RESUMEN

In this cross-over, double-blind study, 12 essential hypertensive patients (stage I, II, and III) with glomerular filtration rate (GFR) between 50 to 80 mL/min/1.73 m2, were submitted to 4 weeks of placebo followed by 12 weeks with isradipine SRO (IS) 5 mg, spirapril (SP) 6 mg, and isradipine plus spirapril (IS + SP). The study evaluated the effects of these drugs on GFR ((99m)Tc DTPA), effective renal plasma flow (ERPF) ((131)I-orthoiodohippurate), urinary sodium excretion (UNaV), urinary kallikrein excretion (UKal), urinary albumin excretion (UAE), and plasma renin activity (PRA). The three protocols significantly reduced mean blood pressure (128 v 107 mm Hg; 126 v 112 mm Hg; 129 v 104 mm Hg with IS, SP and IS + SP, respectively). ERPF and GFR did not change. UNaV increased significantly after IS (0.17 v 0.22 mEq/min) and IS + SP (0.18 v 0.24 mEq/min). UKal increased significantly after IS (58.6%) and IS + SP (53.6%). UAE decreased significantly only after SP. PRA increased significantly after IS (1.31 v 2.84 ng/mL/h), SP (1.10 v 2.15 ng/mL/h), and after IS + SP (1.23 v 3.21 ng/mL/min). In conclusion, IS, SP and IS + SP were effective in reducing blood pressure while keeping renal function stable. Only SP significantly decreased UAE. Enhanced UKal may have played a role in natriuresis observed after IS and IS + SP.

Asunto(s)

Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Antihipertensivos/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Bloqueadores de los Canales de Calcio/administración & dosificación , Enalapril/análogos & derivados , Hipertensión Renal/tratamiento farmacológico , Isradipino/administración & dosificación , Enfermedades Renales , Natriuresis/efectos de los fármacos , Circulación Renal/efectos de los fármacos , Anciano , Albuminuria/inducido químicamente , Estudios Cruzados , Método Doble Ciego , Quimioterapia Combinada , Enalapril/administración & dosificación , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Humanos , Hipertensión Renal/fisiopatología , Calicreínas/efectos de los fármacos , Calicreínas/orina , Enfermedades Renales/tratamiento farmacológico , Enfermedades Renales/fisiopatología , Masculino , Persona de Mediana Edad , Flujo Plasmático Renal Efectivo/efectos de los fármacos , Método Simple Ciego

RESUMEN

La hipertrofia ventricular izquierda (HVI) es un factor de riesgo cardiovascular importante, frecuentemente asociado a hipertensión arterial (HTA). Su regresión en estos paciem¿ntes podría asociarse a beneficios en la historia natural de la enfermedad hipertensiva, lo que pareciera depender en alguna medida del control de las cifras de presión arterial. La eficacia en inducir regresión de HVI en seres humanos pudiera ser diferente según el tipo de fármaco antihipertensivo. Hemos evaluado la hipótesis de isradipino, un antagonista del calcio con marcada selectividad vascular, en dosis normotensantes induce regresión de HVI en nuestros pacientes hipertensos que presentan HVI. 19 pacientes (edad promedio 59 años, 9 mujeres) con HTA esencial e HVI (séptum + pared posterior VIò 23 mm) comenzaron a ser tratados con isradipino (Dynacirc SROr) y 18 pacientes completaron 12 meses con una sola dosis diaria matinal normotensante (promedio final 16,4 ñ 3,3 mg/día). En 7 pacientes se complementó con una dosis baja de hidroclorotiazida y triamterene con objeto de mantener cifras tensionales normales. Se realizó ecocardiograma basal, a los 3, 6 y 12 meses de tratamiento, midiéndose séptum VI (sp,mm), pared posterior de VI (pp,mm) y dimensión diastólica (DD,mm), con lo que se calculó la masa ventricular VI. Además de la normotensión mantenida se observó una disminución significativa, a contar del tercer mes de tratamiento de los grosores del sp,pp y diámetros de la cavidad VI, así como de la masa VI, la que alcanzó a los 12 meses un 81 por ciento de la masa inicial del VI. No hubo modificaciones de la función ventricular ni de la frecuencia cardíaca. Tampoco se modificó la función renal. En conclusión, estos resultados demuestran que isradipino, en una sola dosis diaria normotensante, es capaz de inducir regresión significativa de HVI en pacientes con HTA. Esta regresión está dad por disminución tanto del grosor de las paredes como de las dimensiones del VI y comenzó a observarse desde los 3 meses de tratamiento

