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Yohimbine and Atipamezole on the Treatment of Experimentally Induced Amitraz Intoxication in Cats

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Yohimbine and Atipamezole on the Treatment of Experimentally Induced Amitraz Intoxication in Cats Yohimbine and Atipamezole on the Treatment of Experimentally Induced Amitraz Intoxication in Cats Silvia Franco Andrade, DVM1 Michiko Sakate, DVM2 Cecília Braga Laposy, DVM3 Fabíola Sangiorgio, MSc4 1Departamento de Clínica Médica de Pequenos Animais Farmacologia e Toxicologia do Curso de Medicina Veterinária da Universidade do Oeste Paulista (UNOESTE) São Paulo, Brazil 2Departamento de Clínica Médica de Pequenos Animais e Toxicologia FMVZ-UNESP Botucatu, São Paulo, Brazil 3Laboratório de Patologia Clínica do Hospital Veterinário da UNOESTE São Paulo, Brasil 4Curso de Pós-Graduação FMVZ-UNESP Botucatu, São Paulo, Brazil KEY WORDS: amitraz, yohimbine, INTRODUCTION atipamezole, intoxication, cats Amitraz is a very popular acaricide and tic- kicide included in the formamidine pesticide ABSTRACT group and used in veterinary medicine in Experimental amitraz intoxication and its many countries.1,2 In Brazil, a recent study reversal by atipamezole and yohimbine showed that 13.9% of intoxications in dogs were studied in cats. Twenty four cats were from use of pesticides on farms (39.3% organophosphorous, 35.7% carba- were randomly divided equally into 3 mate insecticides, and 25.0% amitraz), and groups: Group A (amitraz); Group AY intoxication in cats were 27.6% (46.1% car- (amitraz/yohimbine) and Group AA (ami- bamate, 38.5% organophosphorous, and traz/atipamezole). Sedation, loss of reflex- 15.4% other insecticides).3 es, hypothermia, bradycardia, Amitraz has been used to eliminate mites, bradyarrhythmia, hypotension, bradypnea, lice, and ticks in cattle, swine, and dogs, but mydriasis, and initial transitory hyper- has been contraindicated for use in horses glycemia occurred in Group A. Median because it can cause fatal colon impaction.2 α intervals for sedation return, in minutes, In mammals, amitraz is a 2-adrenergic ago- were significantly lower in amitraz-intoxi- nist1 and inhibits monoamine oxidase cated cats treated with either yohimbine or (MAO)2 and prostaglandin synthesis.4 atipamezole. Yohimbine and atipamezole Classical signs of amitraz intoxication are were very effective in the treatment of characterized by nervous system changes, such as sedation, loss of reflexes, and motor amitraz intoxication, although atipamezole incoordination. Other clinical signs include was more effective in reversal of arrhyth- bradycardia, hypotension, hypothermia, mias, mydriasis, and sedation induced by polyuria, hyperglycemia, emesis, mydriasis, this acaricide in cats. and decreased intestinal transit.1,2 200 Intern J Appl Res Vet Med • Vol. 4, No. 3, 2006. Because little information is available Botucatu (Protocol no. 47/2001). Mixed- about this intoxication in cats,5-7 the manu- breed adult cats (males and females) facturer has not recommended the use of obtained from the UNOESTE cat pound amitraz in this species, despite its effica- were used. First, the cats were sorted by ciousness in treating feline scabies and health condition and only those with normal demodicosis.8,9 Although amitraz could be values for the following physiological used in such treatments, lack of experimen- parameters were used: temperature (T), res- tal studies for the treatment of amitraz piratory rate (RR), heart rate (HR), systolic intoxication in cats prevents such a recom- arterial pressure (SAP), electrocardiogram α mendation. The 2-adrenergic antagonists (ECG), pupil diameter (PD), red (RBC) and yohimbine and atipamezole are usually cho- white (WBC) blood cell count, urea, creati- sen for treatment of amitraz intoxication nine, alanine aminotransferase (ALT), and associated with other therapeutic procedures aspartate aminotransferase (AST). Blood (dermal and gastrointestinal decontamina- samples were collected by jugular puncture. tion).5,10 One day before running the experiment, the α Yohimbine is a 2-adrenergic antagonist cats were socially isolated and held in indi- found in the bark of the tree Pausinystalia vidual stainless steel cages under 12:12 arti- yohimbe and in the root of Rauwolfia.2 It ficial light-dark cycle, room temperature α has high affinity for the 2-adrenergic about 25°C, and fed ad libitum. α α α receptors 2A, 2B, and 2C, and a low affini- Experimental Procedure ty for the α receptor.11,12 Its is also a 5-HT 2D Twenty four healthy cats were randomly antagonist,12 but in higher doses it acts as a divided into 3 groups (4 males and 4 5-HT agonist inhibiting sympathetic activ- 1A females each). Cats (mean weight, 3.5 ± 0.6 ity.13 This α -adrenergic antagonist also acts 2 kg) in Group A (amitraz, Mitrax®, indirectly in other receptors, such as Agribrands Purina, Paulínia, Brazil) were GABAergics, cholinergics, dopaminergics, administered 1 mg amitraz/kg iv at a 1.5% or serotoninergics.14 concentration (by dilution of 0.6 mL of ami- Atipamezole is a potent and selective traz, 75 mg, in 4.4 mL of