Karlberg KE, Saldeen T, Wallin R, et al. In spite of the fact that the concept of nitrate tolerance was first put forward many years ago, the question of tolerance has remained controversial. In this review, I discuss the factors which may have contributed to conflicting results in different studies, in particular recent findings on the rapidity of onset and reversal of tolerance. By continuing you agree to the Copyright © 2020 Elsevier B.V. or its licensors or contributors. The compensatory neuro-hormonal activation of the body is the initial mechanism for the loss of effect seen with nitrates. It remains to be seen whether a nitrate free interval might prevent the development of tolerance during patch therapy, as has been shown with other forms of nitrate treatment. In the long term, the decrease in the biotransformation of the nitrates by the inhibition of the ALDH-2 is a proposed reason.

There is widespread agreement that tolerance does occur to the effects of nitrates on arterial pressure. Recent investigations, however, have indicated that nitrate-mediated benefit to patients with CHF may be limited by resistance to their hemodynamic effects seen in many patients and by early development of tolerance. Organic nitrates are commonly used in the treatment of chronic congestive heart failure (CHF).
It is most likely to occur when plasma nitrate levels are constant and least likely when nitrate levels fluctuate. They suggest that nitrate prophylaxis should not be used continuously, if this can be avoided. In addition, tolerance appears to be a function of plasma nitrate profile. By continuing you agree to the Copyright © 2020 Elsevier B.V. or its licensors or contributors. 8), tolerance, with all its implications, remains a limitation to the therapy with nitrates. ScienceDirect ® is a registered trademark of Elsevier B.V.Nitrate resistance and tolerance: Potential limitations in the treatment of congestive heart failureScienceDirect ® is a registered trademark of Elsevier B.V. Efavirenz is always used in combination with other HIV medicines.

These drugs have been shown to improve exercise capacity and reduce symptoms and in combination with hydralazine to prolong life in patients with mild-to-moderate symptoms of CHF. Similarly, the possibility that a nitrate free interval might lead to withdrawal effects and exacerbation of angina needs to be excluded.We use cookies to help provide and enhance our service and tailor content and ads. Nitrate Resistance and Tolerance: Potential Limitations in the Treatment of Congestive Heart Failure Uri Elkayam, MD, Anil Mehra, MD, Avraham Shotan, MD, and Enrique Ostrzega, MD Organic nitrates are commonly used in the treat- ment of chronic congestive heart failure (CHF). Reduction of blood-nitrate concentrations to low levels for 4 to 12 hours each day usually maintains effectiveness in such patients. The adequacy of antianginal protection with drug regimens incorporating a nitrate free interval requires further assessment. In contrast, tolerance to the venous and pulmonary effects is disputed. Intravenous nitroglycerin for the treatment of angina at rest unresponsive to standard nitrate therapy. Am J Cardiol 1983; 51:694.

3,4,35,63,64 There is a lack of well-designed studies showing that treatment with more than one class of drug is superior to combination treatment with a different class of antianginal drugs. Monotherapy in optimal doses,is often as effective as combination therapy using two or more agents. Efavirenz is a prescription medicine approved by the U.S. Food and Drug Administration (FDA) for the treatment of HIV infection in adults and in children at least 3 months of age who weigh at least 7 lb 12 oz (3.5 kg). In 1995 Münzel and colleagues described that 3 days of nitroglycerin treatment in rabbits was associated with increased superoxide production by the aortic endothelium ().They demonstrated that tolerance to nitroglycerin was dependent on the endothelium and went on to hypothesize that the increased free radical production, by scavenging NO released by the nitrate, was the mechanism …

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