Asunto(s)

Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Hipertensión/complicaciones , Hipertrofia Ventricular Izquierda/tratamiento farmacológico , Isradipino/farmacología , Ecocardiografía , Frecuencia Cardíaca , Función Ventricular Izquierda , Hidroclorotiazida/administración & dosificación , Hidroclorotiazida/farmacología , Hipertrofia Ventricular Izquierda/etiología , Isradipino/administración & dosificación , Plasma/metabolismo , Plasma/fisiología , Presión Sanguínea , Estimulación Química , Resultado del Tratamiento

RESUMEN

PURPOSE: To evaluate clinical efficacy and tolerability of isradipine SRO (I.SRO), 5 mg O.D. in essential hypertensives. METHODS: Eighty-three of 87 selected outpatients with a mean age of 51.3 years (ranging from 25 to 65), 33 male, 48 white, 29 black and others of different races, who had clinical supine and orthostatic diastolic blood pressure (DBP) > or = 95 mmHg and < or = 115 mmHg underwent the study. After a three-week wash-out period, patients received I.SRO 5 mg O.D. at 8:00 am for a six-week period (phase I). After this phase, patients received I.SRO 5 mg O.D. at 8:00 pm for a six-week period (phase II). The patients had a follow-up with an interval of three weeks and the ambulatorial blood pressure monitoring (ABPM) for 24 hours was performed with a SpaceLabs 90207 or Del Mar Avionics devices after the wash-out period and at the end of phases I and II. Measurements were performed at 15-min intervals during the day (6 am to 10 pm) and at 30-min intervals during the night (10 pm to 6 am). RESULTS: a) Heart rate did not show significant changes during the treatment period (phases I and II) when compared with the wash-out period; b) causal blood pressure: at the end of both treatment periods (phases I and II) there were statistically significant decreases (p < 0.001) in supine SBP and DBP compared with wash-out values. The mean SBP decreased from 161.6 +/- 14 to 144.3 +/- 13 mmHg (phase I) and to 141.8 +/- 13 mmHg (phase II). The mean DBP decreased from 103.4 +/- 6 to 91.2 +/- 7 (phase I) and to 89.1 +/- 8 (phase II); c) ABPM: the mean systolic 24-h ambulatory blood pressure was significantly reduced (p < 0.001) from 148.8 +/- 17 to 137.2 +/- 15 mmHg (phase I) and to 133.4 +/- 13 mmHg (phase II). The mean diastolic 24-h ambulatory blood pressure was significantly decreased (p < 0.001) from 94.3 +/- 9 to 87.0 +/- 9 (phase I) and to 85.8 +/- 8 mmHg (phase II). The mean daytime and nighttime, systolic and diastolic 24-h ambulatory blood pressure were: wash-out--152.3 +/- 17, 140.2 +/- 21, 97.4 +/- 9, 86.8 +/- 13; phase I--139.9 +/- 15, 130.0 +/- 17, 89.3 +/- 9, 81.3 +/- 10; phase II--136.7 +/- 13, 125.3 +/- 15, 88.5 +/- 8, 79.1 +/- 10, respectively. Blood pressure load (percentage of systolic blood pressure values > 140 mmHg or of diastolic blood pressure values > 90 mmHg) was significantly reduced from 62.2/62% (SBP/DBP), on the was-out, to 37.9/39.9% (SBP/DBP) on phase I and to 32.3/34.3% (SBP/DBP) on phase II; d) side effects: most frequently related were palpitations (2.3%), headache (1.1%), flush (1%) and ankle oedema (1%). They were in general, mild-to-moderate and disappeared after the first 3 weeks of treatment. Only two patients were withdrawn because of headache (one of them with previous diagnosis of migraine). CONCLUSION: I.SRO, given by oral route, in the dosage of 5 mg O.D. as monotherapy, was effective and well tolerated, promoted significant reduction on 24-h ambulatory blood pressure attenuating the early morning rise and did not interfere with the circadian rhythm of blood pressure. No significant differences were detected in the BP lowering effect when I.SRO was given during the morning or evening. These results may indicate that the drug is as suitable as one of the first choice for treating mild and moderate hypertensive patients.

