SKRIPSI

ANIS KHOIRUN SAUMA

STUDI PENGGUNAAN ANTIHIPERTENSI

GOLONGAN ANGIOTENSIN RESEPTOR

BLOKER PADA PASIEN CHRONIC KIDNEY

DISEASE (CKD) ( Penelitian dilakukan di RSUD Dr. Iskak Tulungagung)

PROGRAM STUDI FARMASI

FAKULTAS ILMU KESEHATAN

UNIVERSITAS MUHAMMADIYAH MALANG

2018

ii

Lembar pengesahan

iii

Lembar Penguji

iv

KATA PENGANTAR

Puji syukur tercurahkan kepada Allah SWT, Tuhan semesta alam karena

berkat rahmat serta ridloNya, penulis dapat menyelesaikan skripsi yang berjudul

“Studi Penggunaan Antihipertensi Angiotensin Reseptor Bloker Pada Pasien

Chronic Kidney Disease (CKD) (Penelitian dilakukan di RSUD Dr. Iskak

Tulungagung)”.

Skripsi ini diajukan untuk memenuhi syarat mencapai gelar Sarjana Farmasi

pada program Studi Farmasi Universitas Muhammadiyah Malang. Dalam

penyusunan skripsi ini penulis tidak lepas dari peran penting pembimbing dan

bantuan dari seluruh pihak. Oleh karena itu, dengan segala kerendahan hati, penulis

ingin mengucapkan terima kasih kepada :

1. Allah SWT, Tuhan semesta alam yanng memberikan rahmat, nikmat dan

hidayahNya kepada umatnya, Rosulullah SAW, yang sudah menuntun kita

menuju jalan yang lurus.

2. Bapak Faqih Ruhyanudin, M.Kep., Sp.Kep.KMB. selaku Dekan Fakultas

Ilmu Kesehatan Universitas Muhammadiyah Malang yang telah memberikan

kesempatan kepada penulis belajar di Fakultas Ilmu Kesehatan Universitas

Muhammadiyah Malang.

3. Direktur RSUD Dr. Iskak Tulungagung beserta jajarannya yang telah

memberikan kesempatan pada penulis untuk melakukan penelitian di RSUD

Dr, Iskak Tulungagung.

4. Bapak Drs. Didik Hasmono, Apt., Ms. selaku dosen pembimbing I, Ibu

Hidajah Rachmawati, S.Si., Apt., Sp.FRS. selaku dosen pembimbing II dan

ibu Binti Muzayyanah, M. Farm., Apt selaku pembimbing III di lapangan

yang telah memberi pengarahan dan motivasi sampai terselesaikan skripsi ini.

5. Ibu Dra. Lilik Yusetyani, Apt., Sp.FRS. selaku dosen penguji I dan ibu Dra.

Uswatun Chasanah., M.Kes., Apt. selaku penguji II yang telah memberikan

banyak saran dan masukan demi kesempurnaan skripsi ini.

6. Staf pegawai Rekam Medik Kesehatan RSUD Dr. Iskak Tulungagung yang

telah banyak membantu dalam proses pengambilan data skripsi.

v

7. Kedua Orang tua saya Bapak Abu Kholik Cokrosoetomo, dan Ibu Fatimah

Bakeri Taha yang selalu memberikan do’a, semangat dan motivasi serta kerja

kerasnya demi keberhasilan dan kesuksesan putrinya.

8. Rekan-rekan seperjuangan skripsi Kukuh, Mahmudah, Khorik, Anissa, Vivi

dan Wiwid atas kerja sama, motivasi dan bantuannya kepada saya.

9. Keluargaku yang tercinta “HIMFA PARACELSUS UMM”.

10. Teman- teman hedon saya Velia, dan April, yang selalu membantu saya

mengurus berkas selam 4 tahun kuliah bahkan sampai berkas wisuda.

11. Teman-teman farmasi 2014 “OCTOPHAR”, terima kasih atas 4 tahun yang

kita lewati bersama di dalam menuntut ilmu dalam suka dan cita.

12. Untuk semua pihak yang belum disebutkan namanya, penulis mohon maaf

dan terima kasih yang sebesar-besarnya. Semua keberhasilan dalam

penyelesaian skripsi ini tidak luput dari bantuan dan doa kalian semua.

