RESUMO
The aim of this study was to compare the effects of cisapride and tegaserod on intestinal smooth muscle activity in equines. Efficacy was evaluated through measurement of gastrointestinal transit time, bowel movements per day, stool weight, and bowel sounds. Drug safety was evaluated via heart rate, respiratory rate, and rectal temperature. Records were obtained throughout three periods: a control phase without treatment, a period of cisapride administration at a dose of 0.22 mg/kg, and a period of tegaserod treatment at a dose of 0.27 mg/kg. Gastrointestinal transit time, bowel movements per day, and stool weight were significantly improved on administration of both cisapride and tegaserod, as compared with the control phase. With tegaserod administration, gastrointestinal transit time accelerates more than to cisapride administration; however, no significant difference was seen in bowel movements per day and stool weight. In terms of heart rate, respiratory rate, and rectal temperature, no significant variations were seen between the three sample phases. Because of the above findings, tegaserod can be considered an effective stimulant of intestinal smooth muscle, accelerating gastrointestinal transit time in healthy horses and representing a potential therapeutic agent similar to cisapride.
Assuntos
Defecação , Indóis , Animais , Cisaprida/farmacologia , Cavalos , Indóis/farmacologia , Músculo LisoRESUMO
Nowadays, the pharmacological therapy for the treatment of Chagas disease is based on two old drugs, benznidazole and nifurtimox, which have restricted efficacy against the chronic phase of the illness. To overcome the lack of efficacy of the traditional drugs (and their considerable toxicity), new molecular targets have been studied as starting points to the discovery of new antichagasic compounds. Among them, polyamine transporter TcPAT12 (also known as TcPOT1.1) represents an interesting macromolecule, since polyamines are essential for Trypanosoma cruzi, the parasite that causes the illness, but it cannot synthesize them de novo. In this investigation we report the results of a combined ligand- and structure-based virtual screening for the discovery of new inhibitors of TcPAT12. Initially we filtered out ZINC and Drugbank databases with similarity and QSAR models and then we submitted the candidates to a validated docking based screening. Four structures were selected and tested in T. cruzi epimastigotes proliferation and two of them, Cisapride and [2-(cyclopentyloxy)phenyl]methanamine showed inhibitory effects. Additionally, we performed transport assays which demonstrated that Cisapride interferes with putrescine uptake in a specific mode.
Assuntos
Doença de Chagas/tratamento farmacológico , Cisaprida/farmacologia , Proteínas de Protozoários/antagonistas & inibidores , Putrescina/antagonistas & inibidores , Trypanosoma cruzi/efeitos dos fármacos , Transporte Biológico/efeitos dos fármacos , Cisaprida/uso terapêutico , Avaliação Pré-Clínica de Medicamentos/métodos , Ligantes , Proteínas de Membrana Transportadoras/efeitos dos fármacos , Simulação de Acoplamento Molecular/métodos , Estrutura Molecular , Poliaminas/farmacocinética , Putrescina/farmacocinética , Trypanosoma cruzi/metabolismoAssuntos
Humanos , Feminino , Idoso , Esvaziamento Gástrico , Gastroparesia , Gastroparesia/diagnóstico , Cintilografia/métodos , Cisaprida/administração & dosagem , Transtornos da Motilidade Esofágica , Fármacos Gastrointestinais/uso terapêutico , Comportamento Alimentar , Metoclopramida/administração & dosagem , Motilidade GastrointestinalRESUMO
Prokinetic agents are a very large family of drugs with different mechanisms of action. Only QT prolongation by cisapride has made notable impact and deserved its partial restriction and/or withdrawal from the market. Postmarketing surveillance initially showed that cisapride was generally safe and well tolerated, but in the past decade, more recent data have shown some risk in the patient populations. QT prolongation by prokinetic agents can raised from different mechanisms: some involve increased plasma concentrations of cisapride due to increased bioavailability by inhibiting P glycoprotein, and inhibition of metabolism or deficit in the elimination. On the other hand, pharmacodynamic interactions can also enhance the arrhythmogenic effect of cisapride. The present article presents the mechanisms and reviews the main interactions studied so far, and the role of pharmacovigilance in the detection of rare clinical events. We emphasize the need for physicians to look for conditions (either clinical or not) prone to increase the risk of QT interval prolongation.
