aminoglikosida

KUMPULAN REFERAT Qonita Minggu, 22 Mei 2011 OTOTOKSIK KARENA KONSUMSI AMINOGLIKOSIDA OTOTOKSIK KARENA KONSUMSI AMINOGLIKOSIDA

BAB I PENDAHULUAN

A. Latar Belakang Akhir-akhir ini penyebab ketulian memang belum jelas, tetapi setelah dilakukan anamnesis secara teliti pada penderita, maka terungkap bahwa sebagian besar ketulian penderita disebabkan karena obat atau yang biasa disebut dengan ototoksik, selain karena akibat mekanik atau faktor  eksternal lain. Penyebab umum gangguan pendengaran, terutama di negara-negara berkembang, adalah ototoxicity. ototoxic yang berupa kehilangan pendengaran terjadi ketika seseorang mengambil atau diberi obat yang menyebabkan gangguan pendengaran sebagai salah satu dari efek samping. Kadang-kadang obat yang diperlukan untuk menyelamatkan nyawa, dan gangguan pendengaran adalah harga yang harus dibayar untuk bisa hidup Ototoksik sudah lama dikenal sebagai efek samping pengobatan kedokteran, dan dengan  bertambahnya obet-obatan yang lebih poten daftar obat-obatan ototoksik makin bartambah. Pada tahun 1990 Werner melakukan tinjauan pustaka yang menerangkan efek ototoksik dari berbagai macam zat termasuk Arsen, etil, metal alcohol, nikotin, toksin bakteri dan senyawa-senyawa logam berat. Dengan ditemukannya antibiotika an tibiotika streptomisin, kemoterapi pertama yang efektif  terhadap kuman tuberculosis, menjadi pemicu terjadinya gangguan pendengaran dan vestibuler. Antibiotik golongan Aminoglikosida lain yang kemudian digunakan diklinik rupanya memperkuat efek ototoksik seperti yang diakibatkan oleh streptomisin. Konsumsi Aminoglikosid dapat menyebabkan kerentanan yang tidak biasa dari telinga dalam, sehingga dalam  pemberiannya harus secara hati-hati baik pada penderita dewasa, anak-anak, bayi, bahkan juga  pada ibu hamil yang dapat mengakibatkan efek teratogenik. Gejala mula-mula ialah timbulnya tinitus atau kadangkadang disertai dengan gangguan keseimbangan, sehingga bila obat diteruskan pemberiannya akan mengakibatkan ketulian. Sifat ketulian tersebut dapat reversibel atau irreversibel bila pemberian obat dihentikan.

B. Tujuan Penulisan Adapun tujuan dari penulisan ini adalah : 1. Mengetahui dan memahami lebih dalam tentang Ototoksik khususnya yang disebabkan oleh obat golongan Aminoglikosida. 2. Mengetahui penatalaksanan dari Ototoksik yang terjadi karena konsumsi obat ototoksik  hususnya Aminoglikosida.

C. Manfaat Penulisan Untuk dapat memberikan penyuluhan tentang efek konsumsi obat golongan Aminoglikosida terhadap organ pendengaran. Sehingga diharapkan dalam penggunaan obat golongan Aminoglikosida dapat berhati-hati.

BAB II TINJAUAN PUSTAKA

Pengertian Ototoksik  Ototoksik adalah gangguan yang terjadi pada alat pendengaran yang terjadi karena efek samping dari konsumsi obat-obatan. Gangguan yang terjadi pada pendengaran biasanya bermanifestasi menjadi tuli sensoryneural. Yang dapat bersifat reversibel dan bersifat sementara, atau tidak  dapat diubah dan permanen. Obat-obatan yang biasanya memberikan efek ototoksik antaralain adalah obat golongan Aminoglikosida, Loop Diuretics, Obat Anti Inflamasi, Obat Anti Malaria, Obat Anti Tumor, da n Obat Tetes Telinga Topikal.