Asunto(s)

Hipertensión/tratamiento farmacológico , Isradipino/administración & dosificación , Adulto , Anciano , Presión Sanguínea/efectos de los fármacos , Determinación de la Presión Sanguínea , Femenino , Humanos , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico

RESUMEN

PURPOSE--To evaluate clinical efficacy and tolerability of isradipine SRO (I.SRO), 5 mg O.D. in essential hypertensives. METHODS--Eighty-three of 87 selected outpatients with a mean age of 51.3 years (ranging from 25 to 65), 33 male, 48 white, 29 black and others of different races, who had clinical supine and orthostatic diastolic blood pressure (DBP) > or = 95 mmHg and < or = 115 mmHg underwent the study. After a three-week wash-out period, patients received I.SRO 5 mg O.D. at 8:00 am for a six-week period (phase I). After this phase, patients received I.SRO 5 mg O.D. at 8:00 pm for a six-week period (phase II). The patients had a follow-up with an interval of three weeks and the ambulatorial blood pressure monitoring (ABPM) for 24 hours was performed with a SpaceLabs 90207 or Del Mar Avionics devices after the wash-out period and at the end of phases I and II. Measurements were performed at 15-min intervals during the day (6 am to 10 pm) and at 30-min intervals during the night (10 pm to 6 am). RESULTS--a) Heart rate did not show significant changes during the treatment period (phases I and II) when compared with the wash-out period; b) causal blood pressure: at the end of both treatment periods (phases I and II) there were statistically significant decreases (p < 0.001) in supine SBP and DBP compared with wash-out values. The mean SBP decreased from 161.6 +/- 14 to 144.3 +/- 13 mmHg (phase I) and to 141.8 +/- 13 mmHg (phase II). The mean DBP decreased from 103.4 +/- 6 to 91.2 +/- 7 (phase I) and to 89.1 +/- 8 (phase II); c) ABPM: the mean systolic 24-h ambulatory blood pressure was significantly reduced (p < 0.001) from 148.8 +/- 17 to 137.2 +/- 15 mmHg (phase I) and to 133.4 +/- 13 mmHg (phase II). The mean diastolic 24-h ambulatory blood pressure was significantly decreased (p < 0.001) from 94.3 +/- 9 to 87.0 +/- 9 (phase I) and to 85.8 +/- 8 mmHg (phase II). The mean daytime and nighttime, systolic and diastolic 24-h ambulatory blood pressure were: wash-out--152.3 +/- 17, 140.2 +/- 21, 97.4 +/- 9, 86.8 +/- 13; phase I--139.9 +/- 15, 130.0 +/- 17, 89.3 +/- 9, 81.3 +/- 10; phase II--136.7 +/- 13, 125.3 +/- 15, 88.5 +/- 8, 79.1 +/- 10, respectively. Blood pressure load (percentage of systolic blood pressure values > 140 mmHg or of diastolic blood pressure values > 90 mmHg) was significantly reduced from 62.2/62 per cent (SBP/DBP), on the was-out, to 37.9/39.9 per cent (SBP/DBP) on phase I and to 32.3/34.3 per cent (SBP/DBP) on phase II; d) side effects: most frequently related were palpitations (2.3 per cent ), headache (1.1 per cent ), flush (1 per cent ) and ankle oedema (1 per cent ). They were in general, mild-to-moderate and disappeared after the first 3 weeks of treatment. Only two patients were withdrawn because of headache (one of them with previous diagnosis of migraine). CONCLUSION--I.SRO, given by oral route, in the dosage of 5 mg O.D. as monotherapy, was effective and well tolerated, promoted significant reduction on 24-h ambulatory blood pressure attenuating the early morning rise and did not interfere with the circadian rhythm of blood pressure. No significant differences were detected in the BP lowering effect when I.SRO was given during the morning or evening. These results may indicate that the drug is as suitable as one of the first choice for treating mild and moderate hypertensive patients

Asunto(s)

Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Isradipino/administración & dosificación , Hipertensión/tratamiento farmacológico , Determinación de la Presión Sanguínea , Hipertensión/fisiopatología , Monitoreo Fisiológico , Presión Arterial

RESUMEN

The efficacy and tolerability of an infusion of isradipine, a calcium antagonist of the dihydropyridine type, were tested in patients in hypertensive crisis. Ten patients with symptomatic and significant elevations in blood pressure were infused for 12 h with isradipine at 1.2, 2.4, 4.8, and 7.2 micrograms/kg/h (3 h of each infusion level). No untoward effects or adverse reactions were noted. No alterations were observed on electrocardiographic tracings, and blood pressure was significantly reduced only at doses of 7.2 micrograms/kg/h. Thus, isradipine as an infusion is useful and safe for hypertensive crisis, starting at a rate of 7.2 micrograms/kg/h. Higher doses may yet prove to be safe, well tolerated, and even more efficacious.

