STUDI PENGGUNAAN CAPTOPRIL PADA PASIEN STROKE ISKEMIK (Penelitian di Rumah Sakit Umum Daerah Sidoarjo)

SKRIPSI
BARLANTY FATHANAHIYAH

STUDI PENGGUNAAN CAPTOPRIL PADA
PASIEN STROKE ISKEMIK
(Penelitian di Rumah Sakit Umum Daerah Sidoarjo)

PROGRAM STUDI FARMASI
FAKULTAS ILMU KESEHATAN
UNIVERSITAS MUHAMMADIYAH MALANG
2015

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KATA PENGANTAR

Bismillahirrohmanirrohim
Assalamu’alaikum warohmatullahi wabarokatuh
Puji syukur tercurahkan kepada ALLAh SWT, tuhan semesta alam karena

berkat rahmad dan ridhonya, penulis dapat menyelesaikan skripsi yang berjudul
STUDI PENGGUNAAN CAPTOPRIL PADA PASIEN STROKE ISKEMIK
(Penelitian di Rumah Sakit Umum Daerah Sidoarjo).
Skripsi ini diajukan untuk memenuhi syarat untuk mencapai gelar Sarjana
Farmasi pada Program Studi Farmasi Fakultas Ilmu Kesehatan Universitas
Muhammadiyah Malang. Dalam penyusunan skripsi ini penulis tidak terlepas dari
peranan pembimbing dan bantuan dari seluruh pihak. Oleh karena itu, dengan
segala kerendahan hati, penulis ingin mengucapkan banyak terima kasih kepada:
1.

ALLAH SWT, tuhan semesta alam yang memberikan rahmat, nikmat dan
hidayahNYA kepada umatnya, Rosulullah SAW, yang sudah menuntun
kita menuju jalan yang lurus.

2.

Bapak Yoyok Bekti Prasetyo, M.Kep., Sp. Kom selaku Dekan Fakultas
Ilmu

Kesehatan Universitas Muhammadiyah

Malang

yang telah

memberikan kesempatan penulis belajar di Fakultas Ilmu Kesehatan
Universitas Muhammadiyah Malang.
3.

Ibu Nailis Syifa, S.Farm., MSc., Apt selaku Ketua Program Studi Farmasi
Universitas Muhammadiyah Malang yang telah memberi motivasi dan
kesempatan penulis belajar di Program Studi Farmasi Universitas
Muhammadiyah Malang.

4.

dr. Atok Irawan, Sp. P selaku Direktur Rumah Sakit Umum Daerah
Sidoarjo beserta jajarannya yang telah memberikan kesempatan pada
penulis untuk melakukan penelitian di Rumah Sakit Umum Daerah
Sidoarjo.

iv

5.

Staf pengawai RMK RSUD Sidoarjo yang banyak membantu dalam proses
pengambilan data skripsi.

6.

Ibu

Nailis

Syifa’,S.Farm.,M.Sc.,Apt.,

dan

Bapak

Drs.

Didik

Hasmono,M.S.,Apt., selaku Dosen Pembimbing I dan II, disela kesibukan
Bapak dan Ibu masih bisa meluangkan waktu untuk membimbing dan
memberi pengarahan dan dorongan moril sampai terselesaikannya skripsi
ini.
7.

Ibu Dra. Lilik Yusetyani, Apt., Sp.FRS., dan Ibu Hidajah Rachmawati,
S.Si., Apt., Sp.FRS selaku Dosen Penguji I dan II, yang telah banyak
memberikan saran dan masukan demi kesempurnaan skripsi ini.

8.

Ibu Sovia Aprina Basuki, S.Farm., Apt., M. Si. selaku Dosen wali. Terima
kasih banyak atas arahan, nasehat, dan bimbingannya selama ini.

9.

Untuk semua Dosen Farmasi Universitas Muhamadiyah Malang yang
sudah memberikan waktunya untuk mengajarkan ilmu-ilmu yang sangat
berguna, khususnya kepada Ibu Sendi Lia Yunita, S.Farm., Apt., selaku
Dosen penanggung jawab skripsi yang telah susah payah membantu
jalanya ujian skripsi sehingga kami dapat melaksanakan ujian skripsi
dengan baik.

