Uso de morfina em gatos: prós e contras

The cat population is increasing more and more, and with it the concern about the treatment for pain in these animals. Although better treated for pain now, the cats are still less treated than dogs, especially when it comes to opioids such as morphine. It is known that morphine is very effective in the treatment of acute post-surgical pain and is an extremely safe drug. However, in regard to cats, morphine may act differently, due to the deficiency that these animals have in the enzyme responsible for the metabolism of morphine, and may have prolonged effects, toxicity and less analgesia. This drug can cause many adverse effects, but if administered in correct doses and intervals they are rare and there is the possibility of reversal with other drugs

Diagnóstico molecular da alteração mutagênica nt 230 (del4) no gene MDR1 em cães

P-glycoprotein is an adenosine triphosphate (ATP)-driven drug efflux carrier responsible for transport of xenobiotics and multiple classes of drugs, many usually use in veterinary medicine. Encoded by MDR1 gene, also referred to as ABCB1, located on chromosome 14, is expressed in many tissues with secretory or excretory functions, such as liver, kidney and intestine, where it limits drug absorption from the gut and promotes drug excretion into the bile and urine of their substrates. In 2001, a 4 base pair gene deletion mutation in the canine MDR1 gene was identified as MDR1-1▲, ABCB1-1▲, MDR1 MDR1 nt 230 (del4) and associated with an non-functional Pglycoprotein. The clinical correlation is the (hyper) sensitivity of certain dogs breeds, mostly collies, to a few classes of drugs such as anticancer drugs (doxorubicin, vincristine, vinblastine), immunosuppressants (cyclosporine), antiparasitic drugs (ivermectin, moxidectin), steroids hormones (aldosterone, cortisol, dexamethasone), antimicrobial agents (tetracycline, doxycycline, levofloxacin, ketoconazole, itraconazole), analgesics (morphine, methadone), antidiarrheals (loperamide), antiepileptic agents (phenothiazine), cardiac drugs (digoxin, diltiazem, verapamil, talinolol) and others. Dogs with homozygous MDR1 nt 230 (del4) MDR1 mutations (MDR1 - / -) have a higher predisposition to intoxication with substrates of P-gp than heterozygous (MDR1 + / -) and these are more likely than dogs homozygous nonmutant (MDR1 +/ +). After the identification of nt230 (del4) mutation, several molecular techniques have been developed for identification of mutant animals as a diagnostic method. The importance of molecular diagnosis is, after the identification of mutant animals, establish treatment protocols safe, exclude this animals from reproduction (genetic selection program) and investigating the history of adverse drugs reactions... (Complete abstract click electronic access below)

Avaliação da motilidade e do trânsito gastrintestinal de equinos após injeção epidural de morfina ou tramadol

Pós-graduação em Cirurgia Veterinária - FCAV

Analgesic and antihyperalgesic effects of dipyrone, meloxicam or a dipyrone-meloxicam combination in bitches undergoing ovariohysterectomy

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Selective suprascapular and axillary nerve block provides adequate analgesia and minimal motor block. Comparison with interscalene block

Shoulder arthroscopic surgeries evolve with intense postoperative pain. Several analgesic techniques have been advocated. The aim of this study was to compare suprascapular and axillary nerve blocks in shoulder arthroscopy using the interscalene approach to brachial plexus blockade. According to the technique used, sixty-eight patients were allocated into two groups: interscalene group (IG, n=34) and selective group (SG, n=34), with neurostimulation approach used for both techniques. After appropriate motor response, IG received 30 mL of 0.33% levobupivacaine in 50% enantiomeric excess with adrenalin 1:200,000. After motor response of suprascapular and axillary nerves, SG received 15 mL of the same substance on each nerve. General anesthesia was then administered. Variables assessed were time to perform the blocks, analgesia, opioid consumption, motor block, cardiovascular stability, patient satisfaction and acceptability. Time for interscalene blockade was significantly shorter than for selective blockade. Analgesia was significantly higher in the immediate postoperative period in IG and in the late postoperative period in SG. Morphine consumption was significantly higher in the first hour in SG. Motor block was significantly lower in SG. There was no difference between groups regarding cardiocirculatory stability and patient satisfaction and acceptability. Failure occurred in IG (1) and SG (2). Both techniques are safe, effective, and with the same degree of satisfaction and acceptability. The selective blockade of both nerves showed satisfactory analgesia, with the advantage of providing motor block restricted to the shoulder.

