ABSTRACT
Entre los fármacos utilizados actualmente en el tratamiento de las afecciones cardiovasculares, se encuentran el fosfato de disopiramida, un agente antiarrítmico tipo I, estabilizante del potencial de membrana en reposo. Una de las formas farmacéuticas en que este se presenta es la de inyectable, con una dosificasión de 13 mg/mL para la base, por lo que en este trabajo se realizó el estudio acelerado de estabilidad y el estudio de vida útil de 3 lotes de este innyectable. En las condiciones ensayadas, el medicamento resultó estable, por lo que se propuso una fecha de vencimiento de 2 años(AU)
Subject(s)
Disopyramide/therapeutic use , Disopyramide/pharmacology , Drug Stability , Anti-Arrhythmia Agents/therapeutic use , Anti-Arrhythmia Agents/pharmacologyABSTRACT
The block of the transient outward K(+) current (I(to)) by disopyramide was studied in isolated rat right ventricular myocytes using whole cell patch-clamp techniques. Disopyramide at a concentration of 10 to 1000 microM reduced peak I(to) and accelerated the apparent rate of current inactivation. The onset of block was assessed using a double pulse protocol with steps from -70 to +50 mV. As the duration of the first (conditioning) pulse was increased from 1 to 50 ms, block was increased. Further prolongation of the conditioning pulse resulted in relief of block, which was nearly complete with a 1-s conditioning pulse. In the absence of drug, the recovery from inactivation of I(to) at -70 mV was fast and best fit with a single exponential function having a time constant of 33 +/- 13 ms. In contrast, in the presence of 100 microM disopyramide, recovery from apparent inactivation was biexponential with time constants of 35 +/- 13 ms and 7.16 +/- 1.5 s. The time course of the slow component was used to estimate recovery of channels from block by disopyramide. Recovery from block was voltage-dependent, suggesting that disopyramide was trapped by the open channel. Taken together, these results suggest that disopyramide rapidly blocks channels in the open state and that unblock occurs from the inactivated state.
Subject(s)
Anti-Arrhythmia Agents/pharmacology , Disopyramide/pharmacology , Potassium Channel Blockers , Algorithms , Animals , Cell Separation , Heart/drug effects , In Vitro Techniques , Ion Channel Gating , Myocardium/cytology , Myocardium/metabolism , Patch-Clamp Techniques , Rats , Time FactorsSubject(s)
Blood Pressure/drug effects , Disopyramide/pharmacology , Heart Rate/drug effects , Myocardial Infarction/physiopathology , Pyridines/pharmacology , Adult , Aged , Arrhythmias, Cardiac/drug therapy , Female , Humans , Male , Middle Aged , Myocardial Infarction/complications , PhonocardiographyABSTRACT
La respuesta presora inducida por la galantamina en la rata, es un modelo experimental para el estudio de drogas hipotensoras que actúan a través del Sistema Nervioso Central (SNC). El presente trabajo fue realizado con el objetivo de determinar un posible componente central en el mecanismo de acción de la clonidina, la tiamenidina y la disopiramida, y se comprobó que estas drogas no antagonizaron la respuesta presora a la galantamina, bajo nuestras condiciones experimentales(AU)