Semoga amalan kalian mendapat imbalan Allah SWT. Penulis juga menyadari

bahwa skripsi ini jauh dari kesempurnaan, oleh karena itu penulis mengharapkan

kritik dan saran yang membangun dari pembaca demi kebaikan skripsi ini, semoga

hasil penulisan ini dapat memberikan manfaat bagi pembaca dan penelitian

selanjutnya, aamiinn.

Malang, 21 Juli 2018

Penyusun

(Anis Khoirun Sauma)

vi

RINGKASAN

STUDI PENGGUNAAN ANTIHIPERTENSI GOLONGAN ANGIOTENSIN

RESEPTOR BLOKER PADA PASIEN CHRONIC KIDNEY DISEASE

(CKD) (Penelitian Dilakukan di RSUD Dr. Iskak Tulungagung)

Chronic kidney disease (CKD) adalah kerusakan struktur atau fungsi ginjal selama ≥3 bulan atau penurunan GFR <60 ml/min/1,73 m2 . Dari laporan kasus pengobatan ESRD di Amerika Serikat, dari 188.014 orang 44 % disebabkan oleh diabetes, 29 % disebabkan oleh hipertensi, 20% disebabkan hal lain, dan 7% tidak diketahui penyebabnya (CDC, 2017). Data dari Indonesian renal registry (IRR) tahun 2015 30.554 pasien CKD yang menjalani hemodialisa. Jumlah ini meningkat dibandingkan pada tahun 2013 tercatat 15.128 pasien CKD yang menjalani hemodialisa (Penferi, 2015). Kematian pada pasien yang menjalani hemodialisis selama tahun 2015 tercatat sebanyak 1.243 orang dengan lama hidup dengan HD (hemodialisis) 1-317 bulan. CKD merupakan cedera kronis pada ginjal yang mengakibatkan kehilangan nefron ireversibel mengakibatkan hipertrofi dan hiperfiltrasi. Hiperfiltrasi dan peningkatan tekanan pada glomerulus, peningkatan tekanan pada glomerulus dan hiperfiltrasi dapat meningkatkan tekanan darah (hipertensi). Hipertensi dan proteinuria merupakan faktor progresif yang dapat meningkatkan kerusakan pada ginjal serta dapat terjadi fibrosis dan sclerosis. Penatalaksanaan stadium awal CKD mencakup langkah untuk mengurangi resiko penyakit kardiovaskular, sehingga direkomendasikan pemberian terapi antihipertensi ARB juga menurunkan perkembangan albuminuria. ARB berkerja dengan memblokir (AT2) dari (AT1) yang ada pada semua jaringan. ARB menyebabkan vasodilatasi dan mengurangi retensi perifer.

Tujuan dari penelitian ini untuk mengetahui pola penggunaan Angiotensin Reseptor Bloker (ARB) pada pasien Chronic Kidney Disease (CKD) di Instalasi Rawat Inap Inap RSUD Dr. Iskak Tulungagung.

Penelitian ini menggunakan rancangan penelitian retrospektif dengan kriteria inklusi adalah pasien CKD di RS Dr. Iskak Tulungagung, dengan data Rekam Medik Kesehatan (RMK) lengkap dengan terapi ARB dan obat lain yang menyertai dalam periode 1 Juli 2017 – 31 September 2017.

Berdasarkan hasil penelitian, RMK yang memenuhi kriteria inklusi sebanyak 103 sampel. Data demografi sampel terkait jenis kelamin menunjukkan bahwa perempuan lebih banyak (57%) sedangkan laki laki (43%). Pada demografi usia menunjukkan bahwa sampel dengan diagnosa CKD yang terbanyak adalah sampel dengan rentang usia 50-61 tahun dengan jumlah (35%) dimana masing-masing pasien laki-laki (15%) dan perempuan (20%). Seluruh sampel pasien didiagnosa menderita CKD stadium 5 (100%). Pasien yang dirawat inap dengan diagnosa CKD kebanyakan pasien dengan status BPJS (87%). Pasien di instalasi Rawat Inap RSUD Dr. Iskak Tulungagung periode bulan 1 Juli 2017–31 Agustus 2017 mendapatkan terapi ARB tunggal 11 pola (7%). Pemberian terapi tunggal tertinggi pada penggunaan Valsartan (1x80mg) PO 9 pola (82%). Penggunaan terapi kombinasi tertinggi pada kombinasi II, 72 pola (48%). Pemberian terapi kombinasi II tertinggi pada penggunaan valsartan (1x80mg) PO, dengan furosemid (3x40mg) IV, 19 pola (24%). Penggunaan terbanyak pada kombinasi III ARB, CCB dan diuretic loop sejumlah 49 pola (84%), dan yang tertinggi pada kombinasi valsartan

