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1-2013 Efficacy of maropitant in preventing in premedicated with hydromorphone Bonnie L. Hay Kraus Iowa State University, [email protected]

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This Article is brought to you for free and open access by the Veterinary Clinical Sciences at Iowa State University Digital Repository. It has been accepted for inclusion in Veterinary Clinical Sciences Publications by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. Efficacy of maropitant in preventing vomiting in dogs premedicated with hydromorphone

Abstract Objective The og al of this study was to evaluate the effectiveness of maropitant (Cerenia®) in preventing vomiting after with hydromorphone.

Study design Randomized, blinded, prospective clinical study.

Animals Eighteen dogs ASA I/II admitted for elective orthopedic surgical procedures. The dogs were a mixed population of males and females, purebreds and mixed breeds, 1.0–10.2 years of age, weighing 3–49.5 kg.

Methods Dogs were admitted to the study if they were greater than 1 year of age, healthy and scheduled to undergo elective orthopedic surgery. Dogs were randomly selected to receive one of two treatments administered by . Group M received 1.0 mg kg−1 of maropitant, Group S received 0.1 mL kg−1 of saline 1 hour prior to anesthesia premedication. Dogs were premedicated with 0.1 mg kg−1 of hydromorphone intramuscularly. A blinded observer documented the presence of vomiting, retching and/or signs of nausea for 30 minutes after premedication.

Results All dogs in S vomited (6/9), retched (1/9) or displayed signs of nausea (2/9). None (0/9) of the dogs in M vomited, retched or displayed signs of nausea. Dogs in M had significantly fewer incidences of vomiting (p=0.0090), vomiting and retching (p=0.0023) and vomiting, retching and nausea (p<0.0001) when compared to S.

Conclusion and clinical relevance Maropitant prevents vomiting, retching and nausea associated with intramuscular hydromorphone administration in dogs.

Keywords dogs, hydromorphone, maropitant, vomiting

Disciplines Small or Companion Animal Medicine | Veterinary Toxicology and Pharmacology

Comments This is the peer-reviewed version of the following article: Kraus, Bonnie L. Hay. "Efficacy of maropitant in preventing vomiting in dogs premedicated with hydromorphone." Veterinary Anaesthesia and Analgesia 40, no. 1 (2013): 28-34, which has been published in final form at DOI: 10.1111/j.1467-2995.2012.00788.x. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self- Archiving. Posted with permission.

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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

This article is available at Iowa State University Digital Repository: https://lib.dr.iastate.edu/vcs_pubs/29 Veterinary Anaesthesia and Analgesia, 2012 doi:10.1111/j.1467-2995.2012.00788.x

