annisa puspita dewi studi penggunaan golongan...
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SKRIPSI
ANNISA PUSPITA DEWI
STUDI PENGGUNAAN GOLONGAN
ANGIOTENSIN CONVERTING ENZYME
INHIBITOR (ACEI) PADA PASIEN CHRONIC
KIDNEY DISEASE (CKD) (Penelitian di Rumah Sakit Umum Daerah Sidoarjo)
PROGRAM STUDI FARMASI
FAKULTAS ILMU KESEHATAN
UNIVERSITAS MUHAMMADIYAH MALANG
2017
ii
Lembar Pengesahan
iii
Lembar Pengujian
iv
KATA PENGANTAR
Bismillahirohmanirrahim
Assalamualaikum warohmatullahi wabarokatuh.
Puji syukur penulis haturkan kepada Allah SWT atas limpahan berkah dan
karunia-Nya, sehingga penyusunan skripsi yang berjudul “STUDI
PENGGUNAAN GOLONGAN ANGIOTENSIN CONVERTING ENZYME
INHIBITOR (ACEI) PADA PASIEN CHRONIC KIDNEY DISEASE (CKD)
(Penelitian di Rumah Sakit Umum Daerah Sidoarjo)” ini dapat terselesaikan.
Shalawat berangkai salam tak lupa tercurahkan kepada Nabi besar junjungan kita
Muhammad SAW hingga akhir zaman.
Skripsi ini diajukan untuk memenuhi persyaratan untuk mencapai gelar
Sarjana Farmasi pada Program Studi Farmasi Fakultas Ilmu Kesehatan
Universitas Muhammadiyah Malang. Dalam pembuatan skripsi ini tidak terlepas
dari bantuan, bimbingan serta dukungan dari berbagai pihak. Oleh karena itu
dalam kesempatan yang baik ini izinkan penulis ingin menyampaikan rasa
terimakasih yang setulus-tulusnya kepada:
1. Bapak Yoyok Bekti P., M.Kep., Sp.Kom selaku Dekan Fakultas Ilmu Kesehatan
Universitas Muhammadiyah Malang yang telah memberikan kesempatan penulis
untuk menuntut ilmu di Fakultas Ilmu Kesehatan Universitas Muhammadiyah
Malang.
2. Bapak Drs. Didik Hasmono, M.S., Apt sebagai Dosen Pembimbing I yang telah
mencurahkan perhatian, arahan serta bimbingan yang sangat berarti bagi penulis.
3. Ibu Nailis Syifa’, S.Farm, M.Sc., Apt selaku Dosen Pembimbing II yang
senantiasa meluangkan waktu serta kesabaran agar skripsi ini cepat selesai.
4. Direktur Rumah Sakit Umum Daerah Sidoarjo Bapak dr. Atok Irawan, Sp.P yang
telah mengizinkan penulis untuk melakukan penelitian di RSUD Sidoarjo.
5. Ibu Drs.Lilik Yusetyani Apt., Sp.FRS dan Bapak Andri Tilaqza, S.Farm.,
M.Farm., Apt selaku Dosen Penguji I dan II yang telah banyak memberikan
masukan serta saran bagi kesempurnaan skripsi ini.
6. Kedua orang tua saya yang selama masa perkuliahan senantiasa mendukung,
mendengarkan, dan memberi kepercayaan. Semoga penulis berkesempatan untuk
membalasnya. Amiin.
v
7. Keluarga saya teruntuk Adik saya tersayang Ririn yang selalu menantikan saya
pulang ke rumah setiap waktu liburan tiba. Prima sepupu yang telah banyak
mengantarkan dan membantu menghafalkan jalan Malang untuk pertama kalinya.
8. Seluruh staf pengajar Prodi Farmasi di Universitas Muhammadiyah Malang, yang
memberikan begitu banyak ilmu dan pengalaman yang berharga hingga penulis
menjadi seorang sarjana.