Gejala Gejala ototoxicity bervariasi dari obat satu dengan obat lain dan dan dari orang satu dengan lainya. Yang dapat termanifestasi menjadi Tinitus , gangguan pendengaran ataupun vertigo merupakan gejala utama ototoksisitas

Golongan Aminoglikosida Aminoglikosida adalah kelompok antibiotika penting yang digunakan baik secara topikal atau  pun sistemik untuk pengobatan infeksi yang d isebabkan bakteri gram negatif. Aminoglikosida memberi efek membunuh bakteri melalui pengikatan subunit ribosomal 30S dan mengganggu sintesis protein. Aminoglikosida dihasilkan oleh fungi Streptomyces dan micromonospora. Mekanisme kerjanya:  bakterisid, berpenetrasi pada dinding bakteri dan mengikatkan diri pada ribosom dalam sel Termasuk golongan ini: Streptomisin, Gentamisin, Neomisin, Kanamisin, Amikasin, Tobramisin, Kapreomisin. Spektinomisin dan Viomisin memiliki bagian struktur aminoglikosida, tetapi secara kimiawi tidak memiliki inti yang sama. Pemakaian obat golongan Aminoglikosida dapat melalui telinga dalam melalui sistem darah, melalui inhalasi, atau melalui difusi dari telinga tengah ke telinga bagian dalam. Selain itu dapat d apat  juga dengan memasuki aliran darah dalam jumlah terbesar bila diberikan secara intravena (oleh IV).

Mekanisme kerja aktivitas tergantung pada kadarnya, pada kadar rendah bersifat bakteriostatik, dan kadar tinggi  bersifat bakterisid terhadap mikroba yang sensitif. Juga aktivitas potensinya lebih kuat pada suasana alkali daripada suasana asam. Pada keadaan anaerobik akan menurunkan potensi aktivitas. Golongan ini mengikatkan diri pada subunit 30S ribosom yang sensitive dari mikroba tersebut. Di samping ,efek terhadap ribosom tersebut juga menimbulkan berbagai efek sekunder  terhadap fungsi sel mikroba, yaitu terhadap respirasi, adaptasi enzim, ke untuhan membran dan keutuhan RNA. Perbedaan antar sesama aminoglikosida bersifat kuantitatif. Pada Kanamisin, Amikasin dan Gentamisin, potensi antimikrobanya melebihi Streptomisin.

Spektrum Pada umumnya menunjukkan banyak persamaan dengan Streptomisin, a.l. terhadap Brucella. H. ducreyi, Actinobacilles, P. pestis dan Shigella, juga terhadap E. coli, M. tbc., Nocardia, Proteus.

Farmakokinetika Sangat sukar diabsorpsi melalui saluran cerna. Pada pemberian peroral tujuannya hanya untuk  mendapatkan khasiat lokal dalam saluran cerna saja; umpamanya pada infeksi saluran cerna. Untuk mendapatkan kadar sistemik yang efektif, aminoglikosida perlu diberikarl secara perenatal dan biasanya dalam bentuk garam sulfat. Kadar puncak dalam darah dicapai dalam waktu 1/2 sampai 2 jam. Peningkatan oleh protein plasma darah jelas terlihat pada Streptomisin yang  berjumlah ± 1/3 dari seluruh aminoglikosida dalam darah. Distribusi cukup meluas ke dalam seluruh cairan tubuh, kecuali ke dalam cairan otak. Ekskresi Terutama melalui ginjal dengan filtrasi glomeruler. Aminoglikosida yang diberikan dalam d osis tunggal, menunjukkan jumlah ekskresi renal yang kurang dari dosis yang diberikan. Karena ekskresi hampir seluruhnya berlangsung melalui ginjal, keadaan ini menunjukkan adanya sekuestrasi ke dalam jaringan terutama pada Gentamisin., menunjukkan adanya kumulasi tertinggi dalam jaringan hati, media ginjal, otot skelet d an kelenjar ± 15%. Adanya hambatan fungsi ginjal akan menghambat ekskresi aminoglikosida yang berakibat terjadinya kumulasi dan cepat meningkatnya kadar dalam darah sampai lebih cepat mencapai kadar toksik. Juga pada bayi yang baru lahir/prematur dan penderita usia lanjut, dengan adanya gangguan ekskresi, masa paruh akan cepat meningkat. Patofisiologi Toksisitas aminoglikosida terutama target ginjal dan sistem cochleovestibular, namun tidak jelas ada korelasi antara tingkat nephrotoxicity dan ototoxicity. Toksisitas koklea yang mengakibatkan gangguan pendengaran biasanya dimulai dalam frekuensi tinggi dan sekunder untuk kerusakan

