Comparison of electrophysiological effects of calcium channel blockers on cardiac repolarization

Dihydropyridine (DHP) calcium channel blockers (CCBs) have been widely used to treat of several cardiovascular diseases. An excessive shortening of action potential duration (APD) due to the reduction of Ca2+ channel current (I(Ca)) might increase the risk of arrhythmia. In this study we investigated the electrophysiological effects of nicardipine (NIC), isradipine (ISR), and amlodipine (AML) on the cardiac APD in rabbit Purkinje fibers, voltage-gated K+ channel currents (I(Kr), I(Ks)) and voltage-gated Na+ channel current (I(Na)). The concentration-dependent inhibition of Ca2+ channel currents (I(Ca)) was examined in rat cardiomyocytes; these CCBs have similar potency on I(Ca) channel blocking with IC50 (the half-maximum inhibiting concentration) values of 0.142, 0.229, and 0.227 nM on NIC, ISR, and AML, respectively. However, ISR shortened both APD50 and APD90 already at 1 microM whereas NIC and AML shortened APD50 but not APD90 up to 30 microM. According to ion channel studies, NIC and AML concentration-dependently inhibited I(Kr) and I(Ks) while ISR had only partial inhibitory effects (<50% at 30 microM). Inhibition of I(Na) was similarly observed in the three CCBs. Since the I(Kr) and I(Ks) mainly contribute to cardiac repolarization, their inhibition by NIC and AML could compensate for the AP shortening effects due to the block of I(Ca).

A case of gingival hyperplasia caused by felodipine / 대한내과학회지

Felodipine is a calcium channel blocker that is used in the management of hypertension. Calcium channel blockers, along with phenytoin and cyclosporin, are implicated as a cause of gingival hyperplasia. Calcium channel blockers associated with this undesired side-effect include nifedipine, nicardipine, isradipine, amlodipine, felodipine, verapamil, and diltiazem. Several cases of adverse gingival hyperplasia related to felodipine have been reported since 1991, although no case has been reported in Korea. We report a case of gingival hyperplasia in a 55-year-old man on long-term felodipine.

Glycemia in newborns of hypertensive mothers according to maternal treatment

OBJETIVO: Avaliar o comportamento da glicemia em recém-nascidos (RN) de mães hipertensas conforme o tratamento materno. MÉTODOS: Estudo prospectivo, randomizado, incluindo 93 RN de mães tratadas com isradipina(n=39), atenolol (n=40) ou dieta - controle (n=14). Determinou-se a glicemia ao nascimento (mãe e RN, pela glicose oxidase) e na 1ª., 3ª., 6ª., 12ª. e 24ª. horas (RN, por fita reagente). A evolução da glicemia, em cada grupo, foi analisada (Teste de Friedman). Os grupos foram comparados, quanto às glicemias, em cada momento (Teste de Kruskall-Wallis) e foram ajustados modelos de regressão linear para as glicemias (variável independente = glicemia materna; variáveis dependentes = glicemias de cordão, 3ª. e 6ª. horas). RESULTADOS: Não houve diferença estatisticamente significante entre as glicemias médias dos 3 grupos, em qualquer uma das coletas. Houve correlação entre as glicemias materna e de cordão umbilical nos grupos isradipina (r =0,61; p<0,05) e controle (r =0,84; p<0,05); entre as glicemias materna e 3ª. e 6ª. horas, houve apenas no grupo controle (materna X 3ª.hora: r = 0,65; p<0,05; materna X 6a.hora: r =0,68; p<0,05). Não houve correlação em nenhum momento no grupo atenolol. Detectou-se hipoglicemia em 51,3% (Isradipina), 60% (Atenolol) e 35,7% (Controle), mais freqüentemente na 1ª. hora de vida, em todos os grupos. CONCLUSÕES: Os resultados sugerem efeito semelhante dos 3 tipos de terapêutica sobre a glicemia do RN. As análises de correlação sugerem que a isradipina possa ter efeitos sobre a glicemia somente após o nascimento (correlação apenas em cordão umbilical), enquanto o atenolol, possa atuar mais precocemente (não se correlacionou em nenhum momento). Também reforçam a necessidade de controle glicêmico desde a 1ª. hora de vida em RN de mães hipertensas, submetidas ou não a tratamento medicamentoso.

