ABSTRACT
Objetivos Determinar los posibles resultados negativos asociados a la medicación mediante la metodología de búsqueda activa de posibles interacciones medicamentosas en bases de datos de pacientes afiliados al Sistema General de Seguridad Social en Salud. Métodos A partir de las bases de datos de dispensación de medicamentos de Audifarma S.A a unos 4 millones de usuarios del país, se hizo una revisión sistemática de estadísticas de una serie de medicamentos identificados por presentar interacciones de riesgo, dosis diferentes a las recomendadas o dispensación irregular. Los casos son socializados con las EPS responsables. Resultados Se encontró un caso de nefrotoxicidad por ácido zoledrónico; el 37,0 por ciento de los usuarios de clopidogrel recibían concomitantemente omeprazol, que reduce la efectividad del primero; el 29,9 por ciento de los pacientes que toman losartan están recibiendo dosis superiores a las recomendadas para su indicación; el 2,0 por ciento de los pacientes que toman metoprolol o verapamilo, los recibe simultáneamente, con riesgo de generar bradicardia sinusal, bloqueos auriculoventriculares o disfunción sistólica. Todos los casos fueron notificados a los responsables en la EPS que atienden estos pacientes. Discusión La farmacovigilancia activa permite optimizar recursos, prevenir eventos adversos que puedan potencialmente causar morbilidad importante o incluso letalidad o determinar problemas que podrían ser responsables del fracaso terapéutico. Este tipo de estrategia se anticipa a la aparición de posibles riesgos para el paciente por lo que se recomienda considerarla para reforzar los programas de vigilancia de uso de medicamentos en el país.
Objectives Determining negative results associated with medication through an active search of possible drug interactions in databases for patients affiliated to the Colombian general social security/health system. Methods Statistics related to Audifarma S.A. dispensation drug databases for about 4 million Colombian users were systematically reviewed for identifying drugs having known interactions involving risk, doses different from recommended ones or irregular dispensation. The pertinent health-care providing services were made aware of the above. Results There was one case of nephrotoxicity being caused by zoledronic acid. 37 percent of clopidogrel users concomitantly received omeprazole which reduces the former's effectiveness. 29.9 percent of patients who were taking losartan were receiving doses higher than the recommended ones. 2.0 percent of patients who were taking metoprolol or verapamil were simultaneously receiving them, at the risk of generating first-degree heart block, bradycardia, or systolic dysfunction. All these cases were notified to the pertinent health-care services. Conclusions Active pharmacosurveillance leads to resources being optimised, adverse events which can potentially cause morbidity or lethality being prevented or even determining problems which could be responsible for therapeutic failure. This type of strategy anticipates the appearance of possible risks for patients, meaning that drug use monitoring programmes in Colombia should be reinforced.
Subject(s)
Humans , Adverse Drug Reaction Reporting Systems , Drug-Related Side Effects and Adverse Reactions/epidemiology , Medication Systems/statistics & numerical data , National Health Programs/statistics & numerical data , Adverse Drug Reaction Reporting Systems/organization & administration , Adverse Drug Reaction Reporting Systems/statistics & numerical data , Calcium Channel Blockers/administration & dosage , Calcium Channel Blockers/adverse effects , Calcium Channel Blockers/pharmacokinetics , Colombia , Diphosphonates/adverse effects , Drug Interactions , Imidazoles/adverse effects , Losartan/adverse effects , Medication Systems/organization & administration , Metoprolol/administration & dosage , Metoprolol/adverse effects , Metoprolol/pharmacokinetics , Omeprazole/administration & dosage , Omeprazole/pharmacokinetics , Retrospective Studies , Social Security , Software , Ticlopidine/administration & dosage , Ticlopidine/adverse effects , Ticlopidine/analogs & derivatives , Ticlopidine/pharmacokineticsABSTRACT
Objetivo: Evaluar el efecto agudo del metoprolol sobre la función autonómica cardiaca en sujetos seropositivos para T. cruzi asintomáticos. Métodos: Un estudio aleatorizado doble ciego, cruzado, placebo controlado fue realizado en 18 sujetos asintomáticos con serología positiva para T. cruzi. Presión arterial no invasiva y frecuencia cardíaca (FC) fueron registradas continuamente. Las intervenciones al azar fueron: 1 Bolos sucesivos de metoprolol de 5 mg i.v (5 cc) cada 5 minutos, máximo 15 mg (15 cc) buscando disminuir en un 20 por ciento la FC y 2. Bolos sucesivos de solución salina normal (SSN) de 5 cc hasta 3 dosis cada 5 minutos utilizando el mismo criterio. Los marcadores autonómicos calaculados previo y posterior a la intervención: 1. variabilidad de la FC en reposos durante 5 minutos, poder total (TP), poder de baja (LFn) y alta frecuencia (HFn) en unidades normalizadas, ïndice LF/HF y RMSSD. 2. Sensibilidad barorrefleja (BRS) utilizando bolos de fenilefrina (FNF) 150 Mg y nitropusiato (NTP) 100 Mg. El estudio se realizó en dos días consecutivos. Resultados: Los marcadores de la actividad tónica vagal (promedioñSD) antes y después de de la intervención con metoprolol fueron: FC 62.3ñ1.7 vs 55.6ñ1.6 lat/min, LFn 62.8ñ4.4 vs 49.8ñ4.7 ms², LF/HF 2.67ñ0.4 vs 1.42ñ0.2 y RMSSD 26.8ñ3.6 vs 41.9ñ6.4 ms, con valores de p<0.05. Conclusiones: La administración de metoprolol mejoró los marcadores de actividad tónica vagal, sin alterar el tono vagal fásico evaluado por la SBR. Los reflejos cardiovagales pueden ser modificados por la administración aguda de metoprolol en sujetos asintomáticos seropositivos para T. cruzi. Palabras clave: Enfermedad de Chagas, metoprolol, sistema nervioso autónomo, barorreflejo