ireversibel luar sel-sel rambut pada organ Corti, terutama pada p ergantian basal koklea. Mekanisme aminoglikosida ototoxicity diperantarai oleh gangguan sintesis protein mitokondria, dan pembentukan radikal oksigen bebas. Mekanisme awal aminoglikosida dalam merusak   pendengaran adalah penghancuran sel-sel rambut koklea, khususnya sel-sel rambut luar.. Aminoglikosida muncul untuk menghasilkan radikal bebas di dalam telinga bagian dalam dengan mengaktifkan nitric oksida sintetase yang dap at meningkatkan konsentrasi oksida nitrat. Radikal oksigen kemudian bereaksi dengan oksida nitrat untuk membentuk radikal peroxynitrite destruktif, yang dapat secara langsung merangsang sel mati. Apoptosis adalah mekanisme utama kematian sel dan terutama diperantarai oleh kaskade mitokondria intrinsik. Nampaknya aminoglikosida berinteraksi dengan logam transisi seperti sebagai besi dan tembaga mungkin terjadi pembentukan radikal bebas tersebut. Akhirnya fenomena ini menyebabkan kerusakan  permanen pada sel-sel rambut luar koklea, yang mengakibatkan kehilangan pendengaran  permanen. Ototoxicity aminoglikosida kemungkinan multifaktor, dan penyelidikan lebih lanjut terus  berlanjut. Beberapa penelitian sedang menyelidiki chelators besi dan antioksidan sebagai agen mungkin untuk mencegah gangguan pendengaran selama terapi, sementara studi lain mengeksplorasi bentuk terapi gen sebagai pilihan pengobatan di masa depan. Saat ini, tidak ada perawatan yang tersedia selain dari amplifikasi dan implantasi koklea, karena itu, pencegahan sangat penting. Faktor risiko Faktor-faktor tertentu bisa menempatkan pasien pada peningkatan risiko untuk ototoxicitas.. Ototoxicity aminoglikosida lebih mungkin terjadi dengan dosis yang lebih besar, tingkat darah tinggi, atau lebih lama terapi. Lain pasien risiko tinggi termasuk pasien usia lanjut, mereka yang gagal ginjal, mereka yang memiliki masalah pendengaran yang sudah ada sebelumnya, orangorang dengan sejarah keluarga ototoxicity, dan mereka yang menerima diuretik loop atau ototoxic lainnya atau obat-obatan nefrotoksik. Sebuah kecenderungan genetik mitokondria ada di mutasi RNA 1555A> G, yang telah ditemukan untuk dihubungkan dengan nonsyndromic dan aminoglikosida-akibat gangguan  pendengaran. Hal tersebut menyebabkan perubahan dalam sintesis protein mitokondria yang memiliki potensi lebih cepat dalam menimbulkan dampak ototksisitas karena Aminoglikosida.. Evaluasi yang teliti terhadap sejarah keluarga adalah penting dan dapat mencegah banyak kasus.. Selain itu, beberapa telah menyarankan bahwa populasi berisiko tinggi (misalnya, pasien dengan fibrosis kistik, sejarah keluarga, dan disfungsi kekebalan) harus diperiksa untuk antisipasi terjadinya efek ototoksik. Efek samping Dapat dibagi 3 kelompok : 1) allergi 2) reaksi irritasi dan toksik  3) perubahan biologik. 1. Reaksi allergi Reaksi alergi yang timbul dengan intensitas beragam mulai dari pruritis, urtikaria, eritema, ruam morbiliform dan makulopapular. Pada yang berat ialah dermatitis eksfoliativa.

