April 2023

By Debbie Martin, KPA CTP, Faculty Emeritus, LVT, Veterinary Technician Specialist in Behavior, Elite Fear Free Certified® Professional, TEAM Education in Animal Behavior, LLC, Spicewood, TX

Basic behavior pharmacology for veterinary technicians and nurses

In this VETgirl online veterinary continuing education blog, Debbie Martin, KPA CTP, Faculty Emeritus, LVT, VTS (Behavior) reviews all you need to know about some common behavioral medications used in dogs and cats in veterinary medicine! Read on for a basic behavior pharmacology review for veterinary technicians and nurses.

As a veterinary technician, it is important to recognize potential side effects and contra-indications of behavioral medications patient’s in your care may be taking. This is important not only for our safety when working with animals, but also so we can advise pet owners on possible side effects. Although this article will not explore what medications to use for specific behavioral conditions, recognizing when behavioral medications might be indicated as part of a complete behavioral treatment plan is important. Medication alone will not teach a pet how to change their behavior. However, it may lower the pet’s anxiety/stress level enough to help facilitate the learning process. Fear and anxiety can impede the animal’s ability to learn, hindering behavior modification and training.

After a behavior diagnosis, the following are circumstances when behavioral medications might be considered by a veterinarian:

1. The human-animal bond is waning, broken, or severely damaged due to the problem behavior and rapid results are needed. The owner might be afraid of the pet, seeking help as “a last resort,” or contemplating euthanasia or re-homing.

2. The pet is suffering from an emotional or learning disorder associated with fear, anxiety, and/or stress. The pet may be exhibiting panic, phobia, over-arousal, hyperexcitability, impulsiveness or aggression as a result of fear, anxiety, frustration, and/or conflict.

3. The health and welfare of the pet is compromised. This can include physical health, cognitive health, longevity, and emotional well-being.

puggle playing

Image by Artur Pawlak from Pixabay

The following are conditions when behavioral medications might be considered by a veterinarian:

1. Aggression: If there are multiple triggers, triggers cannot be identified or avoided, the threshold for aggression is low, or a non-graduated response occurs, medication might be indicated. There are no FDA approved medications for treating aggression.

2. Fear, Anxiety, Panic, and/or Phobia: When there are multiple stimuli, the stimuli cannot be avoided, the intensity cannot be controlled, a non-stressful starting point cannot be determined, or self-injurious behaviors are occurring, medication might be indicated.

3. Repetitive, Hyperkinetic, Stereotypic, or Compulsive Behaviors: Medication might help decrease the frequency/intensity of the behaviors so behavior modification is possible or medication might decrease the frequency/intensity of conflict behaviors that have the potential for developing into a compulsive behavior (usually from frustration).

4. Cognitive Dysfunction: Medications might slow the progression of cognitive dysfunction. Medications can also be used to treat symptoms associated with cognitive dysfunction syndrome.

5. Other: Little progress is being made with an appropriate behavior modification plan only for the above conditions or circumstances.

CLASSES OF MEDICATIONS
There are a variety of pharmaceuticals and supplements available to treat behavioral disorders in pets. This article will focus on some of the more commonly used behavior medications in a veterinary behavior specialty clinic. Generally, there are medications that are used as the primary or mainstay daily medication and there are situational or event medications that are used on an as needed basis. All medications are considered off-label use for treating behavior conditions in dogs and cats unless FDA approval for a specific condition is noted.

Common Primary Mainstay Medications
Mainstay medications generally take several weeks to take full effect and must be given at least daily. Classes of common mainstay medications are selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs).

Selective Serotonin Reuptake Inhibitors (SSRIs)
Examples include fluoxetine (Prozac® or Reconcile®), paroxetine (Paxil®), and sertraline (Zoloft®). Reconcile® is FDA approved for treating separation anxiety in dogs. SSRIs increase the level of serotonin in the synaptic cleft. It can take 4 to 6 weeks or longer for full effect. Potential side effects include GI (decreased appetite, nausea, vomiting, diarrhea, constipation), urinary retention (especially with paroxetine), behavioral calming/lethargy, paradoxical anxiety/agitation/aggression, dilated pupils.