1 2 2 RESEARCH PAPER 3 4 Efficacy of maropitant in preventing vomiting in dogs 5 6 premedicated with hydromorphone 7 8 9 Bonnie L. Hay Kraus 10 Department of Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, USA 11 12 13 Correspondence: Bonnie L. Hay Kraus, Iowa State University-College of Veterinary Medicine, 1600 South 16th Street, Ames, IA 50011- 14 1250, USA. E-mail: [email protected] 15 16 17 18 19 Conclusion and clinical relevance Maropitant pre- Abstract 20 vents vomiting, retching and nausea associated 21 Objective The goal of this study was to evaluate the with intramuscular hydromorphone administration 22 effectiveness of maropitant (Cerenia) in preventing in dogs. 23 vomiting after pre-medication with hydromorphone. Keywords dogs, hydromorphone, maropitant, vomi- 24 ting. 25 Study design Randomized, blinded, prospective clin- 26 ical study. 27 Introduction 28 Animals Eighteen dogs ASA I/II admitted for elective 29 orthopedic surgical procedures. The dogs were a mixed are commonly used for chemical restraint 30 population of males and females, purebreds and mixed and as preanesthetic medications in veterinary 31 breeds, 1.0–10.2 years of age, weighing 3–49.5 kg. medicine. Full mu- offer dose dependent 32 sedation and analgesia and are used to treat moder- 33 Methods Dogs were admitted to the study if they ate to severe pain. They may also be used as induction 34 were greater than 1 year of age, healthy and agents and as intra- and post-operative in 35 scheduled to undergo elective orthopedic surgery. veterinary patients. Adverse side effects may include 36 Dogs were randomly selected to receive one of two respiratory depression, bradycardia, behavioral 37 treatments administered by subcutaneous injection. changes including sedation, dysphoria or excite- ) 38 Group M received 1.0 mg kg 1 of maropitant, ment, urine retention and decreased urine produc- ) 39 Group S received 0.1 mL kg 1 of saline 1 hour tion and gastrointestinal effects including salivation, 40 prior to anesthesia premedication. Dogs were pre- nausea, vomiting and defecation (Wilson 1992; ) 41 medicated with 0.1 mg kg 1 of hydromorphone Branson & Gross 2001; Lamont & Mathews 2007). 42 intramuscularly. A blinded observer documented Hydromorphone is approximately five to seven 43 the presence of vomiting, retching and/or signs of times more potent than morphine, exhibits similar 44 nausea for 30 minutes after premedication. efficacy, and at equianalgesic doses, produces a 45 similar adverse effect profile as morphine (Mahler & 46 Results All dogs in S vomited (6/9), retched (1/9) or Forrest 1975; Coda et al.1997). However, neither 47 displayed signs of nausea (2/9). None (0/9) of the hydromorphone nor oxymorphone were found to 48 dogs in M vomited, retched or displayed signs of increase plasma histamine concentrations after 49 nausea. Dogs in M had significantly fewer inci- intra-venous administration (Smith et al. 2001) as 50 dences of vomiting (p = 0.0090), vomiting and is seen with morphine (Doenicke et al. 1995). 51 retching (p = 0.0023) and vomiting, retching and Oxymorphone also causes less vomiting than either 52 nausea (p < 0.0001) when compared to S. morphine or hydromorphone in dogs (Valverde

