Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002962 (angina)
 21,142 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epanolol (200 mg once daily) was compared with nifedipine (20 mg twice daily) in a multicentre, double-blind, randomised, crossover study in which 571 patients with stable angina pectoris were entered. Efficacy was assessed by anginal attack rate and short-acting nitrate consumption. Symptoms and treatment preference of the patients were assessed by questionnaires. Assessments were made at baseline and after each 4-week treatment period. Both treatments were equally efficacious as demonstrated by weekly anginal attack rates and nitrate usage. Of those patients who expressed a preference for treatment, 61% expressed a preference for epanolol compared with 39% for nifedipine. Significantly fewer patients reported experiencing flushing, pedal oedema or feeling generally unwell (p less than 0.01) during the epanolol treatment period. Patients withdrew from nifedipine treatment more often than from epanolol because of adverse effects. Hence, epanolol was found to be as efficacious as nifedipine in patients with stable angina pectoris, but exhibited a superior tolerability profile and was preferred by more patients.
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PMID:A comparison of epanolol and nifedipine in stable angina patients: results of a multicentre trial. 168 42

The presence of sulfhydryl (SH) groups appears to be fundamental to nitrate-induced vasodilation and N-acetylcysteine (NAC), a sulfhydryl (SH)-donor substance, potentiates hemodynamic responsiveness to nitrates. We investigated the effect of simultaneous administration of NAC and isosorbide dinitrate (ISDN) on development of nitrate tolerance. In a double-blind, randomized, placebo-controlled cross-over study, seven patients with stable angina pectoris were treated for two 8-day periods with ISDN (40 mg four times daily, q.i.d.) together with NAC (controlled release 600 mg q.i.d.) or matching placebo. Bicycle exercise tests were performed before treatment was started, 1 h after treatment was started, and at day 8. After 8-day treatment with ISDN + placebo, responses determined by exercise testing were diminished as compared with responses obtained during acute therapy and did not differ from baseline values, suggesting development of tolerance to ISDN. During treatment with ISDN + NAC, time to 1-mm ST depression was significantly prolonged (441 +/- 44 vs. 381 +/- 40 s, mean +/- SEM) and total ST segment depression significantly reduced (1.9 +/- 0.7 vs. 3.5 +/- 0.8 mm) as compared with baseline values. The reduction in ST segment depression was significantly more pronounced during ISDN + NAC (46%) as compared with ISDN + placebo (23%). Although exercise time and time to angina pectoris were unaffected. NAC augmented the antiischemic effects of ISDN as assessed by ECG. This finding may suggest that development of nitrate tolerance is modified by chronic oral high-dose NAC administration.
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PMID:Continuous oral N-acetylcysteine treatment and development of nitrate tolerance in patients with stable angina pectoris. 171 11

In this study, the effect of bradykinin on coronary flow in the isolated rat heart was significantly potentiated when cysteine or the sulfhydryl-containing converting enzyme inhibitors captopril and zofenoprilat were administered simultaneously. In contrast, the effect of concomitant administration of enalaprilat only slightly increased the effect of bradykinin on coronary flow. In nitrate-tolerant hearts of rats pretreated with isosorbide dinitrate (15 mg daily), the increase in coronary flow by nitroglycerin and bradykinin was significantly less when compared to control hearts. The effect of captopril was not affected by pretreatment. The involvement of endothelium-derived relaxing factor (EDRF) in the effect of captopril was apparent from experiments with L-arginine, the precursor of EDRF, and L-NMMA, the "false" precursor of EDRF. L-Arginine increased the effect of captopril, whereas L-NMMA showed a competitive antagonism for the effect of captopril on coronary flow in the isolated rat heart. Clinically, the effect of captopril was studied in 10 patients with stable, exercise-induced angina pectoris that had been treated for 3 weeks with slow-release isosorbide dinitrate (20 mg four times daily). At day 7, a baseline exercise test was obtained. Subsequently, patients with chest pain and at least 1-mm ST-segment depression on the ECG during exercise were included. They received on day 14 and 21 either captopril (25 mg) or placebo 1 h before exercise testing in a randomized, double-blind, crossover design. Captopril significantly improved the combined score of maximal ST-segment depression, maximal workload, and time to angina when compared to placebo. No differences in the pressure-rate index at rest and during exercise were seen. These results indicate that the sulfhydryl group of certain angiotensin converting enzyme inhibitors can potentiate their effect on the endogenous nitrovasodilator EDRF. In the clinical situation, this may lead to an improved exercise performance in patients with stable angina pectoris during chronic nitrate treatment, independent of its systemic vascular effects.
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PMID:Converting enzyme inhibitors and the role of the sulfhydryl group in the potentiation of exo- and endogenous nitrovasodilators. 172 Aug 43