10. Untuk semua angggota tata usaha Program Studi Farmasi Fakultas Ilmu
kesehatan Universitas Muhammadiyah Malang, yang telah banyak
membantu untuk kebutuhan administrasi kelengkapan skripsi.
11. Orang Tuaku tercinta, Bapak Tri Akbari Hadi dan Ibu Sarulin, yang tiada
hentinya memotivasi dalam segala hal, dengan sabar mendoakan untuk
kebaikan dan kesuksesan anak-anaknya. Terima kasih banyak atas didikan
dan kerja keras untuk membuat anak-anaknya bahagia serta mendapatkan
ilmu yang bemanfaat.
12. Saudariku Hazra Farahiyah Ramadhani dan Albirr Rifqi Raziz, terima
kasih buat motivasi dan doanya sehingga skripsi ini dapat selesai tepat
waktu.
13. Sahabat seperjuanganku Dwi Qurrothul Aini, Zeni Putri A.D.T, Nifda

Novi A, Siti Maslahah S, dan Bernika Ika I terima kasih atas kebersamaan,

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bantuan, motivasi, semangat kalian selama ini sebagai sahabat yang
membantu dan mendukung saat senang maupun susah.
14. Teman-teman seperjuangan kelompok skripsi Dwi, Zeni, Ayu, Fina dan
Alif dengan keceriaan dan semangat kalian selama ini sebagai sahabat
yang membantu dan mendukung sehingga skripsi ini dapat terwujud.
15. Teman-teman Farmasi UMM 2011, khususnya Farmasi D terima kasih
atas kebersamaan dan kenangan indah selama ini, terima kasih atas
pelajaran hidup yang diberikan.
16. Keluarga besar kontrakan MSC AS SYFA terima kasih banyak atas
kebersamaannya, dukungan, semangat, doa, dan motivasinya serta ilmu
agama yang telah diajarkan kepada saya hingga Insyaallah bermanfaat
nantinya.
17. Untuk semua pihak yang belum disebutkan namanya, penulis mohon maaf
dan terima kasih yang sebesar-besarnya. Semua keberhasilan ini tak luput
dari bantuan, doa yang telah kalian semua berikan.
Jasa dari semua pihak yang telah membantu dalam penelitian ini, penulis

tidak mampu membalas dengan apapun. Semoga amal baik semua pihak
mendapat imbalan dari Allah SWT. Penulis menyadari bahwa skripsi ini jauh dari
kesempurnaan, oleh karena itu penulis mengharapkan saran

dan kritik yang

membangun dari pembaca demi kebaikan skripsi ini. Semoga penulisan ini dapat
berguna bagi penelitian berikutnya, amiin.
Wassalamu’alaikum warohmatullohi wabarokatuh

Malang, 26 Juni 2015
Penyusun

(Barlanty Fathanahiyah)

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DAFTAR ISI
Halaman
HALAMAN JUDUL........................................................................................

i

DAFTAR ISI .................................................................................................... ii
DAFTAR TABEL ............................................................................................ iv
DAFTAR GAMBAR ....................................................................................... v
BAB I PENDAHULUAN ............................................................................. 1
1.1 Latar Belakang ............................................................................ 1
1.2 Rumusan Masalah ........................................................................ 4
1.3 Tujuan .......................................................................................... 4
1.4 Manfaat ........................................................................................ 4
BAB II TINJAUAN PUSTAKA .................................................................... 5
2.1 Tinjauan Tentang Stroke .............................................................. 5
2.1.1 Definisi ............................................................................ 5
2.1.2 Epidemiologi ................................................................... 5
2.1.3 Etiologi ............................................................................ 6
2.1.3.1 Aterosklerosis ............................................................. 6
2.1.3.2 Emboli ........................................................................ 7
2.1.3.3 Trombosis................................................................... 7
2.1.3.4 AIDS .......................................................................... 8

2.1.3.5 Infeksi ......................................................................... 8
2.1.3.6 Angiitis granulomatosa .............................................. 8
2.1.3.7 Obat-obatan ................................................................ 9
2.1.3.8 Vena atau sinus trombosis.......................................... 9
2.1.3.9 Infark lakunar ............................................................. 10
2.1.4 Klasifikasi ....................................................................... 10
2.1.5 Faktor Resiko .................................................................. 13
2.1.5.1 Usia ............................................................................ 13
2.1.5.2 Jenis kelamin .............................................................. 13
2.1.5.3 Faktor Genetik ............................................................ 14
2.1.5.4 Ras .............................................................................. 14
2.1.5.5 Hipertensi ................................................................... 15
2.1.5.6 Diabetes ...................................................................... 15
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2.1.5.7 Merokok ..................................................................... 16
2.1.5.8 Dislipidemia ............................................................... 16
2.1.5.9 Konsumsi Alkohol ..................................................... 17
2.1.6 Patofisiologi .................................................................... 18
2.1.7 Komplikasi ...................................................................... 20

