Analgesia perioperatória de gatas submetidas a ovariohisterectomia eletiva - uso preemptivo de carprofeno ou grapiprant / Perioperative analgesia in cats undergoing elective ovariohysterectomy - preemptive use of carprofen or grapiprant

Background: The nonsteroidal anti-inflammatory drugs (NSAIDs) exert their analgesic effect through peripheral inhibition of prostaglandin synthesis and a variety of other peripheral and central mechanisms. However, NSAIDs are associated with some adverse effects, mainly related to the gastrointestinal, renal, and hepatic systems, highlighting the need for research to develop safer drugs. Therefore, the aim of this study was to evaluate the efficacy of preoperative oral administration of carprofen or grapiprant in female cats submitted to elective ovariohysterectomy on the quality of perioperative analgesia and the need for hypnotic and analgesic drugs. Materials, Methods & Results: Thirty-three adult female cats were selected, without defined breed and healthy based on physical examination, routine laboratory analyses (complete blood count, total protein, Heinz body investigation and serum quantification of alanine transaminase [ALT], aspartate transaminase [AST], gamma glutamyl transpeptidase [GGT], alkaline phosphatase [ALP], urea, frutosamine, and glucose) and negative tests for feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV). After 3 days of adaptation, they were submitted to ovariohysterectomy by celiotomy and randomly allocated into 2 groups according to the preoperative drug used: GCAR [carprofen - 4 mg/kg, VO, 2 h before surgery; n = 11] and GGRA (grapiprant - 2 mg/kg IV, 2 h before surgery; n = 21]. The cats were pre-medicated with acepromazine 0.05 mg/ kg IV and later submitted to general anesthesia with propofol intravenously. Anesthesia was maintained with isoflurane in 100% oxygen. After anesthetic induction, a continuous infusion of remifentanil at a rate of 10 µg/kg/h was initiated. During the transanesthetic period, the parameters of heart rate; respiratory rate; systolic, mean, and diastolic arterial pressure using the oscillometric method; electrocardiogram; rectal temperature; partial pressure of CO2 at the end of expiration: and partial saturation of O2 in hemoglobin were continuously monitored. The evaluation of nociception was based on the changes in the aforementioned physiological parameters. The rate of remifentanil used did not change over time with the use of carprofen. However, animals that received grapiprant required a lower remifentanil dose at 20, 25, and 30 min during the procedure. The female cats that received carprofen showed an increase in mean heart rate at 30 min compared to that at 20 and 25 min. In the Grapiprant group, the heart rate at 35 min was higher only than that observed at 25 min. Discussion: The remifentanil rate did not differ between the groups, even between the times for GCAR. However, the remifentanil rate was lower from 20 min of the procedure for GGRA. This decrease may be related to a decrease in the need for anesthetics and analgesics by decreasing temperature, which causes decreases in metabolism and surgical stimulation. The increase in systolic, mean, diastolic, and heart rate arterial pressure parameters observed in both treatments after 15 min of anesthesia is related to the nociceptive stimulus resulting from traction and ligation of the ovarian pedicles and maneuvers for exteriorization of the uterus. These are considered the moments of greater surgical stimulus during ovariohysterectomy, evidenced by the greater release of cortisol and increase in physiological parameters. The results of this study show that the administration of carprofen or grapiprant was clinically similar when used preemptively for perioperative analgesia in cats submitted to elective ovariohysterectomy.

Evaluation of carbon nanotubes as chiral selectors for continuous-flow enantiomeric separation of carvedilol with fluorescent detection.

Single-walled carbon nanotubes (SWNT) are proposed as chiral selectors for separation of carvedilol stereoisomers beginning since its racemic mixture. The novel developed FIA-methodology employs a microcolumn (mC) packed with a few milligrams of SWNT which showed to be effective in S(-) and R(+) carvedilol separation. Attending to spectral properties of analytes, molecular fluorescence was employed in the detection step. Separation of carvedilol enantiomers was achieved in less than 70s with an acceptable resolution factor of 3.16. Variables that influence the chiral separation such as pH and composition of eluent solution, sample injection volume and flow rate, activation mode of NTs and mass of the same in column have been examined in detail. At optimal operational conditions, well repeatability was achieved using the same column for more than 100 injections, putting in evidence the stability of nanomaterial and the efficacy and versatility of the proposed FIA-configuration. The new methodology was successfully applied to S(-) and R(+) carvedilol quantification in pharmaceutical preparations, resulting an attractive alternative to traditional separative methods being fast, simple, using low cost instrumentation and producing scarce waste.