Tricyclic Antidepressants (TCAs)
Examples include clomipramine (Clomicalm®- FDA approved for treating separation anxiety in dogs) and amitriptyline (Elavil®). TCAs work variably on serotonin and other neurotransmitters. The time to effect is usually 3 to 4 weeks or longer. They are best if given twice a day rather than once a day because of their half-life. Some potential side effects include GI signs, such as nausea, vomiting, diarrhea, and/or constipation, urinary retention, antihistamine effects, such as sedation, dry mouth, and/or dry eye. Behavioral side effects could include calming/lethargy, decreased appetite, and increased agitation/aggression.

Monoamine Oxidase Inhibitor (MAOI)
In veterinary behavioral medicine selective monoamine oxidase type B inhibitors are used. Examples include selegiline, L-deprenyl or Anipryl®. Anipryl is an FDA approved medication for treating cognitive dysfunction syndrome in dogs. It is also used to treat pituitary dependent hyperadrenocorticism in dogs. The time to effect is 4 to 8 weeks. Potential side effects include GI (nausea, vomiting, diarrhea), increased activity (should be given in the morning!), agitation, restlessness, and/or disorientation.

jumping-dog

Image by michel kwan from Pixabay

SEROTONIN SYNDROME
Serotonin syndrome is a group of symptoms related to serotonin excess and/or toxicity. The condition may occur following routine administration of serotonergic medications in certain patients (typically patients receiving high dosages), with an acute overdose of a serotonergic drug, or with combined administration of several serotonin modulating drugs, herbals, and/or supplements. Symptoms of serotonin syndrome fall in three categories:

1. Altered mental status or mood (confusion, irritability, agitation, restlessness, and anxiety)
2. Neuromuscular hyperactivity (tremors, shivering, muscle rigidity, muscle spasms, and tonic-clonic seizures)
3. Autonomic hyperactivity (rapid heartbeat, rapid respiration – panting, high blood pressure, sweaty paws, and fever)

Symptoms of serotonin syndrome, in order of appearance as the condition worsens, include: 1) confusion, mydriasis (dilated pupils), diarrhea, 2) restlessness to extreme agitation, 3) tremors, hyperreflexia, ataxia (loss of coordination), autonomic instability with possible rapid fluctuations of vital signs (heart rate, blood pressure), 4) hyperthermia, uncontrollable shivering, neuromuscular rigidity, myoclonus, seizures, 5) delirium, coma, status epilepticus, cardiovascular collapse, and death.

Owners should be made aware of signs of serotonin syndrome especially if medications which effect serotonin are being combined. In the case of symptoms related to combined administration of serotonin modulating drugs, discontinuation of offending serotonergic agents should be implemented as soon as symptoms are recognized. Supportive therapy may be needed depending on the severity of the symptoms. MAOIs have more possible medication interactions than other behavioral medications.

SITUATIONAL EVENT MEDICATIONS
These are medications that might be used on an as needed basis. For example, a dog that has a fear of thunderstorms might be on a primary mainstay medication and then have a situational event medication to be administered just prior to storms. Sometimes these medications are also used as adjuncts or augmentation strategies (given routinely, or at least daily) combined with a primary mainstay medication. There are numerous medication options, we will focus on some of the most common ones such as alpha-2 agonists, benzodiazepines, gabapentin, and trazodone. It is recommended that situational event medications are tested in a non-stressful environment prior to their use to address an impending fear-inducing situation. This allows the owner to assess the time to effect, duration of action, and side effects.

Alpha-2 Agonists
Clonidine (Catapres®) is an oral alpha-2 agonist that comes in a tablet form. The time to effect is 1 to 2 hours and the duration of effect is 4 to 6 hours. While generally well tolerated in dogs, side effects can include dose related sedation, uncommon paradoxical agitation, or rare increased sound sensitivity. Other potential side effects are vomiting, dry mouth, constipation, transient increased blood glucose, low blood pressure, and slow heart rate.

Sileo® (dexmedetomidine oromucosal gel) is FDA approved to treat noise aversions in dogs. It is an oromucosal gel. The time to effect is 30 to 60 minutes and duration of effect is 2 to 3 hours. Side effects may include vomiting, pale mucous membranes, and sedation. Gloves should be worn when applying and owners should be coached on how to dose the medication to avoid an accidental overdose. Here is a video link that shows the process: https://www.youtube.com/watch?v=lXHTmKYMRdc

Alpha-2 agonists should be avoided in dogs with severe cardiovascular, respiratory, liver or kidney diseases or are otherwise compromised. Limited information regarding the oral use of alpha-2 agonists in cats is available.

