Farmakologi Losartan

Oleh :

dr.Eveline Yuniarti

Farmakologi losartan adalah sebagai penghambat reseptor angiotensin atau angiotensin receptor blocker. Losartan menyebabkan vasodilatasi arteri dan menurunkan tekanan darah.[1-3]

Farmakodinamik

Losartan mencegah pengikatan angiotensin II ke reseptor AT1 secara reversibel dan kompetitif di jaringan seperti otot polos pembuluh darah dan kelenjar adrenal. Losartan dan metabolit aktifnya mengikat reseptor AT1 dengan afinitas 1000 kali lebih tinggi dibandingkan reseptor AT2. Metabolit aktif losartan 10-40 kali lebih kuat dibandingkan losartan yang tidak termetabolisme. Efek yang timbul dari konsumsi losartan adalah relaksasi otot polos pembuluh darah yang akan menurunkan tekanan darah.[1-3,13-22]

Referensi

1. Teixido-Tura G, Forteza A, Rodríguez-Palomares J, González Mirelis J, Gutiérrez L, Sánchez V, et al. Losartan Versus Atenolol for Prevention of Aortic Dilation in Patients With Marfan Syndrome. J Am Coll Cardiol 2018;72:1613–8. https://doi.org/10.1016/j.jacc.2018.07.052.
2. van Driest SL, Sleeper LA, Gelb BD, Morris SA, Dietz HC, Forbus GA, et al. Variants in ADRB1 and CYP2C9: Association with Response to Atenolol and Losartan in Marfan Syndrome. Journal of Pediatrics 2020;222:213-220.e5. https://doi.org/10.1016/j.jpeds.2020.03.064.
3. Oh NA, Hong X, Doulamis IP, Meibalan E, Peiseler T, Melero-Martin J, et al. Abnormal Flow Conditions Promote Endocardial Fibroelastosis Via Endothelial-to-Mesenchymal Transition, Which Is Responsive to Losartan Treatment. JACC Basic Transl Sci 2021;6:984–99. https://doi.org/10.1016/j.jacbts.2021.10.002.
13. DrugBank Losartan. 2022. https://go.drugbank.com/drugs/DB00678.
14. MIMS. Losartan. 2022. https://www.mims.com/indonesia/drug/info/losartan
15. Zou J, Zhou X, Ma Y, Yu R. Losartan ameliorates renal interstitial fibrosis through metabolic pathway and Smurfs-TGF-β/Smad. Biomedicine and Pharmacotherapy 2022;149. https://doi.org/10.1016/j.biopha.2022.112931.
16. Kim DY, Choi MJ, Ko TK, Lee NH, Kim OH, Cheon HG. Angiotensin AT1 receptor antagonism by losartan stimulates adipocyte browning via induction of apelin. Journal of Biological Chemistry 2020;295:14878–92. https://doi.org/10.1074/jbc.RA120.013834.
17. Yun HH, Park S, Chung MJ, Son JY, Park JM, Jung SJ, et al. Effects of losartan and L-serine in a mouse liver fibrosis model. Life Sci 2021;278. https://doi.org/10.1016/j.lfs.2021.119578.
18. Pitcher A, Spata E, Emberson J, Davies K, Halls H, Holland L, et al. Angiotensin receptor blockers and β blockers in Marfan syndrome: an individual patient data meta-analysis of randomised trials. The Lancet 2022;400:822–31. https://doi.org/10.1016/S0140-6736(22)01534-3.
19. Sellers SL, Milad N, Chan R, Mielnik M, Jermilova U, Huang PL, et al. Inhibition of Marfan Syndrome Aortic Root Dilation by Losartan: Role of Angiotensin II Receptor Type 1–Independent Activation of Endothelial Function. American Journal of Pathology 2018;188:574–85. https://doi.org/10.1016/j.ajpath.2017.11.006.
20. Khokher W, Iftikhar S, Beran A, Burmeister C, Kesireddy N, Altujjar M, et al. The Use Of Atenolol And Losartan In Reducing Aortic Dilation In Patients With Marfan Syndrome A Systematic Review And Meta-Analysis. JACC, 2022. 1808.
21. Chiu WC, Chiang JY, Juang JM, Wu CK, Tsai CT, Tseng YZ, et al. Reduction of blood pressure elevation by losartan in spontaneously hypertensive rats through suppression of LARG expression in vascular smooth muscle cells. Journal of the Formosan Medical Association 2020;119:164–72. https://doi.org/10.1016/j.jfma.2019.03.015.
22. Kucukdurmaz F, Efe E, Kurutas EB, Olmez C, Temizer M, Resim S. Losartan treatment significantly attenuates the fibrotic changes in the corpus cavernosum of castrated rats. Rev Int Androl 2020;18:14–20. https://doi.org/10.1016/j.androl.2018.07.001.
23. He C, Liu Y, Wang Y, Tang J, Tan Z, Li X, et al. 1H NMR based pharmacometabolomics analysis of metabolic phenotype on predicting metabolism characteristics of losartan in healthy volunteers. J Chromatogr B Analyt Technol Biomed Life Sci 2018;1095:15–23. https://doi.org/10.1016/j.jchromb.2018.07.016.
24. Rizwan F, Yesmine S, Banu SG, Chowdhury IA, Hasan R, Chatterjee TK. Renoprotective effects of stevia (Stevia rebaudiana Bertoni), amlodipine, valsartan, and losartan in gentamycin-induced nephrotoxicity in the rat model: Biochemical, hematological and histological approaches. Toxicol Rep 2019;6:683–91. https://doi.org/10.1016/j.toxrep.2019.07.003.
25. Salmani H, Hosseini M, Baghcheghi Y, Moradi-Marjaneh R, Mokhtari-Zaer A. Losartan modulates brain inflammation and improves mood disorders and memory impairment induced by innate immune activation: The role of PPAR-γ activation. Cytokine 2020;125. https://doi.org/10.1016/j.cyto.2019.154860.
26. McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2021;42:3599–726. https://doi.org/10.1093/eurheartj/ehab368.
27. Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol 2022;79:e263–421. https://doi.org/10.1016/j.jacc.2021.12.012.

(Konten ini khusus untuk dokter. Registrasi untuk baca selengkapnya)

Masuk atau Daftar

Nomor Ponsel Sudah Terdaftar

Masuk dengan Email

Masuk dengan Email

Masuk dengan Facebook

Farmakologi Losartan

Referensi

Masuk atau Daftar

Artikel Terkait