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1 et al. 2004) however, it is significantly more Materials and methods 2 expensive (Pettifer & Dyson 2000). The ability to 3 give hydromorphone intravenously (IV), without Study population 4 the risk of histamine release, and the decreased cost, 5 contribute to its widespread use as an This study was approved by the Iowa State Uni- 6 drug in veterinary medicine. versity Institutional Animal Care and Use Commit- 7 The incidence of vomiting in dogs given opioids as tee. Dogs presented to the Lloyd Veterinary Medical 8 anesthetic pre-medications is 50–75% with mor- Center at Iowa State University College of Veteri- 9 phine (Valverde et al. 2004; Wilson et al. 2007), nary Medicine for elective orthopedic surgery were 10 44–100% with hydromorphone (Valverde et al. included in the study. The owners’ gave consent for 11 2004; KuKanich et al. 2008) and 33% with each animal to be included in the study. The study 12 oxymorphone (Valverde et al. 2004). The incidence population included 18 dogs, classified as ASA sta- 13 of vomiting is affected by the specific drug and its tus 1 or 2 based on complete physical examination 14 lipid solubility profile, the dose and route of admin- and normal routine blood chemistry and complete 15 istration and concomitant drug administration. blood count. There were 13 spayed females, 4 cas- 16 Decreasing incidence of vomiting is observed with trated males and one intact male, aged 1– 17 higher doses, higher lipid solubility and prior 11.2 years and weighing 3.0–49.5 kg. Ten different 18 administration of (Blancquaert et al. breeds of were represented in the study 19 1986; Hersom & Mackenzie 1987; Gross 2001; including two mixed breed dogs, four Labrador 20 Valverde et al. 2004; KuKanich et al. 2008). Retrievers, four Golden Retrievers, and single rep- 21 Vomiting and regurgitation, especially when asso- resentatives of Boxer, Mastiff, Pomeranian, Brussells 22 ciated with anesthesia have been documented as risk Griffon, Newfoundland, Blue Heeler, German Shep- 23 factors for development of herd, Miniature Pinscher. 24 (Fransson et al. 2001; Alwood et al. 2006; Tart et al. 25 2010). Additional risk factors for aspiration include Study protocol 26 underlying esophageal, laryngeal and neurological 27 disease, prolonged anesthesia, cervical disc lesions On entry into the study, dogs were randomly 28 and the use of hydromorphone as an intra-operative assigned to receive one of two treatments prior to 29 analgesic; all of which can be commonly encountered preanesthetic medication. Group M received 1.0 mg ) ) 30 in clinical anesthesia practice (Fransson et al. 2001; kg 1 (0.1 mL kg 1) of maropitant and Group S ) 31 Alwood et al. 2006; Kogan et al. 2008; Tart et al. received saline 0.1 mL kg 1 subcutaneously 1 hour 32 2010). In addition, vomiting may be particularly prior to anesthesia premedication. The dose of saline 33 undesirable in certain cases such as penetrating eye was selected to parallel the volume of maropitant ) 34 wounds, intra-ocular surgery and patients with head needed to deliver a 1.0 mg kg 1 dose. All subcuta- 35 trauma or a brain tumor where increasing intraoc- neous injections were administered in the loose skin 36 ular or intracranial pressure caused by vomiting may on the midline between the scapulae to allow 37 lead to increased patient morbidity (Cunningham & monitoring of subsequent injection reaction at the ) 38 Barry 1986; Yusufu 2002; Slettedal & Bragad 2005; site. Dogs were premedicated with 0.1 mg kg 1 of 39 Eberhart et al. 2007). hydromorphone intra-muscularly in the lumbar 40 Maropitant (Cerenia, Pfizer, NY, USA) is a neu- epaxial muscles. A trained observer blinded to 41 rokinin-1 receptor (NK1) antagonist that has been treatment group documented the emetic events and 42 approved to prevent and treat vomiting in dogs. It the presence of signs of nausea for each dog for 43 has been shown to be highly effective in preventing 30 minutes after premedication. Vomiting was 44 vomiting secondary to a broad spectrum of emetic defined by expulsion of stomach contents from the 45 stimuli including , , copper mouth. Retching was defined as forceful contraction 46 sulfate, and a wide range of clinical of abdominal muscles without expulsion of stomach 47 causes of vomiting (Benchaoui et al. 2007; De La contents from the mouth. Signs interpreted as 48 Puente-Rendondo et al. 2007a,b; Vail et al. 2007; nausea included salivation, increased frequency of 49 Conder et al. 2008; Ramsey et al. 2008). The goal or exaggerated swallowing motions and licking of 50 of this study was to evaluate the effectiveness of lips. Each discrete emetic event was recorded. All 51 maropitant in preventing vomiting after pre-medi- dogs were evaluated the following day for pain and 52 cation with hydromorphone. swelling at the injection site.

Ó 2012 The Author. Veterinary Anaesthesia and Analgesia 2 Ó 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists Maropitant prevents hydromorphone induced vomiting BL Hay Kraus

