New mechanisms of action of nsaids: focus on cardiovascular safety


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

In recent years, cardiovascular safety of non-steroidal anti-inflammatory drugs (NSAIDs) is the object of attention of researchers and doctors. In patients receiving NSAIDs, increased risk of cardiovascular disease has several reasons, including prohypertensive effects. The greatest prohypertensive effect was described for naproxen and indomethacin. The therapeutic effect of NSAIDs is accomplished by blocking the enzyme cyclooxygenase-2 (COX-2) induced in the focus of inflammation, which leads to reduced formation of prostaglandin H2 and subsequent products of its metabolism. Recent studies of COX in combination with oxicams presented the first detailed description of the method of binding of oxycams through the network with two water molecules in the main channel of the active COX site. Also, interest to this class of NSAIDs has increased due to the discovery of the fact that certain derivatives of oxicams are not only potent inhibitors of microsomal prostaglandin E1 synthase, but microsomal prostaglandin E2 synthase, which is involved in the final synthesis of the primary mediator of inflammation - prostaglandin E2 (PGE2). These data open a prospect for the development of a new class of selective PGE2 inhibitors.

Full Text

Restricted Access

About the authors

N. A Shostak

FSBEI HE RNSMU n.a. N.I. Pirogov of RMH

Email: Shostakkaf@yandex.ru
MD, Prof., Honoured Doctor of the Russian Federation, Head of the Department of Faculty Therapy n.a. Acad. A.I. Nesterov

