Chronic stable angina treatment nitrates
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Chronic stable angina Microchapters | ||
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Differentiating Chronic Stable Angina from Acute Coronary Syndromes | ||
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Editors-In-Chief: C. Michael Gibson, M.S., M.D. [1] Phone:617-632-7753; Cafer Zorkun, M.D., Ph.D. [2]; Associate Editors-In-Chief: John Fani Srour, M.D.; Jinhui Wu, MD
Overview
Mechanism of benefit:
- Nitroglycerin and other nitrates are endothelium independent vasodilators that produce their beneficial effects both by decreasing myocardial oxygen requirements and by improving myocardial perfusion.
- It has been postulated that nitrates, after entering the vessel wall, are converted to nitric oxide (NO), which stimulates guanylate cyclase to produce cyclic guanosine mono phosphate (cGMP), the substance that is responsible for vasodilation.
- Nitrates dilate large coronary arteries and collateral vessels, thereby increasing collateral blood flow to the ischemic myocardium and relieve coronary vasospasm
- Nitrates also decrease the degree of coronary artery stenosis produced by an eccentric atherosclerotic plaque.
- Nitrates also decrease myocardial oxygen requirements by decreasing intra cardiac volumes consequent to reduced venous return resulting from peripheral venous dilatation and by reducing arterial pressure. These beneficial effects may be offset partly by a reflex increase in heart rate, which can be prevented by simultaneous beta adrenergic blockade.
Indications:
Nitrates are effective for the management of various clinical subsets of stable angina pectoris.
- In patients with exertional angina, nitrates improve exercise tolerance, the time to the onset of angina, and ST segment depression during the treadmill exercise test.
- In patients with vasospastic angina, nitrates relax the smooth muscles of the epicardial coronary arteries and thereby relieve coronary artery spasm.
- In patients with mixed angina and postprandial angina, nitrates reduce myocardial oxygen demand and promote coronary vasodilation.
Nitrates Dosing:
A variety of nitrate preparations are currently available.
- The onset of action of sublingual nitroglycerin tablets or nitroglycerin spray is within 1 to 3 minutes, making these the preferred agents for the acute relief of effort or rest angina.
- The patient should be instructed that active nitroglycerin will cause some tingling under the tongue, and that if this does not occur, the efficacy of their nitroglycerine tablets may be expired.
- Isosorbide dinitrate should not be used more frequently than three times a day, or a transdermal patch more often than every 12 hours.
Prophylaxis with Nitrates:
- Nitroglycerin is also very useful for prophylaxis when used several minutes before planned exertion. However, its short duration of action (20 to 30 min) makes it less practical for long-term prevention of ischemia in patients with stable angina.
- For angina prophylaxis, long acting nitrate preparations such as isosorbide dinitrate, mono nitrates, transdermal nitroglycerin patches, and nitroglycerin paste are preferable.
Nitrate Tolerance:
- The major clinical problem for long term nitrate therapy is nitrate tolerance.
- Tolerance develops not only to antianginal and hemodynamic effects but also to platelet antiaggregatory effects.
- The mechanism for development of nitrate tolerance remains unclear.
- The decreased availability of sulfhydryl (SH) radicals, activation of the renin-angiotensin-aldosterone system, an increase in intravascular volume due to an altered transvascular Starling gradient, and generation of free radicals with enhanced degradation of nitric oxide have been proposed.
- The concurrent administration of an SH donor such as SH-containing ACE inhibitors, acetyl or methyl cysteine ,and diuretics has been suggested to reduce the development of nitrate tolerance.
- Concomitant administration of hydralazine has also been reported to reduce nitrate tolerance.
- However, the most reliable method for the prevention of nitrate tolerance is to ensure a nitrate free period of approximately 10 hours, usually including sleeping hours, in patients with effort angina.
Side Effects:
- Throbbing headache, which tends to decrease with continued use.
- Postural dizziness and weakness occur in some patients, frank syncope due to hypotension is relatively uncommon.
Contraindications:
- Nitrates do not worsen glaucoma, once thought to be a contraindication to their use, and they can be used safely in the presence of increased intraocular pressure.
- Nitrates are relatively contraindicated in hypertrophic obstructive cardiomyopathy, because in these patients, nitrates can increase LV outflow tract obstruction and severity of mitral regurgitation and can precipitate presyncope or syncope. For the same reason, nitrates should be avoided in patients with aortic valve stenosis.
ACC/AHA Guidelines- Pharmacotherapy to Prevent MI and Death and Reduce Symptoms (DO NOT EDIT)[1][2]
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Class I1. Calcium channel blocker (short-acting dihydropyridine calcium antagonists should be avoided) and/or long-acting nitrates as initial therapy when beta blockers are contraindicated. (Level of Evidence: B) 2. Calcium channel blocker (short-acting dihydropyridine calcium antagonists should be avoided) and/or long-acting nitrates in combination with beta blockers when initial treatment with beta blockers is not successful. (Level of Evidence: B) 3. Calcium channel blocker (short-acting dihydropyridine calcium antagonists should be avoided) and/or long-acting nitrates as a substitute for beta blockers if initial treatment with beta blockers leads to unacceptable side effects. (Level of Evidence: C) 4. Sublingual nitroglycerin or nitroglycerin spray for the immediate relief of angina. (Level of Evidence: C) |
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See Also
Sources
- The ACC/AHA/ACP–ASIM Guidelines for the Management of Patients With Chronic Stable Angina [1]
- TheACC/AHA 2002 Guideline Update for the Management of Patients With Chronic Stable Angina [2]
- The 2007 Chronic Angina Focused Update of the ACC/AHA 2002 Guidelines for the Management of Patients With Chronic Stable Angina [3]
References
- ↑ 1.0 1.1 Gibbons RJ, Chatterjee K, Daley J, Douglas JS, Fihn SD, Gardin JM et al. (1999)guidelines for the management of patients with chronic stable angina: executive summary and recommendations. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Patients with Chronic Stable Angina).Circulation 99 (21):2829-48. PMID: 10351980
- ↑ 2.0 2.1 Gibbons RJ, Abrams J, Chatterjee K, Daley J, Deedwania PC, Douglas JS et al. (2003) ACC/AHA 2002 guideline update for the management of patients with chronic stable angina--summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Chronic Stable Angina). Circulation 107 (1):149-58. PMID: 12515758
- ↑ Fraker TD, Fihn SD, Gibbons RJ, Abrams J, Chatterjee K, Daley J et al. (2007) 2007 chronic angina focused update of the ACC/AHA 2002 Guidelines for the management of patients with chronic stable angina: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines Writing Group to develop the focused update of the 2002 Guidelines for the management of patients with chronic stable angina. Circulation 116 (23):2762-72. DOI:10.1161/CIRCULATIONAHA.107.187930 PMID: 17998462