Nitrates
Nitrates are organic nitrate esters that are bioactivated to nitric oxide, relaxing vascular smooth muscle and reducing venous preload more than afterload. Sublingual or intravenous nitroglycerin is the first-line agent for acute anginal pain and hypertensive pulmonary edema, while oral isosorbide mononitrate or dinitrate prevents recurrent angina and, combined with hydralazine, improves survival in selected heart failure patients.
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What this article covers
- Overview
Nitrates are organic nitrate esters, nitroglycerin, isosorbide dinitrate, and isosorbide mononitrate, that are metabolized to nitric oxide (NO) and relax vascular smooth muscle.
- Epidemiology
Nitrates are one of the oldest cardiovascular drug classes still in routine use, dating to nineteenth-century treatment of angina, and remain among the most widely prescribed antianginal agents.
- Risk factors
Volume depletion or borderline blood pressure: hypovolemic or hypotensive patients develop exaggerated, preload-dependent falls in blood pressure with any nitrate dose.
- Pathophysiology
Nitroglycerin is bioactivated chiefly by mitochondrial aldehyde dehydrogenase-2 in vascular smooth muscle, releasing nitric oxide, which activates soluble guanylate cyclase and raises intracellular cyclic guanosine monophosphate (cGMP).
- Clinical features
Headache: the most common adverse effect, from meningeal vasodilation, often lessens with continued use over days.
- Differential diagnosis
Beta blockers: first-line antianginal therapy, lowering oxygen demand via heart rate and contractility rather than vasodilation; unlike nitrates, they cause no tolerance and carry a post-infarction mortality benefit.
- Diagnosis
Establishing the need for nitrate therapy: nitrates are symptom-directed treatment, not a diagnostic test; they are started once angina or ACS is established by exertional or rest chest discomfort…
- Management
First-line for acute anginal pain: give sublingual nitroglycerin 0.4 mg, repeated every 5 minutes for up to 3 doses if systolic blood pressure stays above 90 to 100 mmHg and there is no recent PDE5 inhibitor use.
- Complications
Tolerance: loss of antianginal effect with continuous exposure, most common with patches or prolonged infusions; an 8- to 12-hour nitrate-free interval restores responsiveness.
- Prognosis
Nitrates give effective, rapid symptomatic relief of angina and acute pulmonary edema, but as monotherapy for chronic stable angina they have not been shown to lower mortality, unlike beta blockers or high-intensity statin therapy.
- Prevention
Scheduled nitrate-free interval: build every long-acting regimen around an 8- to 12-hour nitrate-free window, generally overnight, to prevent tolerance.
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Related articles
- Chronic stable angina
Chronic stable angina is reproducible, exertional chest discomfort from fixed coronary stenosis causing demand-related ischemia, relieved by rest or nitroglycerin. Diagnosis combines the typical anginal pattern with stress testing or coronary imaging, and treatment is antianginal and secondary-prevention medical therapy, with revascularization for refractory symptoms or high-risk anatomy.
- Vasospastic (Prinzmetal) angina
Vasospastic (Prinzmetal) angina is angina from transient epicardial coronary artery spasm, causing rest chest pain with transient ST elevation, typically at night or in the early morning. Diagnosis rests on documenting spasm or reversible ST changes, and treatment is calcium channel blockers and nitrates while strictly avoiding non-selective beta-blockers and triggers.
- Unstable angina
Unstable angina is acute myocardial ischemia from a non-occlusive coronary thrombus causing rest, new, or crescendo angina without a troponin rise, placing it on the acute coronary syndrome spectrum just short of NSTEMI. Diagnosis is clinical with ischemic ECG changes and negative serial troponins, and management mirrors NSTE-ACS with antithrombotic therapy and risk-guided angiography.
- Heart failure
Heart failure is a clinical syndrome of impaired cardiac filling or ejection causing congestion and reduced perfusion, classified by ejection fraction. Diagnosis integrates symptoms, signs, natriuretic peptides, and echocardiography, and treatment of reduced-ejection-fraction disease is quadruple guideline-directed therapy, with device therapy and cause-specific management.
- Hypertensive emergency
Hypertensive emergency is severe hypertension (usually above 180/120 mmHg) with acute target-organ damage such as encephalopathy, stroke, acute heart failure, myocardial ischemia, aortic dissection, or acute kidney injury. It requires controlled intravenous blood pressure reduction, with the target and pace determined by the specific end-organ involved.
- Erectile dysfunction
Erectile dysfunction is the inability to achieve or maintain an erection sufficient for satisfactory sexual performance for at least 6 months, most often from vascular, neurologic, medication, endocrine, or psychological causes, and is a significant marker of coronary risk. Diagnosis is clinical from history and exam with targeted labs, and first-line treatment is an oral phosphodiesterase-5 inhibitor unless the patient takes nitrates.