Ketamine is one of the most commonly used anesthetics in human and veterinary medicine, but its clinical effectiveness is often compromised due to tolerance to its anesthetic effects. Although ketamine tolerance has been demonstrated in a number of behavioral measures, no published work has investigated tolerance to ketamine's anesthetic effects other than duration of anesthesia. In addition, a reported practice in anesthesiology is to alter anesthetic doses for procedures when the patient has a history of drug abuse. Empirically investigating the effects of administration of a drug of abuse on ketamine's potency and efficacy to produce anesthesia could help in the creation of anesthetic plans that maximize safety for both clinicians and patients. The goal of the current study was to test the effects of repeated administration of ketamine, morphine, or cocaine on ketamine's ability to produce anesthesia. In 2 studies, male Sprague-Dawley rats received daily injections of ketamine (32 or 100 mg/kg IP), morphine (3.2 or 5.6 mg/kg IP), or cocaine (3.2 or 10 mg/kg IP) for 14 consecutive days and then were tested on day 15 for ketamine-induced anesthesia by using a cumulative-dosing procedure (32 to 320 mg/kg IP). Chronic treatment with either ketamine or morphine-but not cocaine-produced tolerance to ketamine's anesthetic effects in a dose-dependent manner. These results suggest that ketamine's clinical effectiveness as an anesthetic will vary as a function of its history of use. Furthermore, given that chronic morphine administration produced tolerance to ketamine's anesthetic effects, various pain medications may reduce ketamine's effectiveness for anesthesia.

Fluoroquinolones are a widely used class of chemotherapeutics within veterinary medicine, prized for their broad-spectrum bactericidal activity. These drugs present a known risk of retinal phototoxicity in domestic cats (Felis catus); therefore, using lower doses and alternative antibiotic classes is encouraged in this species. This adverse drug effect of fluoroquinolones, and enrofloxacin specifically, has been determined to be species-specific in domestic felids. Four feline-specific missense variants in ABCG2 result in four amino acid changes (E159M, S279L, H283Q, and T644I) that are unique to the domestic cat compared with multiple other nonfeline mammalian species. These changes alter the ABCG2 protein involved with the cellular transmembrane transport of drugs, including fluoroquinolones, making the protein functionally defective in domestic cats. The predisposition to fluoroquinolone-mediated phototoxicity in nondomestic felids was explored in this study. At least eight nondomestic felids share the four ABCG2 missense variants with domestic cats, and eleven other felids shared at least three of the four domestic cat variants. Taken together, these results suggest the genetic potential for nondomestic felids to also experience fluoroquinolone-induced retinal phototoxicity; therefore, cautions similar to those for domestic cats should be followed for these drugs in the entire feline taxon.

OBJECTIVE To evaluate physical compatibility of small animal (SAE) and large animal (LAE) injectable formulations of enrofloxacin with select IV fluids and drugs. SAMPLE 162 admixtures containing SAE or LAE with saline (0.9% NaCl) solution, lactated Ringer solution (LRS), Plasma-Lyte A (PLA), 6% hydroxyethylstarch 130/0.4 (HES), metoclopramide, or ampicillin-sulbactam. PROCEDURES In the first of 2 simultaneously conducted experiments, admixtures containing enrofloxacin (10 mg/kg) and a volume of IV fluid that would be administered over a 20-minute period when dosed at the maintenance infusion rate (40 mL/kg/d for saline solution, LRS, and PLA and 20 mL/kg/d for HES) were created. In the second experiment, enrofloxacin (10 mg/kg) was admixed with saline solution (40 mL/kg/d) and metoclopramide (2 mg/kg/d) or ampicillin-sulbactam (30 mg/kg). In both experiments, admixture components were infused into a flask over 20 minutes assuming patient weights of 5, 10, and 20 kg. Admixtures were created by use of undiluted SAE and SAE diluted 1:1 with saline solution and undiluted LAE and LAE diluted 1:1 and 1:10 with saline solution. Admixtures were assessed for physical incompatibility at 0, 15, 30, and 60 minutes after completion of mixing. Physical incompatibility was defined as gross precipitation, cloudiness, Tyndall effect, or change in turbidity. RESULTS Admixtures containing undiluted SAE or LAE were physically incompatible with saline solution, PLA, LRS, and HES. Because saline solution was used to dilute SAE and LAE, all admixtures containing diluted SAE or LAE were also physically incompatible. Physical compatibility of enrofloxacin with metoclopramide or ampicillin-sulbactam could not be assessed because those admixtures also contained saline solution. CONCLUSIONS AND CLINICAL RELEVANCE Enrofloxacin was physically incompatible with all tested solutions.

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