Amfoterisin B: Perbedaan antara revisi

|<span data-segmentid="258" class="cx-segment">Resisten<ref name=":42" /><ref name=":0205">{{Cite journal|last=Hamill|first=Richard J.|date=2013-06-01|title=Amphotericin B Formulations: A Comparative Review of Efficacy and Toxicity|journal=Drugs|volume=73|issue=9|pages=919–934|doi=10.1007/s40265-013-0069-4|issn=0012-6667|pmid=23729001}}</ref></span>

|<span data-segmentid="270" class="cx-segment">Resisten secara intrinsik<ref name=":0205" /></span>

<span data-segmentid="279" class="cx-segment">Amfoterisin B [[Kelarutan|tidak larut]] dalam [[larutan garam fisiologi]]s pada [[pH]] 7.</span> <span data-segmentid="283" class="cx-segment">Oleh karena itu, dibuat beberapa formulasi untuk meningkatkan bioavailabilitas intravena. <ref name=":7">{{Cite journal|last=Dutcher|first=James D.|date=1968-10-01|title=THe discovery and development of amphotericin b|journal=Chest|volume=54|issue=Supplement_1|pages=296–298|doi=10.1378/chest.54.Supplement_1.296|issn=0012-3692}}</ref></span> <span data-segmentid="284" class="cx-segment">Formulasi amfoterisin B berbasis lipid tidak lebih efektif dibandingkan formulasi konvensional, walau terdapat bukti bahwa formulasi berbasis lipid memiliki efek samping yang lebih sedikit.<ref>Steimbach, Laiza M., Fernanda S. Tonin, Suzane Virtuoso, Helena HL Borba, Andréia CC Sanches, Astrid Wiens, Fernando Fernandez‐Llimós, and Roberto Pontarolo. "Efficacy and safety of amphotericin B lipid‐based formulations—A systematic review and meta‐analysis." Mycoses 60, no. 3 (2017): 146-154.</ref></span>

<span data-segmentid="286" class="cx-segment">Formulasi awal menggunakan natrium [[Asam deoksikolat|deoksikolat]] untuk meningkatkan kelarutan.<ref name=":005">{{Cite journal|last=Hamill|first=Richard J.|date=2013-06-01|title=Amphotericin B Formulations: A Comparative Review of Efficacy and Toxicity|journal=Drugs|volume=73|issue=9|pages=919–934|doi=10.1007/s40265-013-0069-4|issn=0012-6667|pmid=23729001}}</ref></span> <span data-segmentid="288" class="cx-segment">Amfoterisin B deoksikolat (AmBD) diberikan secara[[Infus|intravena]].<ref name=":1">{{Cite journal|last=Maertens|first=J. A.|date=2004-03-01|title=History of the development of azole derivatives|journal=Clinical Microbiology and Infection|volume=10|pages=1–10|doi=10.1111/j.1470-9465.2004.00841.x|issn=1469-0691|pmid=14748798}}</ref></span> Formulasi ini <span data-segmentid="290" class="cx-segment">sering disebut sebagai amfoterisin "konvensional".<ref>{{Cite journal|last=Clemons|first=KV|last2=Stevens|first2=DA|date=April 1998|title=Comparison of Fungizone, Amphotec, AmBisome, and Abelcet for Treatment of Systemic Murine Cryptococcosis|url=|journal=Antimicrobial Agents and Chemotherapy|volume=42|issue=4|pages=899–902|doi=10.1128/AAC.42.4.899|pmc=105563|pmid=9559804}}</ref></span>

<span data-segmentid="292" class="cx-segment">Agar pasien dapat menggunakan amfoterisin B dengan aman dengan efek samping yang lebih rendah, telah dikembangkan formulasi lain yang berbasis lipid.<ref name=":0305">{{Cite journal|last=Hamill|first=Richard J.|date=2013-06-01|title=Amphotericin B Formulations: A Comparative Review of Efficacy and Toxicity|journal=Drugs|volume=73|issue=9|pages=919–934|doi=10.1007/s40265-013-0069-4|issn=0012-6667|pmid=23729001}}</ref></span> Berdasarkan hasil uji klinis, amfoterisin B dengan f<span data-segmentid="293" class="cx-segment">ormulasi liposom memiliki toksisitas pada ginjal yang lebih rendah dibandingkan deoksikolat,<ref>{{Cite journal|last=Botero Aguirre|first=Juan Pablo|last2=Restrepo Hamid|first2=Alejandra Maria|date=2015-11-23|title=Cochrane Database of Systematic Reviews|journal=Cochrane Database of Systematic Reviews|language=en|issue=11|pages=CD010481|doi=10.1002/14651858.cd010481.pub2|isbn=|pmid=26595825|quote=}}</ref><ref>{{Cite journal|last=Mistro|first=Sóstenes|last2=Maciel|first2=Isis de M.|last3=Menezes|first3=Rouseli G. de|last4=Maia|first4=Zuinara P.|last5=Schooley|first5=Robert T.|last6=Badaró|first6=Roberto|date=2012-06-15|title=Does Lipid Emulsion Reduce Amphotericin B Nephrotoxicity? A Systematic Review and Meta-analysis|url=http://cid.oxfordjournals.org/content/54/12/1774|journal=Clinical Infectious Diseases|volume=54|issue=12|pages=1774–1777|doi=10.1093/cid/cis290|issn=1058-4838|pmid=22491505}}</ref> dan lebih sedikit kejadian reaksi setelah pemberian melalui infus.<ref name=":0305" /></span> Formulasi ini memiliki harga yang <span data-segmentid="294" class="cx-segment">lebih mahal dibandingkan dengan amfoterisin B deoksikolat.<ref>{{Cite journal|last=Bennett|first=John|date=2000-11-15|title=Editorial Response: Choosing Amphotericin B Formulations—Between a Rock and a Hard Place|url=http://cid.oxfordjournals.org/content/31/5/1164|journal=Clinical Infectious Diseases|language=en|volume=31|issue=5|pages=1164–1165|doi=10.1086/317443|issn=1058-4838|pmid=11073746}}</ref></span>