Terhadap komponen darah ialah eosinofilia, trombopenia. Gejala lain ialah stomatitis dan demam. Reaksi hipersensitivitas jarang terjadi pada Tobramisin, Kanamisin, dan G entamisin. 2. Reaksi iritasi dan toksik  Timbulnya reaksi iritasi dan rasa nyeri terjadi ditempat suntik. EfekI ototoksik; terutama terhadap saraf N VIII mengenai vestibuler dan akustik. Streptomisin dan Gentamisin lebih mempengaruhi komponen vestibuler, sedangkan pada Neomisin, Kanamisin dan Amikasin lebih mempengaruhi komponen akustik. Ototoksisitas arninoglikosida dapat ditingkatkan oleh  pelbagai faktor, antara lain besarnya dosis, gangguan faal ginjal, usia lanjut. Pada penderita yang  pernah mendapat suatu obat ototoksik dan juga bila diberikan asam etakrinat (diuretika kuat). Gangguan vestibular gejala dininya ialah sakit kepala yang kemudian diikuti fase akut dengan gejala pusing, mual, muntah dan gangguan keseimbangan. Pada fase kronik, gejala nyata waktu  berjalan. Pada fase kompensasi, gejala bersifat laten dan hanya menjadi nyata bila menutup mata. Gejala –gejala ini bersifat reversibel dan kadang-kadang juga pada beberapa penderita timbul sekuele. Pemulihan sempuma 12 sampai 18 bulan. Secara patologis, kerusakan terdapat pada nuklei koklearis ventrikuler di batang otak yang meluas ke ujung serabut saraf di koklea. Dengan dosis 2 gram per hari selama 60 sampai 120 hari, gejala terlihat pada 75% penderita. Dan dengan dosis 1 gram per hari, gejala terlihat pada 25% penderita. Gentamisin mempunyai angka ototoksisitas 2%, dan 66% di antaranya berupa gangguan vestibuler, sedangkan untuk Kanamisin sekitar 7%. Pada gangguan akustik, tidak selalu terjadi  pada kedua telinga sekaligus. Pada mulanya kepekaan terhadap golongan frekuensi tinggi akan  berkurang dan ini tidak disadari oleh penderita. Gejala dini berupa tinitus bernada tinggi. Patologi kerusakan akustik terutama berupa degenerasi berat sel-sel rambut luar pada telinga dalam. Sel organ Corti juga mengalami kerusakan. Frekuensi gangguan akustik akibat Streptomisin 4 sampai 15%, bila terapi lebih dari 1 minggu. Gentamisin 34% dari 2% ototoksisitas. Kanamisin 30%. Neomisin paling mudah menimbulkan tuli saraf. Penggunaan topikal atau irigasi luka dengan larutan Neomisin 5% pada penderita dengan ginjal normal, juga dapat menimbulkan tuli saraf. Pada Tobramisin terjadinya gangguan vestibuler dan akustik  masing -masing sebanyak 0,4%. Amikasin bila diberikan lebih dari 14 hari juga akan menimbulkan gangguan pendengaran. Selain efek ototoksik, juga timbul effek nefrotoksik dan neurotoksik. 3. Perubahan biologi Adanya pola mikroflora tubuh dan gangguan absorpsi di usus.Adanya interaksi obat yang pe rlu diperhatikan ialah, golongan aminoglikosida dengan suatu diuretika kuat akan menaikkan ototosik dan nefrotoksik.

Macam obat golongan Aminoglikosida dan interaksinya • Streptomisin: Streptomisin adalah aminoglikosida yang pertama diterapkan secara klinis dan bberhasil digunakan untuk melawan bakteri gram negatif di masa lalu. Lebih mempengaruhi sistem vestibular daripada sistem pendengaran. Kerusakan Vestibular akibat streptomisin adalah umum dengan penggunaan jangka panjang dan pada pasien dengan gangguan fungsi ginjal. Karena

sifatnya yang ototoksik agen ini jarang digunakan saat ini. Namun, penggunaan streptomisin meningkat untuk pengobatan TBC. • Gentamicin: Seperti streptomisin, gentamisin memiliki kecenderungan untuk mempengaruhi sistem vestibular. Indeks terapi sebesar 10-12 mcg / mL pada umumnya dianggap aman tapi masih dapat bersifat ototoksik pada beberapa pasien. Hati-hati dalam pemberian dosis pada pasien dengan penyakit ginjal. • Neomycin: Agen ini adalah salah satu yang paling cochleotoxic bila diberikan secara peroral dan dalam dosis tinggi, karena itu, penggunaan sistemik umumnya tidak dianjurkan. Neomisin merupakan salah satu aminoglikosida yang paling lambat un tuk mempengaruhi Perilimfe; akibatnya dapat muncul 1-2 minggu setelah konsumsi ataupun dapat terjadi kemudian setelah penghentian terapi.  Neomisin Meskipun umumnya dianggap aman bila digunakan topikal dalam saluran telinga atau  pada lesi kulit kecil, sama efektifnya alternatif yang tersedia. • Kanamycin: Meskipun kurang bersifat ototoksiks dibandingkan neomisin, kanamycin c ukup bersifat ototoxic. Kanamycin memiliki kecenderungan mendalam menyebabkan kerusakan sel rambut koklea, ditandai frekuensi tinggi gangguan pendengaran, dan lengkap tuli. Efek yang merusak terutama ke koklea, sedangkan sistem vestibular biasanya terhindar dari cedera. penggunaan klinis saat ini sudah dibatasi. Sepertihalnya dengan neomisin, penggunaan secara parenteral umumnya tidak  dianjurkan. • Amikacin: amikasin adalah turunan dari kanamycin dan memiliki toksisitas sangat sedikit terhadap organ vestibular. Efek yang merugikan terutama yang melibatkan sistem pendengaran, namun itu dianggap kurang ototoxic dari pada gentamisin. • Tobramycin: Ototoxicity dari tobramisin adalah serupa dengan amikasin; menyebabkan tuli pada nada  berfrekuensi tinggi. Seperti halnya dengan kanamycin, jarang menyebabkan terjadinya ototoksik  terhadap organ vestibuler. Tobramisin sering digunakan secara otic dan topikal. Terapi Topikal digunakan, umumnya dianggap aman.

