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British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1989 Oct;28(4):421–426. doi: 10.1111/j.1365-2125.1989.tb03522.x

N-acetylcysteine fails to attenuate haemodynamic tolerance to glyceryl trinitrate in healthy volunteers.

J C Hogan 1, M J Lewis 1, A H Henderson 1
PMCID: PMC1379992  PMID: 2511910

Abstract

1. The effects of chronic dosing with N-acetylcysteine (NAC), on nitrate-induced haemodynamic changes during the acute and chronic treatment of healthy volunteers with glyceryl trinitrate (GTN) patches (Transiderm nitro) has been investigated. 2. Seven volunteers were treated in a double-blind randomised crossover manner for two periods of 4 days with 20 mg of transdermal GTN/24 h together with NAC (200 mg three times daily) or matching placebo. There was a washout period of greater than 3 days between treatment periods. 3. Haemodynamic measurements (blood pressure (BP); heart rate (HR] at rest and following maximal treadmill exercise were performed before treatment and 4 h after starting treatment on days 1 and 4. 4. Significant haemodynamic changes as evidenced by a fall in BP and rise in HR, were seen on day 1 in both the NAC and placebo phases. By day 4 the haemodynamic changes had returned towards the pre-treatment values during both the NAC and placebo phases suggesting the development of tolerance in both treatment groups. 5. These findings suggest that concurrent administration of NAC fails to prevent the development of tolerance to GTN.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Fahmy N. R., Gavras H. P. Impact of captopril on hemodynamic and hormonal effects of nitroprusside. J Cardiovasc Pharmacol. 1985 Sep-Oct;7(5):869–874. doi: 10.1097/00005344-198509000-00009. [DOI] [PubMed] [Google Scholar]
  2. Feelisch M., Noack E. Nitric oxide (NO) formation from nitrovasodilators occurs independently of hemoglobin or non-heme iron. Eur J Pharmacol. 1987 Oct 27;142(3):465–469. doi: 10.1016/0014-2999(87)90090-2. [DOI] [PubMed] [Google Scholar]
  3. Ignarro L. J., Lippton H., Edwards J. C., Baricos W. H., Hyman A. L., Kadowitz P. J., Gruetter C. A. Mechanism of vascular smooth muscle relaxation by organic nitrates, nitrites, nitroprusside and nitric oxide: evidence for the involvement of S-nitrosothiols as active intermediates. J Pharmacol Exp Ther. 1981 Sep;218(3):739–749. [PubMed] [Google Scholar]
  4. James M. A., Walker P. R., Papouchado M., Wilkinson P. R. Efficacy of transdermal glyceryl trinitrate in the treatment of chronic stable angina pectoris. Br Heart J. 1985 Jun;53(6):631–635. doi: 10.1136/hrt.53.6.631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Jordan R. A., Seith L., Henry D. A., Wilen M. M., Franciosa J. A. Dose requirements and hemodynamic effects of transdermal nitroglycerin compared with placebo in patients with congestive heart failure. Circulation. 1985 May;71(5):980–986. doi: 10.1161/01.cir.71.5.980. [DOI] [PubMed] [Google Scholar]
  6. Lis Y., Bennett D., Lambert G., Robson D. A preliminary double-blind study of intravenous nitroglycerin in acute myocardial infarction. Intensive Care Med. 1984;10(4):179–184. doi: 10.1007/BF00259434. [DOI] [PubMed] [Google Scholar]
  7. Needleman P., Johnson E. M., Jr Mechanism of tolerance development to organic nitrates. J Pharmacol Exp Ther. 1973 Mar;184(3):709–715. [PubMed] [Google Scholar]
  8. Needleman P. Tolerance to the vascular effects of glyceryl trinitrate. J Pharmacol Exp Ther. 1970 Jan;171(1):98–102. [PubMed] [Google Scholar]
  9. Packer M., Lee W. H., Kessler P. D., Gottlieb S. S., Medina N., Yushak M. Prevention and reversal of nitrate tolerance in patients with congestive heart failure. N Engl J Med. 1987 Sep 24;317(13):799–804. doi: 10.1056/NEJM198709243171304. [DOI] [PubMed] [Google Scholar]
  10. Packer M., Medina N., Yushak M. Hemodynamic changes mimicking a vasodilator drug response in the absence of drug therapy after right heart catheterization in patients with chronic heart failure. Circulation. 1985 Apr;71(4):761–766. doi: 10.1161/01.cir.71.4.761. [DOI] [PubMed] [Google Scholar]
  11. Parker J. O., Farrell B., Lahey K. A., Moe G. Effect of intervals between doses on the development of tolerance to isosorbide dinitrate. N Engl J Med. 1987 Jun 4;316(23):1440–1444. doi: 10.1056/NEJM198706043162303. [DOI] [PubMed] [Google Scholar]
  12. Parker J. O., Farrell B., Lahey K. A., Rose B. F. Nitrate tolerance: the lack of effect of N-acetylcysteine. Circulation. 1987 Sep;76(3):572–576. doi: 10.1161/01.cir.76.3.572. [DOI] [PubMed] [Google Scholar]
  13. Sioufi A., Pommier F. Quantitative determination of nitroglycerin in human plasma by capillary gas chromatography with electron-capture detection. J Chromatogr. 1985 Apr 12;339(1):117–126. doi: 10.1016/s0378-4347(00)84633-2. [DOI] [PubMed] [Google Scholar]
  14. Thadani U., Fung H. L., Darke A. C., Parker J. O. Oral isosorbide dinitrate in angina pectoris: comparison of duration of action an dose-response relation during acute and sustained therapy. Am J Cardiol. 1982 Feb 1;49(2):411–419. doi: 10.1016/0002-9149(82)90518-5. [DOI] [PubMed] [Google Scholar]

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