1 In Group M, one dog exhibited pain on injection Statistical analysis 2 of maropitant. On the day following surgery, there 3 The primary variable used in the analysis of efficacy was no evidence of pain or swelling at the injection 4 was whether the dog experienced one or more site in dogs receiving either saline or maropitant as 5 vomiting episodes. A two-tailed Fisher exact test evidenced by observation and palpation. 6 was performed between the treatment and control 7 group. The Fisher exact test was repeated with the Discussion 8 inclusion of retching and nausea in addition to 9 vomiting. Statistical significance was assessed at Vomiting involves three stages: nausea, retching 10 p £ 0.05. A t-test was used to detect incidental dif- and vomiting (Andrews 1992; Twedt 2000). Nau- 11 ferences that may have occurred between the sea is a sensation that precedes vomiting and may 12 groups for age and weight. A Fisher exact test was or may not lead to vomiting. Signs of nausea in 13 run for the incidence of vomiting in the saline group animals may include depression, salivation, licking 14 between males and females. of lips and increased swallowing. Next, there are 15 retrograde contractions of the proximal small 16 intestine and pylorus and relaxation of the fundus Results 17 (Twedt 2000; Elwood et al. 2010). Retching is the 18 second phase and consists of forceful contractions of There was no significant difference in age or weight 19 the expiratory intercostal muscles, diaphragm and between dogs in Group M and S 20 abdominal muscles with elevation of the larynx and 21 Six of nine dogs (6/9, 66%) that received saline closure of the glottis (Andrews et al. 1990; Elwood 22 vomited at least once after hydromorphone et al. 2010). Decreased tone in the cervical esoph- 23 (Table 1). Three dogs (3/9, 33%) vomited only once agus, pharyngeal and lower esophageal sphincter, 24 and three dogs (3/9, 33%) vomited more than once production of negative intra-thoracic and positive 25 after hydromorphone. One dog (1/9, 11%) in the intra-abdominal pressures and contraction of the 26 saline group retched but did not vomit. Two dogs pylorus and antrum of the stomach, are associated 27 (2/9, 22%) exhibited signs of nausea including with the movement of gastric contents into the 28 profuse salivation and lip licking but did not vomit esophagus (Andrews & Hawthorne 1988; Twedt 29 or retch. Therefore, all dogs in the saline group 2000; Elwood et al. 2010). Vomiting occurs when 30 vomited, retched or displayed signs of nausea. There gastric contents are expelled from the mouth. Res- 31 was no significant difference in the incidence of piration is inhibited and the nasopharynx and 32 vomiting between males and females in the saline glottis close as the vomit passes through the pha- 33 group. ryngeal cavity to prevent aspiration (Twedt 2000; 34 None (0/9) of the dogs that received maropitant Elwood et al. 2010). 35 vomited, retched or displayed signs of nausea. Dogs Central neurologic control of vomiting involves a 36 receiving maropitant had significantly fewer inci- complex set of activities. There are two anatomically 37 dences of vomiting (p = 0.0090), vomiting and and functionally separate units: the vomiting or 38 retching (p = 0.0023) and vomiting, retching and emetic center which consists of the nucleus tractus 39 nausea (p < 0.0001) when compared to saline. solitarius (NTS) and the dorsal motor nucleus of the 40 vagus which are located in the medulla oblongata 41 (Elwood et al. 2010) and the chemoreceptor trigger 42 Table 1 Age, weight and sex distribution of dogs receiving zone (CTZ) which has been identified as the area 43 maropitant (Group M) and saline (Group S) postrema and is located on the dorsal surface of the 44 medulla oblongata adjacent to the fourth ventricle 45 Sex (Elwood et al. 2010). The CTZ lies outside the blood 46 brain barrier (BBB) and is responsive to circulating 47 Group Age (years)* Weight (kg)*à Male Female emetogens (Elwood et al. 2010). Emetogenic signals 48 from the CTZ stimulate neurons of the nucleus 49 M 5.98 ± 2.75 31.7 ± 14.0 2 7 tractus solitarius and from there the central pattern 50 S 5.35 ± 2.75 27.0 ± 16.5 3 6 generator (CPG) of the vomiting reflex which 51 triggers the motor response (Carpenter et al. 52 *Values expressed as mean ± SD; p = 0.6317; àp = 0.5249 1988; Koga & Fukuda 1992). The vomiting center,

Ó 2012 The Author. Veterinary Anaesthesia and Analgesia Ó 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists 3 Maropitant prevents hydromorphone induced vomiting BL Hay Kraus

1 which lies within the BBB, integrates efferent input it was the only effective against both 2 from a number of sources including the cerebral centrally (apomorphine) and peripherally (syrup of 3 cortex (psychogenic vomiting), vestibular input ipecac) acting emetogens (Sedlacek et al. 2008). 4 arising from the semi-circular canals (vomiting Hydromorphone has physicochemical properties 5 associated with motion sickness or vestibular disor- very similar to those of morphine (Pettifer & Dyson 6 ders), vagal and sympathetic afferents from the 2000; Sarhill et al. 2001). Morphine can have both 7 gastrointestinal system and other abdominal organs emetic and anti-emetic effects. The emetic effects are 8 and the CTZ (Carpenter et al. 1983; Tattersall et al. the result of stimulation of delta receptors outside the 9 1996). Convergence of information from the CTZ blood/brain barrier (CTZ) whereas the anti-emetic 10 and higher centers in the nucleus tractus solitarius effects can be attributed to mu-and/or kappa- 11 leads to stimulation of the central pattern generator mediated mechanisms on the vomiting/emetic cen- 12 (CPG) for vomiting, located in the reticular area, ter (Blancquaert et al. 1986; Hersom & Mackenzie ) 13 eliciting the motor act of vomiting (Koga & Fukuda 1987). At low doses (0.3 mg kg 1 IV), morphine 14 1992; Fukuda et al. 1999). caused vomiting in 6/6 dogs whereas doses of 1 and ) 15 , a neuropeptide in the tachykinin 2mgkg 1 resulted in 3/5 and 0/28 incidence of

