NITROGLYCERIN

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Safetychecker Summary for Nitroglycerin
(for details about the summarized interactions, read the full article)

May be Beneficial: Supportive interaction—Taking these supplements may support or otherwise help your medication work better.	N-acetyl cysteine* Vitamin C
Avoid: Adverse interaction—Avoid these supplements when taking this medication because taking them together may cause undesirable or dangerous results.	N-acetyl cysteine*
Depletion or interference	None known
Side effect reduction/prevention	None known
Reduced drug absorption/bioavailability	None known

Interactions with Dietary Supplements

N-acetyl cysteine (NAC)
Continuous nitroglycerin use leads to development of nitroglycerin tolerance and loss of effectiveness. Intravenous (iv) N-acetyl cysteine (NAC), during short-term studies of people receiving continuous nitroglycerin, was reported to reverse nitroglycerin tolerance.^{1 2} In a double-blind study of patients with unstable angina, transdermal nitroglycerin plus oral NAC (600 mg three times per day) was associated with fewer failures of medical treatment than placebo, NAC, or nitroglycerin alone. However, when combined with nitroglycerin use, NAC has led to intolerable headaches.^{3 4} In two double-blind, randomized trials of angina patients treated with transdermal nitroglycerin, oral NAC 200 mg or 400 mg three times per day failed to prevent nitroglycerin tolerance.^{5 6}

Vitamin C
Vitamin C may help maintain the blood vessel dilation response to nitroglycerin. A double-blind study found that individuals taking 2 grams of vitamin C three times per day did not tend to develop nitroglycerin tolerance over time compared to those taking placebo.⁷ In another controlled clinical trial, similar protection was achieved with 500 mg three times daily.⁸

People using long-acting nitroglycerin can avoid tolerance with a ten- to twelve-hour hour nitroglycerin-free period every day. People taking long-acting nitroglycerin should ask their prescribing doctor or pharmacist about preventing nitroglycerin tolerance.

Interactions with Foods and Other Compounds

Alcohol
Alcohol, when consumed during nitroglycerin therapy, may cause low blood pressure and circulatory collapse in extreme cases.⁹ People using nitroglycerin should avoid alcohol.

1. Ghio S, de Servi S, Perotti R, et al. Different susceptibility to the development of nitroglycerin tolerance in the arterial and venous circulation in humans—Effects of N-acetylcysteine administration. Circulation 1992;86:798–802.

2. May DC, Popma JJ, Black WH, et al. In vivo induction and reversal of nitroglycerin tolerance in human coronary arteries. N Engl J Med 1987;317:805–9.

3. Iversen HK. N-acetylcysteine enhances nitroglycerin-induced headache and cranial artery response. Clin Pharmacol Ther 1992;52:125–33.

4. Ardissino D, Merlini PA, Savonitto S, et al. Effect of transdermal nitroglycerin or N-acetyl cysteine, or both, in the long-term treatment of unstable angina pectoris. J Am Coll Cardiol 1997;29:941–7.

5. Hogan JC, Lewis MJ, Henderson AH. N-acetylcysteine fails to attenuate haemodynamic tolerance to glycerol trinitrate in healthy volunteers. Br J Clin Pharmacol 1989;28:421–6.

6. Hogan JC, Lewis MJ, Henderson AH. Chronic administration of N-acetylcysteine fails to prevent nitrate tolerance in patients with stable angina pectoris. Br J Clin Pharmacol 1990;30:573–7.

7. Watanabe H, Kakihana M, Sadanori O, Sugishita Y. Randomized, double-blind, placebo-controlled study of the preventive effect of supplemental oral vitamin C on attenuation of development of nitrate tolerance. J Am Coll Cardiol 1998;31:1323–9.

8. Bassenge E, Fink N, Skatchkov M, Fink B. Dietary supplement with vitamin C prevents nitrate tolerance. J Clin Invest 1998;102:67–71.

9. Thelkeld DS, ed. Diuretics and Cardiovasculars, Antianginal Agents, Nitrates. In Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Apr 1992, 143f–4a.

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Copyright © 2002 Healthnotes, Inc.  All rights reserved. www.healthnotes.com

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The information presented in Healthnotes is for informational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, or traditional usage as cited in each article. The results reported may not necessarily occur in all individuals. For many of the conditions discussed, treatment with prescription or over-the-counter medication is also available. Consult your doctor, practitioner, and/or pharmacist for any health problem and before using any supplements or before making any changes in prescribed medications. Information expires December 2003.

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