Safety and efficacy of fixed-combination travoprost/timolol in patients with open-angle glaucoma or ocular hypertension not controlled with timolol monotherapy

To assess the intraocular pressure (IOP)-lowering effect of travoprost 0.004%/timolol 0.5% fixed-dose combination (TRAV/TIM-FC) in patients not achieving the target IOP of ≤18 mmHg while on timolol 0.5% (TIM) monotherapy. A multicenter, prospective, open-label study (NCT01336569) was conducted in patients with open-angle glaucoma or ocular hypertension. Eligible patients were receiving TIM monotherapy with a screening/baseline IOP of 19-35 mmHg in ≥1 eye. TIM was discontinued on the baseline visit day (no washout period) and TRAV/TIM-FC was initiated and administered once daily at 8 pm for 4-6 weeks. The primary efficacy variable was mean change in IOP from TIM-treated baseline to study end, measured by Goldmann applanation tonometry. Results were analyzed by analysis of variance and paired samples t-test (5% significance). A total of 49 patients were enrolled (mean age, 63 [range, 42-82] years; 55.1% White; 73.5% women), and 45 were included in the intent-to-treat (ITT) population. Mean duration of treatment with TRAV/TIM-FC was 31 days. Mean ± standard deviation IOP reduction from baseline (TIM) to the follow-up visit (TRAV/TIM-FC) was -5.0±3.6 mmHg. IOP decreased significantly (P<0.0001) from baseline (22.1±2.6 mmHg) to study end (17.1±3.9 mmHg) in the ITT population, with a mean IOP reduction of 22.3%. Most patients (n=33/45; 73.3%) achieved IOP ≤18 mmHg. Two patients experienced a total of four adverse events (AEs), including a patient who reported one serious AE (enterorrhagia) that was considered unrelated to treatment, and a patient who reported one event each of drug-related redness, pruritus, and foreign body sensation. Most patients (n=47/49; 95.9%) reported no AEs. TRAV/TIM-FC lowered IOP in patients who were not at target IOP while receiving TIM monotherapy, with most patients achieving an IOP ≤18 mmHg with TRAV/TIM-FC. TRAV/TIM-FC was well tolerated in this population.

Farmacocinética pré-clínica e avaliação toxicológica do novo composto α2-adrenérgico 3-(2-cloro-6-fluorobenzil)-imidazolidina-2,4-diona - PT-31 GIRSUPAN

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Ropivacaína isolada ou associada à morfina, butorfanol ou tramadol pela via peridural em cadelas para realização de Ovariosalpingohisterectomia

The aim of this study was to investigate the use of ropivacaine combined or not with different opioids, for epidural anesthesia in bitches submitted to elective ovariosalpingohisterectomy (OSH). Thirty two mixed-breed female dogs, adults were used with medium weigh of 10.5kg. The animals were premedicated with acepromazine (0.05mg.kg-1, IM) and midazolam (0.2mg.kg-1, IM) and allocated in four experimental groups: group 1(n=8): ropivacaine: 0.3 mL.kg-1; group 2(n=8): ropivacaine + morphine (0.1 mg.kg-1); group 3(n=8): ropivacaine + butorphanol (0.1 mg.kg-1); and group 4(n=8): ropivacaine + tramadol (0.5 mg.kg-1) administered epidurally. Heart and respiratory rate; systolic arterial pressure; rectal temperature; arterial blood gas partial pressures; blood pH; sedation and muscular relaxation degree were evaluated at different experimental moments. The data were submitted to ANOVA and compared by Kruskal Wallis, Friedman, Dunn, Tukey and Chi-square test (p≤0.05). Minimum cardiorespiratory alterations were observed and the group of the ropivacaíne combined with the butorphanol (G3) presented a more cranial blockage, what allowed the accomplishment of OSH without induction in six animals (75%) whereas most of the others needed anesthetic rescue. The results allow us to conclude that the use of ropivacaine sole or combinated with morphine, butorphanol or tramadol, for epidural anesthesia, didn't promote significant cardiorrespiratory depression and the ropivacaine associated to the butorphanol allowed the accomplishment of OSH in bitches.

