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Short and Long-Acting Oral Nitrates for Stable Angina Pectoris

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Nitrates Updated

Summary

Nitroglycerin (NTG) spray and sublingual tablets rapidly relieve an established attack of angina, and their infrequent use is not associated with the development of tolerance. Although, following a suitable nitrate-free interval, the first dose of oral, long-acting nitrates produces significant hemodynamic effects, increases angina free walking, and decreases exercise-induced ischemia, during continued longterm therapy tolerance limits their usefulness. Appropriate dosing regimens of controlled-release formulations of isosorbide dinitrate (ISDN) and controlled-release NTG during long-term therapy have not been established. Use of immediate-release formulation of 15–120 mg of IDSN in a qid regimen lead to a marked reduction in the size and duration of antianginal effects compared to the initial dose. Asymmetric tid therapy with 30 mg of ISDN (7 a.m., 1 p.m, and 6 p.m.) is also associated with the development of partial tolerance and appears to provide antianginal prophylaxis for only a period of 6 hours each day. Asymmetric bid therapy with ISDN at 7 a.m. and noon may give sustained effect but is supported by only a single, small study that did not examine effectiveness after the noon dose in long-term use. Isosorbide-5-mononitrate (IS-5-MN) has been the subject of more recent studies than other nitrates because of attempts to bring a number of products into the U.S. market. IS-5-MN in qid, tid, and standard bid (8 a.m. and 8 p.m.) dosing regimens produce tolerance. Asymmetric regimens of immediate-release IS-5-MN (10 and 20 mg) given bid (once in the morning and again 7 hours later) decrease the development of tolerance compared to symmetric regimens and produce an increased exercise duration after each dose of the day; the 20 mg bid dosing is more effecive. Similarly, once-daily 120 and 240 mg controlled-release IS-5-MN does not produce tolerance and gives a sustained increase in daytime exercise duration. Both asymmetric bid immediate-release and once-daily controlled-release IS-5-MN preparations do not produce deterioration in exercise performance prior to the administration of the medication in the morning (i.e., no zero-hour effect). Further studies are needed to establish useful dosing regimens for ISDN, for controlled-release ISDN, and for controlled-release nitroglycerin. None of the dosing regimens of any oral, long-acting nitrate (including IS-5-MN) provide 24 hour antianginal and antiischemic effects. Although it is intuitively attractive to add an agent (beta-blocker or calcium channel blocker) that exerts 24 hour antianginal and antiischemic effects, which appear to depend on mechanisms different from those of nitrates, there are no studies that allow an evaluation of the usefulness of adding beta-blockers or calcium channel blockers to nitrate therapy (or vice versa).

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  1. Udho Thadani
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  2. Raymond J. Lipicky
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Editors and Affiliations

  1. Health Sciences Center, University of Oklahoma, Oklahoma City, Ok, 73104, USA

    Udho Thadani MBBS, MRCP, FRCPC, FACC (Professor of Medicine, Vice Chief Cardiology and Director of Clinical Research) (Professor of Medicine, Vice Chief Cardiology and Director of Clinical Research)

  2. University of Cape Town, Cape Town, South Africa

    Lionel H. Opie M.D., Ph.D. (Professor of Medicine, Visiting Professor) (Professor of Medicine, Visiting Professor)

  3. Division of Cardiology, Stanford University Medical Center, Stanford, California, USA

    Lionel H. Opie M.D., Ph.D. (Professor of Medicine, Visiting Professor) (Professor of Medicine, Visiting Professor)

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Thadani, U., Lipicky, R.J. (1997). Short and Long-Acting Oral Nitrates for Stable Angina Pectoris. In: Thadani, U., Opie, L.H. (eds) Nitrates Updated. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-1135-5_5

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