Assuntos
Cisaprida/efeitos adversos , Fármacos Gastrointestinais/efeitos adversos , Síndrome do QT Longo/induzido quimicamente , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Sistemas de Notificação de Reações Adversas a Medicamentos , Animais , Disponibilidade Biológica , Cisaprida/farmacocinética , Interações Medicamentosas , Fármacos Gastrointestinais/farmacocinética , Humanos , Fatores de Risco , Agonistas do Receptor de Serotonina/efeitos adversos , Agonistas do Receptor de Serotonina/farmacocinéticaAssuntos
Domperidona/farmacologia , Síndrome do QT Longo/tratamento farmacológico , Animais , Cisaprida/efeitos adversos , Antagonistas de Dopamina/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Refluxo Gastroesofágico/tratamento farmacológico , Humanos , Contração Miocárdica/efeitos dos fármacos , Risco , Fatores de Risco , Torsades de Pointes/etiologia , Torsades de Pointes/prevenção & controleAssuntos
Humanos , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Cisaprida/efeitos adversos , Cisaprida/uso terapêutico , Fatores de RiscoAssuntos
Humanos , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Cisaprida , Fatores de RiscoRESUMO
To evaluate the effects of bethanechol and cisapride on urodynamic parameters in patients undergoing radical hysterectomy for cervical cancer. In this double-blind, placebo-controlled study, 79 patients with cervical cancer were randomized to receive bethanechol (30 mg/day), cisapride (30 mg/day), bethanechol combined with cisapride (same doses) and placebo. Urodynamic study was performed, including flowmetry, cystometry, pressure-flow study and urethral pressure profile before radical hysterectomy. Medication was administered postoperatively during 30 days. At the end of this period, urodynamic evaluation was repeated. There was an increase in both the maximum cystometric capacity and bladder capacity at first desire to void in the placebo group compared to the other groups. The rate of detrusor instability was higher in the group that used bethanechol combined with cisapride. Detrusor pressure at maximum flow was significantly higher when cisapride was used. There was a significant increase in postvoid residual volume in the placebo group. In patients undergoing radical hysterectomy, bethanechol and cisapride determined lower cystometric capacity and decreased bladder capacity at first desire to void, a higher maximum flow rate and higher detrusor pressure at maximum flow, with lower postvoid residual volumes. The early use of bethanechol and cisapride after radical hysterectomies positively modified urodynamic parameters, determining a more efficient detrusor function.
Assuntos
Betanecol/uso terapêutico , Cisaprida/uso terapêutico , Fármacos Gastrointestinais/uso terapêutico , Histerectomia/métodos , Agonistas Muscarínicos/uso terapêutico , Urodinâmica/efeitos dos fármacos , Neoplasias do Colo do Útero/cirurgia , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Manometria , Pessoa de Meia-Idade , Placebos , Pressão , Reologia , Uretra/efeitos dos fármacos , Uretra/fisiopatologia , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/fisiopatologia , Micção/efeitos dos fármacos , Micção/fisiologia , Urina , Urodinâmica/fisiologiaRESUMO
El íleo posquirurgico es una condición en la cual cesa la motilidad gastrointestinal posterior a un procedimiento quirúrgico donde se manipulen las asas intestinales. Nuestro objetivo es determinar el efecto de los farmacos cisapride, lidocaina, eritromicina y ondansetrón en el íleo experimental de ratas. Se realizaron 7 grupos de ratas. Cinco de estos grupos fueron laparotomizados con manipulación intestinal, un grupo con laparotomía sin manipulación y un grupo solo anestesiado sin intervención quirúrgica. A cuatro de los grupos con manipulación intestinal se les administró uno de los fármacos en estudio, el quinto grupo manipulado no recibió nada al igual que los otros dos grupos sin manipulación. A todos los grupos se les administró azul de Evans a través de sonda intragástrica y se midió la migración del colorante a través del intestino. La única droga que mejora significativamente la motilidad post íleo fue el Cisapride (p=0.05) cuando se compara con el grupo de laparotomía y manoseo sin medicación. La motilidad rtetardada de este último grupo también es significativo cuando se compara con los grupos de anestesia sola o de laparotmía sin manoseo. Los demás resultados fueron no significativos. El Cisapride, probablemente a través de su acción estimuladora de la liberación de aceticolina, mejora notablemente el íleo postoperatorio de rata inducido por manipulación intestinal
Assuntos
Animais , Ratos , Traumatismos Abdominais , Cisaprida , Eritromicina , Motilidade Gastrointestinal , Ileostomia , Lidocaína/administração & dosagem , Ondansetron , Gastroenterologia , VenezuelaRESUMO
La eritromicina y el cisapride son fármacos procinéticos con diferentes vías de acción. El objeto del prersente estudio es avaluar comparativamente el efecto de eritromicina y cisapride en segmentos aislados de duodeno de conejo. Se extrajo el duodeno de 6 conejos y se mantuvieron funcionales en un baño de tejido. Se registro la motilidad duodenal usando un trasductor de tensión. El tono muscular duodenal aumentó dependiendo de la concentración del medicamento, siendo la acción de la eritromicina mas potente que la de el cisapride. La actividad de la eritromicina aumentó hasta alcanzar una meseta y no se observaron diferencias en la frecuencia de las contracciones. La eritromicina es un procinético mas potente que el cisapride en el duodeno del conejo