A case is presented of a morbidly obese parturient who had multiple medical problems. She had angina and was receiving nitrate therapy, had insulin-dependent diabetes mellitus, hypertension, asthma and benign intracranial hypertension (pseudotumour cerebri). Lumbar epidural analgesia was chosen for labour and delivery and resulted in an uneventful outcome.
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PMID:Anaesthetic management of a complex morbidly obese parturient. 174 26

The long-term efficacy of transdermal nitrate therapy, in particular the ability of a single patch to provide 24 h prophylaxis against angina, has been questioned. Two mechanisms have been suggested for this loss of effect: the development of pharmacological tolerance, and premature patch exhaustion. This study was designed to investigate this problem, and in particular to investigate the time course of treatment failure. It comprised a randomized, double-blind, cross-over comparison of transdermal glyceryl trinitrate and matching placebo transdermal patches. Significant treatment effects were demonstrated by several criteria for 8 h of continuous therapy, with some limited effect persisting for 15 h. Loss of effect began to develop very soon after treatment was initiated and progressed in a steady, linear fashion so that there was virtually no treatment effect after 24 h. In contrast, during intermittent therapy, treatment effects were maintained on the second day following a nitrate-free interval. Significant benefit was demonstrated for up to 32 h (i.e. 8 h of treatment on day 2). Both nitrate-free intervals (12 and 16 h) seemed to be equally effective in maintaining efficacy after 3 h of treatment on the second day, although this was still somewhat attenuated compared with day 1. These results confirm that loss of therapeutic efficacy of transdermal nitrate is due to the development of tolerance and not premature patch exhaustion. In contrast to previous studies, however, they suggest that tolerance can only partly be reversed by intermittent therapy and also that the onset of tolerance is so rapid that it is well established in less than a day's treatment.
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PMID:Attenuation of nitrate effect during an intermittent treatment regimen and the time course of nitrate tolerance. 177 90

We prospectively studied 69 consecutive patients hospitalized with a primary diagnosis of acute left ventricular failure so as to assess the impact of vasodilators on incidence and morbidity of acute symptomatic left ventricular failure. The determinants of duration of hospitalization, in-hospital mortality and symptomatic status 2 months after discharge were examined. There were 9 in-hospital deaths (13%), and survival at 60 days was 77%. Median duration of hospitalization was 9 days, and 33% of the surviving patients remained in New York Heart Association functional class III-IV 60 days subsequent to discharge. Of the patients, 49 (76%) had previously received treatment for left ventricular failure: 30 (61%) of these had received vasodilators, most commonly angiotensin converting enzyme inhibitors and nitrates. Ischaemic chest pain was present in 34 (49%) of the patients. Acute utilization of vasodilators (45% of patients) was largely limited to nitrate therapy associated with ischaemic chest pain (P less than 0.01). Multiple logistic regression revealed previous left ventricular failure, advanced age and hypokalaemia as significant correlates of prolonged hospitalization (greater than 9 days). Previous left ventricular failure was also predictive of persistent severe disability two months subsequent to discharge. No factor was a significant predictor of in-hospital death. Although preceding treatment with digoxin and incremental angiotensin converting enzyme inhibitor therapy tended to predict brief hospitalization, the parameter of acute ischaemia, other biochemical anomalies and modes of acute or chronic therapy were not significant correlates of any end point. We conclude that preceding disability, rather than mode of treatment, predicts an adverse outcome in acute left ventricular failure.
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PMID:Acute heart failure: determinants of outcome. 179 Oct 90