Asunto(s)

Hipertensión/tratamiento farmacológico , Isradipino/uso terapéutico , Enfermedad Aguda , Presión Sanguínea/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Infusiones Intravenosas , Isradipino/administración & dosificación , Isradipino/farmacología

RESUMEN

PURPOSE: Evaluate the efficacy and tolerability of isradipine, a new dihydropyridine calcium antagonist in the therapy of outpatients hypertensive crisis. PATIENTS AND METHODS: Twenty seven patients with mean age of 37.2 +/- 2.5 years (ages ranging from 18 to 59 years old) of different races (14 white, 13 not white); 15 men and 12 women, with diastolic blood pressure over 130 mmHg and without signs of recent target organ damage were studied. The patients were divided in three groups according to the used dosage of Isradipine tablets by sublingual route. Group I (n = 10): 1.25 mg; Group II (n = 10): 2.5 mg and Group III (n = 7): 5.0 mg. Arterial blood pressure levels and heart rate were determined before the drug administration and every 30 minutes until 120 minutes after dosing. RESULTS: Mean arterial blood pressure (MABP) decrease significantly in all patients from 153.43 +/- 4.3 to 124.0 +/- 2.3 mmHg after 60 minutes and to 118.0 +/- 2.1 mmHg after 120 minutes (p < 0.001). Heart rate did not show significant changes with the drug. Clinical significant side effects were not observed. The comparative analysis of MABP curves did not show significant differences among the groups I, II and III. However, a tendency of a greater decrease in MABP was observed in the patients of group III. CONCLUSION: Isradipine tablets in the dosages of 1.25, 2.5 and 5.0 mg by sublingual route is effective and well tolerated in the treatment of ambulatorial patients with hypertensive crisis.

Asunto(s)

Hipertensión/tratamiento farmacológico , Isradipino/administración & dosificación , Administración Sublingual , Adolescente , Adulto , Presión Sanguínea/efectos de los fármacos , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Hipertensión/fisiopatología , Isradipino/farmacología , Masculino , Persona de Mediana Edad , Pacientes Ambulatorios

RESUMEN

Objetivo - Avaliar a eficácia clínica e a tolerabilidade da isradipina, um novo antagonista do cálcio hipertensiva. Casuística e Métodos - Foram estudados vinte e sete pacientes (14 brancos, 13 näo brancos) com idades variando entre 18 e 59 (média 37,2 ñ 2,5) anos; 15 homens, 13 mulheres cujas pressöes arteriais diastólicas eram superiores a 130 mmHg e que näo apresentavam sinais recentes de lesöes agudas em órgäos-alvo. Estes pacientes foram divididos em três grupos aos quais se administraram diferentes doses de isradipina na forma de comprimidos por via sublingual, conforme segue: grupo I - (n = 10) 1,25 mg; grupo II - (n = 10), 2,5 mg; grupo III - (n = 7) 5,0 mg. A pressäo arterial (PA) e a freqüência cardíaca (FC) dos pacientes foram medidas antes da administraçäo da droga e depois a cada 30 minutos até o máximo de 120 minutos. Resultados - A pressäo arterial média (PAM) reduziu-se significativamente em todos os pacientes 153,43 ñ 4,3 mmg para 124,0 ñ 2,3 mmHg após 60 min de administraçäo da droga e, para 118 ñ 2,1 mmHg após 120 min do seu uso (p < 0,001). A FC näo apresentou variaçöes clinicamente significativas. Näo se observaram também efeitos colaterais limitantes do uso da droga nas doses empregadas. A comparaçäo entre as curvas de variaçäo da PAM dos três grupos näo apresentou diferenças significantes, tendo-se observado, entretanto, uma tendência a maior velocidade de descenso da PA nos pacientes do grupo III. Conclusäo - Os resultados evidenciam que a isradipina administrada na forma de comprimidos por via sublingual, nas doses de 1,25, 2,5 e 5,0 mg reduz eficazmente a PA de pacientes com crise hipertensiva sem a ocorrência de efeitos colaterais importantes. O início de açäo da droga foi rápida (30 min) após a administraçäo e o descenso máximo da PA foi observado após 2h. Näose observaram também reduçöes dose-dependentes da PA

