champion Tibetan Spaniel, Susie, for my mother, with the understanding that should my mother predecease the dog, the dog would come to me. During the time that my mother had Susie, the dog became more fearful of storms of all kinds, as are many dogs in the southeast United States.
Whenever my mother would tell me how much Susie had suffered during the most recent storm, I would launch into my speech about how much medication can help, and how important it is to treat these dogs early and often.
Client resistance My mother's response was invariably that drugs were overused. Susie just needed love. My mother would hold her to get through the storm, and Susie was fine, but tired, the next day. It's entirely possible that my mother could or would have taken advice about medication from anyone but me, but this logic is also something that veterinarians in practice tell me they often hear from clients. Surely, I failed to convince the client to avail herself of expertise.
When my mother died, the people who had been fostering Susie for the months when my mother was unable to care for her asked if they could keep her. I had no choice but to acquiesce: they loved her and were in tears at the thought of me taking her away. Again, I mentioned treatment for storms, but their response was that their other little dog was also distressed during storms and they would just sit with her.
The day after the AVMA meetings wrapped up, I answered the phone to hear the voices of Susie's adopted parents. They wanted me to know that there had been a terrible series of storms the night before.
Susie had trouble breathing during the first one. During the second storm — in the middle of the night and in these people's arms - Susie went into cardiac and respiratory arrest and died.
Susie's adopted parents asked me if she had always been so terrified of storms. My response was no; her terror worsened with time and exposure. How could I revisit the drug argument with someone who held a dead dog?
So, for all the pets who suffer, here's the take home message:
Storm and noise phobias are emergencies.
They will only worsen with exposure, and the rate at which they worsen depends on the neurochemistry of the dog and the severity and unpredictability of the storms.
Data talks Data suggest that ~70 percent of all dogs who react profoundly to miscellaneous noises also have storm phobias, and 90 percent of dogs with storm phobias react badly to other noises.
Co-morbidity is the rule: ~70 percent of dogs seen in a clinical setting with noise or storm phobias also have often undiagnosed separation anxiety. Screen for all of these at every visit.
Dogs experiencing fearful noises (e.g. shipping on a plane) as youngsters may be at increased risk for later development of more profound noise or storm phobias.
Dogs who react to storms may not be reacting to the noise: trigger stimuli could include other sounds (wind, rain), darkness, changes in light intensity, barometric pressure changes, ozone changes and changes in human behavior. Any of these can lead to panic and must be treated. The medications that treat phobias also treat panic.
Strategies to treat Treatment not only saves lives, but it means the difference between a life of quality or a life of pain and suffering. Treatment can involve the dreaded behavior modification, but this is one case where drugs are essential and not optional. The rationale for behavioral medication follows.
Alprazolam (Xanax) is my preferred drug of choice for storm and noise phobias, and for all dogs who panic, whether the panic is a solitary diagnosis or a co-morbid one with separation anxiety or other anxiety-related condition. This benzodiazepine (BZ) is considered the classic "panicolytic" drug in human medicine, and has the advantage of a broad dosage range for anxiolytic effects, and a more narrow range for sedation. With diazepam, the pattern is reversed; however, dogs, like people, are incredibly individual in their response to benzodiazepines. Some dogs do better with one of these while other dogs show the reverse patterns. The only drawback to these medications is that they can be addictive and abused by humans, so there is the occasional household in which such medications should not be placed.
The key to treatment for noise phobias and panic is to give the BZ early and often. The half-life of diazepam in dogs is about 5h, and that of its intermediate metabolite, nordiazepam—which is active and highly sedative—is ~3h. The half-life of alprazolam is somewhere in the 3 or 4-6h range but its intermediate metabolite is not sedating, less active, and more directly excreted so you get a more moderate and continuous patterns of anti-anxiety effects. If clients are expecting storms, and if they can get the dose of alprazolam into the dog two hours before hand and the other half ~30 minutes before hand, they can easily achieve a great anti-anxiety effect.
The medication can then be repeated as needed, but clients should allow at least 2h between doses to assess effects. Generally, alprazolam is repeated q.4-6h. This dosage can be used continuously over a period of days or weeks during a profound thunderstorm season. If this scenario ensues, it is best to slowly withdraw the dog from the meds.
Dosages for alprazolam range from 0.01-0.001 mg/kg for dogs and 0.025-0.05 mg/kg for cats who panic (e.g. coming to the clinic). Most people don't think of storm phobias in cats, but they may well occur because cats hide when distressed. We need to treat all of these cats and dogs.