9. Seluruh laboran dan staf tata usaha Program Studi Universitas Muhammadiyah
Malang yang selama ini telah banyak membantu selama penulis di masa
perkuliahan.
10. Teman-teman Farmasi A atas kebersamaan 4 tahun ini melewati suka duka
bersama, spesial untuk teman/kakak nongkrong penulis Chika, Dina, Lina, Ica,
Pute dan Tia.
11. Teman sempro dan semhas penulis (rahma, yasintha, puthar, dina dan wiryan)
banyak cerita selama penelitian terukir di kereta yang takkan terlupa.
12. Untuk semua pihak yang tidak dapat penulis sebutkan satu-persatu, penulis
memohon maaf dan terimakasih sebesar-besarnya.
Penulis menyadari kekurangan akan selalu menjadi bagian manusia,
kesempurnaan hanya menjadi milik-Nya, untuk itu saran dan kritik akan lebih
menyempurnakan pikiran penulis untuk melangkah lebih lanjut. Semoga skripsi
ini dapat bermanfaat bagi penelitian selanjutnya. Aminn.
Wassalamu’alikum warohmatullahi wabarokatuh.
Malang,
Penulis
(Annisa Puspita Dewi)
x
DAFTAR ISI
Halaman
Halaman Judul .................................................................................................... i
Lembar Pengesahan ........................................................................................... ii
Lembar Pengujian ............................................................................................ iii
KATA PENGANTAR ....................................................................................... iv
RINGKASAN ......................................................... Error! Bookmark not defined.
ABSTRAK .............................................................. Error! Bookmark not defined.
ABSTRACT ........................................................... Error! Bookmark not defined.
DAFTAR ISI ...................................................................................................... x
DAFTAR TABEL ........................................................................................... xiv
DAFTAR GAMBAR ....................................................................................... xvi
DAFTAR LAMPIRAN .................................................................................. xvii
DAFTAR SINGKATAN ............................................................................... xviii
BAB I PENDAHULUAN ....................................... Error! Bookmark not defined.
1.1 Latar Belakang ............................. Error! Bookmark not defined.
1.2 Rumusan Masalah ........................ Error! Bookmark not defined.
1.3 Tujuan Penelitian .......................... Error! Bookmark not defined.
1.3.1 Tujuan Umum ........................ Error! Bookmark not defined.
1.3.2 Tujuan Khusus ....................... Error! Bookmark not defined.
1.4 Manfaat Penelitian ........................ Error! Bookmark not defined.
BAB II TINJAUAN PUSTAKA ............................ Error! Bookmark not defined.
2.1 Anatomi Ginjal ............................. Error! Bookmark not defined.
2.2 Fungsi Ginjal ............................... Error! Bookmark not defined.
2.2.1 Pembentukan Urine ................ Error! Bookmark not defined.
2.2.2 Keseimbangan Elektrolit ........ Error! Bookmark not defined.
xi
2.2.3 Keseimbangan pH .................. Error! Bookmark not defined.
2.2.4 Organ 7Ekskresi ..................... Error! Bookmark not defined.
2.2.5 Fungsi Non-Ekskresi .............. Error! Bookmark not defined.
2.2.6 Pengaturan Tekanan Darah..... Error! Bookmark not defined.
2.3 Tinjauan tentang Chronic Kidney Disease (CKD) ................ Error!
Bookmark not defined.