A. A Klimenko

FSBEI HE RNSMU n.a. N.I. Pirogov of RMH

Department of Faculty Therapy n.a. Acad. A.I. Nesterov

D. A Anichkov

FSBEI HE RNSMU n.a. N.I. Pirogov of RMH

Department of Faculty Therapy n.a. Acad. A.I. Nesterov

A. A Kondrashov

FSBEI HE RNSMU n.a. N.I. Pirogov of RMH

Department of Faculty Therapy n.a. Acad. A.I. Nesterov

References

  1. Farkouh M.E. Non-steroidal anti-inflammatory drugs and cardiovascular risk: At crossroads. Trends Cardiovasc Med. 2015;25(8):736-37.
  2. Ruoff G. Hot Topics in Primary Care: Nonsteroidal Anti- inflammatory Drugs and Cardiovascular Risk: Where Are We Today? J Fam Pract. 2015;64(12 Suppl):S67-70.
  3. Chuang S.Y., Yu Y., Sheu W.H., Tsai Y.T., Liu X., Hsiung C.A., Tsai H.J. Association of short-term use of nonsteroidal anti-inflammatory drugs with stroke in patients with hypertension. Stroke. 2015;46(4):996-1003.
  4. Ungprasert P., Srivali N., Thongprayoon C. Nonsteroidal Anti-inflammatory Drugs and Risk of Incident Heart Failure: A Systematic Review and Meta-analysis of Observational Studies. Clin. Cardiol. 2016;39(2):111-18.
  5. Ungprasert P., Srivali N., Kittanamongkolchai W. Non-steroidal anti-inflammatory drugs and risk of heart failure exacerbation: A systematic review and meta-analysis. Eur J. Intern. Med. 2015;26(9):685-90.
  6. Agca R., Heslinga S.C., Rollefstad S., et al. EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update. Ann. Rheum. Dis. 2016. doi: 10.1136/annrheumdis-2016-209775.
  7. Roubille C., Richer V., Starnino T., McCourt C., McFarlane A., Fleming P., Siu S., Kraft J., Lynde C., Pope J., Gulliver W., Keeling S., Dutz J., Bessette L., Bissonnette R., Haraoui B. The effects of tumour necrosis factor inhibitors, methotrexate, non-steroidal anti-inflammatory drugs and corticosteroids on cardiovascular events in rheumatoid arthritis, psoriasis and psoriatic arthritis: a systematic review and meta-analysis. Ann. Rheum. Dis. 2015;74:480-89.
  8. Lindhardsen J., Gislason G.H., Jacobsen S., et al. Non-steroidal anti-inflammatory drugs and risk of cardiovascular disease in patients with rheumatoid arthritis: a nationwide cohort study. Ann. Rheum. Dis. 2013; Published Online First 8 June
  9. Pope J.E., Anderson J.J., Felson D. A metaanalysis of the effects of nonsteroidal antiinflammatory drugs on blood pressure. Arch. Intern. Med. 1993;153:477-84.
  10. Johnson A., Nguyen T., Day R. Do nonsteroidal anti-inflammatory drugs affect blood pressure? Ann. Intern. Med. 1994;121:289-300.
  11. Conlin P.R., Moore T.J., Swartz S.L., Barr E., Gazdick L., Fletcher C., DeLucca P., Demopoulos L. Effect of indomethacin on blood pressurelowering by captopril and losartan in hypertensive patients. Hypertension. 2000;36:461-65.
  12. Morgan T.O., Anderson A., Bertram D. Effect of indomethacin on blood pressure in elderly people with essential hypertension well controlled on amlodipine or enalapril. Am. J. Hypertens. 2000;13:1161-67.
  13. Morrison A., Ramey D.R., van Adelsberg J., Watson D.J. Systematic review of trials of the effect of continued use of oral non-selective NSAIDs on blood pressure and hypertension. Curr. Med. Res. Opin. 2007;23(10):2395-404.
  14. Sowers J.R., White W.B., Pitt B., Whelton A., Simon L.S., Winer N., Kivitz A., van Ingen H., Brabant T., Fort J.G.; Celecoxib Rofecoxib Efficacy and Safety in Comorbidities Evaluation Trial (CRESCENT) Investigators. The effects of cyclooxygenase-2 inhibitors and nonsteroidal anti-inflammatory therapy on 24-hour blood pressure in patients with hypertension, osteoarthritis, and type 2 diabetes mellitus. Arch. Intern. Med. 2005;165(2):161-68.
  15. Schwartz J.I., Thach C., Lasseter K.C., Miller J., Hreniuk D., Hilliard D.A., Snyder K.M., Gertz B.J., Gottesdiener K.M. Effects of etoricoxib and comparator nonsteroidal anti-inflammatory drugs on urinary sodium excretion, blood pressure, and other renal function indicators in elderly subjects consuming a controlled sodium diet. J. Clin. Pharmacol. 2007;47(12):1521-31.
  16. Аничков Д.А., Шостак Н.А. Суточный профиль артериального давления у больных метаболическим синдромом и остеоартрозом на фоне терапии нестероидными противовоспалительными препаратами. Клин. мед. 2004;82(12):27-30.
  17. Reitblat T., Zamir D., Estis L., Priluk R., Drogenikov T., Viskoper J.R. The different patterns of blood pressure elevation by rofecoxib and nabumetone. J. Hum. Hypertens. 2002;16:431-34.
  18. MacDonald T.M., Reginster J.Y., Littlejohn T.W., Richard D., Lheritier K., Krammer G., Rebuli R. Effect on blood pressure of lumiracoxib versus ibuprofen in patients with osteoarthritis and controlled hypertension: a randomized trial. J. Hypertens. 2008;26(8):1695-702.
  19. White W.B., Kent J., Taylor A., Verburg K.M., Lefkowith J.B., Whelton A. Effects of celecoxib on ambulatory blood pressure in hypertensive patients on ACE inhibitors. Hypertension. 2002;39(4):929-34.
  20. Samuelsson B., Morgenstern R., Jakobsson P.J. Membrane prostaglandin E synthase-1: a novel therapeutic target. Pharmacol. Rev. 2007;59:207-24.
  21. Xu S., Rouzer C.A., Marnett L.J. Oxicams, a class of nonsteroidal anti-inflammatory drugs and beyond. IUBMB Life. 2014;66(12):803-11.
  22. Asghar W., Jamali F. The effect of COX-2-selective meloxicam on the myocardial, vascular and renal risks: a systematic review. Inflammopharmacology. 2015;23(1):1-16.
  23. Ungprasert P., Matteson E.L., Thongprayoon C. Nonaspirin nonsteroidal anti-inflammatory drugs and risk of hemorrhagic stroke: a systematic review and meta-analysis of observational studies. Stroke. 2016; 47:356-64.
  24. Moodley I. Review of the cardiovascular safety of COXIBs compared to NSAIDS. Cardiovasc. J. Afr. 2008;19(2):102-7.
  25. Garcia Rodriguez L.A., Hernandez-Diaz S. Nonsteroidal anti-inflammatory drugs as a trigger of clinical heart failure. Epidemiology. 2003;14(2):240-46.
  26. Varas-Lorenzo C., Riera-Guardia N., Calingaert B., Castellsague J., Salvo F., Nicotra F., Sturkenboom M., Perez-Gutthann S. Myocardial infarction and individual nonsteroidal anti-inflammatory drugs meta-analysis of observational studies. Pharmacoepidemiol Drug Saf. 2013;22(6):559-70.
  27. Gislason G.H., Jacobsen S., Rasmussen J.N., Rasmussen S., Buch P., Friberg J., Schramm T.K., Abildstrom S.Z., Kober L., Madsen M., Torp-Pedersen C. Risk of death or reinfarction associated with the use of selective cyclooxygenase-2 inhibitors and nonselective nonsteroidal antiinflammatory drugs after acute myocardial infarction. Circulation. 2006;113(25):2906-13.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies