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IRBESARTAN IN THE TREATMENT OF HEART FAILURE

IRBESARTAN IN THE TREATMENT OF HEART FAILURE. IRBESARTAN. What is Irbesartan? Irbesartan is a selective non-peptide antagonist of angiotensin II type 1 receptor (AT1). Irbesartan inhibits the action of angiotensin II, which acts through the binding to the AT1 receptor.

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IRBESARTAN IN THE TREATMENT OF HEART FAILURE

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  1. IRBESARTAN IN THE TREATMENT OF HEART FAILURE

  2. IRBESARTAN • What is Irbesartan? • Irbesartan is a selective non-peptide antagonist of angiotensin II type 1 receptor (AT1). Irbesartan inhibits the action of angiotensin II, which acts through the binding to the AT1 receptor. • Indicated for the treatment of hypertension • Irbesartan may also delay progression of diabetic nephropathy • Also indicated for the reduction of renal disease progression in patients with type 2 diabetes, hypertension and microalbuminuria (>30 mg/24 hours) or proteinuria (>900 mg/24 hours). • It has also been shown in the treatment of heart failure.

  3. IRBESARTAN

  4. ROLE PLAYED BY THE ACTIVATION OF AT1 RECEPTORS • Activation of AT1 receptors plays the crucial role in the development of: • Hypertension • Left ventricular hypertrophy • Progression of lipid disorders • Impairment of renal function Therefore, angiotensin II type 1 receptor antagonists could be used as a new therapeutic option in treatment of hypertension which may lead to complications such as Hypertensive cardiomyopathy( Heart failure due to chronically high blood pressure).

  5. CAUSES OF HEART FAILURE

  6. ACTIONS OF AT 1 ANTAGONISTS • Vasoconstriction • Central and peripheral sympathetic stimulation • Release of aldosterone and adrenaline from adrenals • Renal actions promoting salt and water reabsorptions • Central actions like thirst • Vasopressin release • Growth promoting actions on heart and blood vessels

  7. ADVANTAGES OF AT 1 ANTAGONISTS • Oral bioavailability of this AT1 antagonist is relatively high. • long lasting blood pressure lowering action • possibility of taking it once a day

  8. REASONS WHY IRBESARTAN (ANGIOTENSIN ANTAGONIST) IS USED OVER ACE INHIBITORS • They do not interfere with degradation of bradykinin • They result in more complete inhibition of AT 1 receptor activation • They result in indirect AT II receptor activation . Due to blockade of AT1 receptor mediated feedback inhibition- more A II is produced which acts on AT 2 receptor that remains unblocked. ACE inhibitors result in depression of both AT 1 and AT 2 activation. Activation of the renin-angiotensin system in patients with heart failure causes vasoconstriction and retention of sodium and water. • Despite the known benefits of ACE inhibitors and, more recently, beta-adrenergic blocking agents, morbidity and mortality remain unacceptably high in patients treated with ACE inhibitors. • AT1 receptor antagonists represent an alternative therapy that may provide more complete blockade of an activated renin-angiotensin system while avoiding some of the detrimental side effects of ACE inhibitors • Irbesartan is a new, highly selective nonpeptide antagonist of AT1 receptors with pharmacokinetic properties that favor once-per-day dosing.

  9. HAEMODYNAMIC EFFECTS OF IRBESARTAN Reduction of: • Pulmonary Capilary Wedge Pressure(PCWP) • Mean pulmonary arterial pressure (MPAP) • Mean systemic arterial pressure (MSAP) • No dose related effect on heart rate • Slight increase in Cardiac Index after 12 weeks of administration of irbesartan • Tendency for LVEF to increase as a function of dose of irbesartan

  10. THE PHARMACOKINETIC AND PHARMACODYNAMIC OF IRBESARTAN IN HEART FAILURE • Mainly through oral and i.v. administration, the pharmacokinetics of irbesartan indicates that there is little influence of potential changes in organ/tissue perfusion and gut edema on the absorption, distribution, and elimination of irbesartan. • Pharmacodynamic parameters cannot be judged • Therefore no dosage adjustments are needed

  11. SAFETY AND TOLERABILITY OF IRBESARTAN • Irbesartan was generally well-tolerated in patients with mild-to-severe heart failure. • Discontinuation of medication and adverse events are not related to dose of irbesartan.

  12. CONCLUSION • Once-daily administration of Irbesartan 75 mg or 150 mg to patients with symptomatic heart failure and LVEF ≤40% is well-tolerated • Resulting in sustained haemodynamic improvement and prevents worsening of heart failure. • Irbesartan appears to be a promising new therapy for patients with chronic heart failure.

  13. SEARCH STRATAGIES • KEYWORDS USED ARE: • “Irbesartan” • “Heart Failure”

  14. DATABASES AND SEARCH TOOLS • Abstract database : Pubmed,Sciencedirect • Free full-text database: Pubmed ( linked to ScienceDirect)

  15. SEARCH PROCESS • Abstract Database: • Pubmed: Use Pubmed basic search. Use search MeSH =”Heart failure” and found 49 results. I selected the first result and narrowed the search to major subheadings, namely: Drug therapy and Therapy • I restricted the search to these subheadings and combined another search term “irbesartan” by selecting the option Send to Search Box with AND, and searched PubMed.=("HeartFailure/drugtherapy"[Majr] OR "Heart Failure/therapy"[Majr])AND "Irbesartan"[All fields] • I got 27 results in all, out of which 3 are free full text and 10 are from Southern Medical University Library. I referred to these 10 articles from Southern Medical University Library and 2 from all the results.

  16. 2.Sciencedirect: Use Sciencedirect advanced search. I typed “Heart failure” in Abstract-Title-Key AND “Irbesartan” in Title and clicked search . I got 14 results which I referred for my topic

  17. BROWSING THE SEARCH RESULTS AND WRITING THE MOST RELATED CITATIONS PUBMED: 1. Related Articles, Links Zukowska-Szczechowska E, Gosek K, Grzeszczak W. [Irbesartan--antihypertensive treatment in patients with heart failure and diabetes mellitus] Przegl Lek. 2002; 59(3):160-4. Review. Polish. PMID: 12184030 [PubMed - indexed for MEDLINE] 2. Related Articles, Links Kostis JB, Vachharajani NN, Hadjilambris OW, Kollia GD, Palmisano M, Marino MR. The pharmacokinetics and pharmacodynamics of irbesartan in heart failure. J Clin Pharmacol. 2001 Sep; 41(9):935-42. PMID: 11549097 [PubMed - indexed for MEDLINE] 3. Related Articles, Links Carson P, Massie BM, McKelvie R, McMurray J, Komajda M, Zile M, Ptaszynska A, Frangin G; for the I-PRESERVE Investigators. The irbesartan in heart failure with preserved systolic function (I-PRESERVE) trial: rationale and design. J Card Fail. 2005 Oct; 11(8):576-85. PMID: 16230259 [PubMed - indexed for MEDLINE] 4. Related Articles, Links Havranek EP, Thomas I, Smith WB, Ponce GA, Bilsker M, Munger MA, Wolf RA. Dose-related beneficial long-term hemodynamic and clinical efficacy of irbesartan in heart failure. J Am Coll Cardiol. 1999 Apr; 33(5):1174-81. PMID: 10193713 [PubMed - indexed for MEDLINE]

  18. SCIENCEDIRECT: • 5. Predictors of outcome in heart failure with preserved ejection fraction: one year findings rom the Irbesartan in Heart Failure With Preserved Systolic Function Trial (I-PRESERVE)European Journal of Heart Failure Supplements, Volume 7, Supplement 1, June 2008, Page 87P.E. Carson, M. Komajda, R. Mckelvie, J. McMurray, M. Zile, A.A. Ptaszynska, M. Donovan, B. Massie • 6. Diabetes is associated with increased risk of CV events in heart failure with preserved ejection fraction: findings from the Irbesartan in Heart Failure with Preserved Systolic Function TrialEuropean Journal of Heart Failure Supplements, Volume 7, Supplement 1, June 2008, Page 2R.S. Mckelvie, M. Komajda, B.M. Massie, J.J. McMurray, M.R. Zile, M. Donovan, A. Ptaszynska, P. Carson • 7. The Baseline Characteristics of Patients Enrolled in the Irbesartan in Heart Failure with Preserved Systolic Function Trial Are Similar to Those in the Community but Differ from CHARM-PreservedJournal of Cardiac Failure, Volume 12, Issue 6, Supplement 1, August 2006, Page S77Barry Massie, Peter Carson, Michel Komajda, Robert McKelvie, John McMurray, Michael Zile, Gerald Frangin, Agata Ptaszynska • 8. Comparison of angiotensin-converting enzyme inhibitor alone and in combination with irbesartan for the treatment of heart failureInternational Journal of Cardiology, Volume 125, Issue 1, 28 March 2008, Pages 16-21Leo Chi-Chiu Kum, Gabriel Wai-Kwok Yip, Pui-Wai Lee, Yat-Yin Lam, Eugene B. Wu, Anna Kin-Yin Chan, Jeffrey Wing-Hong Fung, Joseph Yat-Sun Chan, Qing Zhang, Shun-Ling Kong, Cheuk-Man Yu

