Abstract:Short-acting nitrates are beneficial in acute myocardial ischemia. However, many unresolved questions remain about the use of long-acting nitrates in stable ischemic heart disease. The use of long-acting nitrates is weakened by the development of endothelial dysfunction and tolerance. Also, we currently ignore whether lower doses of transdermal nitroglycerin would be better than those presently used. Multivariate analysis data from large nonrandomized studies suggested that long-acting nitrates increase the in… Show more
“…2 ) [ 61 ]. While this data from GRACE confirms similar findings of an earlier study, [ 62 ] whether this link is causal remains to be determined [ 63 ]. Fig.…”
Nitrates have been used to treat symptoms of chronic stable angina for over 135 years. These drugs are known to activate nitric oxide (NO)-cyclic guanosine-3′,-5′-monophasphate (cGMP) signaling pathways underlying vascular smooth muscle cell relaxation, albeit many questions relating to how nitrates work at the cellular level remain unanswered. Physiologically, the anti-angina effects of nitrates are mostly due to peripheral venous dilatation leading to reduction in preload and therefore left ventricular wall stress, and, to a lesser extent, epicardial coronary artery dilatation and lowering of systemic blood pressure. By counteracting ischemic mechanisms, short-acting nitrates offer rapid relief following an angina attack. Long-acting nitrates, used commonly for angina prophylaxis are recommended second-line, after beta-blockers and calcium channel antagonists. Nicorandil is a balanced vasodilator that acts as both NO donor and arterial K + ATP channel opener. Nicorandil might also exhibit cardioprotective properties via mitochondrial ischemic preconditioning. While nitrates and nicorandil are effective pharmacological agents for prevention of angina symptoms, when prescribing these drugs it is important to consider that unwanted and poorly tolerated hemodynamic side-effects such as headache and orthostatic hypotension can often occur owing to systemic vasodilatation. It is also necessary to ensure that a dosing regime is followed that avoids nitrate tolerance, which not only results in loss of drug efficacy, but might also cause endothelial dysfunction and increase long-term cardiovascular risk. Here we provide an update on the pharmacological management of chronic stable angina using nitrates and nicorandil.
“…2 ) [ 61 ]. While this data from GRACE confirms similar findings of an earlier study, [ 62 ] whether this link is causal remains to be determined [ 63 ]. Fig.…”
Nitrates have been used to treat symptoms of chronic stable angina for over 135 years. These drugs are known to activate nitric oxide (NO)-cyclic guanosine-3′,-5′-monophasphate (cGMP) signaling pathways underlying vascular smooth muscle cell relaxation, albeit many questions relating to how nitrates work at the cellular level remain unanswered. Physiologically, the anti-angina effects of nitrates are mostly due to peripheral venous dilatation leading to reduction in preload and therefore left ventricular wall stress, and, to a lesser extent, epicardial coronary artery dilatation and lowering of systemic blood pressure. By counteracting ischemic mechanisms, short-acting nitrates offer rapid relief following an angina attack. Long-acting nitrates, used commonly for angina prophylaxis are recommended second-line, after beta-blockers and calcium channel antagonists. Nicorandil is a balanced vasodilator that acts as both NO donor and arterial K + ATP channel opener. Nicorandil might also exhibit cardioprotective properties via mitochondrial ischemic preconditioning. While nitrates and nicorandil are effective pharmacological agents for prevention of angina symptoms, when prescribing these drugs it is important to consider that unwanted and poorly tolerated hemodynamic side-effects such as headache and orthostatic hypotension can often occur owing to systemic vasodilatation. It is also necessary to ensure that a dosing regime is followed that avoids nitrate tolerance, which not only results in loss of drug efficacy, but might also cause endothelial dysfunction and increase long-term cardiovascular risk. Here we provide an update on the pharmacological management of chronic stable angina using nitrates and nicorandil.
“…Recently, the safety of long acting nitrates has been questioned. Long-term use of nitrates has been linked to induction of oxidative stress, increase in sympathetic activation leading to endothelial dysfunction [67]. A study from Japan including 1429 patients with vasospastic angina showed increased risk of adverse cardiovascular events when long acting nitrates were added to CA therapy [68].…”
Introduction
Angina pectoris is the most prevalent symptomatic manifestation of ischemic heart disease, frequently leads to a poor quality of life, and is a major cause of medical resource consumption. Since the early descriptions of nitrite and nitrate in the 19th century, there has been considerable advancement in the pharmacologic management of angina.
Areas covered
Management of chronic angina is often challenging for clinicians. Despite introduction of several pharmacological agents in last few decades, a significant proportion of patients continue to experience symptoms (i.e., refractory angina) with subsequent disability. For the purpose of this review, we searched PubMed and Cochrane databases from inception to August 2016 for the most clinically relevant publications that guide current practice in angina therapy and its development. In this article, we briefly review the pathophysiology of angina and mechanism-based classification of current therapy. This is followed by evidence-based insight into the traditional and novel pharmacotherapeutic agents, highlighting their clinical usefulness.
Expert opinion
Considering the wide array of available therapies with different mechanism efficacy and limiting factors, a personalized approach is essential, particularly for patients with refractory angina. Ongoing research with novel pharmacologic modalities is likely to provide new options for management of angina.
“…Other uses for nitrates include preeclampsia and pulmonary hypertension 8,16 . Nitrates can be divided into long acting agents such as isosorbide mononitrate (ISMN), and short acting agents such as glyceryl trinitrate (GTN) 9 . Routes of administration of the nitrates are sublingual, oral, injectable and transdermal 14 .…”
Section: Introductionmentioning
confidence: 99%
“…These side effects have a major impact on the patient's tolerability and might negatively affects his / her compliance 3 . Additionally, nitrate tolerance is one of the major issues reported with the continued use of nitrates and could be prevented by allowing a daily nitrate-free interval 9,12,18 . These effects make patients' education an important step in the treatment process since the patient tolerability to the adverse effects and reduction of the drugs' tolerance would improve efficacy of the drugs in controlling the disease and consequently the patients' quality of life.…”
Purpose: The aim of this project is to examine the tolerability of patients to the various possible side effects of organic nitrate and how that would affect their compliance. Methods: A PubMed search of the literature was conducted using the terms nitrates tolerability, nitrates side effects, nitrate compliance. Data for this study was collected from a questionnaire that was distributed to 75 patients. Results: The results showed that 69% of patients have experienced side effects when they started using organic nitrates. After continued use, the incidence of side effects decreased to 19 %. The most common side effect was reported to be headache which occurred in the first eight hours of using medication almost as one headache attack daily. Conclusion: Organic nitrates have a good tolerability and compliance among patients, it is clear that the incidence of nitrate side effects especially headache decrease with continued use which might be attributed to the tolerance that might develop with the use of nitrates. Starting nitrates in low doses and leaving a daily free interval have been reported to be associated with reduced frequency and severity of headache, and enhanced their clinical efficacy.
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