Flow injection spectrofluorimetric determination of carvedilol mediated by micelles.

A novel flow injection (FI)-spectrofluorimetric methodology for the determination of carvedilol in microheterogeneous medium has been developed. In the sodium dodecyl sulfate (SDS) surfactant medium, an additional fluorescence enhancement was produced by the electrolyte NaCl. A total enhancement of 3.1-fold in the native fluorescent response was achieved respect to aqueous medium. Using an excitation and emission wavelength of 286 and 341 nm, respectively, a good linear relationship was obtained in the range of 9x10(-8) to 1x10(-6) mol L(-1) with a detection limit of 3.63x10(-9) mol L(-1) (S/N=3). This method was applied to determine carvedilol in commercial pharmaceutical formulations. Good concordance was found between the nominal (6.25, 12.5 and 25.0 mg) and experimental values. The new methodology developed showed high selectivity respect to the common excipients used in pharmaceuticals. The sampling rate was 30 samples h(-1). From the fluorescent properties, binding constant for carvedilol-SDS determined was 3.2x10(2) L mol(-1).

Spectrophotometric determination of carvedilol in pharmaceutical formulations through charge-transfer and ion-pair complexation reactions.

Simple extraction-free spectrophotometric methods have been developed for the determination of carvedilol (CAR). The methods were based either on charge-transfer reaction of the drug with the sigma-acceptor iodine, in acetonitrile, or on ion-pair formation with the acidic sulphophthalein dyes bromothymol blue (BTB) and bromocresol green (BCG), in chloroform. The obtained complexes showed absorbance maxima at 363, 411 and 414 nm, respectively for iodine, BTB and BCG. Beer's law validation, accuracy, precision, and other aspects of analytical merit are presented in the text. The proposed methods were applied for the determination of CAR in tablets and compounded capsules. The results were in good agreement with those obtained by an established UV spectrophotometric method.

Identification of alkyl carbazoles and alkyl benzocarbazoles in Brazilian petroleum derivatives.

Carbozoles are important compounds in crude oils, as they may be used as geochemical tracers, being the major type of nitrogen compounds in petroleum. At the same time, they are regarded as undesirable due to the problems they may cause in the refining process, such as catalyst poisoning, corrosion, gum or color formation in final products. As separation and identification of carbazoles are challenging goals, this work presents a chromatographic method, made of a pre-fractionation on neutral alumina followed by the separation and identification of two classes of carbazoles using FeCl(3)/Chromossorb W and gas chromatograph with mass spectrometer (GC/MS) (SIM-single ion monitoring mode) analysis. For the first time, a series of alkyl carbazoles and alkyl benzocarbazoles were identified in heavy gas oil (HGO) and atmospheric residue of distillation (ARD) obtained from Brazilian petroleum.

HPLC analysis of 5H-benzo[a]carbazole with antifungal activity.

A sensitive and simple high-performance liquid chromatographic (HPLC) method for the assay of 6,11-dihydro-2-methoxy-5H-benzo[a]carbazole (1) and 6,11-dihydro-2-methoxy-11-[2-(1-piperidinyl)]ethyl-5H-benzo[a]carbazole (2) was developed. The procedure is based on the use of the reversed-phase high-performance liquid chromatographic (RP-HPLC) method with UV detector. Each analysis required no longer than 11 min. A linear relationship between the concentration of both the drugs and the UV absorbance at 254 nm was obtained. This linearity was maintained over the concentration ranged from 5 to 80 microg/ml. The detection limits were found to be 1.6 and 0.7 ng for compounds 1 and 2. The quantitation limits were found to be 5.3 and 2.5 ng for compounds 1 and 2, respectively. For recovery studies, several determinations were carried out. Recovery values ranged from 98 to 102.1% for compound 1 and from 98.4 to 101.6% for compound 2. Method precision was also evaluated and RSD% found was less than 2%. This method was applied without any interference from degradation products.