RESUMO
The purpose of this study was to evaluate the antinociceptive interaction between dexketoprofen and tapentadol in three different dose ratios, as well as the ulcerogenic activity of this combination. Dose-response curves were carried out for dexketoprofen, tapentadol, and dexketoprofen-tapentadol combinations in the acetic acid-induced writhing test in mice. On the other hand, the gastric damage of all treatments was assessed after the surgical extraction of the stomachs. Intraperitoneal administration of dexketoprofen and tapentadol induced a dose-dependent antinociceptive effect, reaching a maximal effect of about 58% and 99%, respectively. Isobolographic analysis and the interaction index showed that the three proportions produced an analgesic potentiation (synergistic interaction). Interestingly, the 1:1 and 1:3 ratios of the drugs combination produced minor gastric injury in comparison with the 3:1 proportion. Our data suggest that all proportions of the dexketoprofen-tapentadol combination produced a synergistic interaction in the acetic acid-induced visceral pain model in mice with a low incidence of gastric injury.
Assuntos
Analgésicos/farmacologia , Cetoprofeno/análogos & derivados , Dor Nociceptiva/prevenção & controle , Tapentadol/farmacologia , Trometamina/farmacologia , Analgésicos/administração & dosagem , Analgésicos/efeitos adversos , Animais , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Sinergismo Farmacológico , Cetoprofeno/administração & dosagem , Cetoprofeno/efeitos adversos , Cetoprofeno/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Medição da Dor , Úlcera Gástrica/induzido quimicamente , Tapentadol/administração & dosagem , Tapentadol/efeitos adversos , Trometamina/administração & dosagem , Trometamina/efeitos adversosRESUMO
Dexketoprofen trometamol (DT) is an active S (+) enantiomer of ketoprofen, and a non-steroidal anti-inflammatory agent. DT has a short biological half-life and the dosing interval is quite short when there is a need to maintain the desirable effect for longer time periods. Consequently, a controlled release DT tablet was designed for oral administration aiming to minimize the number of doses and the possible side effects. Calculations of the parameters for controlled release DT tablets were shown clearly. Controlled release matrix-type tablet formulations were prepared using hydroxypropyl methylcellulose (HPMC) (low and high viscosity), Eudragit RS and Carbopol, and the effects of different polymers on DT release from the tablet formulations were investigated. The dissolution rate profiles were compared and analyzed kinetically. An Artificial Neural Network (ANN) model was developed to predict drug release and a successful model was obtained. Subsequently, an optimum formulation was selected and evaluated in terms of its analgesic and anti-inflammatory activity. Although the developed controlled release tablets did not have an initial dose, they were found to be as effective as commercially available tablets on the market. Dissolution and in vivo studies have shown that the prepared tablets were able to release DT for longer time periods, making the tablets more effective, convenient and more tolerable.
Assuntos
Comprimidos/análise , Trometamina/efeitos adversos , Administração Oral , Anti-Inflamatórios não Esteroides/efeitos adversos , Cetoprofeno/agonistas , Dosagem/efeitos adversos , Liberação Controlada de Fármacos/efeitos dos fármacos , Analgésicos/farmacocinéticaRESUMO
Dexketoprofene (De) NSAID was studied as a selective COX-1 inhibitor in comparison with Ketorolac (Ke), a mainly COX-1 inhibitor. De and Ke were administered to different groups of animals in a dose-dependent manner, i.e., 3-15 and 25 mgs/kg. The gastrointestinal mucosa damage was macroscopically and microscopically quantified at 24 hs, as well as leukocyte infiltration (LI) and neosinophilia. Similarly, Indomethacin (Indo) damage (COX-1-COX-2), with 25 mgs/kg. Dose was compared. On the other hand, De and Ke at inhibitory selective COX-1 dose (3 mg/kg) plus Celecoxib, selective COX-2 inhibitor, yielding no gastrointestinal damage, with decreased LI and without neutrophilia, the same as Ke (n.s.). Similarly De at higher dose (2.5 mgs/kg), produced minimal gastrointestinal lesions, showing a preferential COX-1 inhibitor behavior. Ke and Indo produced important gastrointestinal necrotic and erosive lesions with remarkable LI and neutrophilia (p < 0.001). On the other hand, COX-1 De dose plus Celecoxib produced evident gastrointestinal lesions, increased LI and neutrophilia, the same as Indo, pointing out that the gastrointestinal damage is due to COX-1 and COX-2 inhibition.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Inibidores de Ciclo-Oxigenase/efeitos adversos , Mucosa Intestinal/efeitos dos fármacos , Cetoprofeno/análogos & derivados , Cetoprofeno/efeitos adversos , Trometamina/análogos & derivados , Trometamina/efeitos adversos , Análise de Variância , Animais , Celecoxib , Avaliação Pré-Clínica de Medicamentos , Mucosa Gástrica/efeitos dos fármacos , Humanos , Cetorolaco/farmacologia , Pirazóis , Ratos , Ratos Wistar , Sulfonamidas/farmacologiaRESUMO