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Purpose - Evaluate the efficacy and tolerability of isradipine, a new dihydropyridine calcium antagonist in the therapy of outpatients hypertensive crisis. Patients and Methods - Twenty seven patients with mean age of 37.2 ± 2.5 years (ages ranging from 18 to 59 years old ) of different races (14 white, 13 not white); 15 men and 12 women, with diastolic blood pressure over 130 mmHg and without signs of recent target organ damage were studied. The patients were divided in three groups according to the used dosage of Isradipine tablets by sublingual route. Group I (n = 10): 1.25 mg; Group II (n = 101:2.5 mg and Group III (n = 7): 5.0 mg. Arterial blood pressure levels and heart rate were determined before the drug administration and every 30 minutes until 120 minutes after dosing. Results - Mean arterial blood pressure (MABP) decrease significantly in all patients from 153.43 ± 4.3 to 124.0 ± 2.3 mmHg after 60 minutes and to 118.0 ± 2.1 mmHg after 120 minutes (p < 0.001). Heart rate did not show significant changes with the drug. Clinical significant side effects were not observed. The comparative analysis of MABP curves did not show significant differences among the groups I, II and III. However, a tendency of a greater decrease in MABP was observed in the patients of group III. Conclusion - Isradipine tablets in the dosages of 1.25, 2.5 and 5.0 mg by sublingual route is effective and well tolerated in the treatment of ambulatorial patients with hypertensive crisis

Asunto(s)

Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Isradipino/administración & dosificación , Hipertensión/tratamiento farmacológico , Pacientes Ambulatorios , Isradipino/uso terapéutico , Isradipino/farmacología , Administración Sublingual , Frecuencia Cardíaca , Hipertensión/fisiopatología , Presión Arterial

RESUMEN

Con el fin de evaluar en la práctica médica diaria la eficacia, tolerancia y seguridad de un nuevo antihipertensivo calcio antagonista (Isradipino), se realizó un Estudio Abierto Multicéntrico Nacional no comparativo en las 5 principales ciudades de Colombia. El protocolo de estudio contempló un periodo de lavado de 2 semanas seguido de 12 semanas de tratamiento activo con Isradipino 2.5 mg 2 veces al día. Se presentan los resutlados de 599 pacientes hipertensos esenciales: 400 (66.81 por ciento) leves y 199 (33.2 por ciento) moderados; 420 (70.1 por ciento) de los cuales habían recibido algún tratamiento previo, principalmente diuréticos y betabloqueadores y 370 (61.8 por ciento) tenían historia de hipertensión arterial de más de un año de evolución. La eficacia terapéutica en cuanto a la disminución de las cifras tensionales durante la fase de tratamiento activo fue evidente. Al final del estudi la disminución de la presión arterial sistólica (PAS) en promedio fue de -22 mmHG y de la presión arterial diastólica (PAD) fue de -17 mmHG (p<0.05). El 81.3 por ciento de los pacientes no presentaron ningún efecto secundario, mientras que el 18.7 por ciento presentó algún efecto secundario, siendo los principales: cefalea (8.3 por ciento), flushing (3.3. por ciento), mareo (2.7 por ciento) y palpitaciones (2.5 por ciento), los cuales durante el tratamiento tendieron a disminuir o desaparecer. La frecuencia cardíaca en promedio disminuyó 1 latido/minuto mientras que el promedio de peso no registró variaciones. Además la administración de Isradipino en 240 pacientes con enfermedad concomitante (dislipidemia, angina, diabetes, insuficiencia cardíaca congestiva), corroboran la seguridad clínica. En conclusión nuestros resultados indican que el Isradipino es eficaz, bien tolerado y seguro en el tratamiento de la hipertensión arterial leve a moderada

Asunto(s)

Humanos , Isradipino/administración & dosificación , Isradipino/efectos adversos , Isradipino/farmacocinética , Isradipino/normas , Isradipino/uso terapéutico , Hipertensión/tratamiento farmacológico , Hipertensión/rehabilitación