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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitrate monotherapy was assessed by treadmill exercise stress testing in 18 patients with significant but relatively asymptomatic myocardial ischemia who were receiving no other antianginal therapy. In addition, prolonged ambulatory electrocardiographic monitoring was performed in 7 patients with demonstrable ischemia during baseline monitoring. After baseline assessment, 5 treatment periods were used in a random order (each of 1 week duration), incorporating 2 dose levels of transdermal nitrate (10 and 20 mg/24 hours) and isosorbide dinitrate (ISDN) (30 and 60 mg/day in divided doses) with a 10-hour nitrate-free interval every 24 hours, as well as a placebo period using a double-blind technique. All treatment periods (including placebo) showed a significant (p < 0.01) 45 to 69% prolongation in the time to 1 mm ST depression during exercise. Paired baseline times of 231 +/- 28 and 233 +/- 30 seconds increased to 367 +/- 37 seconds with 30 mg/day of ISDN, 393 +/- 37 seconds with 60 mg/day of ISDN, 381 +/- 31 seconds with 10 mg/day of transdermal nitrate, and 372 +/- 33 seconds with 20 mg/day of transdermal nitrate. The value for placebo was 342 +/- 29 seconds, which was not significantly different from active treatment (p > 0.1). Some patients appeared to individually respond to > or = 1 nitrate preparation significantly more than to placebo, but this appeared to be unpredictable and largely independent of dosage level and route of administration. There was a qualitatively similar but statistically insignificant reduction in total ischemic time during ambulatory monitoring.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Placebo effect of nitrate monotherapy for myocardial ischemia. 144 72

Nitro derivates are effective agents for the treatment of myocardial ischemia. The effectiveness of these compounds in anginal disease is due to their ability to induce dilatation of veins which results in decreased left and right ventricular and diastolic pressure. Furthermore nitro derivates also bring about coronary vasodilatation which is present also in conditions of stenosis of epicardial arteries. In these conditions either coronary flow increases or its redistribution is more favorable. As the vasodilatory effect of nitro derivates does not involve sound arterioles, no "theft" of blood occurs. The dilatation of veins induced by nitrates explains also their effectiveness in patients suffering from heart failure with high left ventricular pressure. Mononitrates seem more effective than dinitrates since variability problems due to hepatic metabolism disappear. Nitrate plasters do not appear favourable since they produce constant blood levels and therefore could favour the development of tolerance.
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PMID:[Current status of pharmacology and therapeutic use of nitro derivatives]. 215 28

Recently there has been much progress towards defining the action of nitrates, and related compounds, at a biochemical level. However, in vivo, differences in the effects of nitroglycerin (GTN) between specific sections of the vascular tree and various regions of the circulation are still not well understood. The actions of nitrates as they relate to the alleviation of myocardial ischemia are briefly reviewed. Then, an attempt is made to analyze separately the nitrodilator influences in the large and medium sized arteries, the venous system and the arterioles, in vivo. When pitfalls such as nonselectivity of indexes of drug action and secondary compensatory regulatory influences are considered, a surprising responsiveness of the resistance vessels to GTN is unmasked, revealing a remarkable uniformity in the profile of GTN action within different sections of the vascular tree. Nitrate effects in these vascular sections are then compared among several important regions of the circulation (i.e. mesenteric, skeletal muscle, brain etc.), and similarities or differences in action are noted. Finally the concepts presented here are related to some areas of controversy regarding nitrate action, in an attempt to form a basis for a better understanding of the sometimes confusing nitrate literature.
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PMID:Effects of nitrates in various vascular sections and regions. 309 81

The role of transdermal nitroglycerin (TNTG) in the treatment of ischemic heart disease and congestive heart failure (CHF) is reviewed, with an emphasis on controversies concerning efficacy, hemodynamics, and dosing. Currently marketed rate-controlled transdermal nitroglycerin systems provide steady plasma concentrations of nitroglycerin for 24 hours. However, results of controlled trials in ischemic heart disease and CHF have raised doubts about the ability of TNTG to exert clinically important antianginal or hemodynamic benefit for the full 24-hour period. There is evidence that the duration of effect after TNTG application may persist for 24 hours, but there also is evidence of a lack of efficacy beyond 6 to 12 hours. This issue has not been resolved, but there is a trend toward use of larger doses that produce more persistent effects. The effects of conventional doses of TNTG in ischemic heart disease are modest; efficacy is based on demonstrated improvements in exercise performance. High TNTG doses (40-90 mg/24 hours) are required by many patients. In CHF, TNTG improves venous hemodynamic measurements. A dose-response relationship is not well defined. High-dose TNTG therapy is probably required to increase cardiac output and decrease systemic vascular resistance. Nitrate attenuation appears to be an important phenomenon with TNTG therapy. As with other forms of nitrate therapy, adverse effects may be a limiting factor, and clinical experience with high-dose TNTG therapy is limited. For some patients, TNTG therapy is an important addition to medical therapy. Further studies are needed to confirm reported improvements in exercise performance and hemodynamic benefits and to identify patient subsets likely to benefit from TNTG therapy.
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PMID:Controversies in the use of transdermal nitroglycerin systems. 312 Dec 39

