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SKRIPSI NUR ARDIATUN CAHYATI STUDI PENGGUNAAN PROPRANOLOL PADA PASIEN SIROSIS HEPATIS DENGAN HIPERTENSI PORTAL (Penelitian di Rumah Sakit Umum Daerah Sidoarjo) PROGRAM STUDI FARMASI FAKULTAS ILMU KESEHATAN UNIVERSITAS MUHAMMADIYAH MALANG 2019
Transcript of SKRIPSI - eprints.umm.ac.ideprints.umm.ac.id/53876/1/PENDAHULUAN.pdfNSAID : Nonsteroidal...
SKRIPSI
NUR ARDIATUN CAHYATI
STUDI PENGGUNAAN PROPRANOLOL PADA
PASIEN SIROSIS HEPATIS DENGAN
HIPERTENSI PORTAL
(Penelitian di Rumah Sakit Umum Daerah Sidoarjo)
PROGRAM STUDI FARMASI
FAKULTAS ILMU KESEHATAN
UNIVERSITAS MUHAMMADIYAH MALANG
2019
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iii
iv
KATA PENGANTAR
Assalamu’alaikum warohmatullahi wabarokatuh
Puji syukur tercurahkan kepada Allah SWT yang telah melimpahkan
segala rahmat dan hidayah-Nya sehingga penulis dapat menyelesaikan skripsi yang
berjudul STUDI PENGGUNAAN PROPRANOLOL PADA PASIEN SIROSIS
HEPATIS DENGAN HIPERTENSI PORTAL (Penelitian di Rumah Sakit
Umum Daerah Sidoarjo). Skripsi ini diajukan untuk memenuhi persyaratan
mencapai gelar sarjana farmasi di fakultas ilmu kesehatan universitas
muhammadiyah malang semoga Allah SWT selalu memberi ridho-Nya dalam
setiap langkah dan usaha yang dilakukan penulis. Penulis mengucapkan terima
kasih yang sebesar-besarnya kepada semua pihak yang telah memberi bantuan dan
dorongan baik secara materil spiritual sehingga skripsi ini bisa selesai tepat waktu.
Ucapan terima kasih ini penulis sampaikan kepada:
1. Allah SWT, yang telah memberikan rahmat, nikmat dan hidayah kepada
umat-Nya. Dan kepada Rosulullah SAW, yang telah menuntun kita menuju
jalan yang lurus.
2. Kedua orang tua penulis, Bapak Ahmad, S.Pd dan Ibu Halimah S.Pd., SD
yang telah membesarkan dan mendidik penulis serta selalu mendoakan untuk
kesuksesan penulis, sehingga penulis dapat menyelesaikan skripsi dengan
baik dan tepat pada waktunya.
3. Bapak Faqih Ruhyanudin, M.Kep., Sp.Kep. selaku Dekan Fakultas Ilmu
Kesehatan Universitas Muhammadiyah Malang yang telah mengesahkan
secara resmi judulresmi penelitian sebagai bahan penulisan skripsi sehingga
penulisan skripsi berjalan dengan lancar.
4. Ibu Dr. Dra. Lilik Yusetyani,, Apt., Sp.FRS. selaku Dosen Pembimbing I dan
Bapak Drs. Didik Hasmono, M.S., Apt. selaku Dosen Pembimbing II yang
bersedia meluangkan waktu dan tenaganya untuk memberikan petunjuk,
bimbingan, dorongan, dan nasehat dengan ”telaten” sehingga penulis bisa
menyelesaikan skripsi ini dengan baik.
5. Ibu Dr. Hidajah Rachmawati, S.Si., Apt., Sp.FRS. selaku Dosen Penguji I dan
Ibu Drs. Uswatun Chasanah, M.Kes., Apt. selaku Dosen Penguji II yang telah
v
memberikan saran dan kritik yang sangat berguna dalam perbaikan skripsi
ini.
6. Bapak Ahmad Shobrun Jamil, S.Si., M.P selaku dosen wali yang
membimbing dan memberikan masukkan kepada penulis sejak awal semester
serta untuk seluruh Dosen dan Staf Pengajar Program Studi Farmasi Fakultas
Ilmu Kesehatan Universitas Muhammadiyah Malang yang telah
membimbing dan mengajarkan ilmu-ilmu yang bermanfaat kepada penulis.