vii

(1x80mg) PO, nifedifine (1x30mg) PO, dan furosemide (3x40mg) IV sejumlah 13 pola (23%). Penggunaan terbanyak pada kombinasi IV golongan ARB, CCB, duretik loop dan diuretic loop sejumlah 5 pola (40%). Penggunaan kombinasi V golongan ARB, CCB, alpha bloker, beta bloker, dan diuretic loop; ARB, CCB, CCB, alpha bloker, diuretik loop; ARB, CCB, diuretik loop, diuretik loop, diuretik loop dengan masing masing 1 pola (33%).

x

DAFTAR ISI

Lembar pengesahan .............................................................................................. ii Lembar Penguji .................................................................................................... iii

KATA PENGANTAR .......................................................................................... iv

RINGKASAN ....................................................................................................... vi

ABSTRAK .......................................................................................................... viii

ABSTRACT ....................................................... Error! Bookmark not defined.ix

DAFTAR ISI .......................................................................................................... x

DAFTAR TABEL .............................................................................................. xiv

DAFTAR GAMBAR .......................................................................................... xvi

DAFTAR LAMPIRAN ..................................................................................... xvii

DAFTAR SINGKATAN .................................................................................. xviii

BAB I PENDAHULUAN ...................................................................................... 1

1.1 Latar Belakang .......................................................................................................... 1

1.2 Rumusan Masalah ................................................. Error! Bookmark not defined.4

1.3 Tujuan ........................................................................................................................ 4

1.3.1 Tujuan Umum ......................................................................................................... 4

1.3.2 Tujuan Khusus ........................................................................................................ 4

1.4 Manfaat ...................................................................................................................... 4

1.4.1 Bagi Peneliti ............................................................................................................ 4

1.4.2 Bagi Rumah Sakit .................................................................................................. 4

BAB II TINJAUAN PUSTAKA ........................................................................... 5

2.1 Anatomi Ginjal.......................................................................................................... 5

2.2 Fisiologi Ginjal ......................................................................................................... 6

2.2.1 Pengekskresi produk limbah dan bahan asing .................................................... 9

2.2.2 Pengatur keseimbangan air dan elektrolit ........................................................... 9

2.2.3 Pengatur keseimbangan asam dan basa ............................................................. 10

2.2.4 Mengatur hormon ................................................................................................. 10

2.2.5 Mengatur osmolaritas cairan tubuh ................................................................... 10

2.2.6 Mengatur tekanan dan volume darah ................................................................ 10

2.2.7 Gluconeogenesis .................................................................................................. 11

2.3 Tinjauan Tentang CKD (Chronic Kidney Disease) ........................................... 11

xi

2.3.1 Definisi CKD (Chronic Kidney Disease) ......................................................... 11

2.3.2 Klasifikasi CKD (Chronic Kidney Disease) ..................................................... 11

2.3.3 Epidemiologi CKD .............................................................................................. 14

2.3.4 Etiologi CKD ........................................................................................................ 15

2.3.5 Patofisiologi CKD ................................................................................................ 16

2.3.6 Diagnosa CKD ..................................................................................................... 19

2.3.7 Meninfestasi Klinik CKD ................................................................................... 19

2.3.8 Komplikasi CKD .................................................................................................. 20