2.3.1 Definisi CKD ......................... Error! Bookmark not defined.
2.3.2 Epidemiologi CKD .............. ..Error! Bookmark not defined.
2.3.3 Klasifikasi CKD .................... .Error! Bookmark not defined.
2.3.4 Etiologi CKD ........................ .Error! Bookmark not defined.
2.3.5 Patofisiologi CKD ................. .Error! Bookmark not defined.
2.3.6 Faktor Risiko CKD ............................................................. .17
2.3.7 Manifestasi Klinik CKD ...................................................... .18
2.3.8 Pemeriksaan dan Diagnosa CKD……………………………………………..20
2.3.9 Komplikasi CKD……………………………………………………………………...21
2.3.9.1 CKD-MBD………………………………………………………….……………...21
2.3.9.2 Asidosis Metabolik…………………………………………………………….21
2.3.9.3 Anemia………………………………………………………….…………………...22
2.3.9.4 Disilipidemia…………………………………………………….………………..23
2.3.9.5 Hipertensi…………………………………………………….……………………..23
2.4 Penatalaksanaan Terapi CKD ............. Error! Bookmark not defined.
2.4.1 Terapi Asidosis Metabolik ..... Error! Bookmark not defined.
2.4.2 Terapi Hiperkalemia............... Error! Bookmark not defined.
2.4.3 Terapi Anemia ....................... Error! Bookmark not defined.
2.4.4 Terapi Hiperfosfatemia dan Dislipidemia .... Error! Bookmark
not defined.
2.4.5 Terapi Pengganti Ginjal ......... Error! Bookmark not defined.
xii
2.4.6 Antihipertensi pada Chronic Kidney Disease (CKD) ..... Error!
Bookmark not defined.
2.4.6.1 Calcium Channel Blocker Error! Bookmark not defined.
2.4.6.2 Diuretik…………………………………………………29
2.4.6.3 Angiotensin Receptor Blocker…………………………29
2.4.6.4 Angiotensin Converting Enzyme Inhibitor…………….30
2.5 Tinjauan Obat Golongan ACE-I ........... Error! Bookmark not defined.
2.5.1 Kaptopril ............................... Error! Bookmark not defined.
2.5.1.1 Sediaan Obat di Pasaran .... Error! Bookmark not defined.
2.5.2 Ramipil .................................. Error! Bookmark not defined.
2.5.2.1 Sediaan Obat di Pasaran ... Error! Bookmark not defined.
2.5.3 Enalapril ............................... Error! Bookmark not defined.
2.5.3.1 Sediaan Obat di Pasaran .... Error! Bookmark not defined.
2.5.4 Lisinopril .............................. Error! Bookmark not defined.
2.5.4.1 Sediaan Obat di Pasaran .... Error! Bookmark not defined.
BAB III KERANGKA KONSEPTUAL ................ Error! Bookmark not defined.
3.1 Kerangka Konseptual ............... Error! Bookmark not defined.
3.2 Kerangka Operasional.............. Error! Bookmark not defined.
BAB IV METODOLOGI PENELITIAN .............. Error! Bookmark not defined.
4.1 Rancangan Penelitian ................ Error! Bookmark not defined.
4.2 Bahan Penelitian ....................... Error! Bookmark not defined.
4.3 Populasi dan Sampel Penelitian Error! Bookmark not defined.
4.3.1 Populasi Penelitian ............... Error! Bookmark not defined.
4.3.2 Sampel Penelitian ................. Error! Bookmark not defined.
4.4 Kriteria Inklusi dan Eksklusi ...... Error! Bookmark not defined.
4.4.1 Kriteria Inklusi .................... Error! Bookmark not defined.
4.4.2 Kriteria Eksklusi ................. Error! Bookmark not defined.
4.5 Instrumen Penelitian ................ Error! Bookmark not defined.
4.6 Tempat dan Waktu penelitian .. Error! Bookmark not defined.
xiii
4.7 Definisi Operasional Penelitian Error! Bookmark not defined.
4.8 Prosedur Pengumpulan Data .... Error! Bookmark not defined.
4.9 Analisis Data ........................... Error! Bookmark not defined.
BAB V HASIL PENELITIAN ............................... Error! Bookmark not defined.
5.1 Data Demografi Pasien Chronic Kidney Disease (CKD) .. Error!
Bookmark not defined.