With chronic use of organic nitrates, attenuation of their clinical efficacy in angina pectoris and in congestive heart failure can occur. This attenuation is more pronounced if controlled release preparations for oral or transdermal use, leading to continuous high plasma concentrations of the nitrates, are used. Twenty-four hour protection, e.g. in a patient with angina pectoris, is not possible with nitrates, and other substances such as beta-adrenergic blockers and calcium antagonists will often have to be associated. The introduction of "nitrate-free periods" to overcome tolerance is discussed. The use of SH-providing substances such as N-acetylcystein to counteract the development of nitrate tolerance is, at this moment, only experimental.
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PMID:[Tolerance to nitrate derivatives: clinical implications]. 179 25

10 patients (6 females and 4 males with an average age of 75 years) with stable angina pectoris were treated transdermally with mepindolol in a balanced, randomized, controlled, crossover study to compare the anti-ischemic effects of 12-hour overnight, and 24-hour applications. The number of angina pectoris attacks, the oral nitrate consumption and the ischemic parameters in 24-hour ECG, i.e. episodes of manifest (MMI) and silent (SMI) myocardial ischemia, the total duration of ischemia and 24-hour heart rate profiles were investigated. Both application schemes showed typical systemic beta blocker effects in all patients and significant clinical efficacy. A dose/effect relationship and a time/effect relationship between the two different application schemes were demonstrated across all the parameters investigated. Systemic and local tolerance of the therapy was good. 2 patients showed transient, mild skin irritation, but only during one phase of the study. Premature discontinuation was not necessary in any cases. There were no relevant changes in the clinical-chemistry. The new therapeutic concept of 24-hour treatment for a. pectoris with 12-hour overnight transdermal applications showed both good clinical efficacy and a good safety profile.
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PMID:Transdermal monotherapy with mepindolol BIO TSD in patients with stable angina pectoris. Placebo-controlled, crossover investigation of a new therapeutic concept with 12-hours overnight application. 180 Mar 88

The aim of this study was to investigate antianginal and antiischemic activity and tolerance of a new nitrate derivative, nicorandil (N). This research has been carried out in 18 patients, aged 47-70 years, suffering from stable effort angina with fixed ischemic threshold. The study started with 10 days of washout, during which the patients exercised twice on bicycle to verify the reproducibility of the test. Then, they took N or isosorbide-5-mononitrate (ISM) for 14 days according to a double blinded cross-over balanced study. Between the 2 periods patients took placebo (PL) for 14 days. In the first day and in the last day of each period, 2 hours after the last drug intake, patients performed a stress test on bicycle. Like ISM, N significantly increased, versus PL, 1 mm of ST depression time (ischemic threshold) in the first and in the last day, without differences between the 2 drugs and between the days. Moreover, ST depression was significantly lower at maximal common work (MCW) versus PL. The rate-pressure product was not different from PL after N and ISM at maximal common work, but is was increased at the ischemic threshold. In conclusion, like ISM, N has shown antiischemic activity in patients suffering from stable angina pectoris on effort with fixed ischemic threshold. After 14 days of treatment there was no evidence of tolerance. The activity of N seems essentially due to an increase of coronary blood flow to ischemic zones.
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PMID:[A new anti-ischemic drug for the treatment of stable effort angina pectoris: nicorandil. Comparison with placebo and isosorbide-5-mononitrate]. 183 69

Nitrates have a place in the prophylactic treatment of patients with angina pectoris. Their efficacy is not in doubt. However, there may be some practical problems associated with their use, such as unreliable absorption, short duration of action, treatment-induced headache, development of nitrate tolerance and a suggested rebound phenomenon observed during intermittent dosing. This article discusses how many of these problems may be solved by selection of formulation as well as nitrate compound. Thus, the development of a controlled-release formulation producing sufficiently high nitrate plasma concentrations during part of the day, followed by a low nitrate level rather than a nitrate-free interval, seems to have the potential to prevent both nitrate tolerance and rebound phenomenon. This system would also offer a sufficiently long duration of action with a convenient once-daily dose regimen.
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PMID:Is there an optimal prophylactic nitrate therapy? 187 71


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