Duloxetina para melhoria na qualidade de recuperação anestésica em histerectomia abdominal

Pós-graduação em Anestesiologia - FMB

Renal function after laparoscopic cholecystectomy and analgesia with tramadol and dipyrone or ketorolac

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Antinociception induced by acute oral administration of sweet substance in young and adult rodents: The role of endogenous opioid peptides chemical mediators and mu(1)-opioid receptors

The present work aimed to investigate the effects of acute sucrose treatment on the perception of painful stimuli. Specifically, we sought to determine the involvement of the endogenous opioid peptide-mediated system as well as the role of the mu(1)-opioid receptor in antinociception organisation induced by acute sucrose intake. Nociception was assessed with the tail-flick test in rats (75, 150 and 250 g) of different ages acutely pre-treated with 500 mu L. of a sucrose solution (25, 50, 150 and 250 g/L) or tap water. Young and Adult rats (250 g) showed antinociception after treatment with 50 g/L (during 5 min) and 150 g/L and 250 g/L (during 20 min) sucrose solutions. Surprisingly, this antinociception was more consistent in mature adult rodents than in pups. To evaluate the role of opioid systems, mature adult rodents were pre-treated with different doses (0.25, 1 or 4mg/kg) of the non-selective opioid receptor antagonist naloxone, the selective pi-opioid receptor antagonist naloxonazine or vehicle followed by 250 g/L sucrose solution treatment. Sucrose-induced antinociception was reduced by pre-treatment with both naloxone and naloxonazine. The present findings suggest that sweet substance-induced hypo-analgesia is augmented by increasing sucrose concentrations in young and adult rodents. Acute oral sucrose treatment inhibits pain in laboratory animal by mediating endogenous opioid peptide and mu(1)-opioid receptor actions. (C) 2011 Elsevier Inc. All rights reserved.

Stimulation of peripheral Kappa opioid receptors inhibits inflammatory hyperalgesia via activation of the PI3K gamma/AKT/nNOS/NO signaling pathway

Background: In addition to their central effects, opioids cause peripheral analgesia. There is evidence showing that peripheral activation of kappa opioid receptors (KORs) inhibits inflammatory pain. Moreover, peripheral mu-opioid receptor (MOR) activation are able to direct block PGE(2)-induced ongoing hyperalgesia However, this effect was not tested for KOR selective activation. In the present study, the effect of the peripheral activation of KORs on PGE(2)-induced ongoing hyperalgesia was investigated. The mechanisms involved were also evaluated. Results: Local (paw) administration of U50488 (a selective KOR agonist) directly blocked, PGE(2)-induced mechanical hyperalgesia in both rats and mice. This effect was reversed by treating animals with L-NMMA or N-propyl-L-arginine (a selective inhibitor of neuronal nitric oxide synthase, nNOS), suggesting involvement of the nNOS/NO pathway. U50488 peripheral effect was also dependent on stimulation of PI3K gamma/AKT because inhibitors of these kinases also reduced peripheral antinociception induced by U50488. Furthermore, U50488 lost its peripheral analgesic effect in PI3K gamma null mice. Observations made in vivo were confirmed after incubation of dorsal root ganglion cultured neurons with U50488 produced an increase in the activation of AKT as evaluated by western blot analyses of its phosphorylated form. Finally, immunofluorescence of DRG neurons revealed that KOR-expressing neurons also express PI3K gamma (congruent to 43%). Conclusions: The present study indicates that activation of peripheral KORs directly blocks inflammatory hyperalgesia through stimulation of the nNOS/NO signaling pathway which is probably stimulated by PI3K gamma/AKT signaling. This study extends a previously study of our group suggesting that PI3K gamma/AKT/nNOS/NO is an important analgesic pathway in primary nociceptive neurons.