For most average size dogs, dosages in excess of 4 mg/DOG can result in ataxia, and there is one publication stating that this is the maximum daily dosage. Such logic is unrealistic for big dogs, but as with all BZ, clients will need to experiment with the dose to learn the best dosage level for their dogs. Clients need to learn about the potential side effects of different dosages when the dog or cat is not distressed, and about the best dosage level to treat the panic during the experience. For this reason, I recommend a trial run at the estimated dosage when the clients are home and the animal is calm.
If the animal is seriously sedated, the clients need to adjust the dose to a lesser one. If the animal is fine, but sleeps more quickly or more deeply, the dose is a good one as long as the pet awakens without grogginess.
Tips from the pros Here are some tips to consider. Many people prefer diazepam (0.5-2.0 mg/kg po q. 4-6h - dogs; 0.2-0.4 mg/kg po q. 12-24 h - cats) because they swear that no matter how high the dose they cannot get an effect with alprazolam. There are some individuals who have genetic variants of enzymes that metabolize these drugs that can cause extreme effects. However, mostly I think people confuse an anxiolytic effect with a sedative one. And, they only give one or two doses. Instead, if you use alprazolam as discussed and keep giving it to one full dose as needed, the dogs—and cats—begin to learn that they don't have to be so frightened. This formula also works like a charm for dogs who get upset during veterinary visits. So for a 25 kg dog, I'd give 0.125 or 0.25 mg to start (the smallest tablet available is a scored 0.25 mg one) and evaluate the effect. If in 15-30 minutes the dog isn't noticeably calmer, give him more.
Alprazolam is a true panicolytic drug, meaning that it can also stop a panic attack. So if clients find the dog or cat in distress, giving a whole dose and then evaluate what to do 15-30 minutes later can really work because the panic will be lysed within a relatively short period of time.
Cats do better with alprazolam than diazepam because they have a very slow metabolic rate for nordiazepam, the sedating intermediate metabolite of diazepam. Because the intermediate metabolites of alprazolam are hydroxylated, this may be a safer BZ with cats who may be compromised or who are slow metabolizers than is diazepam.
I know that the common "treatment" for storm and noise phobias and veterinary office visits is acepromazine. In truth, I wish this medication would be placed at the far back of a top shelf and used only exceptionally. Acepromazine is a dissociative anesthetic meaning that it scrambles perceptions. Ask yourself if a scrambling of perceptions will make an anxious or uncertain dog worse or better. It's always worse, and we make many if not most dogs more sensitive to storms by using this drug. In part this is also because sensitivity to noise is heightened.
This is a recipe for disaster for these dogs, and, in fact, they learn to be more fearful and more reactive because of these associations. If what you need is sedation - acepromazine can be an acceptable adjuvant, but it makes most of my really fearful and really reactive patients worse, so all sorts of other drug combos can work better and do less harm than is done by the routine use of acepromazine.
Finally, if the dog or cat calms using alprazolam or another BZ, the clients should be encouraged to do four things:
They should ensure that they are treating any co-morbid anxieties (e.g., separation anxiety, generalized anxiety disorder, most aggressions) with an appropriate tricyclic antidepressant or selective serotonin re-uptake inhibitor, plus the chosen BZ.
The clients should not pet the dog or cat and tell him or her that it is okay. The animal knows it's not okay and such contradictory signals, especially in profoundly obedient pets, increase anxiety. Instead, just talk normally to them, and press firmly, or lie next to them without petting. Such behavior provides closeness and allows the pet's muscles to relax without inadvertently rewarding any of the signs of anxiety.
Clients should work with behavior modification designed to teach the dog or cat to relax when there is no problematic stimulus so that they can start to transfer the learned lessons of physical and physiological relaxation to situations that are provocative.
Clients should have a benign, but clear, rule for how animals will be handled if they become upset or panicked. This will help the client, and it will really help the pet. For example, if a sudden storm surprises us in the night, one of us will take our storm phobic dogs from the room in which they sleep, get the alprazolam, give it immediately, and lead them to the spare bedroom where whomever gets up first will sleep with them. This room is better insulated from noise and storm pyrotechnics and is super-well air-conditioned to remove humidity. The process of removing the dogs from their room and giving the medication takes less than 5 minutes. Within minutes of that we are in bed with them, and last week, both were asleep five minutes later. That's not the medication, alone: that's the learning of the pattern that everything will be okay because it has become okay. That's the benefit of the BZ, alprazolam: the dogs can still learn, and if they are physiologically distressed, such distress is chemically blunted so no or little learning occurs about how to become better distressed during the storm. In this case, medication facilitates complex associative learning about how to relax.
I failed Susie by not making treatment with medication a requirement for her adoption to a foster family. So, in memory of Susie, a wonderful, wonderful dog, I offer this column in the hope that other animals cease to suffer because their people stopped fearing drugs.
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