2.3.8.1 Hipernatremia pada CKD ................................................................................. 20

2.3.8.2 Hiperkalemia pada CKD .................................................................................. 20

2.3.8.3 Asidosis Metabolik pada CKD ........................................................................ 21

2.3.8.4 Anemia Pada CKD ............................................................................................ 21

2.3.8.5 Gangguan mineral dan tulang pada CKD ...................................................... 21

2.3.8.6 Hipertensi pada CKD ........................................................................................ 22

2.3.9 Tatalaksana Terapi CKD ..................................................................................... 22

2.3.9.1 Terapi Farmakologis pada CKD ...................................................................... 22

2.3.9.1.1 Asidosis Metabolik pada CKD...................................................................... 22

2.3.9.1.2 Anemia pada CKD .......................................................................................... 22

2.3.9.1.2.1 Asam Folat .................................................................................................. 23

2.3.9.1.2.2 Zat Besi ....................................................................................................... 23

2.3.9.1.2.3 VitaminB12 ................................................................................................ 24

2.3.9.1.2.4 Eritropoetin ................................................................................................. 24

2.3.9.1.3 Hiperkalemia pada CKD ................................................................................ 25

2.3.9.1.4 Gangguan Mineral dan Tulang pada CKD .................................................. 25

2.3.9.1.5 Edema pada CKD ........................................................................................... 26

2.3.9.1.6 Hipertensi pada CKD ..................................................................................... 27

2.3.9.1.6.1 Renin Inhibitor ........................................................................................... 28

2.3.9.1.6.2 Angiotensin converter enzym inhibitors (ACE-I) ................................. 29

2.3.9.1.6.3 Angiotensin Reseptor Blocker (ARB) .................................................... 30

2.3.9.1.6.3.1 Losartan .................................................................................................... 32

2.3.9.1.6.3.2 Valsartan ................................................................................................... 33

2.3.9.1.6.3.3 Kandesartan .............................................................................................. 35

xii

2.3.9.1.6.3.4 Irbesartan .................................................................................................. 36

2.3.9.1.6.3.5 Telmisartan............................................................................................... 37

2.3.9.1.6.3.6 Eposartan .................................................................................................. 38

2.3.9.1.6.3.7 Olmesartan ............................................................................................... 39

2.3.9.1.6.4 Calcium chanel blocker (CCB) ................................................................ 40

2.3.9.1.6.5 Diuretik ....................................................................................................... 41

2.3.8.1.6.5.1 Diuretik thiazide ...................................................................................... 41

2.3.8.1.6.5.2 Diuretik loop ............................................................................................ 42

2.3.8.1.6.5.3 Diuretik hemat kalium ............................................................................ 43

2.3.9.1.6.6 β-bloker ....................................................................................................... 43

2.3.9.1.6.7 Alfa bloker .................................................................................................. 44

2.3.9.1.6.8 Vasodilator .................................................................................................. 44

2.3.9.2 Terapi non-farmakologi pada CKD ................................................................ 45

2.3.9.2.1 Hemodialisis pada CKD ................................................................................ 45

2.3.9.2.2 Dialisis peritoneal pada CKD ........................................................................ 47

2.3.9.2.3 Transplantasi ginjal ......................................................................................... 47

BAB III KERANGKA KONSEPTUAL DAN OPRASIONAL ...................... 49

3.1 Kerangka konseptual .............................................................................................. 49

3.2 Kerangka oprasional ............................................................................................... 50

BAB IV METODE PENELITIAN .................................................................... 51

4.1 Rancangan Penelitian ............................................................................................. 51

4.2 Populasi dan Sampel .............................................................................................. 51

4.2.1 Populasi ................................................................................................................. 51

4.2.1 Sampel ................................................................................................................... 51

4.3 Bahan Penelitian ..................................................................................................... 51

4.4 Kriteria Data ............................................................................................................ 51

4.4.1 Kriteria Data Inklusi ............................................................................................ 51

4.4.2 Kriteria Data Eksklusi ......................................................................................... 52

4.5 Instrumen penelitian ............................................................................................... 52

4.6 Tempat dan Waktu Penelitian ............................................................................... 52

4.7 Definisi Operasional Parameter Penelitian ......................................................... 52

4.8 Metode Pengumpulan Data ................................................................................... 52

xiii

BAB V HASIL PENELITIAN ........................................................................... 54

5.1 Data Demografi Pasien .......................................................................................... 54

5.1.1 Data Jenis Kelamin dan Usia Pasien CKD ....................................................... 55

5.1.2 Klasifikasi CKD ................................................................................................... 55

