Nitrates in the management of stable angina pectoris
- Joseph P Kannam, MD
Joseph P Kannam, MD
- Assistant Professor of Medicine
- Harvard Medical School
- Bernard J Gersh, MB, ChB, DPhil, FRCP, MACC
Bernard J Gersh, MB, ChB, DPhil, FRCP, MACC
- Editor-in-Chief — Cardiovascular Medicine
- Section Editor — Coronary Heart Disease; Myopericardial Disease
- Professor of Medicine
- Mayo Clinic College of Medicine
- Section Editor
- Juan Carlos Kaski, DSc, MD, DM (Hons), FRCP, FESC, FACC, FAHA
Juan Carlos Kaski, DSc, MD, DM (Hons), FRCP, FESC, FACC, FAHA
- Section Editor — Coronary Heart Disease
- Professor of Cardiovascular Science
- Director, Cardiovascular and Cell Sciences Research Institute
- St. George's, University of London
Nitroglycerin was the first medication used in 1879 by William Murrell for the treatment of angina pectoris  and, in its immediate release forms, still remains first-line drug therapy for many patients [2,3].
While they act as venodilators, coronary vasodilators, and modest arteriolar dilators, the primary antiischemic effect of nitrates is to decrease myocardial oxygen demand by producing systemic vasodilation more than coronary vasodilation. This systemic vasodilation reduces left ventricular systolic wall stress.
In patients with exertional stable angina, nitrates improve exercise tolerance, time to onset of angina, and ST-segment depression during exercise testing. In combination with beta blockers or calcium channel blockers, nitrates produce greater antianginal and antiischemic effects.
Its use, however, is complicated by the development of tolerance with continuous therapy. (See 'Nitrate tolerance' below.)
MECHANISM OF ACTION
Nitrates dilate veins, arteries, and coronary arteries by relaxing vascular smooth muscle . They produce these effects by entering vascular smooth muscle cells where they are metabolized to 1,2-glyceryl dinitrate and nitrite, via mitochondrial aldehyde dehydrogenase-2 (ALDH2 or mtALDH), and then nitric oxide and S-nitrosothiols (figure 1) . Sulfhydryl groups on ALDH2 are required for activity, which can explain the known sulfhydryl requirement for vascular smooth muscle relaxation by nitrates .
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- MECHANISM OF ACTION
- Effect on systemic hemodynamics
- Effect on coronary hemodynamics
- Antiplatelet and antithrombotic properties
- NITRATE TOLERANCE
- Mechanisms of tolerance
- COMMONLY USED NITRATE PREPARATIONS
- Sublingual nitroglycerin
- Nitroglycerin spray
- Isosorbide dinitrate
- Isosorbide mononitrate
- Transdermal nitroglycerin
- Pentaerithrityl tetranitrate
- ADVERSE EFFECTS
- Reduced response in Asians
- RECOMMENDATIONS OF OTHERS
- Sublingual nitroglycerin
- Isosorbide dinitrate
- Isosorbide mononitrate
- Transdermal nitroglycerin