<span data-segmentid="295" class="cx-segment">AmBisome (LAmB) adalah amfoterisin B dengan formulasi liposom yang digunakan secara infus. Liposom dari formulasi tersebut terdiri dari campuran fosfatidilkolin, kolesterol dan distearoil fosfatidilgliserol yang dalam media air akan membentuk vesikel unilamelar mengandung amfoterisin B.<ref name=":0405">{{Cite journal|last=Hamill|first=Richard J.|date=2013-06-01|title=Amphotericin B Formulations: A Comparative Review of Efficacy and Toxicity|journal=Drugs|volume=73|issue=9|pages=919–934|doi=10.1007/s40265-013-0069-4|issn=0012-6667|pmid=23729001}}</ref><ref name=":222">{{Cite journal|last=Slain|first=Douglas|date=1999-03-01|title=Lipid-Based Amphotericin B for the Treatment of Fungal Infections|url=https://archive.org/details/sim_pharmacotherapy_1999-03_19_3/page/306|journal=Pharmacotherapy|volume=19|issue=3|pages=306–323|doi=10.1592/phco.19.4.306.30934|issn=1875-9114}}</ref></span>

<span data-segmentid="308" class="cx-segment">Terdapat pula formulasi dalam kompleks lipid.</span> <span data-segmentid="309" class="cx-segment">Abelcet disetujui oleh [[Badan Pengawas Obat dan Makanan Amerika Serikat|FDA]] pada tahun 1995.<ref name="accessdata.fda.gov">{{Cite web|url=http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails|title=Drugs@FDA: FDA Approved Drug Products|website=www.accessdata.fda.gov|archive-url=https://www.webcitation.org/6SN0rqosx?url=http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails|archive-date=2014-09-05|dead-url=no|access-date=2015-11-03}}</ref></span> Formulasi i<span data-segmentid="311" class="cx-segment">ni terdiri dari amfoterisin B dan dua lipid dalam perbandingan jumlah 1:1 yang membentuk struktur seperti pita besar.<ref name=":05">{{Cite journal|last=Hamill|first=Richard J.|date=2013-06-01|title=Amphotericin B Formulations: A Comparative Review of Efficacy and Toxicity|journal=Drugs|volume=73|issue=9|pages=919–934|doi=10.1007/s40265-013-0069-4|issn=0012-6667|pmid=23729001}}</ref></span> <span data-segmentid="312" class="cx-segment">Amphotec adalah kompleks amfoterisin dan natrium kolestil sulfat dalam perbandingan jumlah 1:1.</span> <span data-segmentid="313" class="cx-segment">Dua molekul tersebut membentuk tetramer yang teragregasi menjadi untaian spiral pada kompleks seperti cakram.<ref name=":22">{{Cite journal|last=Slain|first=Douglas|date=1999-03-01|title=Lipid-Based Amphotericin B for the Treatment of Fungal Infections|journal=Pharmacotherapy|volume=19|issue=3|pages=306–323|doi=10.1592/phco.19.4.306.30934|issn=1875-9114}}</ref></span> Formulasi tersebut <span data-segmentid="314" class="cx-segment">disetujui oleh FDA pada tahun 1996.<ref name="accessdata.fda.gov" /></span>