5.1.3 Status Penjamin .................................................................................................... 56

5.2 Etiologi Pasien Terdiagnosa CKD ....................................................................... 56

5.3 Diagnosa penyerta .................................................................................................. 56

5.4 Data Hemodialisis .................................................................................................. 57

5.5 Pola Penggunaan Angiotensin receptor blockers pada Pasien CKD ............... 57

5.6 Pola Penggunaan Tunggal ARB pada pasien CKD ........................................... 58

5.7 Pola Penggunaan Kombinasi Dua yang diterima pasien CKD ......................... 58

5.9 Pola Penggunaan Kombinasi Empat yang diterima pasien CKD .................... 62

5.10 Pola Penggunaan Kombinasi Lima yang diterima pasien CKD ....................... 64

5.11 Pola Penggunaan ARB dengan pergantian (Switch) Pada Pasien CKD .......... 64

5.12 Lama penggunaan terapi ARB pada pasien CKD .............................................. 85

5.13 Profil tekanan darah pasien CKD ......................................................................... 85

5.14 Terapi lain yang diterima pasien CKD ................................................................ 88

5.15 Lama Masuk Rumah Sakit (MRS) ....................................................................... 88

5.16 Kondisi Keluar Rumah Sakit (KRS) .................................................................... 89

BAB VI PEMBAHASAN .................................................................................... 90

BAB VII KESIMPULAN DAN SARAN ......................................................... 112

7. 1 Kesimpulan ............................................................................................................ 112

7. 2 Saran ....................................................................................................................... 112

DAFTAR PUSTAKA ........................................................................................ 113

LAMPIRAN..…………………………………………………………………..118

xiv

DAFTAR TABEL

Tabel II.1 Klasifikasi CKD berdasarkan GFR ...................................................... 12

Tabel II.2 Klasifikasi keparahan CKD berdasar albuminuria ............................... 13

Tabel II.3 Klasifikasi CKD dilihat dari GFR dan albuminuria ............................. 14

Tabel II.4 Obat golongan angiotensin converter enzyme inhibitor....................... 29

Tabel II.5 Regimen dosis obat golongan ACEI .................................................... 30

Tabel II.6 Regimen dosis losartan ......................................................................... 33

Tabel II.7 dosis obat golongan ARB ..................................................................... 34

Tabel II.8 Regimen dosisi obat kandesartan ......................................................... 35

Tabel II.9 Regimen dosis Irbesartan ..................................................................... 36

Tabel II.10 Regimen dosis Telmisartan ................................................................ 37

Tabel II.11 Regimen dosis eposartan .................................................................... 39

Tabel II.12 Regimen dosis olmesartan .................................................................. 40

Tabel II.13 Mekanisme obat CCB ........................................................................ 40

Tabel II.14 Regimen dosis CCB ........................................................................... 41

Tabel II.15 regimen dosis obat thiazid .................................................................. 42

Tabel II.16 Regimen dosis obat diuretic loop ....................................................... 42

Tabel II.17 Regimen dosis diuretic hemat kalium ................................................ 43

Tabel II.18 regimen dosis beta bloker ................................................................... 44

Tabel II.19 Regimen dosis alfa bloker .................................................................. 44

Tabel II.20 Mekanisme obat vasodilator ............................................................... 45

Tabel V.1 Data Jenis Kelamin dan Usia Pasien CKD .......................................... 55

Tabel V.2 Klasifikasi Pasien CKD........................................................................ 55

Tabel V.3 Data Status Penjamin Pasien CKD ...................................................... 56

Tabel V.4 Etiologi Pasien CKD ............................................................................ 56

Tabel V.5 Diagnosa Penyerta Sampel CKD ......................................................... 57

Tabel V.6 Data hemodialisis pasien CKD ............................................................ 57

Tabel V.0.7 Pola penggunaan ARB tunggal dan kombinasi ................................. 58

Tabel V.8 Pola penggunaan Tunggal ARB ........................................................... 58

