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)

Although many different beta blockers are now in clinical use, there is very little information concerning their relative efficacy, and it is still not clear what clinical importance should be attached to properties such as positive inotropic stimulation (intrinsic sympathomimetic activity or ISA) and membrane stabilizing action ("local anaesthetic effect" or "quinidine-like effect"). In this report we compare the ability of patients with angina to exercise on a bicycle ergometer while receiving a series of commonly used beta blockers, and attempt to determine the importance of ISA. The investigation is in four parts with the drugs given orally or intravenously: statistical analysis of the results was carried out using standard methods, both parametric and non-parametric (Friedmann analysis of variance, Wilcoxon matched pairs signed ranks test) by two independent statisticians. The relevant properties of drugs included in this paper are summarized in Table I. Laboratory reports using many different animal preparations may differ from this assessment under specific conditions, and the Table is intended only as a guide to the generally accepted properties of these drugs when used clinically. Results for sotalol are included for reference in the first part of this paper but the drug was withdrawn from clinical use and was not studied further.
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PMID:Comparative effects of beta adrenergic blocking drugs. 23 3

Coronary heart disease is the most frequent cause of death in Western, industrialized countries. Coronary risk factors are prevalent in such countries and sometimes combine to constitute the so-called syndrome X--hypertension, central obesity, serum lipid and clotting disturbances, and insulin resistance. beta-Blockers, unlike calcium antagonists, have proved highly effective in secondary prevention of myocardial infarction. If present at the time of the myocardial infarction, beta-blockers (unlike calcium antagonists and diuretics) probably decrease mortality 1 month later. Early intervention (within 12 h) of chest pain with intravenous beta-blockers results in a 15% reduction in cardiovascular mortality at 1 week. Later intervention (3-28 days) with oral non-ISA beta-blockers results in a 30% reduction in mortality after 1 year; ISA-containing beta-blockers are probably less effective (less decrease in heart rate). Hydrophilicity/lipophilicity of beta-blockers is unimportant in terms of decreased mortality. Primary prevention of myocardial infarction, unlike stroke, in hypertensive patients has been disappointing, possibly due to treatment-induced biochemical/lipid changes or inappropriate lowering of diastolic blood pressure in high-risk subjects (J-curve effect). beta-Blockers should be first-line therapy for hypertensive patients up to the age of 65 years, particularly men (and nonsmokers) as Q-wave myocardial infarction is significantly decreased by beta-blockers and significantly increased by diuretics. However, in elderly hypertensive subjects, beta-blockers have not significantly decreased myocardial infarction (unlike stroke), whereas diuretics have. The effects of beta-blockers and diuretics on heart size (and thus coronary flow reserve) in the elderly may be important. Thus, beta-blockers should be second-line therapy for the elderly hypertensive individual but first-line if overt ischemia (e.g., angina or recent myocardial infarction) also is present. In patients with angina but normal blood pressure, beta-blockers tend to decrease and calcium antagonists increase cardiovascular events. Thus, beta-blockers are highly effective agents in the secondary prevention of myocardial infarction and are moderately effective in primary prevention of myocardial infarction in hypertensive patients (particularly men) under the age of 65 years.
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PMID:Beta-blockers: primary and secondary prevention. 128 45