2.1.7.1 Pneumonia, Septicemia .............................................. 21
2.1.7.2 Infark miokard, aritmia, dan gagal jantung ................ 21
2.1.7.3 DVT ........................................................................... 21
2.1.7.4 Ketidakseimbangan Cairan ........................................ 21
2.1.8 Tanda dan Gejala............................................................. 21
2.1.9 Penatalaksanaan Terapi ................................................... 22
2.1.10 Terapi Stroke Iskemik ..................................................... 24
2.1.10.1 rTPA ......................................................................... 25
2.1.10.2 Antiplatelet ............................................................... 26
2.1.10.3 Antikoagulan ............................................................ 28
2.1.10.4 Neuroprotektan ......................................................... 28
2.1.10.5 Antihipertensi ........................................................... 29
2.1.11 Rehabilitasi Setelah Stroke ............................................. 34
2.2 Tinjauan Captopril ....................................................................... 35
2.2.1 Struktur Kimia ................................................................... 35
2.2.2 Mekanisme Kerja ............................................................... 36
2.2.3 Dosis .................................................................................. 37
2.2.4 Farmakokinetik .................................................................. 37
2.2.5 Efek Samping ..................................................................... 37
2.2.6 Penggunaan Captopril pada Ischemic CVA ...................... 37

2.2.7 Sediaan ............................................................................... 38
BAB III KERANGKA KONSEP .................................................................... 39
BAB IV METODE PENELITIAN .................................................................. 42
4.1 Rancangan Penelitian ................................................................... 42
4.2 Populasi dan Sampel .................................................................... 42
4.2.1 Populasi .............................................................................. 42
4.2.2 Sampel ............................................................................... 42

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4.2.3 Kriteria Data Inklusi ......................................................... 42
4.2.4 Kriteria Data Eksklusi ........................................................ 42
4.3 Bahan penelitian .......................................................................... 43
4.4 Intrumen Penelitian ...................................................................... 43
4.5 Tempat dan Waktu penelitian ...................................................... 43
4.6 Definisi Operasional ................................................................... 43
4.7 Metode Pengumpulan Data .......................................................... 44
4.8 Analisis Data ................................................................................ 44
BAB V HASIL PENELITIAN ...................................................................... 45
5.1 Data Demografi Pasien ................................................................ 46
5.1.1 Jenis Kelamin .......................................................................... 46
5.1.2 Usia Pasien .............................................................................. 46
5.1.3 Status Pasien ........................................................................... 46
5.2 Faktor Resiko ................................................................................ 47
5.3 Profil Tekanan Darah .................................................................... 47
5.4 Diagnosis Penyerta Pasien Stroke Iskemik ................................... 48
5.5 Pola terapi pada pasien stroke iskemik ......................................... 49
5.6 Pola terapi pendukung pada pasien stroke iskemik ..................... 50
5.7 Pola terapi captopril pada pasien stroke iskemik ......................... 51
5.8 Pola Terapi Captopril Tunggal Tanpa Switch ............................... 51
5.9 Pola Switch Captopril.................................................................... 52
5.10 Kombinasi Obat Captopril dengan Antihipertensi lain ............... 52
5.11 Dosis & Frekuensi Penggunaan Captopril pada Stroke Iskemik 53
5.12 Lama Masuk Rumah Sakit (MRS).............................................. 54
5.13 Kondisi Keluar Rumah Sakit (KRS) ........................................... 55
BAB VI PEMBAHASAN................................................................................ 56
BAB VII KESIMPULAN DAN SARAN ....................................................... 69
7.1 Kesimpulan ................................................................................... 69
7.2 Saran ............................................................................................. 69
DAFTAR PUSTAKA ...................................................................................... 70
LAMPIRAN…. ................................................................................................ 77

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DAFTAR TABEL
Halaman

2.1 Gejala dan tanda-tanda iskemia pada sirkulasi anterior dan posterior ...... 22
2.2 Rekomendasi farmakoterapi stroke iskemik ............................................. 24
2.3 Kriteria inklusi dan eksklusi rtPA pada stroke iskemik ............................ 26
2.4 Sediaan di Indonesia ................................................................................. 37
V.1 Jenis Kelamin Pasien Stroke Iskemik ...................................................... 46
V.2 Usia Pasien Stroke Iskemik ...................................................................... 46
V.3 Status Pasien Stroke Iskemik ................................................................... 47
V.4 Faktor Resiko Stroke Iskemik .................................................................. 47
V.5 Distribusi Tekanan Darah......................................................................... 48
V.6 Diagnosis Penyerta Stroke Iskemik.......................................................... 49
V.7 Terapi Stroke Iskemik .............................................................................. 49
V.8 Terapi Pendukung pada pasien stroke iskemik ........................................ 50
V.9 Pola Penggunaan Captopril pada pasien stroke iskemik .......................... 51
V.10 Pola Captopril Tanpa Switch .................................................................. 52
V.11 Pola Switch Captopril ............................................................................. 52
V.12 Distribusi jumlah, Dosis dan Frekuensi terapi kombinasi captopril ...... 53
V.13 Distribusi Penggunaan Dosis dan Frekuensi Captopril .......................... 54