5.1.1 Berdasarkan Jenis Kelamin .... Error! Bookmark not defined.
5.1.2 Berdasarkan Usia ................... Error! Bookmark not defined.
5.1.3 Berdasarkan Status ................. Error! Bookmark not defined.
5.2 Faktor Risiko ............................. Error! Bookmark not defined.
5.3 Klasifikasi CKD ........................ Error! Bookmark not defined.
5.4 Profil Tekanan Darah ................. Error! Bookmark not defined.
5.5 Distribusi Diagnosis Penyerta .... Error! Bookmark not defined.
5.6 Distribusi Terapi Penyerta Pada Pasien CKD .. Error! Bookmark
not defined.
5.7 Pola Penggunaan Terapi ACEI . Error! Bookmark not defined.
5.7.1 Terapi Kombinasi Dua Antihipertensi dengan ACEI ..... Error!
Bookmark not defined.
5.7.2 Terapi Kombinasi Tiga Antihipertensi dengan ACEI .... Error!
Bookmark not defined.
5.7.3 Terapi Kombinasi Empat Antihipertensi dengan ACEI .. Error!
Bookmark not defined.
5.7.4 Terapi Kombinasi Enam Antihipertensi dengan ACEI ... Error!
Bookmark not defined.
5.8 Distribusi Pergantian ACEI ...... Error! Bookmark not defined.
5.9 Lama Penggunaan Terapi ACEI Error! Bookmark not defined.
5.10 Lama Masuk Rumah Sakit (MRS) .......... Error! Bookmark not
defined.
5.11 Kondisi Saat Keluar Rumah Sakit (KRS) Error! Bookmark not
defined.
BAB VI PEMBAHASAN ....................................... Error! Bookmark not defined.
xiv
BAB VII KESIMPULAN DAN SARAN ............... Error! Bookmark not defined.
7.1 Kesimpulan .................................. Error! Bookmark not defined.
7.2 Saran ............................................ Error! Bookmark not defined.
DAFTAR PUSTAKA ......................................................................................... x
Lampiran................................................................ Error! Bookmark not defined.
DAFTAR TABEL
Tabel Halaman
Tabel II.1 Tipe Komposisi Ion Dalam Plasma ...................................................... 9
Tabel II.2 Klasifikasi CKD Menurut Etiologi ..................................................... 14
Tabel II.3 Klasifikasi CKD Menurut Derajat ...................................................... 14
Tabel II.4 Klasifikasi Proteinuria Dari Berbagai Metode .................................... 19
Tabel II.5 Petunjuk CKD ................................................................................... 20
Tabel II.6 Klasifikasi Tekanan Darah ................................................................. 23
Tabel II.7 Target Manajemen Anemia ................................................................ 25
Tabel II.8 Profil Obat Golongan ARB ................................................................ 30
Tabel II.9 Profil Obat Golongan ACEI ............................................................... 30
Tabel II.10 Tabel Sediaan Kaptopril di Indonesia ............................................... 34
Tabel II.11 Tabel Sediaan Ramipil di Indonesia ................................................. 35
Tabel II.12 Tabel Sediaan Enalapril di Indonesia ............................................... 36
Tabel II.13 Tabel Penyesuaian Dosis Lsinopril Berdasar GFR ........................... 38
Tabel II.14 Tabel Sediaan Lisinopril di indonesia............................................... 38
Tabel V.1 Demografi Berdasarkan Jenis Kelamin .............................................. 46
xv
Tabel V.2 Demografi Berdasarkan Usia ............................................................. 46
Tabel V.3 Demografi Berdasarkan Status ........................................................... 46
Tabel V.4 Distribusi Faktor Risiko CKD ............................................................ 47
Tabel V.5 Distribusi Klasifikasi Pasien CKD ..................................................... 47
Tabel V.6 Distribusi Tekanan Darah Pasien CKD .............................................. 48
Tabel V.7 Distribusi Diagnosis Penyerta ............................................................ 48
Tabel V.8 Distribusi Terapi Penyerta ................................................................. 49
Tabel V.9 Pola Penggunaan ACEI ..................................................................... 50