Nitroglycerin and the long-acting nitrates are beneficial in stable and unstable angina pectoris and acute myocardial infarction and as adjunctive therapy in congestive heart failure. Nitroglycerin compounds relax vascular smooth muscle, producing venous, arterial, and arteriolar dilatation. These actions are modulated by stimulation of intracellular cyclic guanosine monophosphate. Nitrate efficacy in ischemic heart disease is due to peripheral venous and arterial vasodilatation that results in decreased myocardial oxygen consumption. Nitrates also dilate coronary arteries and collaterals, reverse coronary vasoconstriction, and enlarge some coronary atherosclerotic lesions. Nitrates improve exercise performance in stable angina pectoris. Intravenous nitroglycerin should be used in the initial treatment of unstable angina. Nitrates may be beneficial in myocardial infarction for control of ischemic pain, acute hypertension, and left ventricular failure. In subjects with congestive heart failure, nitrates reduce symptoms and improve exercise tolerance. Nitrate tolerance is a problem with continuous nitrate therapy. Tolerance is most likely to occur with frequent dosing or the use of long-acting nitrates, particularly transdermal nitroglycerin disks, and can be prevented or reversed with intermittent-dosing regimens.
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PMID:A reappraisal of nitrate therapy. 327 14

The beneficial effects on nitrates are related to a combination of coronary and non-coronary effects of the drugs. Patients with different forms of ischaemic heart disease may respond differently. For instance, in a patient with rest angina due to coronary artery spasm, nitrates will reverse or prevent coronary artery spasm. In contrast, the patient with severe coronary artery stenosis and reproducible angina during exercise, may obtain relief because nitrates decrease venous return, left ventricular size and left ventricular pressure, thus decreasing myocardial oxygen demands. Nitrates can be used to treat patients with chronic angina, unstable angina and myocardial infarction. In patients with chronic angina, oral nitrate preparations with sustained-release action have been shown to decrease the indices of myocardial oxygen demand for up to 12 h. In patients with unstable angina, intravenous nitrates usually relieve symptoms in patients refractory to oral therapy. In patients with acute myocardial infarction, early administration with intravenous nitrates may benefit patients as suggested by randomized prospective trials. Nitrate tolerance and nitrate dependence does not seem to be an important clinical problem. Perhaps this is related to the way the drug is given, i.e. intermittently. In some instances, however, when high doses are used or the drug is administered intravenously or by the transdermal route, constant levels of nitroglycerine may be attained and the patients may develop tolerance. Although nitrates are effective drugs, it is native to think that they will be used alone to manage the complex problems associated with ischaemic heart disease. Other than hypotension and adverse effects of the drug, there seems to be no contraindication to the combination of nitrates with calcium antagonists or beta blockers.
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PMID:Nitrate therapy for ischaemic heart disease. 399 35

Nitroglycerin and other organic nitrates are beneficial in ischaemic heart disease and myocardial infarction and as adjunctive therapy in congestive heart failure. The nitrates are inactive prodrugs, and their vascular effects depend on metabolic conversion to vasoactive intermediates like nitric oxide and/or nitrosothiols with subsequent stimulation of guanylate cyclase causing increased formation of cyclic GMP. The compounds relax vascular smooth muscle producing venous dilatation at low concentrations and at higher concentrations dilation of coronary arteries and collaterals and systemic arterial vessels. Nitrate tolerance is, however, a problem with continuous nitrate therapy. Tolerance is most likely to occur with frequent dosing or with the use of long-acting nitrates or transdermal applications resulting in constant plasma concentrations. Therapeutic strategies should be designed to provide a daily low-nitrate period or nitrate-free period to obviate the development of tolerance and thus maintain the antianginal effects.
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PMID:[Nitroglycerin preparations. Effect and tolerance]. 806 82

Nitroglycerin and the long-acting nitrates have been used in cardiovascular medicine for >100 years. Nitrates are widely utilized for the various anginal syndromes and are also used in congestive heart failure and patients with left ventricular dysfunction. The potential mechanisms for relief of myocardial ischemia with nitrates are multiple. The nitrovasodilators are a related group of drugs that result in the formation of nitric oxide (NO) within vascular smooth muscle cells. NO stimulates the enzyme guanylate cyclase, which results in increases in cyclic guanosine monophosphate and vasodilation. In the presence of atherosclerosis, endothelial dysfunction is ubiquitous and associated with decreased NO availability, probably due to increased destruction of NO by free radical anions. Nitrovasodilators, including the nitrates, supply exogenous NO to the vascular wall and improve the vasodilator state. When nitrates are administered, endothelial-dependent stimuli cause relaxation rather than constriction in the setting of endothelial dysfunction. Nitrates also have antiplatelet effects, and recent evidence confirms that these drugs decrease platelet aggregation and thrombosis formation. This may play an important role in the therapy of acute unstable myocardial ischemia, including unstable angina and myocardial infarction. Nitrate hemodynamic effects have been long known. They are primarily modulated through a decrease in myocardial work that results from smaller cardiac chambers operating with lower systolic and diastolic pressures. These changes are caused by a redistribution of the circulating blood volume away from the heart to the venous capacitance system, with a fall in venous return to the heart. The afterload or arterial effects of nitrates are also useful in decreasing myocardial oxygen consumption. Considerable evidence confirms a variety of mechanisms whereby nitrates increase coronary blood flow, including epicardial coronary artery dilation, stenosis enlargement, enhanced collateral size and flow, improvement of endothelial dysfunction, and prevention or reversal of coronary artery vasoconstriction. These effects help increase nutrient coronary blood flow to zones of myocardial ischemia. Recent data with the nitroglycerin patch confirm that myocardial ischemia is decreased after nitrate administration. Nitroprusside, another nitrovasodilator, is a commonly used intravenous agent for lowering arterial pressure and left ventricular filling pressure. This drug is highly effective for the treatment of acute or severe hypertension and congestive heart failure. However, there are data suggesting that nitroprusside may be deleterious in the presence of acute myocardial ischemia, perhaps by shunting blood away from zones of jeopardized myocardial blood flow. Therefore, nitroprusside cannot be recommended to treat myocardial ischemia; intravenous nitroglycerin should be used in this context.
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PMID:Beneficial actions of nitrates in cardiovascular disease. 863 24

