86 resultados para morfina


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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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Morphine is a potent analgesic opioid used extensively for pain treatment. During the last decade, global consumption grew more than 4-fold. However, molecular mechanisms elicited by morphine are not totally understood. Thus, a growing literature indicates that there are additional actions to the analgesic effect. Previous studies about morphine and oxidative stress are controversial and used concentrations outside the range of clinical practice. Therefore, in this study, we hypothesized that a therapeutic concentration of morphine (1 μM) would show a protective effect in a traditional model of oxidative stress. We exposed the C6 glioma cell line to hydrogen peroxide (H2O2) and/or morphine for 24 h and evaluated cell viability, lipid peroxidation, and levels of sulfhydryl groups (an indicator of the redox state of the cell). Morphine did not prevent the decrease in cell viability provoked by H2O2) but partially prevented lipid peroxidation caused by 0.0025% H2O2) (a concentration allowing more than 90% cell viability). Interestingly, this opioid did not alter the increased levels of sulfhydryl groups produced by exposure to 0.0025% H2O2), opening the possibility that alternative molecular mechanisms (a direct scavenging activity or the inhibition of NAPDH oxidase) may explain the protective effect registered in the lipid peroxidation assay. Our results demonstrate, for the first time, that morphine in usual analgesic doses may contribute to minimizing oxidative stress in cells of glial origin. This study supports the importance of employing concentrations similar to those used in clinical practice for a better approximation between experimental models and the clinical setting.

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

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Pós-graduação em Anestesiologia - FMB

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The present study investigated the benefits of tumescent anesthesia with lidocaine in dogs undergoing mastectomy, seeking the patients' comfort and their postoperative recovery. Seven animals, with different weight and breed, who had cancer in the region of mammary chain underwent mastectomy surgery. All animals received the same anesthetic protocol being used as the association between acepromazine and morphine doses of 0.04mg.kg-1 and 0.4mg.kg-1 (IM), respectively. After 15 minutes a catheter was placed in the cephalic vein and induction with propofol 4mg.kg-1 and 0.2mg.kg-1 followed by maintenance with isoflurane anesthesia was done. After instrumentation, we proceeded to the tumescent anesthesia technique with ice-cold solution consisting of Ringer's lactate, lidocaine 2% without epinephrine and adrenaline in a total volume of 15mL.kg-1. The average duration of the procedure was 74±18 minutes. The plasmatic peak of lidocaine was between 30 and 60 minutes after infiltration. The rescue analgesic was performed after approximately seven hours of infiltration. It can be concluded that the tumescent anesthesia with lidocaine should be considered as a constituent of anesthetic and analgesic protocol in dogs undergoing mastectomy surgery providing parameter stability, safety and good quality postoperative recovery.

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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)

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The aims of this study were to evaluate the isoflurane sparing and clinical effects of a constant rate infusion of morphine - lidocaine - ketamine (MLK) in healthy sheep undergoing experimental gastrointestinal surgery. Twelve adult female sheep (Texel breed) were used, weighing 36.5 +/- 8.1 kg. The sheep were anesthetized for the implantation of duodenal cannulas. The sheep were premedicated with 0.3 mg kg(-1) intramuscular (IM) morphine and 20 mu g kg(-1) intravenous (IV) detomidine. After premedication, anesthesia was induced using 5 mg kg(-1) ketamine and 0.5 mg kg(-1) diazepam IV and maintained using isoflurane in 100% oxygen. After the induction of anesthesia, the animals were allocated into two groups (each n=6); the GMLK (MLK group - 10 mg morphine, 150 mg lidocaine, 30 mg de ketamine were added in 500 mL saline) received a 10 mL kg(-1)h(-1) MLK infusion during the maintenance of anesthesia, and GCON (control group) received 10 mL kg(-1)h(-1) of 0.9% sodium chloride. The animals were mechanically ventilated. Cardiopulmonary variables and end-tidal isoflurane concentration (FE'Iso) were measured at baseline (immediately before the surgery) and 15, 30 and 45 minutes after initiation of surgery. In GMLK, there was a decrease in the FE 'Iso at 15, 30 and 45 minutes, a reduction of up to 75.6% during the surgery. The HR was lower in GMLK compared with GCON at 30 minutes, and the MAP was at during baseline in GCON compared with GMLK. The standing time was less in GMLK than in GCON. The use of intravenous MLK was demonstrated to offer great efficiency as part of a balanced anesthesia protocol in sheep, with a 75.6% reduction in the need for isoflurane, providing stability of the cardiovascular parameters and blood gases with a shortened recovery period.

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The prophylactic effect of ondansetron on subarachnoid morphine-induced pruritus is controversial, while evidence suggests that droperidol prevents pruritus. The aim of this study is to compare the effects of droperidol and ondansetron on subarachnoid morphine-induced pruritus. 180 ASA I or II patients scheduled to undergo cesarean sections under subarachnoid anesthesia combined with morphine 0.2mg were randomized to receive, after the child's birth, metoclopramide 10mg (Group I - control), droperidol 2.5mg (Group II) or ondansetron 8mg (Group III). Postoperatively, the patients were assessed for pruritus (absent, mild, moderate or severe) or other side effects by blinded investigators. Patients were also blinded to their group allocation. The tendency to present more severe forms of pruritus was compared between groups. NNT was also determined. Patients assigned to receive droperidol [Proportional odds ratio: 0.45 (95% confidence interval 0.23-0.88)] reported less pruritus than those who received metoclopramide. Ondansetron effect was similar to metoclopramide [Proportional odds ratio: 0.95 (95% confidence interval 0.49-1.83)]. The NNT for droperidol and ondansetron was 4.0 and 14.7, respectively. Ondansetron does not inhibit subarachnoid morphine-induced pruritus.

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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Pós-graduação em Anestesiologia - FMB