First derivative spectrophotometometric analysis of isradipine in the presence of its degradation products

A stability indicating first derivative spectrophotometric method had been proposed for the evaluation of isradipine in pure form and pharmaceutical formulations. The method depends on measuring the delta-A/delta-gamma values at 248 nm where the degradation products do not interfere. It was also determined that the excipients in the tablet and capsule preparations did not interfere with the assay. The suggested procedure showed a linear relation in the range 5-35 mug.ml -1 on plotting delta-A/delta-gamma as a function of concentration. The mean accuracy was found to be 100.1 +/- 0.95

Conduta na crise hipertensiva / Treatment of hypertensive crisis

As Crises Hipertensivas (CH) säo complicaçöes frequentes nos serviços de pronto-atendimento, englobando tanto as urgências como as emergências hipertensivas. Definem-se emergências hipertensivas (EH) as condiçöes que cursam com lesöes agudas de órgäos-alvo, nas quais o risco de vida é iminente e o tratamento deve ser imediato. As urgências hipertensivas (UH) säo decorrentes de elevaçäo da pressäo arterial, näo acompanhada de repercussöes graves em órgäos nobres, näo oferecendo risco imediato de vida para o paciente. Nestes casos, os autores preconizam a reduçäo da pressäo arterial em até 24 horas através do uso de drogas via oral, podendo ser utilizado captopril, clonidina, isradipina ou diuréticos.

Regresión de hipertrofia ventricular izquierda con isradipino en pacientes hipertensos / Regression of left ventricular hypertrophy with isradipine in hypertensive patients

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

Comparative study of some pharmacological and clinical effects of calcium channel blockers: isradipine [Lomir] and diltiazem [Tieldiem]

This work included evaluation and comparison of isradipine and dilitiazem on the cardiovascular system and smooth muscles of experemintal animals. Clinical studies were also performed on hypertensive patients undergoing surgery. Isradipine [50-800 micro g/kg] and dilatiazem [0.75-12 mg/kg] produced sudden and transient fall in blood pressure of anaesthetized cats and this drop was shown to be peripherally. Isradipine was found to be superior in its hypertensive action. No abnormality in the ECG pattern was observed apart from the bradycardia which happended only with high doses of both drugs. Isradipine only in doses ranging from 4-16 micro g while all concentrations of diltiazem [12.5-200 micro g], in the present study, included a significantly dose dependent cardio-inhibitory effect, probably due to a direct action. On isolated rabbit's aortic spiral strip, both isradipine [0.2-3.2 micro g/ml] and diltilazem [2.5-40 micro g/ml] did not alter the basal tone of the strip but they reduced the amplitude of noradrenaline induced aortic contractions significantly. The effect of isradipine was greater than that of diltiazem. On smooth muscles, isradipine and diltiazem elicited a direct spasmolytic action on rabbit's intestinal contractions. This was confirmed by the relief of the drugs to barium chloride-induced spasm of the smooth muscles. The antispasmodic effect of isradipine was found to be highly superior than that of diltiazem and the difference was found to be significant. As regards the effect on tracheal preparations, isradipine [0.25-4 micro g/ml] and diltiazem [2.540 micro g/ml] did not alter the basal tone of tracheal preparations, but in case of histamine-induced contractions, only diltiazem reduced that response. The clinical study was conducted, in the present study, on patients of ASA grade I and II. By comparing the haemodynamic effects of isradipine and diltiazem with the control group of patients, it was found that the reduction of systolic and mean arterial blood pressure was greater in the isradipine treated patients than in those receiving dilitiazem; whereas the decrease of diastolic blood pressure was not different. The cardiac output is slightly increased in both groups. The heart rate remained unchanged in patients treated with isradipine but it was decreased significantly in those receiving diltiazem. As regards the metabolic effect, isradipine produced a decrease in total serum cholesterol with no significant effect on blood sugar level, however diltiazem increased both. Isradipine, in the present study, was better tolerated tam diltiazem and patients under isradipine therapy complained of fewer side effects. So it can be concluded that isradipine can be safely administered to hypertensive patients, regardless of concomitant disease. Unlike diltiazem, it preserves cardiac function and has no negative impact on lipids or blood chemistry. So it can be safely administered to hyperetensive patients with asthma, diabetes or congestive heart failure

Nifedipine versus isradipine as antiatherogenic modalities in cholesterol fed rabbits

The antiatherogenic effect of nifedipine and isradipine was experimentally studied in cholesterol fed-rabbits. Our results demonstrate that isradipine in therapeutic doses relevant to human use, has antiatherogenic activity in cholesterol-fed rabbit model. On the other hand nifedipine has a comparable effect but at doses that are much higher than equivalent human doses. Furthermore isradipine significantly increased [P 0.05], while nifedipine insignificantly decreased high density lipoprotein-cholesterol [HDL] level than in the non-atherosclerotic control group of rabbits. We concluded that isradipine, and not nifedipine. is an effective and applicable antiatherogenic modality in proper clinical setting

Estudo multicêntrico brasileiro de avaliaçäo de eficácia clínica e tolerabilidade da isradipina SRO através da monitorizaçäo ambulatorial da pressäo arterial no tratamento da hipertensäo arterial leve e moderada / Tolerability and Antihypertensive Effects of Isradipine SRO on Clinical and Ambulatorial Blood Pressure Monitoring in Essential Hypertensives. A Brazilian Multicenter Study