7. Staf pegawai RMK RSUD Sidoarjo yang banyak membantu dalam proses
pengumpulan data.
8. Kakak saya Nunung Almaidah, Abang saya Muhammad Tafriet dan Adik
saya Lailatul Ramdhaningsih tersayang yang telah mendoakan, memotivasi
dan atas semua bantuan yang telah diberikan.
9. Teman dekat saya Agung Wahyudi yang telah memberikan motivasi dan
bantuan selama melakukan penelitian serta dalam mengerjakan skripsi dari
awal sampai selesai.
10. Sahabat Acefor terutama Iin Nurmutmainah, Sri Ratna Wahyuni, dan
Syafrudin yang selalu menghibur dan mengajak jalan-jalan setiap penulis
bosan dan stress dalam mengerjakan skripsi.
11. Rofidah Nur Umar yang selalu memberikan saya motivasi untuk mengerjakan
skripsi sehingga skripsi penulis dapat terselesaikan dengan baik.
Semoga Allah SWT memberikan berkah dan rahmat-nya kepada semuanya
akhirnya, hanya kepada allah SWT penulis serahkan segalanya, mudah-mudahan
dapat bermanfaat bagi semua pihak, khususnya bagi yang berkecimpung
dibidangnya.
Malang, 24 Agustus 2019
Penulis
Nur Ardiatun Cahyati
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DAFTAR ISI
HALAMAN JUDUL .............................................................................................. i
LEMBAR PENGESAHAN .................................................................................. ii
LEMBAR PENGUJIAN ...................................................................................... iii
KATA PENGANTAR .......................................................................................... iv
RINGKASAN ....................................................................................................... vi
ABSTRAK .......................................................................................................... viii
ABSTRACT ........................................................................................................... x
DAFTAR ISI ........................................................................................................ xii
DAFTAR GAMBAR ......................................................................................... xvii
DAFTAR TABEL ............................................................................................ xviii
DAFTAR LAMPIRAN ...................................................................................... xix
DAFTAR SINGKATAN ..................................................................................... xx
BAB I PENDAHULUAN ...................................................................................... 1
1.1 Latar Belakang ............................................................................................... 1
1.2 Rumusan Masalah .......................................................................................... 4
1.3 Tujuan Penelitian ........................................................................................... 4
1.3.1 Tujuan Umum ..................................................................................... 4
1.3.2 Tujuan Khusus .................................................................................... 4
1.4 Manfaat Penelitian ......................................................................................... 4
1.4.1 Bagi Peneliti........................................................................................ 4
1.4.2 Bagi Institusi Kesehatan ..................................................................... 5
1.4.3 Bagi Instalasi Terkait .......................................................................... 5
1.4.4 Bagi Masyarakat ................................................................................. 5
BAB II TINJAUAN PUSTAKA ........................................................................... 6
2.1 Hati ................................................................................................................ 6
2.1.1 Anatomi dan Struktur Hati.................................................................. 6
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2.1.2 Histologi Hati...................................................................................... 6
2.1.3 Sirkulasi Hati ...................................................................................... 7
2.1.4 Fungsi Hati ......................................................................................... 9
2.1.4.1 Metabolisme Karbohidrat .................................................... 9
2.1.4.2 Metabolisme Lemak ............................................................ 9
2.1.4.3 Metabolisme Protein ............................................................ 9
2.1.4.4 Metabolisme Empedu .......................................................... 9
2.1.4.5 Ekskresi Bilirubin .............................................................. 10
2.1.4.6 Detoksifikasi ...................................................................... 10
2.1.4.7 Fungsi Lain ........................................................................ 11
2.2 Sirosis Hati .................................................................................................. 11
2.2.1 Definisi Sirosis Hati .......................................................................... 11
2.2.2 Epidemiologi Sirosis Hati ................................................................. 12
2.2.3 Etiologi Sirosis Hati .......................................................................... 12