  19. 9. The Irbesartan in Heart Failure With Preserved Systolic Function (I-PRESERVE) Trial: Rationale and DesignJournal of Cardiac Failure, Volume 11, Issue 8, October 2005, Pages 576-585Peter Carson, Barry M. Massie, Robert McKelvie, John McMurray, Michel Komajda, Michael Zile, Agata Ptaszynska, Gerald Frangin and for the I-PRESERVE Investigators • 10. Effects of angiotensin-converting enzyme inhibitor plus irbesartan on maximal and submaximal exercise capacity and neurohumoral activation in patients with congestive heart failureAmerican Heart Journal, Volume 149, Issue 5, May 2005, Page 938Martine Blanchet, Richard Sheppard, Normand Racine, Anique Ducharme, Daniel Curnier, Jean-Claude Tardif, Pierre Sirois, Marie-Catherine Lamoureux, Jacques De Champlain, Michel White • 11. Synergistic efficacy of irbesartan and benazepril on exercise performance and oxygen consumption at peak exercise in hypertensives with congestive heart failureAmerican Journal of Hypertension, Volume 17, Issue 5, Supplement 1, May 2004, Page S165Maria Leonarda De Rosa, Orazio Viola, Michele Polimeno, Massimo Chiariello • 12. 1012-129 Dual angiotensin-II suppression with angiotensin-converting enzyme inhibitor and irbesartan improves submaximal exercise time without changes in exercise-induced neurohumoral response in patients with congestive heart failureJournal of the American College of Cardiology, Volume 43, Issue 5, Supplement 1, 3 March 2004, Page A159Martine Blanchet, Richard Sheppard, Daniel Curnier, Jacques de Champlain, Pierre Sirois, Hélène Créo, André Roof, Lucette Whittom, Jean-Claude Tardif, Anique Ducharme, Normand Racine, Michel White • 13. A multicenter, randomized, double-blind study of the antihypertensive efficacy and tolerability of irbesartan in patients aged ≥65 years with mild to moderate hypertensionClinical Therapeutics, Volume 22, Issue 10, October 2000, Pages 1213-1224Yves Lacourcière • 14. Dose-related beneficial long-term hemodynamic and clinical efficacy of irbesartan in heart failure : Havranek EP, Thomas I, Smith WB, et al: J Am Coll Cardiol 33: 1174–1181,1999Journal of Cardiothoracic and Vascular Anesthesia, Volume 13, Issue 5, October 1999, Page 642

  20. 15. Dose-related beneficial long-term hemodynamic and clinical efficacy of irbesartan in heart failureJournal of the American College of Cardiology, Volume 33, Issue 5, April 1999, Pages 1174-1181Edward P. Havranek, Ignatius Thomas, William B. Smith, George A. Ponce, Martin Bilsker, Mark A. Munger, Robert A. Wolf, for the Irbesartan Heart Failure Group • 16. Irbesartan decreases atrial natriuretic peptide levels and improves ejection fraction in diabetic patients with congestive heart failureJournal of Cardiac Failure, Volume 4, Issue 3, Supplement 1, September 1998, Page 48Donald S. Chang, Linda G. Tan, Stanley A. Tan • 17. Irbesartan compared with lisinopril in patients with mild to moderate heart failureJournal of the American College of Cardiology, Volume 31, Supplement 1, 1998, Page 68N. Vijay, I. A. Alhaddad, D. Marty Denny, D. Ruff, M. Yasin, L. Yellen, S. Lyver, C. Bryson, C. -S. Lin, R. A. Wolf • 18. Irbesartan combined with conventional therapy, including angiotensin converting enzyme inhibitors, in heart failureJournal of the American College of Cardiology, Volume 31, Supplement 1, 1998, Page 188M. Tonkon, N. Awan, I. Niazi, P. Hanley, L. Baruch, C. -S. Lin, D. Costagliola, G. Cucinotta, R. A. Wolf, A. J. Block

  21. THANK YOU • PRESENTED BY: AKSHAY JAYASWAL (87) • OTHER MEMBERS: • SHAHEEN BIN HAMEED (117) • BOBIN BABU PHILLIP (120) • DHEERAJ NARLA (72)

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