16 family and a potent at the NK1 receptor, is vomiting respectively (Blancquaert et al. 1986). 17 found in high concentrations in areas of the brain The higher doses of morphine also prevented 18 stem involved in emesis including the nucleus vomiting induced by apomorphine; 3/5 and 0/23 ) 19 tractus solitarius, the and the dorsal for doses of 1 and 2 mg kg 1 respectively. It is 20 motor nucleus of the vagus (Ariumi et al. 2000; postulated that the lower dose of morphine reaches 21 Hargreaves 2002) and is considered to be the key the CTZ but not the vomiting center, therefore 22 neurotransmitter involved in vomiting (Diemunsch resulting in emesis, whereas the higher dose can 23 & Grelot 2000). Injection of substance P into the reach the VC and block the effects on the CTZ 24 brainstem of ferrets rapidly causes vomiting (Gard- (Blancquaert et al. 1986). Highly lipid soluble 25 ner et al. 1995). Vomiting induced by emetogens opioids have an anti-emetic effect due to their effect ) 26 such as apomorphine, copper sulfate and cisplatin on the VC. Fentanyl, at doses of 5 and 10 lgkg 1 27 can be prevented in dogs by inhibiting NK1 recep- IV did not cause vomiting in 6/6 and 12/12 dogs ) 28 tors for substance P (Watson et al. 1995). Confir- respectively, and 10 lgkg1 prevented the emetic

29 mation of the role of NK1 receptors in the final effect of apomorphine and copper sulfate in 4/7 and 30 common pathway in vomiting in dogs came by 4/5 dogs respectively (Blancquaert et al. 1986).

31 selective antagonism of NK1 receptors in decere- Methadone and sufentanil, also highly lipid soluble, 32 brate dogs exposed to abdominal vagal stimulation did not cause vomiting in dogs (Blancquaert et al. 33 (Fukuda et al. 1999). The proposed site of anti- 1986; Hersom & Mackenzie 1987).

34 emetic action of NK1 receptor antagonists is located The incidence of vomiting in the saline group was 35 in the CPG or in the pathway connecting the 6/9 (66%). This is slightly higher than previously 36 nucleus tractus solitarius to the CPG (Fukuda et al. reported by Valverde et al. (2004) who found an

37 1999; Andrews et al. 2001). NK1 receptor antag- incidence of 7/16 (44%) in a group of dogs receiving ) 38 onists, by acting at the center coordinating the hydromorphone (0.1 mg kg 1) intra-muscularly 39 vomiting response to various central (neural) and 15 minutes prior to administration of aceproma- 40 peripheral (humeral) stimuli, can provide broad- zine. This discrepancy may be due to the relatively 41 spectrum inhibition of vomiting (Gardner et al. low numbers of dogs in each study or differences in 42 1996; Fukuda et al. 1999). administration site. All dogs in the present study

43 Maropitant, a selective NK1 receptor antagonist were injected in the lumbar epaxial muscles. 44 has been shown to be effective for prevention of Absorption of drugs given in non-postural muscles 45 vomiting caused by stimulation of both central and is slower than in postural muscles (Self et al. 2009). 46 peripheral pathways (De La Puente-Rendondo et al. Slower absorption may have an effect similar to 47 2007c, Sedlacek et al. 2008). Maropitant has been lower opioid doses on the CTZ, leading to a more 48 shown to significantly reduce vomiting relative to a pronounced emetic effect. The site of intra-muscular 49 saline negative control for both apomorphine (cen- injection was not specified in the Valverde et al. 50 trally acting emetogen) and (periph- (2004) study. The incidence of vomiting after intra- 51 erally acting emetogen). When compared to muscular administration is higher than when 52 , and , hydromorphone is administered intravenously at

Ó 2012 The Author. Veterinary Anaesthesia and Analgesia 4 Ó 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists Maropitant prevents hydromorphone induced vomiting BL Hay Kraus

) ) 1 doses of 0.1 mg kg 1 (3/9, 33%) 0.5 mg kg 1 (0/7, of administration in a clinic setting (De La Puente- ) 2 0%) but lower than when administration is by Rendondo et al. 2007b). Oral dosing of 2 mg kg 1at ) 3 subcutaneous injection at doses of 0.1 mg kg 1 (6/ least 2 hours prior to administration of hydromor- ) 4 8, 75%) and 0.5 mg kg 1 (8/8, 100%) (KuKanich phone may provide a more appropriate route for 5 et al. 2008). owners administering the product at home for the 6 When additional prodromal signs of vomiting prevention of emesis prior to a planned elective 7 such as retching and nausea were included, a 100% surgery where use of hydromorphone or other 8 incidence was observed in the saline group. In opioid drugs that are known to elicit vomiting will 9 Valverde et al.’s (2004) study, inclusion of retching be administered. 10 and salivation increased the incidence of signs of The randomized clinical study reported here 11 vomiting to 28/40 (70%) dogs. However, it was not demonstrated that maropitant was effective in the 12 indicated whether these dogs received oxymor- prevention of vomiting after administration of ) 13 phone, morphine or hydromorphone. However, it hydromorphone 0.1 mg kg 1 intra-muscularly 14 is clear that the incidence of prodromal signs is when given 1 hour prior to anesthetic premedica- 15 higher than overt vomiting. tion. Avoidance of peri-operative nausea and vom- 16 Acepromazine, when administered at a dose of iting may decrease patient discomfort, risk of peri- ) 17 0.05 mg kg 1 IM 15 minutes prior to hydromor- operative aspiration pneumonia and morbidity 18 phone, decreased the incidence of vomiting from 7/ associated with increased intra-ocular or intra- 19 16 (44%) to 5/21 (24%), which is thought to be due cranial pressures. 20 to blockade of dopamine receptors in the chemore- 21 ceptor trigger zone (Valverde et al. 2004). Marop- Acknowledgements 22 itant decreased the incidence of vomiting after 23 hydromorphone to 0/9, making it a more effective, The author wishes to thank Amanda Jirak Ayers for 24 reliable anti-emetic. technical assistance with this project. Maropitant 25 In human anesthetic patients, satisfaction with was provided by Pfizer Animal Health, New York, 26 their anesthesia experience is closely tied to the NY. 27 ability to avoid peri-operative nausea and vomiting. 28 This issue ranks ahead of pain, death and myocar- References 29 dial infarction as a patient concern. In a recent 30 interview study of 12,276 patients, 3652 (30%) Alwood AJ, Brainard BM, LaFond E et al. (2006) Postop- 31 reported at least one perioperative complaint, of erative pulmonary complications in dogs undergoing 32 these 1705 (46%) were related to perioperative laparotomy: frequency, characterization and disease- 33 nausea and vomiting (Lehmann et al. 2010). related risk factors. J Vet Emerg Crit Care 16, 176–183. Andrews PL (1992) Physiology and nausea and vomiting. 34 Avoiding the discomfort associated with peri-oper- Br J Anaesth 69(7 Suppl), 2S–19S. 35 ative nausea and vomiting may also be a consider- Andrews PLR, Hawthorne J (1988) The neurophysiology 36 ation for veterinary patients. of vomiting. Baillieres Clin Gastroenterol 2, 141–168. 37 Maropitant was completely effective in preventing Andrews PLR, Bhandari P, Garland S et al. (1990) Does 38 vomiting, retching and nausea associated with retching have a function: an experimental study in the 39 administration of the opioid analgesic hydromor- ferret. Pharmacodyn Ther 9, 135–152. 40 phone in this study. The standard dosage recom- Andrews PLR, Kovacs M, Watson JW (2001) The anti- 41 mendations for treatment or prevention of vomiting emetic action of the neurokinin-1 receptor antagonist ) ) 42 are 1.0 mg kg 1 by SC injection or 2.0 mg kg 1 as CP-99,994 does not require the presence of the area 43 oral tablets (De La Puente-Rendondo et al. 2007b). postrema in the dog. Neurosci Lett 314, 102–104. 44 The pharmacokinetic data demonstrate that in Ariumi H, Saito R, Nago S et al. (2000) The role of tachykinin NK receptors in the area postrema of ferrets 45 dogs, these two maropitant doses provide similar 1 ) in emesis. Neurosci Lett 286, 123–126. 46 peak plasma concentrations (92 ng mL 1 for )1 )1 )1 Benchaoui HA, Cox SR, Schneider RP et al. (2007) The 47 1mgkg SC, 81 ng mL for 2 mg kg PO) (De of maropitant, a novel neurokinin 48 La Puente-Rendondo et al. 2007b). However, the type-1 receptor antagonist, in dogs. J Vet Pharmacol 49 time taken to achieve maximum plasma concentra- Ther 30, 336–344. 50 tion is shorter following SC administration Blancquaert JP, Lefebvre RA, Willems JL (1986) Emetic ) 51 (0.75 hours for 1 mg kg 1 SC and 1.9 hours for and antiemetic effects of opioids in the dog. Eur J ) 52 2mgkg 1 PO), thus making it the preferred route Pharmacol 128, 143–150.