2.2.4 Klasifikasi Sirosis Hati ..................................................................... 13
2.2.4.1 Mikronodular ..................................................................... 13
2.2.4.2 Makronodular ..................................................................... 13
2.2.4.3 Campuran ........................................................................... 13
2.2.5 Patofisiologi Sirosis Hati .................................................................. 13
2.2.6 Manifestasi Klinis Sirosis Hati ......................................................... 14
2.2.6.1 Hematemesis dan atau Melena .......................................... 15
2.2.6.2 Varises Esofagus ................................................................ 15
2.2.6.3 Asites ................................................................................. 16
2.2.6.4 Spontaneus Bacterial Peritonitis (SBP) ............................. 17
2.2.6.5 Ensefalopati Hepatik .......................................................... 18
2.2.7 Data Klinik dan Data Laboratorium Sirosis Hati ............................. 19
2.2.7.1 Data Klinik ......................................................................... 19
2.2.7.2 Data Laboratorium ............................................................. 20
2.2.8 Penatalaksanaan Sirosis Hati ............................................................ 22
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2.2.8.1 Penatalaksanaan Sirosis Hati dengan Hematemesis dan atau
Melena ............................................................................................. 22
2.2.8.2 Penatalaksanaan Sirosis Hati dengan Varises Esofagus .... 22
2.2.8.3 Penatalaksanaan Sirosis Hati dengan Asites ...................... 22
2.2.8.4 Penatalaksanaan Sirosis Hati dengan Spontaneus Bacterial
Peritonitis (SBP) ............................................................................. 22
2.2.8.5 Penatalaksanaan Sirosis Hati dengan Ensefalopati Hepati 24
2.3 Hipertensi Portal .......................................................................................... 25
2.3.1 Definisi Hipertensi Portal ................................................................. 25
2.3.2 Epidemiologi Hipertensi Portal ........................................................ 26
2.3.3 Etiologi Hipertensi Portal ................................................................. 26
2.3.4 Klasifikasi Hipertensi Portal ............................................................. 27
2.3.4.1 Prehepatik .......................................................................... 27
2.3.4.2 Intrahepatik ........................................................................ 27
2.3.4.3 Posthepatik ......................................................................... 27
2.3.5 Patofisiologi Hipertensi Portal .......................................................... 27
2.3.6 Penatalaksanaan Hipertensi Portal .................................................... 29
2.3.6.1 Terapi Non Farmakologi .................................................... 29
2.3.6.1.1 Balon Tamponade ............................................. 29
2.3.6.1.2 Ligasi Varises Endoskopik (LVE) dan Sklerosis
Varises endoskopik (SVE) ................................................. 29
2.3.6.1.3 Transjugular Intrahepatik Portosistemik Shunt
(TIPS) ................................................................................ 29
2.3.6.2 Terapi Farmakologi ............................................................ 30
2.3.6.2.1 Derivat Vasopresin ........................................... 30
2.3.6.2.2 Somatostatin dan Analog Somatostatin Long-
acting.................................................................................. 31
2.3.6.2.3 Non Selektif β-bloker dan Kombinasi
Vasodilator ......................................................................... 31
2.3.6.2.4 Carvedilol ......................................................... 32
2.4 Propranolol pada Sirosis Hati dengan Hipertensi Portal ............................. 33
2.4.1 Indikasi Propranolol ......................................................................... 33
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2.4.2 Mekanisme Kerja .............................................................................. 34
2.4.3 Farmakodinamik Propranolol ........................................................... 34
2.4.4 Farmakokinetik Propranolol ............................................................. 34
2.4.4.1 Absorpsi ............................................................................. 34
2.4.4.2 Distribusi ............................................................................ 35
2.4.4.3 Metabolisme dan Ekskresi ................................................ 35
2.4.5 Dosis dan Rute Pemberian Propranolol ............................................ 35
2.4.6 Interaksi Obat Propranolol ................................................................ 36
2.4.7 Kontraindikasi Propranolol ............................................................... 36
2.4.8 Efek Samping Propranolol ................................................................ 36
2.4.9 Sediaan Propranolol yang Beredar di Indonesia ............................... 37
BAB III KERANGKA KONSEPTUAL ............................................................ 38
