Today's Veterinary Practice

MAY-JUN 2017

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103 MAY/JUNE 2017 ■ TVPJOURNAL.COM FOCUS ON PHARMACOLOGY unstable on stairs or as they move through complex environments). If these effects appear, lowering the dose may ameliorate them. Trazodone, a serotonin antagonist/reuptake inhibitor (SARI), may help the dog to calm its activity level because the main effect of this drug is a slightly sedative one— trazodone increases sleep time, 15–17 and its receptor profile (5-HTA/B antagonist, partial 5-HT 1A agonist) is consistent with this. Panic If the dog is panicking, there are 2 additional suitable choices. The first, alprazolam, can be given before or during the distressing event. In fact, if it is given regularly (usually q12h but up to q6h) before anticipated events, it can raise the threshold for reaction but provide central inhibitory effects, as well as peripheral effects on muscle tension that may accompany and provide a positive feedback response associated with panic. The second choice is dexmedetomidine, which has anxiolytic, sedative, analgesic, and sympatholytic properties. 18 As an oral transmucosal (OTM) gel (Sileo; zoetisus.com ), it has no first-pass effects; instead, it directly exerts agonist effects on presynaptic α2 receptors in the locus ceruleus. The locus ceruleus is the region of the brainstem that gives rise to all NA/NE brain tracts and is where sympathetic arousal may originate and is modulated. In essence, this region is the source of anticipatory anxiety and arousal. Accordingly, without involving the CYP 450 enzyme system, OTM dexmedetomidine may have profound panicolytic effects and may prevent and/or modulate the arousal that makes it so difficult for humans to use any behavioral or environmental management strategies or for dogs to use any operant or cognitive-behavior management skills they may have learned. Nausea With both separation anxiety and noise phobia/ reactivity, dogs may feel nauseous. Distressed dogs cannot eat because of antagonism of parasympathetic effects due to sympathetic arousal. However, the distress itself may contribute to nausea. For dogs that retch, salivate, chew on nonfood substances, have diarrhea before or after the event, stop eating before the event, and take a long time to eat after the event, we should consider whether maropitant (Cerenia; cereniadvm.com ), the neurokinin 1 receptor antagonist/substance P blocker, could be beneficial. This compound may have a role in directly treating aspects of depression, fear, and anxiety 19 but may be helpful for the more immediate gastrointestinal effects that may be associated with distress. In dogs with combined abnormalities that cause them to react to noise and absences, medications from 2 to 4 classes may need to be combined to achieve maximal resolution of signs. As to be expected from the patterns of receptor response, when medications that share a direct mechanism of action and/or a potential adverse effect are combined (eg, sedation, shared CYP 450 enzymes), dosages should be lowered. Occasionally, frequencies may be altered, rather than dosages lowered, depending on the dog's response. If 2 medications that are combined both affect serotonin, reduce the dose of both to minimize the risk for serotonin syndrome. This condition is rare and usually idiopathic, and data in dogs are lacking; however, it can be tragic. Although not discussed here, monoamine oxidase inhibitors (eg, selegiline) should not be combined with TCAs, SSRIs, or SARIs. SUMMARY Behavioral medicine and neuroscience are about pattern recognition. This brief introduction to thinking in a neurobehavioral mechanistic manner is intended to introduce clinicians to how to recognize and use relevant patterns for the benefit of the patients. We are learning more about genetic and functional patterns daily, and new applications for medications may result. By using the tables in this article to inform medication choice and to become comfortable with a few different treatment combinations, clinicians can make great improvements in their patients' mental health and in everyone's quality of life.

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