Ó 2012 The Author. Veterinary Anaesthesia and Analgesia Ó 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists 5 Maropitant prevents hydromorphone induced vomiting BL Hay Kraus

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Ó 2012 The Author. Veterinary Anaesthesia and Analgesia 6 Ó 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists Maropitant prevents hydromorphone induced vomiting BL Hay Kraus

1 Smith LJ, Yu JK, Bjorling DE et al. (2001) Effects of induced emesis in dogs presented as veterinary patients. 2 hydromorphone or oxymorphone, with or without Vet Comp Oncol 5, 38–46. 3 acepromazine, on preanesthetic sedation, physiologic Valverde A, Cantwell S, Hernandez J et al. (2004) Effects of 4 values, and histamine release in dogs. J Am Vet Med acepromazine on the incidence of vomiting associated 5 Assoc 218, 1101–1105. with opioid administration in dogs. Vet Anaesth Analg Tart KM, Babski DM, Lee JA (2010) Potential risks, prog- 31, 40–45. 6 nostic indicators, and diagnostic and treatment modal- Watson JW, Gonsalves SF, Fossa AA et al. (1995) The 7 ities affecting survival in dogs with presumptive anti-emetic effects of CP-99,994 in the ferret and 8 aspiration pneumonia: 125 cases (2005-2008). J Vet the dog: role of the NK1 receptor. Brit J Pharmacol 115, 9 Emerg Crit Care 20, 319–329. 84–94. 10 Tattersall FD, Rycroft W, Francis B et al. (1996) Tachyk- Wilson DV (1992) Advantages and guidelines for using 11 inin NK1 receptor antagonists act centrally to inhibit opioid agonists for anesthesia induction. Vet Clin North 12 emesis induced by the chemotherapeutic agent cisplatin Amer Small Anim Pract 22, 269–272. 13 in ferrets. Neuropharmacology 35, 1121–1129. Wilson DV, Evans AT, Mauer WA (2007) Pre-anesthetic 14 Twedt DC (2000) Vomiting. In: Textbook of Veterinary meperidine: associated vomiting and gastroesophageal 15 Internal Medicine Vol. 1 (5th edn). Ettinger SJ, Feldman reflux during the subsequent anesthetic in dogs. Vet 16 EC (eds). WB Saunders Co., Philadelphia, PA, USA. pp. Anaesth Analg 34, 15–22. 117–121. Yusufu LMD (2002) Post operative nausea and vomiting. 17 Vail DM, Rodabaugh GA, Conder JF et al. (2007) Efficacy Ann African Med 1, 1–7. 18 TM of injectable maropitant (Cerenia ) in a randomized 19 clinical trial for prevention and treatment of cisplatin- Received 2 September 2011; Accepted 3 October 2011. 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52

Ó 2012 The Author. Veterinary Anaesthesia and Analgesia Ó 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists 7