Applying a metaanalysis, it was examined whether a combination of drugs is superior to monotherapy in the treatment of angina pectoris. The three classical groups of anti-anginal drugs, nitrates, calcium channel blockers and beta-receptor blockers were investigated. For data analysis, patients were divided in those suffering from "angina pectoris" and those suffering from "angina pectoris despite monotherapy." In patients with the inclusion criterium "angina pectoris" combination of drugs is not superior to monotherapy. This applies to the evaluation criteria "improvement of symptoms" and "reduction of ischemia". In patients with the inclusion criterium "angina pectoris despite monotherapy" however, there is a clear superiority of drug combination as compared to monotherapy. Again this applies to the evaluation criteria "improvement of symptoms" and "reduction in myocardial ischemia". With respect to antianginal efficacy all three possible combinations appear to be similar. If the evaluation criterium is "improvement of prognosis" no data are available with regard to drug combination. Furthermore no data are available on the prognostic effect of an anti-anginal therapy in patients with stable angina pectoris. A significant improvement of prognosis could be demonstrated for beta-receptor blocking agents without ISA in unstable angina, acute myocardial infarction, and in the postinfarction period. The effect of calcium channel blockers on prognosis depends on the substance class applied and on the presence or absence of signs of congestive heart failure. Monotherapy with nifedipine in instable angina and acute myocardial infarction fails to improve prognosis, and there even may be a tendency to adverse effects. In the absence of signs of congestive heart failure verapamil has been demonstrated to improve prognosis in the post infarction period. Likewise, improvement of prognosis by the administration of diltiazem in acute myocardial infarction only could be demonstrated in patients without signs of heart failure. In contrast, in patients with signs of congestive heart failure diltiazem increased the rate of reinfarction and mortality. For nitrates only in acute myocardial infarction a trend towards improved prognosis has been shown. Especially for nitrates the data on prognosis in coronary heart disease available so far are not convincing.
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PMID:[Anti-angina therapy of coronary heart disease. Mono- or combination treatment]. 167 65

The therapeutic relevance of differences between beta-adrenoceptor antagonists, related to their ancillary pharmacological properties, is debated. Celiprolol is a novel cardioselective beta-blocking agent with attributed cardio-stimulating properties. Its hemodynamic profile was compared with that of atenolol (cardioselective; no ISA) in a comparative dose-response study of 24 patients with angiographically documented coronary artery disease. Following a stable control period four i.v. boluses of equivalent beta-blocking doses of atenolol (1, 1, 2, and 4 mg) or celiprolol (1, 1, 2, and 4 mg) were administered, and hemodynamics and left ventricular ejection fraction were determined. The comparative actions of the two drugs on the hemodynamics of exercise-induced angina were compared by exercise testing in the control state and following the maximum cumulative dose of each drug. At rest, atenolol reduced heart rate, cardiac index, and left ventricular ejection fraction (EF); systemic vascular resistance index increased without change in systemic arterial or pulmonary artery occluded pressures. Celiprolol increased cardiac index and ejection fraction without change in other variables. During exercise both drugs reduced cardiac index and heart rate; neither altered the exercise EF. The cardiac function curve, relating cardiac index to left ventricular end-diastolic pressure, was significantly depressed by atenolol but was elevated at rest by celiprolol. Thus these studies demonstrated hemodynamic differences between atenolol and celiprolol, presumably related to the ancillary properties of the latter. The relevance of such differences to the therapy of patients with coronary artery disease deserves further examination.
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PMID:Differential actions of atenolol and celiprolol on cardiac performance in ischemic heart disease. 242 45

In 242 patients with hypertension and/or angina pectoris, a new cardioselective betablocker without ISA, bisoprolol (Concor), was tested. The average mean value of 168/102 mm Hg was lowered in the 174 hypertensive patients by a systolic value of 17 and a diastolic value of 11 mm Hg. A normal diastolic pressure of 95 mm Hg or below was attained within 4 weeks in 73% of patients. Angina pectoris improved from 7 attacks per week before treatment to 3 attacks after 2 weeks; patients with additional hypertension showed a further improvement after another two weeks to an average of 1.7 attacks per week. Side effects were most frequently dizziness, headache and fatigue and also a few patients with gastrointestinal symptoms, an unusual side effect with this treatment. The results show the effective antihypertensive and antianginal action of bisoprolol in a large group of outpatients.
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PMID:[A new beta 1-receptor blocker in the therapy of essential hypertension and angina pectoris]. 256 85