Nitrate tolerance has been reported to be reversed by certain types of angiotensin-converting enzyme (ACE) inhibitors. We examined whether alacepril, a new long-acting oral ACE inhibitor, has beneficial effects against exercise-induced angina in patients with stable effort angina after substantial isosorbide dinitrate (ISDN) treatment. Thirteen men with stable effort angina were treated with oral ISDN (80 mg/d) for >3 weeks. After this period, efficacy of single oral administration of either alacepril (50 mg) or its placebo on exercise-induced angina and electrocardiographic changes was examined by treadmill exercise test in a double-blind crossover design. Alacepril significantly improved the exercise duration by 9.1% (p=0.03), the time to 1 mm ST-segment depression by 19% (p<0.01), and the maximal ST-segment depression by 33% (p=0.015) compared with placebo. Alacepril did not significantly alter the rate-pressure product, a marker of myocardial oxygen demand, during exercise test compared with placebo. Plasma renin activity was significantly increased (p<0.05) after administration of alacepril, indicating that alacepril significantly blocked ACE activity in our patients. In conclusion, a single oral administration of the ACE inhibitor alacepril (50mg) elicited beneficial effects against exercise-induced myocardial ischemia in patients with stable effort angina during chronic nitrate treatment. These effects may be mediated by increased coronary blood flow.
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PMID:Effects of angiotensin-converting enzyme inhibitor alacepril in patients with stable effort angina during chronic isosorbide dinitrate treatment. 865 Oct 88

Nitrates have been periodically controversial since their introduction in 1867 as a treatment for angina pectoris. The goal of this synopsis is to delineate the special and unchanged high ranking of nitrates in the treatment of angina pectoris with particular consideration to the dosage and dosage intervals. The anti-anginal/anti-ischemic effect of nitrates originates predominantly from the preload reduction induced by venous dilation; additionally, an accompanying coronary dilation can be of assistance. The special role of the preload reduction differentiates nitrates from beta blockers and calcium antagonists. But the initial positive anti-anginal/anti-ischemic effect can be lost under long-term treatment due to nitrate tolerance. This development of tolerance has been demonstrated for oral, intravenous and transdermal administration. Various mechanisms have been held accountable for this complex occurrence: exhaustion of the thiol pool, neurohumoral counter-regulation, and recently, an overproduction of free radicals. Nitrate tolerance has mean-while been recognized as a relevant clinical problem. The key to avoidance of nitrate tolerance lies in the interval therapy recommended by Stewart as early as 1905: it concludes that continual, 24-hour protection by nitrates alone is impossible. The ideal compromise between avoiding the development of tolerance and an optimal anti-ischemic protection, the duration of which should be as long as possible, demonstrates that approximately 12 hours of protection are clinically possible. As we showed in 1983, the administration of a single, high dose of slow-release ISDN effects this compromise. Asymmetric dosage intervals that guarantee the maintenance of anti-anginal/anti-ischemic nitrate effect may be alternatively used. A 12-hour patch-free interval is generally recommended for treatment with nitrate patches. Similarly, a 12-hour infusion-free period has been recommended for intravenous nitrate administration in patients with stable angina pectoris. In patients with unstable angina pectoris, the situation is more complex-probably due to the anti-platelet effect of nitrates. As has been the practice in the past, nitrates are to be the basic treatment of angina pectoris; as opposed to nifedipine, nitrates lead to a decrease in end-diastolic volume primarily through preload reduction. Nitrates have been documented to be highly effective in treating angina pectoris and myocardial ischemia; they demonstrate a high rate of "responders". Nitrates are the physiological substitute treatment of atherosclerotic vessels with EDRF-deficiency; they improve hemodynamics in the presence of congestive heart failure. Nitrates inhibit platelets in vivo and are standard medication for PTCA as well as other coronary interventions. They demonstrate only few untoward effects and are inexpensive.
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PMID:[Characteristics of angina pectoris therapy with nitrates]. 876 20


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