Tabel V.9 Pola penggunaan Kombinasi Dua Pada Pasien CKD .......................... 59

Tabel V.10 Pola penggunaan Kombinasi Tiga Pada Pasien CKD ........................ 60

Tabel V.11 Pola penggunaan Kombinasi Empat Pasien (CKD) ......................... 62

xv

Tabel V.12 Pola penggunaan Kombinasi Lima Pada Pasien (CKD) .................... 64

Tabel V.13 Pola penggunaan ARB pergantian (Switch) pada Pasien CKD ......... 65

Tabel V.14 Lama penggunaan terapi Angiotensin Receptors blockers (ARB) .... 85

Tabel V.15 Data profil tekanan darah pasien CKD .............................................. 85

Tabel V.16 Terapi selain ARB yang diterima Pasien CKD .................................. 88

Tabel V.17 Lama Pasien CKD MRS .................................................................... 88

Tabel V.18 Kondisi KRS Pasien CKD ................................................................. 89

xvi

DAFTAR GAMBAR

Gambar 2.1 Anatomi ginjal ..................................................................................... 5

Gambar 2.2 Nefron Ginjal....................................................................................... 7

Gambar 2.3 Glomerolus .......................................................................................... 8

Gambar 2.4 Patofisiologi CKD ............................................................................. 17

Gambar 2.5 Patofisiologi hipertensi pada CKD dan Intervensi ............................ 18

Gambar 2.6 Algoritma Hipertensi pada CKD ....................................................... 27

Gambar 2.7 Aksi dari Renin Inhibitor; Ace inhibitor; dan ARB .......................... 28

Gambar 2.8 Struktur kimia Losartan ..................................................................... 32

Gambar 2.9 struktur kimia valsartan ..................................................................... 33

Gambar 2.10 Struktur kimia Kandesartan ............................................................. 35

Gambar 2.11 struktur kimia Irbesartan ................................................................. 36

Gambar 2.12 struktur kimai Telmisartan .............................................................. 37

Gambar 2.13 struktur kimia eposartan .................................................................. 38

Gambar 2.14 struktur kimia Olmesartan ............................................................... 39

Gambar 2.15 Proses Hemodialisis ........................................................................ 46

Gambar 2.16 Dialisis peritoneal ............................................................................ 47

Gambar 3.1 Kerangka konseptual ......................................................................... 59

Gambar 3.2 Kerangka operasional ........................................................................ 50

Gambar 5.1 Skema Inklusi dan Eksklusi Penelitian pada Pasien CKD ................ 54

xvii

DAFTAR LAMPIRAN

Lampiran 1 Daftar Riwayat Hidup ...................................................................... 118

Lampiran 2 Surat Pernyataan .............................................................................. 119

Lampiran 3 Surat Tugas ...................................................................................... 120

Lampiran 4 Surat Ijin Penelitian ......................................................................... 121

Lampiran 5 Ethical Clerence ............................................................................... 122

Lampiran 6 Daftar Nilai Normal ......................................................................... 123

Lampiran 7 Tabel Lembar Pengumpul data ........................................................ 124

Lampiran 8 Tabel Induk ...................................................................................... 421

xviii

DAFTAR SINGKATAN

ACE Angiotensin Converting Enzym

ACR Albumin-to-creatinine ratio

AER Albumin excretion rate

ADH Antidiuretic Hormone

ARB Angiotensin Receptors Blocker

BP Blood Pressure

CDC Centers for Disease Control and Prevention

CKD Chronic Kidney Disease

CVD Cardiovascular Disease

ECFV Ekstra Celular Fluid Volume

EPO Eritropoetin

ESRD End Stage Renal Disease

GFR Glomerular Filtration Rate

GIT Gastrointestinal Tract

Hct Hematocrit

HD Hemodialisis

Hgb Hemoglobin

HIV Human immunodeficiency virus

IRR Indonesian Renal Registry

KDIGO Kidney Disease Improving Global Outcome

LDL Low Density Lipoprotein

MBD Mineral Bone Disorder

NSAID Non Steroid Anti Inflamtion Drug

PTH Paratiroid Hormon

RAAS Renin Angiotensin Aldosteron System

RSUD Rumah Sakit Umum Daerah

113

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