Within the last decade it became obvious that the treatment of angina pectoris alone is not sufficient. Modern goals include the optimization of anti-ischemic treatment ("silent myocardial ischemia") without compromising quality of life, as well as the reduction of fatal and non-fatal cardiac events. The failure of nitrates to continuously protect from myocardial ischemia ("nitrate tolerance") requires a modification of the current step-care recommendations for medical treatment. Numerous combinations of nitrates, betablockers and calcium channel blockers compensate for each other regarding their effects on heart rate, contractility, peripheral resistance and coronary blood flow. Recommendations for combination therapy decisively depend on the choice of the first-line drug. Only nitrates reduce myocardial preload by venodilation and substitute for EDRF-deficiency. After headaches disappear, nitrates do not affect quality of life and they are cheap. The nitrate-induced acceleration of heart rate should be compensated by the addition of beta-blockers or heart rate-decreasing calcium channel blockers. Therefore, the combination of nitrates with heart-rate-increasing calcium channel blockers, such as nifedipine, should be avoided. Many studies have proven the superiority of different double and triple therapies, as compared to their single components. A few reports, however, did not confirm this increase of anti-ischemic efficacy with combination therapy. The improvement of prognosis is proven for beta blockers without ISA in subgroups of patients with acute or post myocardial infarction and can be assumed for nitrates as well. With regard to prognosis, calcium channel blockers were inferior to nitrates and beta blockers. The combination of nitrates with a non-ISA betablocker should be preferred in post myocardial infarction patients with ventricular arrhythmias, whereas the combination of nitrates with a heart rate decreasing calcium channel blocker should be preferred in patients with COPD, severe peripheral arterial disease or severe diabetes. The combination of nitrates with a heart-rate-increasing calcium channel blocker should be considered in patients with sinus bradycardia, first degree AV-block, or proven coronary spasm. In patients with congestive heart failure, betablockers and calcium channel blockers should be avoided. To optimize medical treatment of ischemic heart disease, intermittent high dosage ISDN plus a beta blocker without ISA or ISDN plus a calcium channel blocker like verapamil are recommended. Frequently, however, the patient decides by himself, based on unacceptable side effects.
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PMID:[Combination of anti-angina drugs]. 257 81

In a placebo-controlled, randomized double-blind study the effect of ICI 141.292 (beta 1-selective beta-blocker with intrinsic sympathomimetic activity = ISA) was studied in 11 patients with severe angina pectoris. The doses used were 100, 200 and 300 mg once daily. The 24-hour heart rate was significantly reduced by all regimens, and the Holter-monitoring pattern indicated the presence of ISA-effect at least 20 hours after the 300-mg dose. Maximal heart rate and blood pressure were significantly reduced and exercise duration increased during a symptom-limited bicycle exercise test on 200 and 300 mg, but not on 100 mg daily. Resting heart rate and blood pressure were uninfluenced on all regimens. ICI 141.292 is an effective agent in patients with severe angina pectoris. The response pattern suggests the presence of clinically relevant ISA.
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PMID:A new water-soluble, selective beta-blocker with intrinsic sympathomimetic activity (ICI 141.292) in angina pectoris. 289 47

beta-Blockers are effective in the symptomatic relief of angina pectoris by decreasing myocardial oxygen demand during effort and emotional stress. Agents with ISA such as pindolol produce effective beta-blockade during effort or emotional stress while conferring significant protection from myocardial depression and bradycardia at rest. In addition, agents with ISA have been shown to depress respiratory function to a lesser extent and to induce fewer peripheral vascular side effects than compounds devoid of this property. These potential effects of ISA may be counterbalanced by the consideration that ISA may be undesirable in angina occurring at rest or at low exercise levels. Additional well-controlled trials in patients with angina and resting bradycardia or impaired left ventricular function are needed to further document the clinical importance of ISA.
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PMID:Clinical relevance of intrinsic sympathomimetic activity of beta blockers. 611 37