bi-distilled water). α -adrenergic antagonist approved by the 2 Amitraz dose and dilution were based on a US Food and Drug Administration in 1996 model described for dogs.15 The other 2 for treatment to reverse sedative and anal- groups received the same concentration and gesic effects of medetomidine in dogs.2,15 It dose of amitraz as group A and 60 min later is considered a new generation of α -adren- 2 (T60): Group AY (amitraz/yohimbine; ergic antagonist due to its high selectivity of yohimbine, Yobine®, VET-A-MIX, Iowa, α -adrenergic receptors,16 like α , α , and 2 2A 2B USA) (mean weight, 3.0 ± 0.9 kg) were α receptors, and a 100-times higher affini- 2C administered 0.1 mg yohimbine/kg iv at a 2 ty for the α receptor than that of yohim- 2D mg/mL concentration; and Group AA, (ami- bine in the sheep brain.12,17 Atipamezole has traz/atipamezole; atipamezole, Antisedan®, no antagonistic effect on other receptors.2 Pfizer, New York, USA) (mean weight, 3.2 The objective of this study was to inves- ± 0.7 kg) were administered 0.2 mg ati- tigate the efficacy of yohimbine and ati- pamezole/kg iv as a 5 mg/mL concentration. pamezole in the treatment of amitraz Values of T, RR, HR, SAP, ECG, and intoxication in cats. PD were measured at times 0, 30, 60, 120, 180, 240, and 360 min of the experiment MATERIALS AND METHODS (yohimbine and atipamezole were adminis- Experimental Animals tered at the 60-min time point). Glucose, The experiment was approved by the insulin, and cortisol were measured at 0, 60, Ethical Committee of FMVZ-UNESP- 180, and 360 min. Levels of RBC, WBC, Intern J Appl Res Vet Med • Vol. 4, No. 3, 2006. 201 urea, creatinine, ALT, and AST were meas- administration reduced the respiratory rate ured at 24 hours before and after amitraz from 120 min to 360 min. However, this administration. decreased RR was abolished in groups receiving either yohimbine or atipamezole. Specific Procedures Heart rate was decreased by amitraz from 30 Systolic arterial pressure was measured by min to 360 min of observations. Yohimbine an indirect or non-invasive method, with reestablished HR after 260 min, while ati- Doppler Ultrasonic equipment (Parks pamezole restored earlier (after 180 min) HR Medical-841-A). Electrocardiogram of cats to basal values. Considering SAP, amitraz in right lateral recumbency was recorded decreased this parameter, an effect reversed using an automated electrocardiograph more by yohimbine than atipamezole. (Cardiotest EK51). The mean value of 5 Cardiac rhythm was affected by amitraz consecutives heart beats was recorded on at 180 min after the drug administration lead II (paper speed of 50 mm/s, 1 cm = 1 (Table 2). This effect was not found in mv) for each parameter. Cardiac rhythm groups AA and AY, but heart rhythm was was evaluated by occurrence of a) sinusal; changed earlier in the AY group and b) sinusal arrhythmia; c) sinusal bradycar- remained unchanged in the AA group. dia; d) 1st degree A-V block; or e) sinus Moreover, only AY cats showed heart arrest.18 Pupil diameter was assessed by rhythm different from the control group (A: direct punctiform light toward the pupil. 30, 60, 120, and 180 min). Some cats indi- Three levels were scored: normal (1), vidually presented arrhythmias during intox- mydriasis (2), and myosis (3). Mean interval ication by the amitraz (Group A), such as for sedation return (MISR) was considered sinusal bradycardia, sinusal arrhythmia, and the time (min) necessary for the animal to 1st A-V block. recover protective pupillary, palpebral, and interdigital reflexes, and also to stand up Amitraz intoxication induced mydriasis without ataxia after the experimental drug in all the cats until 240 min. In AY cats, administration. Clinical signs were evaluat- mydriasis persisted until T120, and in AA ed at the end of the treatments and consisted cats it persisted until T60 (Table 3). The of occurrence of vomiting, diarrhea, sialor- MISR was drastically reduced by either rhea, diuresis, vocalization, ataxia, tremors, yohimbine or atipamezole, both adminis- 3rd eyelid prolapse, and increased appetite. tered during amitraz intoxication (Table 4). Regarding blood variables, amitraz Statistical Analysis increased glucose levels in all groups (Table 5), Profile analysis19 compared means among but this effect was shortened by AY treat- groups and within a group (over time). ment, where cats had reestablished basal Whenever normality and/or homocedasticity glucose levels by 360 min. Cats receiving were not achieved, non-parametric tests atipamezole reestablished these levels earli- were used: Friedmam for comparisons with- er, at 180 min. Considering insulin levels, in groups, over time; and Kruskal-Wallis for the 3 groups showed a similar profile com- comparing among groups.20 A significance pared with the respective basal levels: level of P < 0.05 was adopted. insulin level increased, then decreased, and then increased again. However, the RESULTS increased values at 180 min were lower in both yohimbine and atipamezole groups Amitraz decreased temperature significantly respective to the control amitraz group.
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