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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