BAB IV METODE PENELITIAN .................................................................... 40
4.1 Rancangan Penelitian................................................................................... 40
4.2 Populasi dan Sampel .................................................................................... 40
4.2.1 Populasi ............................................................................................ 40
4.2.2 Sampel .............................................................................................. 40
4.3 Bahan Penelitian .......................................................................................... 40
4.3.1 Kriteria Data Inklusi ......................................................................... 40
4.3.2 Kriteria Data Eksklusi....................................................................... 41
4.4 Instrumen Penelitian .................................................................................... 41
4.5 Tempat dan Waktu Penelitian ...................................................................... 41
4.6 Definisi Operasional .................................................................................... 41
4.7 Metode Pengumpulan Data.......................................................................... 42
4.8 Analisis Data ................................................................................................ 42
BAB V HASIL PENELITIAN ........................................................................... 44
5.1 Demografi Pasien ......................................................................................... 44
5.1.1 Jenis Kelamin.................................................................................... 44
5.1.2 Usia Pasien........................................................................................ 45
5.1.3 Status Pasien ..................................................................................... 45
5.2 Etiologi Pasien Terdiagnosis Sirosis Hati .................................................... 46
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5.3 Penggunaan Propranolol pada Pasien Sirosis Hepati dengan Hipertensi
Portal ..................................................................................................................... 46
5.3.1 Pola Penggunaan Terapi pada Pasien Sirosis Hepatis dengan
Hipertensi Portal .......................................................................................... 46
5.3.2 Pola Penggunaan Terapi Tunggal Propranolol pada Pasien Sirosis
Hepatis dengan Hipertensi Portal ............................................................... 47
5.3.3 Pola Penggunaan Kombinasi Dua Propranolol pada Pasien Sirosis
Hepatis dengan Hipertensi Portal ................................................................ 47
5.3.4 Pola Penggunaan Kombinasi Tiga Propranolol pada Pasien Sirosis
Hepatis dengan Hipertensi Portal ................................................................ 49
5.3.5 Pola Penggunaan Propranolol Dengan Switch .................................. 50
5.4 Diagnosis Selain Hipertensi Portal............................................................... 52
5.5 Profil Terapi Selain Propranolol pada Pasien Sirosis Hepatis dengan
Hipertensi Portal ................................................................................................... 52
5.6 Lama Penggunaan Terapi Propranolol pada Pasien Sirosis Hati dengan
Hipertensi Portal.................................................................................................... 54
5.7 Lama Rawat Inap Pasien Sirosis Hati dengan Hipertensi Portal ................. 54
5.8 Kondisi Pasien Keluar Rumah Sakit (KRS)................................................. 54
BAB VI PEMBAHASAN .................................................................................... 56
BAB VII KESIMPULAN DAN SARAN ........................................................... 69
7.1 Kesimpulan .................................................................................................. 69
7.2 Saran ............................................................................................................. 69
DAFTAR PUSTAKA .......................................................................................... 71
LAMPIRAN ......................................................................................................... 77
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DAFTAR GAMBAR
Gambar
Halaman
2.1 Struktur Hati ...................................................................................................... 6
2.2 Pembuluh Kolateral Portosystemic dalam Hipertensi Portal ............................. 8
2.2 Gambar Endoskopi Representati Menunjukkan Varises Esofagus .................. 15
2.3 Pembentukan Asites ......................................................................................... 16
2.4 Komplikasi pada Asites.................................................................................... 26
2.5 Patofisiologi Hipertensi Portal ......................................................................... 28
2.6 Struktur Propranolol ......................................................................................... 33
3.1 Skema Kerangka Konseptual ........................................................................... 38