Topical Treatment Using Amphotericin B and DMSO for an Atypically Located Equine Cutaneous Pythiosis

Background: Cutaneous lesions by Pythium insidiosum infection are commonly observed in horses, especially in those living at flooded environments. Equine pythiosis is characterized by the development of tumoral masses that are frequently located at distal limbs, ventral abdomen, thorax, breast and face. The lesions are usually granulomatous, serosanguineous and ulcerated, most often destroyed by self-mutilation due to the intense pruritus. The proposed treatment includes surgical excision followed by antifungal drugs administration, which can be done systemically or topically. Amphotericin B and dimethyl sulfoxide (DMSO) in association has been successfully used for cutaneous pythiosis topical treatment due to the DMSO property to carry any substance through plasmatic membranes. Case: The present report concerns a 12-year-old mixed breed gelding presenting with self-mutilation of a tumoral mass located at the left flank. The owners reported that the horse had initially presented a small wound that had evolved to a 20-cm in diameter mass in 4 weeks. Tissue samples were collected, processed and stained by the Gomori's methenamine silver (GMS) method. The histopathological analysis revealed Pythium insidiosum hyphae in a granulomatous tissue, especially located at peripheral region, where kunkers were present. Surgical excision of the mass followed by cauterization was indicated as initial treatment, and due to financial reasons, the owners elected only the topical antifungal therapy to control the fungus infection after surgery. Flunixin meglumine was also administrated for five days aiming the control of pain and inflammation. The wound was cleaned with povidone-iodine solution and rinsed with a solution containing, 50 mg, of amphotericin B in 10 mL of sterile water and 10 mL of DMSO. This procedure was carried Out twice a day. The wound healed fast due to an excellent centripetal epithelialization. and the horse was discharged after 64 days showing only 5% of the initial wound area. The owner reported by telephone the complete healing and hair growth 10 days after discharge. Discussion: Despite the atypical location of the tumoral lesion described at the present report, the history and clinical manifestations, especially the intense pruritus, showed similarity with other characteristic reports of equine cutaneous pythiosis. The diagnosis was confirmed by the histopathological examination showing hyphae structures, as described to be evidences of the presence of Pythium insidiosum in the tissue. The surgical procedure was the first step to provide remission of clinical signs, and one day after surgery the pruritus desapeared. After excision of the granulomatous tissue and cauterization, daily topical administration of amphotericin B associated with DMSO was effective in destroying the infectious agent, as observed by the excellent epithelization. A pink granulation tissue grew up providing an ideal surface for epithelial migration and the healing process progressed quickly. Centripetal epithelialization reduced the wound area until 3% of the initial area in 64 days of treatment, when the remaining wound was found almost completely healed and covered with hair. At the present report, the horse presenting pythiosis was only topically treated. The recommended therapy using amphotericin B and DMSO solution was effective, economically viable and low risk, considering that the systemic antifungal therapy usually suggested is expensive and extremely nephrotoxic. The atypical location of the lesion on the left flank shows that any anatomical region can be affected by the fungus, since the conditions for its development were present.

Determination of Opiates in Whole Blood and Vitreous Humor: A Study of the Matrix Effect and an Experimental Design to Optimize Conditions for the Enzymatic Hydrolysis of Glucuronides

Faculty of Medicine University of Sao Paulo

Opioid mu-receptors in the rostral medullary raphe modulate hypoxia-induced hyperpnea in unanesthetized rats

Aim: It has been suggested that the medullary raphe (MR) plays a key role in the physiological responses to hypoxia. As opioid mu-receptors have been found in the MR, we studied the putative role of opioid mu-receptors in the rostral MR (rMR) region on ventilation in normal and 7% hypoxic conditions. Methods: We measured pulmonary ventilation ((V) over dotE) and the body temperatures (Tb) of male Wistar rats before and after the selective opioid l-receptor antagonist CTAP ( d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2, cyclic, 0.1 mu g per 0.1 mu L) was microinjected into the rMR during normoxia or after 60 min of hypoxia. Results: The animals treated with intra-rMR CTAP exhibited an attenuation of the ventilatory response to hypoxia ( 430 +/- 86 mL kg) 1 min) 1) compared with the control group ( 790 +/- 82 mL kg) 1 min) 1) ( P < 0.05). No differences in the Tb were observed between groups during hypoxia. Conclusion: These data suggest that opioids acting on l-receptors in the rMR exert an excitatory modulation of hyperventilation induced by hypoxia.