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

Isradipine in Pakistani hypertensive patients

Isradipine, a calcium channel blocker, was given to 124 [29 females and 32 males] hypertensive patients for eight weeks after three weeks on placebo treatment. Mean age was 46.5 +/- 0.86 years, mean weight before treatment was 70.04+1-1.2 kg, after treatment it was 69.7 +/- 1.3 Kg, mean height was 154.5 +/- 0.8 cm and mean duration of hypertension was 4.2 +/- 0.31 years. Mean sitting systolic pressure decreased from 164 +/- 1.5 mmHg to 146 +/- 2.19 mmHg [p<.001] while mean sitting diastolic pressure dropped from 106.5 +/- 0.62 mmHg to 93.1 +/- 0.8 mmHg [p<.001]. Mean standing systolic pressure fell from 166 +/- 1.08 mmHg to 147 +/- 1.8 mmHg [p<.01] while erect diastolic pressure fell from 108 +/- 0.6 mmHg to 96.9 +/- 1.7 mmHg [p<.001]. Mean sitting arterial pressure decreased from 125 mmHg to 110 mmHg while standing mean arterial pressure decreased from 127 mmHg to 119 mmHg. No statistically significant fall in heart rate both in supine and standing position was observed. Laboratory results did not show any variation. After eight weeks on active treatment 34% of the patients were taking 1.25 mg B.D while 66% of the patients were on 2.5 mg B.D. Isradipine was found effective and safe in patients with mild to moderate hypertension who tolerated the drug

A comparative study of isradipine and nifedipine in the monotherapy of mild to moderate hypertension in the Ghanaian

Clinical experience with the new dihydropyridine calcium antagonist; isradipine; is reported. Isradipine was compared with nifedipine in a multicentre open; parallel group; clinical therapeutic trial involving 70 patients with mild to moderate hypertension. A four week placebo washout period was followed by a 12 week active treatment period during which patients were randomized to receive either 2.5mg isradipine twice daily (n=40) or 10mg nifedipine three times daily (n=30). Isradipine significantly reduced sitting systolic/diastolic blood pressures from 176.7+/-21.0/106.7+/-7.0mmHg to 142.9+/-15/93.1+/-7.7mmHg (p0.001) at the end of 12 weeks. Similarly; nifedipine reduced sitting systolic/diastolic blood pressures from 170.1+/-19.5/106.2+/-7.4mmHg to 139.1+/-9.7/92.1+/-7.8mmHg (p0.001). Normalisation (diastolic 90mmHg) rates were 67 per cent and 60 per cent for isradipine and nifedipine respectively while good response (diastolic fall 10mmHg) rate was over 85 per cent on either drug. Heart rate did not significantly change with either treatment. Three (3) patients taking isradipine experienced headache and 7 patients taking nifedipine had drug related adverse effects (5 had headache; 1 insomnia and 1 first dose hypotension). Therapy was withdrawn in 4 patients taking nifedipine and 1 taking isradipine. It is concluded that isradipine is comparable to nifedipine and is an effective and well tolerated antihypertensive agent in the Ghanaian

Antihypertensive Effects and Safety of Isradipine in Patients with Essential Hypertension

BACKGROUND: Antihypertensive treatment represents the modification of one of the most important risk factors on the development of cardiovascular, cerebrovascular and peripheral vascular disease. In cases of markedly developed atherosclerosis, reduction of blood pressure can improve the survival of patients by reducing the incidence and/or severity cerebrovascular events. We studied a new dihydropyridine calcium antagonist isradipine to evaluate the efficacy and safety in patients with essential hypertension. METHOD: After a placebo run-in phase of four weeks duration, 2.5mg isradipine once daily orally was administered for four weeks to 84 patients (48 males, 36 females ; mean age ; 50.8 years). And then 5.0mg isradipine once daily was administered for four weeks to 59 patients whose diastolic pressure did not decrease less than 90 mmHg. RESULTS: 1) At the end of 8 weeks of therapy, systolic and diastolic blood pressure were significantly reduced from 158.2+/-11.5/101.7+/-5.1mmHg in sitting, 156.8+/-13.7/102.3+/-5.6mmHg in standing to 138.3+/-13.8/90.1+/-6.7mmHg in sitting, 137.6+/-13.7/91.2+/-7.6mmHg in standing (p<0.001). And the effectiveness rate was 84.3% in sitting, 83.2% in standing and normalization rate below 90mmHg in diastolic pressure was 67.5% in siting and 61.5% in standing position. 2) The sitting and standing pulse rate did not change significantly (72.7+/-7.4beats/min at baseline vs. 73.4+/-6.8 beats/min after 8 weeks trial in sitting, 73.5+/-7.2beats/min at baseline vs. 74.1+/-7.2 beats/min after 8 weeks trial in standing). 3) The reduction of mean systolic and diastolic blood pressure at the end of 8 weeks were 19.9/11.6mmHg in sitting and 19.2/11.1mmHg in standing. 4) At the end of 8 weeks the successes of therapy in sitting were 67.5% in excellent, 10.8% in good, and 6.0% in fair response. 5) There was no serious side effect except mild symptom of 5 cases(5.9%) of exertional dyspnea and one episode of (1.2%) tachycardia. CONCLUSION: These results indicate that isradipine is effective and safe antihypertensive agent in the treatment of essential hypertension.