Benzodiazepines
Benzodiazepines are anxiolytics and they stimulate the major inhibitory neurotransmitter, GABA. Examples include diazepam (Valium®), alprazolam (Xanex®), lorazepam (Ativan®), and clonazepam (Klonopin®). At the time of writing this article, a new medication has been approved by the FDA for treating noise aversions in dogs, but it is not yet available in the United States. It is imepitoin (Pexion™); an anticonvulsant used in Europe to treat epilepsy in dogs. Imepitoin acts as a low affinity partial benzodiazepine receptor agonist. Dosing should begin several days prior to the noise event.

Benzodiazepines given orally usually take 1 to 2 hours to take effect. Duration varies depending on the medication. Alprazolam duration is around 4-6 hours and clonazepam is 8-12 hours. Side effects might include an increased appetite, disinhibited aggression, muscle relaxation, wobbliness, sedation, amnesia, and paradoxical excitation. Benzodiazepines should be used with caution in patients with aggression. Oral diazepam use in cats should probably be avoided due to the risk for acute hepatic necrosis. Because time to peak plasma concentrations of lorazepam is 12 hours in cats, it might need to be given routinely once or twice a day as time to effect might be prolonged and it is difficult to schedule on an as needed basis for less predictable situational events.

Gabapentin
Gabapentin is an anticonvulsant medication and also used for treating neuropathic pain. It is also an anxiolytic. Although its mechanism of action is not fully understood, gabapentin is thought to decrease the release of the excitatory neurotransmitter glutamate. Time to effect is usually 2 to 3 hours and duration of effect may be 6 to 8 hours. There are few side effects, but they can include slightly increased appetite and at higher dosages sedation, incoordination, and urinary incontinence (rare). There is a wide dosage range on this medication, and it is often used to help facilitate Fear Free® veterinary visits for dogs and cats.

Trazodone
Trazodone is a SARI (serotonin antagonist and reuptake inhibitor). Trazodone is weakly serotonergic. Although often combined on an as needed basis with other primary mainstay medications that also effect serotonin, owners should be made aware of the potential risks of serotonin syndrome. When used as needed, it is likely to result in sedation. Routine use as an adjunct medication or augmentation strategy results in serotonin increases after 3 to 4 weeks. When used as a situational or event medication duration is maybe 6 to 12 hours. Given on an empty stomach will result in a faster onset of action yet increase the potential for gastrointestinal side effects. Side effects might include vomiting, diarrhea, sedation, and irritability/anxiety/aggression.

Acepromazine
Historically, oral acepromazine has been used routinely in veterinary medicine with dogs who are difficult to handle. However, it is important to realize that acepromazine is at best a chemical tranquilizer which has poor anxiolytic effects. Effects are quite variable when administered orally. Acepromazine impairs learning and can result in profound sedation lasting up to 24 hours. It may produce paradoxical excitation, increased aggression, and loss of bite inhibition. Acepromazine should never be used alone to treat fear, anxiety, stress, or aggression.

CONCLUSION
As veterinary technicians we need to be aware of the potential side effects of behavioral medications for the safety of our patients, clients and ourselves. Medications are only effective if the client can safely administer them to their pet. Therefore, it is important for veterinary technicians to be able to coach owners on how to safely and in a non-stressful manner administer medications. See the provided recommended resources for more information.

RESOURCES
Martin D, Shaw J editors. Canine and Feline Behavior for Veterinary Technicians and Nurses, 2nd edition. Wiley-Blackwell Publishing. 2023. Available for preorder at https://www.wiley.com/en-us/Canine+and+Feline+Behavior+for+Veterinary+Technicians+and+Nurses%2C+2nd+Edition-p-9781119765400

Video regarding giving medications to pets: https://www.fearfreehappyhomes.com/video/giving-medications-to-your-pet-putting-the-treat-into-treatments/

Video detailing oral and topical administration of medications: https://www.fearfreehappyhomes.com/video/administering-oral-and-topical-medications/

Please note the opinions and views of this author and not directly or indirectly endorsed by VETgirl.

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