3.2 Skema Kerangka Operasional .......................................................................... 39
5.1 Skema inklusi dan eksklusi pasien sirosis hepatis dengan hipertensi portal .... 44
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DAFTAR TABEL
Tabel
Halaman
V.1 Jenis kelamin pasien sirosis hati dengan hipertensi portal ............................. 45
V.2 Usia pasien sirosis hati dengan hipertensi portal ............................................ 45
V.3 Status pasien sirosis hati dengan hipertensi portal ......................................... 46
V.4 Etiologi sirosis hati dengan hipertensi portal .................................................. 46
V.5 Pola penggunaan terapi pada pasien sirosis hepatis dengan hipertensi
portal ...................................................................................................................... 47
V.6 Pola penggunaan terapi tunggal propranolol pada pasien sirosis hepatis dengan
hipertensi portal ...................................................................................................... 47
V.7 Pola penggunaan kombinasi dua propranolol pada pasien sirosis hepatis dengan
hipertensi portal ...................................................................................................... 48
V.8 Pola penggunaan kombinasi tiga propranolol pada pasien sirosis hepatis dengan
hipertensi portal ...................................................................................................... 49
V.9 Pola penggunaan terapi propranolol dengan pergantian (switch) pada pasien
sirosis hati dengan hipertensi portal ....................................................................... 50
V.10 Diagnosis selain hipertensi portal ................................................................. 52
V.11 Profil terapi selain propranolol pada pasien sirosis hati dengan hipertensi
portal ...................................................................................................................... 53
V.12 Lama penggunaan terapi propranolol pada pasien sirosis hati dengan
hipertensi portal ..................................................................................................... 54
V.13 Lama rawat inap pasien sirosis hati dengan hipertensi portal ....................... 54
V.14 Kondisi KRS pasien sirosis hati dengan hipertensi portal ............................ 55
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DAFTAR LAMPIRAN
Lampiran
Halaman
1 Daftar Riwayat Hidup ..................................................................................... 77
2 Surat Tugas Skripsi ......................................................................................... 78
3 Surat Pernyataan ............................................................................................. 79
4 Hasil Deteksi Plagiasi ..................................................................................... 80
5 Surat Ijin Penelitian ......................................................................................... 82
6 Surat Laik Etik ................................................................................................ 84
7 Lembar Pengumpulan Data ............................................................................. 85
8 Tabel Data Induk ........................................................................................... 150
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DAFTAR SINGKATAN
ALT : Alanine Aminotransferase
ALP : Alkaline Phosphate
AMP : Adenosina Monofosfat
ASI : Air Susu Ibu
AST : Aspartate Transaminase
AV : Antrioventrikel
BAB : Buang Air Besar
BPJS : Badan Penyelenggara Jaminan Sosial
BPJS NON PBI : Badan Penyelenggara Jaminan Sosial Non Penerima Bantuan
Iuran
CI : Cardiac Index
CHB : Chronic Hepatitic B
CHC : Chronic Hepatitic C
CHE : Cover Hepatic Encephalopathy
CYP : Cytochrome P450
DEPKES : Departemen Kesehatan
ECM : Extracelluler Matrix
GGT : Gamma-glutamil transpeptidase
GMP : Guanosin Monofosfat
HBV : Hepatitis B Virus
HE : Hepatic Encephalopathy
HH : Hemochromatosis
HSC : Hepatic Stellate Cells
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HVPG : Hepatic Venous Pressure Gradient
ISMN : Isosorbida-5-mononitrat
IV : Intravena
Kapolri : Kepolisian Negara Republik Indonesia
KRS : Keluar Rumah Sakit
LOLA : L-Ornithine L-Aspartate
LPS : Liopolisakarida
LSECs : Liver Sinusoidal Endothelial Cells
LVE : Ligasi Varises Endoskopik
MAP : Mean Arterial Pressure
MRS : Masuk Rumah Sakit
NO : Nitrit oksida
NSBB : Non Selektif Beta Bloker
NSAID : Nonsteroidal Anti-inflammatory Drugs
OHE : Overt Hepatic Encephalopathy
PO : Peroral
PNS : Pegawai Negeri Sipil
PTFE : Polytetrafluoroethylene
RAAS : Renin Angiotensin Aldosteron System
RI : Republik Indonesia
RMK : Rekam Medik Kesehatan
RSUD : Rumah Sakit Umum Daerah
SB : Sengstaken-Blakemore
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SBP : Spontaneus Bacterial Peritonitis
SEC : Sinusoidal Endothelial Cells
SEARO : South East Asia Regional Office
SVE : Sklerosis Varises Endoskopik
SVR : Systemic Vascular Resistence
TIPS : Transjugular Intrahepatik Portosistemik Shunt
Terlipressin : Triglycyl Lysine Vasopressin
TGF-β : Transforming Growth Factor β
TNI : Tentara Nasional Indonesia
TNF-α : Tumor Necrosis Factors
WHO : World Health Organization
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