Tabel V.10 Kombinasi Dua Antihipertensi ......................................................... 50
Tabel V.11 Kombinasi Tiga Antihipertensi ........................................................ 51
Tabel V.12 Kombinasi Empat Antihipertensi ..................................................... 52
Tabel V.13 Kombinasi Enam Antihipertensi ...................................................... 52
Tabel V.14 Distribusi Pergantian ACEI ............................................................. 52
Tabel V.15 Lama Penggunaan Terapi ACEI....................................................... 53
Tabel V.16 Lama Masuk Rumah Sakit ............................................................... 53
Tabel V.17 Kondisi Saat Keluar Rumah Sakit .................................................... 53
xvi
DAFTAR GAMBAR
Gambar Halaman
Gambar 2.1 Anatomi Ginjal ................................................................................. 5
Gambar 2.2 Struktur Nefron ................................................................................. 6
Gambar 2.3 Patofisiologi CKD .......................................................................... 17
Gambar 2.4 Jalur RAAS .................................................................................... 31
Gambar 2.5 Rumus Bangun Kaptopril ................................................................ 33
Gambar 2.6 Rumus Bangun Ramipil .................................................................. 34
Gambar 2.7 Rumus Bangun Enalapril ................................................................ 36
Gambar 2.8 Rumus Bangun Lisinopril ............................................................... 37
Gambar 3.1 Skema Konseptual .......................................................................... 40
Gambar 3.2 Skema Operasional ......................................................................... 41
Gambar 5.1 Skema Inklusi dan Ekskusi ............................................................. 45
xvii
DAFTAR LAMPIRAN
Lampiran Halaman
Lampiran 1. Daftar Riwayat Hidup .................................................................... 77
Lampiran 2. Surat Pernyataan ............................................................................ 78
Lampiran 3. Daftar Nilai Normal Data Klinik dan Laboratorium ........................ 79
Lampiran 4. Nota Dinas ..................................................................................... 80
Lampiran 5. Surat Ijin Penelitian ........................................................................ 81
Lampiran 6. Kode Etik ....................................................................................... 82
Lampiran 7. Tabel Pengumpulan Data ............................................................... 83
Lampiran 8. Tabel Data Induk............................................................................ 95
xviii
DAFTAR SINGKATAN
ACEI : Angiotensin Converting Enzyme Inhibitor
ADH : Anti Diuretik Hormon
AIHW : Australian Institute of Health and Welfare
ARB : Angiotensin Receptor Blocker
BGA : Blood Gas Analysis
CAPD : Continous Ambulatory Peritoneal Dialysis
CCB : Calsium Channel Blocker
CKD : Chronic Kidney Disease
CKD-MBD : Chronic Kidney Disease Mineral Bone Disorder
CRR : Continous Renal Replacement
CVA : Cerebral Vascular Accident
e-GFR : Estimated-Glomerular Filtration Rate
EPO : Erythropoetin
xix
ESA : Erythropoeitin Stimulating Agent
ESRD : End Stage Renal Disease
FGF : Fibroblast Growth Factor
GFR : Glomerular Filtration Rate
GGT : Gagal Ginjal Terminal
Hb : Hemoglobin
HCO3 : Bikarbonat
HDL : High Density Lipoprotein
IRR : Indonesian Renal Registry
JNC :Joint National Committee
KDOQI : Kidney Disease Outcome Quality Initiative
LDL : Low Density Lipoprotein
LFG : Laju Filtrasi Glomerolus
mEq : Miliequivalent
mmHg : Mili Meter Raksa
NaCl : Natrium Klorida
NH3 : Amonia
NKF : National Kidney Foundation
PKD :Polycystic Kidney Disease
PTH : Hormon Paratiroid
RAAS : Renin Angiotensin Aldosteron System
RMK : Rekam Medik Kesehatan
xx
SN :Syndrom Nefrotik
TGF β : Transforming Growth Factor β
VLDL : Very Low Density Lipoprotein
69
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