Beta-adrenoceptor blockade is responsible for the therapeutic action of beta-adrenoceptor-blocking drugs in the treatment of hypertension and angina pectoris. Many aspects of their effects can therefore be studied in relatively simple clinical pharmacologic experiments. Cardiac beta-adrenoceptor blockade can be measured in terms of the reduction of isoprenaline-induced and exercise-induced tachycardia. Based on these experimental procedures pindolol is, on a weight-for-weight basis, about 20 times more potent than propranolol. The duration of action of pindolol, measured by the reduction in exercise-induced tachycardia, is longer than that of many other beta-adrenoceptor-blocking drugs such as propranolol, alprenolol, and slow-release oxprenolol tested at equipotent beta-adrenoceptor-blocking doses. Pindolol is a beta-adrenoceptor-blocking drug with partial agonist activity (intrinsic sympathomimetic activity [ISA]). Drugs of this type are as effective in inhibiting beta-adrenoceptor stimulation as drugs devoid of this property, but unlike the latter they produce some stimulation of beta adrenoceptors. The ISA of pindolol is sufficient to counterbalance the diminution in resting sympathetic tone that results from beta-adrenoceptor blockade. In hemodynamic studies pindolol does not alter or only slightly reduces normal cardiac output. This is in contrast to drugs lacking ISA, which consistently depress cardiac output. In addition, propranolol has been shown to markedly reduce blood flow in the calf, whereas pindolol and placebo do not differ from one another in their effect on this parameter. A linear correlation exists between the logarithm of plasma concentrations of pindolol and cardiac beta-adrenoceptor blockade expressed as a reduction of exercise-induced tachycardia. The high systemic availability of pindolol after oral administration, due to good oral absorption and low first-pass effect, is revealed not only in pharmacokinetic studies but also in pharmacodynamic experiments; beta-adrenoceptor blockade 75 minutes after intravenous administration was equivalent to that observed 2 hours after the same doses given orally.
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PMID:Clinical pharmacology of pindolol. 612 94

This trial comprised 40 patients with angina pectoris and reproducible ischaemic ST segment depression in the exercise ECG. Whenever possible the diagnosis of coronary heart disease was confirmed by coronary angiography. After a preliminary 7-day placebo period, 20 of these patients were treated for 4 weeks with 5-(3-tert-butylamino-2-hydroxy-propoxy)-3, 4-dihydro-2(1H)-quinolinone hydrochloride (carteolol hydrochloride, Endak, Endak mite), a nonselective beta-receptor blocker, having adrenergic properties (ISA) up to 30 times more powerful than those of propranolol. The trial was double-blind and randomized; standard medication (pindolol) was given to the controls. In general, the results obtained with carteolol--and also with pindolol--may be regarded as "good" or "very good". The average weekly incidence of anginal attacks fell from 6 to 4 (p less than 0.05). Carteolol produced a definite decrease in ST segment depression during exercise, at the end of exercise and in the recovery phase (p less than 0.05). The same was true for the patients treated with pindolol. There was no statistically significant difference between the treatment groups. Pulse rate and systolic blood pressure--measured before exercise and at the end of the recovery phase--did not change; however, readings made at the end of exercise showed a significant decrease (p less than 0.05). Diastolic pressure remained essentially unaltered. There were no changes in the chest radiograph or resting ECG. Laboratory results remained unchanged in both groups. In one patient of each group treatment needed to be discontinued because of dyspnoea, mainly during exercise. This reaction could probably be related to the beta-blocker therapy. The overall response to treatment, as assessed by the physician conducting the trial, was "good" or "very good" in 75% of the patients receiving carteolol and in 70% of those receiving pindolol. 70% of the patients who had received carteolol assessed the therapeutic result as "good" or "very good"; in the pindolol group 55% made the same judgment.
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PMID:The treatment of angina pectoris with the new beta-receptor blocker carteolol. Results of a controlled trial in comparison with pindolol. 634 Jul


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