<span data-segmentid="380" class="cx-segment">Amfoterisin B berikatan dengan [[ergosterol]], komponen membran sel jamur. Setelah itu, amfoterisin B membentuk pori-pori yang menyebabkan kebocoran [[Valensi|ion monovalen]] dengan cepat ([[Kalium|K⁺]], [[Natrium|Na⁺]], [[Hidrogen|H⁺]] dan [[Klorida|Cl^-]]), sehingga menyebabkan kematian sel jamur.</span> Mekaninsme tersebut merupakan mekanisme <span data-segmentid="387" class="cx-segment">utama amfoterisin B sebagai antijamur.<ref name=":3">{{Cite journal|last=Mesa-Arango|first=Ana Cecilia|last2=Scorzoni|first2=Liliana|last3=Zaragoza|first3=Oscar|date=2012-01-01|title=It only takes one to do many jobs: Amphotericin B as antifungal and immunomodulatory drug|journal=Fungi and Their Interactions|volume=3|pages=286|doi=10.3389/fmicb.2012.00286|pmc=3441194|pmid=23024638}}</ref><ref name="O'Keeffe">{{Cite journal|last=O'Keeffe|first=Joseph|last2=Doyle|first2=Sean|last3=Kavanagh|first3=Kevin|date=2003-12-01|title=Exposure of the yeast Candida albicans to the anti-neoplastic agent adriamycin increases the tolerance to amphotericin B|journal=Journal of Pharmacy and Pharmacology|volume=55|issue=12|pages=1629–1633|doi=10.1211/0022357022359|issn=2042-7158|pmid=14738588}}</ref></span> <span data-segmentid="388" class="cx-segment">Kompleks amfoterisin B/ergosterol yang membentuk pori-pori tersebut bersifat stabil karena adanya interaksi Van der Waals.<ref>{{Cite journal|title=Molecular modelling of amphotericin B-ergosterol primary complex in water II|journal=Biophysical Chemistry|volume=141}}</ref></span> <span data-segmentid="389" class="cx-segment">Amfoterisin B juga menyebabkan [[stres oksidatif]] dalam sel jamur,<ref name="Baginski2009Baginski20092">{{Cite journal|last=Baginski|first=M.|last2=Czub|first2=J.|year=2009|title=Amphotericin B and Its New Derivatives–Mode of Action|journal=Current Drug Metabolism|volume=10|issue=5|pages=459–69|doi=10.2174/138920009788898019|pmid=19689243}}</ref> tetapi masih belum diketahui sejauh mana stres oksidatif ini mempengaruhi efektivitas obat.<ref name=":3" /></span>  

<span data-segmentid="400" class="cx-segment">Baik membran sel mamalia dan jamur memiliki sterol, target utama bagi amfoterisin B. Karena membran mamalia dan jamur memiliki kemiripan dalam hal struktur dan komposisi, amfoterisin B memiliki efek samping yang berat.</span> <span data-segmentid="401" class="cx-segment">Amfoterisin B dapat membentuk pori-pori di membran inang serta membran jamur.</span> Kerusakan membran inilah yang membuat amfoterisin B memiliki efek samping yang mengancam jiwa<span data-segmentid="402" class="cx-segment">.<ref name="Baginski20092">{{Cite journal|last=Baginski|first=M.|last2=Czub|first2=J.|year=2009|title=Amphotericin B and Its New Derivatives–Mode of Action|journal=Current Drug Metabolism|volume=10|issue=5|pages=459–69|doi=10.2174/138920009788898019|pmid=19689243}}</ref><ref name="Laniado-Laborin R 200920092">Laniado-Laborin R. and Cabrales-Vargas MN. Amphotericin B: side effects and toxicity. Revista Iberoamericana de Micologia. (2009): 223–7.</ref><ref>Pfizer. Amphocin. Accessed at {{Cite web|url=http://www.pfizer.com/files/products/uspi_amphocin.pdf|title=Archived copy|archive-url=https://web.archive.org/web/20110419194646/http://www.pfizer.com/files/products/uspi_amphocin.pdf|archive-date=2011-04-19|dead-url=yes|access-date=2010-02-18}} on Feb 18 2010.</ref></span> <span data-segmentid="403" class="cx-segment">Ergosterol yang merupakan komponen membran sel jamur memiliki sensitivitas yang lebih tinggi terhadap amfoterisin B dibandingkan kolesterol yang merupakan komponen membran sel mamalia.</span> <span data-segmentid="404" class="cx-segment">Reaktivitas dengan membran juga bergantung pada konsentrasi sterol.<ref>{{Cite journal|last=Vertut-Croquin|first=Aline|last2=Bolard|first2=Jacques|last3=Chabbert|first3=Marie|last4=Gary-Bobo|first4=Claude|year=1983|title=Differences in the Interaction of the Polyene Antibiotic Amphotericin B with Cholesterol- or Ergosterol-Containing Phospholipid Vesicles. A Circular Dichroism and Permeability Study|journal=Biochemistry|volume=22|issue=12|pages=2939–2944|doi=10.1021/bi00281a024}}</ref></span>

<span data-segmentid="406" class="cx-segment">Pemberian amfoterisin dibatasi oleh reaksi setelah infus.</span> Hal i<span data-segmentid="407" class="cx-segment">ni diduga karena produksi imun bawaan dari sitokin proinflamasi.<ref name="Laniado-Laborin R 20092">Laniado-Laborin R. and Cabrales-Vargas MN. Amphotericin B: side effects and toxicity. Revista Iberoamericana de Micologia. (2009): 223–7.</ref><ref>Drew, R. Pharmacology of amphotericin B. Uptodate. Sep 2009. Accessed at http://www.utdol.com/online/content/topic.do?topicKey=antibiot/4619&selectedTitle=2~150&source=search_result{{Dead link|date=August 2018 |bot=InternetArchiveBot |fix-attempted=yes }} on Feb 18 2010.</ref></span>

[[Kategori:Anti jamurAntijamur]]