Safety and compatibility of betaxolol hydrochloride combined with diltiazem or nifedipine therapy in stable angina pectoris
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Betaxolol
The antianginal effects of a combination of nifedipine and diltiazem were investigated in 6 patients with stable effort angina. Patients received one-week courses of successive treatment with 80 mg/day of nifedipine, 120 mg/day of nifedipine, then a combination of 120 mg/day of nifedipine and 120 mg/day of diltiazem, respectively. Patients then performed a symptom-limited treadmill exercise test at the end of each period of treatment. Mean exercise duration was 383 sec after receiving 80 mg/day of nifedipine 389 sec after receiving 120 mg/day of nifedipine and was then increased to 498 sec after receiving the nifedipine-diltiazem combination. The mean plasma nifedipine concentration at the end of one-week treatment increased from 134. 5 ng/ml during administration of 120 mg/day of nifedipine to 335.5 ng/ml during administration of the nifedipine-diltiazem combination. This study demonstrated that a combination of nifedipine and diltiazem is of value in the treatment of effort angina, partly because of an increase in the plasma nifedipine concentration as a result of the pharmacokinetic interaction between nifedipine and diltiazem.
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In a double blind 7-week randomized study the authors compared in 29 patients with stable angina the action of placebo, nifedipine and diltiazem. Nifedipine was administered in amounts of 60 mg/day for three weeks, diltiazem 270 mg/day also for three weeks. Nifedipine and diltiazem exerted a significant antianginous action in patients with occluded but collateralized coronary arteries (group A), as well as in patients without collaterals (group B). In both these groups diltiazem improved the load tolerance significantly more than nifedipine. Nifedipine and diltiazem were useful also in patients with mild (group E), medium (group D) and severe (group C) affections of the coronary arteries. Groups C and E differed significantly as to the different effect of nifedipine and diltiazem on load S-T depressions (in group C diltiazem was significantly more effective, in group E nifedipine was insignificantly better), and it was not possible to explain these differences by a different effect on Robinson's index. The authors conclude that neither nifedipine nor diltiazem led in the amounts used to the "steal phenomenon" with clinical impact. In patients with mild affections of the coronary arteries their antiischaemic and antianginous action was similar, in patients with severe affection of the coronary arteries diltiazem was more effective.
Coronary arteries
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The antianginal effects of diltiazem and nifedipine alone and in combination were evaluated in a double-blind, randomized, placebo-controlled trial in 11 patients (nine men and two women, 57 +/- 8 years old) with stable effort angina. Each patient received placebo, 30 mg of diltiazem, 10 mg of nifedipine, and 30 mg of diltiazem plus 10 mg of nifedipine four times daily for 1 week each. Antianginal efficacy was assessed by means of a treadmill exercise test. The exercise tolerance time was significantly prolonged from 235.1 +/- 52 (placebo period) to 342.2 +/- 101 sec by diltiazem (p less than .01) and to 325.6 +/- 73 sec by nifedipine (p less than .01). The drug combination further prolonged exercise time to 451.1 +/- 103 sec, which was significantly longer than the interval attained with either diltiazem (p less than .01) or nifedipine (p less than .01) alone. The plasma concentration of diltiazem was unaffected by the addition of nifedipine, whereas the plasma nifedipine concentration was significantly increased from 34.8 +/- 11 to 106.4 +/- 37 ng/ml (p less than .001) by the concomitant administration of diltiazem. These data suggest that exercise tolerance in patients with effort angina is increased by the concomitant administration of diltiazem and nifedipine associated with an increase in the nifedipine plasma concentration.
Concomitant
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Objective:To study the therapeutic effect of diltiazem with nifedipine after kidney-transplantation with ciclosporin(CsA). Methods:Fourty patients were randomly divided into 2 group evenly. The treatment group took diltiazem 30 mg, po, bid, and nifedipine 10mg, po, tid. The control group received nifedipine 10 mg, po, tid. The drug dosages were adjusted according to the level of blood pressure. The artery pressure and renal function were checked for more than 2 years. Results:Diltiazem changed the metabolism of CsA, resulting in a forty percent reduction in CsA dose. But the risk of CsA toxicity did not increase. Conclusion:Diltiazem with nifedipine can safely be used in the treatment of hypertension after kidney transplantation, and can lower the dose of CsA.
Ciclosporin
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To compare efficacy of diltiazem and nifedipine in single dose and long-term treatment.A randomised double-blind cross-over study enrolled 17 patients suffering from coronary heart disease (CHD) with stable angina of effort (SAE). For 1 month, each patient received diltiazem and nifedipine (60-90 mg 4 times a day and 20-30 mg 4 times a day, respectively). The effect was assessed by the pharmacodynamic test after the initial dose and in the end of each treatment course.In 14 eligible patients both drugs reduced the number of SAE attacks and nitroglycerin tablets, diltiazem efficiency being somewhat higher. Single doses of diltiazem and nifedipine produced the same action. In long-term treatment nifedipine effect became shorter, diltiazem effect did not change. Before the morning dose of nifedipine (11.5 hours after the previous dose) exercise tolerance of this drug worsened. This may be due to withdrawal syndrome. As to diltiazem, its exercise tolerance improved.In long-term treatment of CHD with SAE diltiasem is more effective and safe than nifedipine.
