- Pendahuluan
- Farmakologi
- Formulasi
- Indikasi dan Dosis
- Efek Samping dan Interaksi Obat
- Penggunaan pada Kehamilan dan Ibu Menyusui
- Kontraindikasi dan Peringatan
- Pengawasan Klinis
Pendahuluan Losartan
Losartan merupakan obat antihipertensi golongan penghambat reseptor angiotensin atau angiotensin receptor blocker. Losartan berfungsi menurunkan tekanan darah dan preload jantung. Obat ini biasanya digunakan sebagai terapi lini pertama hipertensi dan gagal jantung.[1-3]
Efek terapi losartan berupa hambatan terhadap menempelnya angiotensin II pada reseptor I angiotensin II, serta efek vasodilatasi melalui peningkatan produksi nitric oxide pada endotelium pembuluh darah.[2-4]
Selain dapat digunakan untuk hipertensi dan gagal jantung, losartan juga digunakan untuk nefropati diabetikum dan mencegah stroke. Losartan juga sedang diteliti potensinya untuk aneurisma pada penderita sindroma Marfan, mengurangi peradangan dan abrasi sendi pada osteoarthritis, mencegah pembentukan keloid, dan adjuvan kemoterapi pada kanker paru.
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.
4. Deng Z, Chen F, Liu Y, Wang J, Lu W, Jiang W, et al. Losartan protects against osteoarthritis by repressing the TGF-β1 signaling pathway via upregulation of PPARγ. J Orthop Translat 2021;29:30–41. https://doi.org/10.1016/j.jot.2021.03.005.
5. Zheng B, Fang QQ, Wang XF, Shi BH, Zhao WY, Chen CY, et al. The effect of topical ramipril and losartan cream in inhibiting scar formation. Biomedicine and Pharmacotherapy 2019;118. https://doi.org/10.1016/j.biopha.2019.109394.
6. Hong S, JianCheng H, JiaWen W, ShuQin Z, GuiLian Z, HaiQin W, et al. Losartan inhibits development of spontaneous recurrent seizures by preventing astrocyte activation and attenuating blood-brain barrier permeability following pilocarpine-induced status epilepticus. Brain Res Bull 2019;149:251–9. https://doi.org/10.1016/j.brainresbull.2019.05.002.
7. Stein MB, Jain S, Simon NM, West JC, Marvar PJ, Bui E, et al. Randomized, Placebo-Controlled Trial of the Angiotensin Receptor Antagonist Losartan for Posttraumatic Stress Disorder. Biol Psychiatry 2021;90:473–81. https://doi.org/10.1016/j.biopsych.2021.05.012.
8. Badan Pengawas Obat dan Makanan (BPOM) RI. Losartan Kalium. Pusat Informasi Obat Nasional Badan Pengawas Obat Dan Makanan. 2022. https://pionas.pom.go.id/monografi/losartan-kalium
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10. TGA. Prescribing medicines in pregnancy database. 2021.
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14. MIMS. Losartan. 2022. https://www.mims.com/indonesia/drug/info/losartan
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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.
28. BPOM. Cek BPOM. 2022. https://cekbpom.pom.go.id//home/produk/6gssti26g2f9uq59fpdvv8sdog/all/row/10/page/3/order/4/DESC/search/5/losartan
29. Tsiailanis AD, Renziehausen A, Kiriakidi S, Vrettos EI, Markopoulos GS, Sayyad N, et al. Enhancement of glioblastoma multiforme therapy through a novel Quercetin-Losartan hybrid. Free Radic Biol Med 2020;160:391–402. https://doi.org/10.1016/j.freeradbiomed.2020.08.007.
30. Joshi D, Katyal J, Arava S, Gupta YK. Effects of enalapril and losartan alone and in combination with sodium valproate on seizures, memory, and cardiac changes in rats. Epilepsy and Behavior 2019;92:345–52. https://doi.org/10.1016/j.yebeh.2018.12.019.
31. Perhimpunan Dokter Hipertensi Indonesia. Konsensus Penatalaksanaan Hipertensi. 2021.
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