Subject(s)
Humans , Metoprolol/administration & dosage , Metoprolol/metabolism , Metoprolol/pharmacokinetics , Trypanosoma cruzi/cytology , Trypanosoma cruzi/isolation & purification , Trypanosoma cruzi/pathogenicity , Trypanosoma cruzi/physiologyABSTRACT
En las fases iniciales del infarto del miocardio se prolonga el tiempo de la relajación ventricular. Para caracterizar el efecto del metoprolol, un agente ß-bloqueador sobre la constante T, índice derivado de la curva ventricular en la fase de relajación isovolumétrica, se estudiaron 12 perros a los que se les ligó la arteria descendente anterior. La constante T, la presión diastólica ventricular, la frecuencia cardiaca y la presión arterial media, se midieron en forma basal y a los 15, 30, 60, 120, y 180 minutos después de la oclusión. Sirvieron seis perros de control y a otros seis se les administró metoprolol a la dosis de 35 mg/kg/min, durante 5 minutos. Los perros control tuvieron constantes T más prolongadas, mayores niveles de presión diastólica ventricular y mayor hipotensión severa al final del estudio, en comparación con los tratados que mantuvieron la función diastólica y no tuvieron cambios importantes de la presión arterial. El ß-bloqueador disminuye la alteración de la relajación ventricular, preserva la presión de llenado ventricular e impide el desarrollo de hipotensión en este modelo de infarto experimental
Subject(s)
Animals , Dogs , Diastole/drug effects , Experiment of Substances , Heart Rate , Metoprolol/administration & dosage , Metoprolol/pharmacokinetics , Muscle Relaxation , Myocardial Infarction , Blood Pressure , Heart VentriclesABSTRACT
CYP1A2, CYP2D6 and N-acetyltransferase activities were estimated in 100 patients with bladder cancer and 84 control subjects from measurements of theophylline, metoprolol and isoniazid and their metabolites in urine, respectively. The frequency of occurrence of slow acetylators of isoniazid and poor metabolizers of metoprolol were 16.7% and 1.2% in the control group and 16.3% and 2.0% in the cancer patient group. These differences were not significant. The recovery ratio of 1-methyluric acid(1-MU) from theophylline was significantly higher in patients with bladder cancer than in control subjects(0.340 +/- 0.016 versus 0.260 +/- 0.020, p< 0.05). The 1-MU recovery ratio was a significant, independent risk factor among the metabolic capacities tested as shown by logistic regression analysis, controlling for N-acetylation of isoniazid, hydroxylation of metoprolol, age, sex, and smoking. We concluded that the capacity for 3-demethylation of theophylline, as a reflection of CYP1A2 activity, is significantly associated with increased risk of nonoccupational urinary bladder cancer.
Subject(s)
Adult , Aged , Female , Humans , Male , Acetylation , Amines/metabolism , Urinary Bladder Neoplasms/enzymology , Carcinoma, Transitional Cell/enzymology , Case-Control Studies , Cytochrome P-450 CYP1A2 , Cytochrome P-450 CYP2D6 , Cytochrome P-450 Enzyme System/metabolism , Disease Susceptibility , Enzyme Induction , Isoniazid/pharmacokinetics , Korea/epidemiology , Logistic Models , Methylation , Metoprolol/pharmacokinetics , Middle Aged , Mixed Function Oxygenases/metabolism , Mixed Function Oxygenases/metabolism , Oxidoreductases/urine , Smoking , Theophylline/pharmacokinetics , Uric Acid/analogs & derivativesABSTRACT
The haemodynamic effects of the two cardioselective B- adrenoceptor blockers, betaxolol and metoprolol were studied in experimental animals both in vivo and in vitro. In Vitro studies; Betaxolol had 8 times the potency of metoprolol in suppression of isoprenaline chronotropic activity and 5 times its potency in inhibition of myocardial contractility in isolated rabbit heart. In addiotn, betaxolol had less antagonistic effect than metoprolol to the isoprenaline effect on isolated guinea pig tracheal spiral strips. In vivo studies, betaxolol had 4 times the potency of metoprolol in oppression of isoprenaline induced tachycarida in anaesthetized 'dogs. Both betaxolol and metoprolol had no intrinsic sympathomimetic effect as they failed to increase heart rate in reserpinized rats. The IV injection of betaxolol in small doses O.I mg/kg 0.1 mg to 0.4 mg / kg induced rapid significant reduction in the arterial blood pressure of anaesthetized dog while metoprolol up to 0.8 mg/kg intravenously did not produce acute effect on the blood pressure. Chronic administration of the two beta adrenoceptor blockers in oral doses of 2.5 and 5mg/kg for 4 weeks were able to attenuate the rise in the blood pressure in the two kidney one-clip adult hypertensive rats. However, betaxolol effect was more pronounced and early occurred. In conclusion, the new beta adrenoceptor blocker betaxolol had more beneficial haemodnamic effect than metoprolol by which betaxolol is suggested to be a useful addition to the beta adrenoceptor blacker family