Penatalaksanaan Saat ini, tidak ada pengobatan yang dapat mengembalikkan kerusakan telinga yang terjadi karena konsumsi obat-obatan golongan Aminoglikosida. Bila pada waktu pemberian obat-obatan ototoksik terjadi gangguan pada telinga dalam (dalam diketahui secara audiiometrik), maka  pengobatan dengan obat-obatan tersebut harus segera dihentikan. Berat ringannya ketulian tergantung dari jenis obat, jumlah, dan lamanya penggunaan obat. Hal tersebut lebih rentan terjadi pada pasien dengan insufisiensi ginjal dan jenis obat itu sendiri. Pengobatan yang tersedia saat ini ditujukan untuk mengurangi dampak kerusakan dan merehabilitasi fungsi. Individu dengan gangguan pendengaran dapat dibantu dengan alat bantu dengar, psikoterapi, auditory training, termasuk dengan mengguanakn sisa pendengaran dewngan alat bantu dengar, belajar komunikasi total dengan blajar bahasa isyarat. Dan mereka yang mengalami gangguan pendengaran bilateral yang sudah mendalam dapat diatasi dengan melakukan implan koklea. Dalam kasus kehilangan fungsi keseimbangan, terapi fisik merupakan

hal yang sangat bernilai bagi banyak individu. Tujuannya adalah untuk membantu otak menjadi terbiasa dengan informasi yang berubah dari telinga bagian dalam dan untuk membantu individu dalam mengembangkan cara lain untuk menjaga keseimbangan Tetapi dalam kasus-kasus tertentu yang terjadi karena rusaknya organ vestibuler seperti terjadinya tinnitus, vertigo, ataupun kehilangan keseimbangan rupanya juga dapat ditanggulangi dengan obat aminoglikosida, dengan mempengaruhi system vestibuler yang sebenarnya sudah mengalami kelainan pada awalnya. kelainan awal di organ vestibuler yang sudah terbentuk  mekanismenya di rusak oleh aminoglikosida yang bersifat ototoksik terhadap organ vestibuler, sehingga gejala awal seperti tinnitus ataupun vertigo menjadi berkurang, walaupun pada akhirnya dapat memberikan efek ototoksik pada organ vestibuler lainnya atau organ akustik yang lain. Pencegahan Berhubung tidak ada pengobatan untuk tuli akibat ototoksik , maka pencegahan menjadi lebih  penting. Dalam melakukan pencegahan ini termasuk mempertimbangkan pengguanaan obat-obat ototoksik, menilai kerentanan pasien, memonitor efek samping secara dini, yaitu dengan memperhatikan gejala-gejala ototoksisitas pada telinga dalam yang timbul seperti tinnitus, kurang pendengaran dan vertigo. Pada pasien yang menunjukan mulai ada gejala-gejala tersebut harus dilakukan evaluasi audiologik dan menghentikan pengobatan Prognosis Prognosis sangat tergantung kepada jenis obat, jumlah , lamanya pengobatan, dan kerentanan  pasien. Pada umumnya prognosis tidak begitu baik  BAB III KESIMPULAN DAN SARAN Kesimpulan Obat-obat yang dapat menyebabkan ketulian: golongan aminoglikosida, obat anti malaria, golongan salisilat, dan obat anti kanker. Dari golongan amonoglikosida, yang paling sering pemakaiannya dan sering menimbulkan ketulian ialah Spreptomisin, Gentamisin dan Neomisin. Pemakaian kanamisin cukup banyak, tetapi persentase ketulian lebih kecil dibandingkan dengan ketiga obat tersebut. Efek teratogenik  sering terjadi pada pemberian golongan aminoglikosida, yaitu berupa ketulian pada janin. Walaupun Samapai saat ini belum ditemukan pengobatan untuk menyembuhkan tuli sensoryneural yang terjadi karena efek penggunaan obat golongan Aminoglikosida, penanganan yang membantu dapat dilakukan dengan implant coclea selain itu juga dapat dilakukan dengan terapi fisik untuk menjaga keseimbangan.