Nas gestantes säo frequentes as infecçäoes do trato urinário, devendo ser diagnosticadas e tratadas antes da 16ª semana de gestaçäo, devido às suas repercussöes tardias como referido na literatura. Entre estas, a bacteriúrias assintomática que, se näo tratada, leva à pielonefrite em cerca de 25 por cento dos casos. Considerando as vantagens que oferece o tratamento em dose única, os autores realizaram um estudo 50 mulheres em idde fértil, gestantes ou näo, portadoras de cardiopatia, sem repercussäo hemodinâmica, de graus funcionais New York Heart Association (NYHA) I e II e com infecçäo dotrato urinário. A todas foi administrada fosfomicina trometamol em dose única de 3 g. Foram realizadas avaliaçöes clínicas, incluindo eletrocardiograma com 12 derivaçöes e as oportunas análises laboratoriais antes e após o tratamento. As pacientes gestantes foram acompanhadas até o termo, analisando-se os dados maternos de parto e puerpério e os dados dos recém-nascidos em relaçäo ao peso, comprimento e desenvolvimento. No grupo de 28 gestantes, 25 responderam positivamente ao tratamento (89,3 por cento); em três casos foi necessário o emprego de outras drogas, conforme indicaçäo do antibiograma. Em um caso de nova infecçäo foi repetido o tratamento com fosfomina trometamol com bom resultado. No grupo de 22 näo-gestantes, 21 pacientes responderam positivamente ao tratamento (95,5 por cento). Só um caso näo respondeu ao tratamento, sendo tratado com êxito com cefoxitina. A análise dos recém-nascidos mostrou que o tratamento com fosfomicina trometamol, em dose única de 3 g, näo influenciou o desenvolvimento dos conceptos, independentemente da idade gestacional em que a droga foi utilizada. Os efeitos colaterais limitaram-se a três casos de náuseas e um de vômito (no total, 8 por cento)
Assuntos
Humanos , Feminino , Gravidez , Adolescente , Adulto , Fosfomicina/administração & dosagem , Fosfomicina/efeitos adversos , Cardiopatias , Infecções Urinárias/tratamento farmacológico , Complicações Cardiovasculares na Gravidez , Trometamina/administração & dosagem , Trometamina/efeitos adversos , Anti-Infecciosos Urinários , Sistema Urinário/lesõesRESUMO
OBJECTIVE: To report a case of ketorolac tromethamine-induced acute renal failure and to discuss the risk factors that make patients more susceptible to the renal effects of nonsteroidal antiinflammatory drugs (NSAIDs). DATA SOURCES: Case reports and review articles identified by MEDLINE. Indexing terms included ketorolac, renal failure, and NSAIDs. DATA EXTRACTION: Data were abstracted from pertinent published English-language sources and were reviewed by all authors. DATA SYNTHESIS: Ketorolac is an intramuscularly administered NSAID with many of the same adverse effects associated with other oral NSAIDs. Although reversible depression of renal function has been associated with several NSAIDs, to date there have been no published reports of acute renal failure secondary to ketorolac administration. A 71-year-old woman received three doses of ketorolac to control the pain associated with pelvic and T11-T12 compression fractures. Over the next two days, the patient developed signs and symptoms of acute renal failure, including significant increases in blood urea nitrogen, serum creatinine, and peripheral edema. These signs and symptoms resolved over the next three to four days. Certain risk factors, several of which were present in this woman, make individual patients more susceptible to the renal affects of NSAIDs. These risk factors include advanced age, cirrhosis, volume depletion, congestive heart failure, gastrointestinal bleeding, and preexisting mild renal dysfunction. CONCLUSIONS: Caution should be taken when initiating ketorolac or any NSAID therapy with specific attention to risk factors that predispose a patient to renal dysfunction.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Falência Renal Crônica/induzido quimicamente , Tolmetino/análogos & derivados , Trometamina/efeitos adversos , Idoso , Anti-Inflamatórios não Esteroides/administração & dosagem , Combinação de Medicamentos , Feminino , Humanos , Injeções Intramusculares , Cetorolaco de Trometamina , Tolmetino/administração & dosagem , Tolmetino/efeitos adversos , Trometamina/administração & dosagemRESUMO
OBJECTIVE: To report a case of an anaphylactoid reaction to injectable ketorolac tromethamine in a patient with no prior history of allergies or risk factors associated with nonsteroidal anti-inflammatory drug-induced hypersensitivity reactions. CASE SUMMARY: A 37-year-old man without a significant medical history presented to an emergency department with vague, dull, left-sided chest pain. Myocardial infarction was ruled out based on an unremarkable electrocardiogram, chest X-ray, and laboratory data that were within normal limits. Sublingual nitroglycerin 0.4 mg, magnesium/aluminum hydroxide gel 30 mL, and intravenous ranitidine 50 mg were administered without resolution of symptoms. Ketorolac tromethamine 60 mg was administered intramuscularly with resolution of symptoms. The patient was discharged; however, within 30 minutes, he returned to the emergency department with facial swelling, shortness of breath, and chest tightness. Multiple doses of aerosolized albuterol and intravenous methylprednisolone and diphenhydramine were administered, resulting in a slight improvement of symptoms. The patient was admitted for a complete cardiac evaluation that proved negative. The allergic symptoms resolved and the patient was discharged without medication after a three-day hospitalization. DISCUSSION: Ketorolac tromethamine is the first injectable nonsteroidal antiinflammatory drug approved for short-term pain management. A review of the literature revealed no similar cases of anaphylactoid reaction. CONCLUSIONS: Healthcare professionals must be aware of the potential risks of anaphylactoid reactions, especially in light of the increased use of injectable ketorolac in the ambulatory setting and availability of the oral formulation.