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The effect of durations of diltiazem pretreatment on nifedipine kinetics was evaluated. Eighteen healthy male subjects were randomly allocated to three groups, 6 subjects each, for single doses of 60 mg diltiazem, and 3 days and 6 days with diltiazem 60 mg three times a day. All subjects received 20 mg nifedipine orally on two occasions using a double‐blind cross‐over, placebo‐controlled method. No significant difference on pharmacokinetic parameters of nifedipine without diltiazem were observed among three groups. The single dose with 60 mg diltiazem significantly increased the area under the plasma concentration‐time curve (AUC) for nifedipine compared with that in control an average of 35.1% (P < .05) and decreased the total body clearance (CL) an average of 24.0% (P < .05). Three days and 6 days pretreatment with diltiazem 60 mg three times a day significantly increased mean nifedipine AUC to 151.1% (P < .01), 188.0% (P < .05) of control values, and decreased CL to 58.2% (P < .01), 63.9% (P < .05) of control values, respectively. The elimination half‐life (t1/2) of nifedipine were significantly prolonged both after 3 days' and after 6 days' pretreatment of diltiazem. These results suggest that diltiazem affects the nifedipine kinetics rapidly and pretreatment duration dependently. A clinically important drug interaction may occur when both drugs are administered simultaneously.
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The treatment of chilblains remains unsatisfactory. Nifedipine in higher doses remains the mainstay of treatment.To compare the efficacy of diltiazem with that of nifedipine, and to determine the efficacy of nifedipine in lower doses, 36 chilblains cases were studied.Group A (12 patients) was treated with diltiazem 60 mg thrice daily, and Group B (24 patients) with 10 mg nifedipine thrice daily till complete relief and then maintained on a sustained release preparation of nifedipine 20 mg twice daily.Two patients in Group A showed complete relief in 7 days, and 3 patients in about 21 days, but in 7 cases there was little or no response. In group B, 21 cases showed 80-90% relief by the fourteenth day.We conclude that nifedipine remains the drug of choice in chilblains but can be used in a smaller dosage in the Indian population. Diltiazem is less effective in the conventional dose, which may be optimized.
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Background: Cyclosporine A (CsA) and calcium channel blockers induce gingival overgrowth in humans and animals. Recently, nifedipine and diltiazem have often been used to control CsA‐related hypertension in organ transplant patients. The purpose of this study was to examine the effects of a combined oral treatment of CsA and nifedipine or diltiazem on the severity of gingival overgrowth in rats. Methods: Fifteen‐day‐old Fischer rats were treated orally with single or combined applications of CsA, nifedipine, and/or diltiazem for 40 days; and induced gingival overgrowth, rat growth, and blood drug levels were compared among the different experimental groups. The experiment consisted of 6 groups: one control group (group A) and 5 test groups treated with CsA (group B), nifedipine (group C), and diltiazem (group D), as well as those concurrently treated with CsA and nifedipine (group E), and CsA and diltiazem (group F). Gingival overgrowth was determined by measuring the depth of the gingival sulcus. Results: The mandibular buccal gingival sulcus depth of group A was 365 ± 41.2 μm. Among the test groups, the most remarkable gingival overgrowth was seen in group E (1,020 ± 63.3 μm), followed by group F (895 ± 43.8 μm), group B (870 ± 48.3 μm), group C (525 ± 116 μm), and then group D (505 ± 83.2 μm). Rat body weight gain was reduced significantly by oral CsA treatment. Neither nifedipine nor diltiazem suppressed rat growth when used independently; however, rat growth reduced by CsA was further suppressed by a combined use of diltiazem, but not nifedipine. CsA blood levels were reduced by concurrent oral treatment with nifedipine or diltiazem along with the blood levels of those calcium channel blockers when treatment was in combination with CsA. Conclusions: These results suggest that gingival overgrowth is induced in rats as a side effect of CsA, nifedipine, or diltiazem, and the combined use of these drugs influences rat growth, blood drug levels, and the severity of gingival overgrowth. J Periodontol 2000;71:438‐443.
Diltiazem hydrochloride
Ciclosporin
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The antianginal effects of diltiazem and nifedipine alone and in combination were evaluated in a double-blind, randomized, placebo-controlled trial in 11 patients (nine men and two women, 57 +/- 8 years old) with stable effort angina. Each patient received placebo, 30 mg of diltiazem, 10 mg of nifedipine, and 30 mg of diltiazem plus 10 mg of nifedipine four times daily for 1 week each. Antianginal efficacy was assessed by means of a treadmill exercise test. The exercise tolerance time was significantly prolonged from 235.1 +/- 52 (placebo period) to 342.2 +/- 101 sec by diltiazem (p less than .01) and to 325.6 +/- 73 sec by nifedipine (p less than .01). The drug combination further prolonged exercise time to 451.1 +/- 103 sec, which was significantly longer than the interval attained with either diltiazem (p less than .01) or nifedipine (p less than .01) alone. The plasma concentration of diltiazem was unaffected by the addition of nifedipine, whereas the plasma nifedipine concentration was significantly ...
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AIM:To compare the therapy effects and adverse reactions between diltiazem and nifedipine in treatment of unstable angina pectoris (UAP). METHODS: A total of 61 UAP patients [M 42, F 19; age 51.0 a± s 2.6 a (45-66 a)] were randomly divided into diltiazem group ( n =31) and nifedipine group ( n =30). Thirty one patients received diltiazem 180 mg, po , bid in diltiazem group. Thirty patients received nifedipine 10 mg, po , tid in nifedipine group. RESULTS: The differences of therapy effect between the diltiazen group and nifedipine group were significant before and after treatment. The total effective rate was 94% and 77% respectively and the effective rate of improvement of electrocardiogram was 90% and 57% respertively ( P 0.05). There was significant difference in adverse reartions. CONCLUSION: Diltiazem is superior to nifidine in treatment of UAP.
Unstable angina
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