Saran • Hendaknya berhati-hati dalam memberikan obat-obatann yang dapat menjadi pemicu timbulnya tuli sensory neural yang terjadi karena reaksi ototksisitas obat baik pada neonatus,

 bayi, anak, orang dewasa, orang tua dan juga pada ibu hamil. • Apabila dalam terapi yang memerlukan pengobatan dengan obat-obatan yang bersifat ototoksik, semisal obat golongan Aminoglikosida hendaknya sebelum memulai pengobatan terlebihdahulu ditentukan tingkat pendengaran dasar dari pasien selain itu dilakukan juga uji keseimbangan dan tak lupa mengingatkan pasien tentang potensial ototoksisitas dari obat yang digunakannya. Sebaiknya pemantauan dilakukan selama penggunaan terapi dengan obat yang  bersifat ototoksik. Sehingga bila terjadi efek ototoksisitas, hal tersebut dapat ditanggulangi lebih dini. • Hendaknya selama pengobatan monitoring fungsi pendengaran jangan diabaikan

Daftar pustaka Arsyad efiaty et all., 2006, Buku Ajar Ilmu Kesehatan Telingga Hindung Tenggorok Kepala Leher: edisi 5, Jakarta : Fakultas Kedokteran Universitas Indonesia. Boies adam., 2002, Buku Ajar Penyakit THT: Edisi 6, Jakarta: EGC. Edmunds ann L., November 2008. Iner Ear Ototoxycity. www.emedicine.com Sriwidodo., 1998, Cermin dunia kedokteran: problema dan tatalaksana gangguan pendengaran, Jakarta: PT KalbeFarma. Diposkan oleh Qonita Imma Irfani di 23:10 010009000003ef0300000000c80200000000c802000026060f008605574d4643010000000000010 097dd0000000001000000640500000000000064050000010000006c00000000000000000000001 10000001100000000000000000000007a0200007a02000020454d4600000100640500000f00000 0010000000000000000000000000000005605000000030000e20100000f0100000000000000000 00000000000665a070055220400460000002c00000020000000454d462b014001001c000000100 000000210c0db010000006000000060000000460000008001000074010000454d462b224004000 c000000000000001e4009000c00000000000000244001000c00000000000000304002001000000 0040000000000803f214007000c0000000000000008400005cc000000c00000000210c0db01000 000000000000000000000000000000000000100000047494638396112001200e30000d0c7bbaa6 a34545350e5a325000000161616100903d08f29493512b98817e2a353281506332606ffc131fcb62 3d0c7bb21f9040100000f002c000000001200120000044ff0c949abbd9360bc8cde1411041e2815c a31961ba300c00a224ea328c287218d33a8ba0bcf774814400c073181001906cbe686902006a418 d172610a005281e0a50083892f84f2794c20604df04a04003b00000840010824000000180000000 210c0db01000000030000000000000000000000000000001b40000040000000340000000100000 002000000000000bf000000bf000090410000904103000000000080b3000080b3ffff8f41000080b 3000080b3ffff8f412100000008000000620000000c00000001000000150000000c000000040000 00150000000c00000004000000460000001400000008000000544e50500601000051000000c800 00000000000000000000110000001100000000000000000000000000000000000000120000001 200000050000000300000008000000048000000000000008600ee0012000000120000002800000 01200000012000000010001000000000000000000000000000000000000000000000000000000 0000ffffff0000000000780000007c0000ff7e0000ff3f0000ff3f8000ff1fc000ff0fe000ff07f000ff03f  800ff01fc00ff00fe00ff007f00ff003f80ff001f00ff000e00ff000400ff000000005100000090010000

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cedera kepala

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