Tratamento da crise hipertensiva em pacientes ambulatoriais com isradipina sublingual / Outpatients hypertensive crisis therapy with isadipine by sublingual route

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

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

Isradipina: novo anti-hipertensivo diidropiridínico / Isradipine: a new dihydropyridine antihypertensive

Revisäo suscinta da isradipina, com suas propriedades farmacoldinâmicas e farmacocinéticas e emprego terapêutico

A Study of Antihypertensive Effect of Isradipine(Dynacirc)

Essential hypertension is an important public health problem in Korea-being common, asymptomatic, easily treatable, and often leading to lethal complication in left untreated. The number of patients with hypertension has been significantly increased, and this factor may be an importnat one responsible for the increase in cardivascular mortality during past 20 years in Korea. As the drug therapy for hypertension needs longer period, it is very important to evaluate the efficacy and the adverse effects. Thirty patients(17 men and 13 womon) with essential hypertension were evaluated in this study. All patients had received oral Isradipine 1.25~2.5mg b.i.d. for 8 weeks. 1) The systolic and diastolic pressure were decreased significantly(166.8+/-9.0mmHg vs 147.3+/-12.0mmHg, p<0.001 and 100.3+/-4.0mmHg vs 90.3+/-6.1mmHg, p<0.001, respectively) 2) Heart rate, body weight, laboratory tests, chest X-ray, ECG studies were not changed significantly. 3) The systolic pressure was lowered by 20mmHg or more in 17 cases(56.7% of total), and the diastolic pressure was lowered by 10mmHg or more in 20 cases(66.7% of total) at 8 weeks after Isradipine administration. 4) The adverse effects of Isradipine were edema in 3(10%), constipation in 2(6.7%), headache in 2(6.7%), and insomnia, dizziness and dry mouth in 1 patient respectively, and none of them discontinued Isradipine administration due to adverse effects. In many patients with essential hypertension there is an effective response to Isradipine, even though there may be some mild adverse effects.

Comparative study of verapamil, isradipine and cimetidine on the gastric changes induced by stress or indomethacin

The influence of the calcium channel blockers verapamil and isradipine on gastric ulceration and glandular wall mast cell count in rats was investigated and compared with that of cimetidine [H2 antagonist]. Two different models for induction of experimental gastric ulcer were performed; cold restraint stress ulcer and indomethacin - induced gastric ulcer. Restraint at 4°C for 1 h or single bolus dose of indomethacin 30 mg/kg p.o, produced a marked gastric mucosal ulceration in saline pretreated controls. The pretreatment with single I.P injection. of either cimetidine [100 mg/ kg], verapamil [4 mg/kg] or isradipine [0.5 mg/kg] 30 minutes before cold restraint or indomethacin administration produced a significant reduction in mean gastric ulcer severity score and reduced incidence of ulceration in both macroscopic and microscopic examinations of stomachs of different groups. Both verapamil and isradipine are more or less equally effective in reducing gastric damage produced by either stress or indomethacin, however, cimetidine produced significant greater protective action. Cold restraint produced a marked decrease in mucosal mast cell count. This degranulating action of stress was prevented with verapamil or isradipine but cimetidine did not produce any significant effect. It is possible that decreased amine release [Histamine and 5 HT.] from mast cell may be responsible for the antiulcer effect of Ca channel blockers, since mast cell degranulation seems to play an important role in pathogenesis of stress gastric ulcers. Other suggested anti-ulcer mechanisms of Ca[++] channel blockers are discussed in the light of the available literature, including decreased stomach wall motility, reduced gastric acidity, peripheral and central interference with vagal overactivity, stimulation of gastric PG, synthesis and/or antioxidant action that counteract stimulation of gastric lipid peroxidation produced by stress or indomethacin. This study proved the potential value of Ca" channel blockers in the management of two different models of experimental gastric ulcers, however, a controlled clinical study is needed before any attempt to extrapolate ulcer therapy in rats to ulcer therapy in man