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DAFTAR GAMBAR
Halaman
2.1

Penyebab stroke...................................................................................... 8

2.2

Stroke iskemik........................................................................................ 10

2.3

Stroke hemoragik ................................................................................... 11

2.4

Klasifikasi stroke.................................................................................... 12

2.5

Patofisiologi stroke................................................................................. 19

2.6

Managemen stroke dan TIA ................................................................... 23

2.7

Struktur kimia captopril ......................................................................... 36

2.8

Mekanisme kerja captopril ..................................................................... 36

3.1

Skema Kerangka Konseptual ................................................................. 40

3.2

Skema Kerangka Operasional ................................................................ 41

5.1

Skema Inklusi Pasien Stroke Iskemik .................................................... 45

5.2

Distribusi Lama MRS Pasien stroke iskemik ............................................ 54

5.3

Distribusi Status KRS Pasien stroke iskemik ........................................ 55

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DAFTAR LAMPIRAN

Lampiran

Halaman

1. Daftar Riwayat Hidup .............................................................................. 77
2. Surat Pernyataan....................................................................................... 78
3. Surat Ijin Rumah Sakit ............................................................................. 79
4. Surat Ijin Bakesbangpol Provinsi ............................................................. 81
5. Surat Ijin Bakesbangpol Kabupaten ......................................................... 82
6. Harga Normal Data Labolatorik dan Klinik............................................. 84

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DAFTAR SINGKATAN

ACCESS

: Acute Candesartan Cilexetil Therapy in Stroke Survivors

ACEI

: Angiotensin-Converting Enzyme Inhibitors

ACTIVE I

: The Atrial Fibrillation Clopidogrel Trial with Irbesartan for
Prevention of Vascular Events

ADP

: Adenosine Diphosphate

ADVANCE

: Action in Diabetes and Vascular Disease: Preterax and Diamicron
MR Controlled Evaluation

AHA

:American Heart Association

AIDS

: Acquired Immune Deficiency Syndrom

AIS

: Acute Ischemic Stroke

ALLHAT

: The Antihypertensive and Lipid-Lowering Treatment

APTT

: Activated Partial Thromboplastin Time

ARB

: Angiotensin Receptor Blocker

ARIC

: Atherosclerosis Risk In Communities

ASA

: American Stroke Association

ASI

: Air Susu Ibu

AT1

: Angiotensin I

BP

: Blood Pressure

BPJS PBI

: Badan Penyelenggara Jaminan Sosial Penerima Bantuan Iuran

BPJS Non PBI : Badan Penyelenggara Jaminan Sosial Non Penerima Bantuan Iuran
CAPP

: Captopril Prevention Project

CAST

: Chinese Acute Stroke Trial

CBF

: Cerebral Blood Flow

CCB

: Calcium Channel Blockers

CDC

: Centers for Disease Control and Prevention

CSF

: Cairan Serebrospinal

CT-Scan

: Computerized Tomography Scan

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CVA

: Cerebrovascular Accident

DVT

: Deep Vein Thrombosis

ECASS

: European Cooperative Acute Stroke Study

GCS

: Glasgow Coma Scale

GIT

: Gastro Intestinal Tract

HDL

: High Density Lipid

HMGCoA

: 3-hydroxy-3-methylglutaryl-CoA

IGD

: Instalasi Gawat Darurat

ICH

: Intracranial Hemmorrage

INR

: International Normalized Ratio

IST

: International Stroke Trial

JNC-7

: The Seventh Report of the Joint National Committee

KRS

: Keluar Rumah Sakit

LDL

: Low Density Lipid

LMWH

: Low-Molecular-Weight Heparin

MCA

: Middle Cerebral Artery

mmHg

: millimeter merkuri Hydragyrum

MOSES

: Morbidity and Mortality After Stroke-Eprosartan vs. Nitrendipine
for Secondary Prevention

MRI

: Magnetic Resonance Imaging

MRS

: Masuk Rumah Sakit

NCEP

: National Cholesterol Education Program

NIH

: National Institute of Health

NIHSS

: National Institute of Stroke Scale

NINDS

: National Institute of Neurological Disorders and Stroke

ONTARGET

: Ongoing Telmisartan Alone and in Combination with Ramipril
Global Endpoint Trial

PCD

: Programmed Cell Death

PJK

: Penyakit Jantung Koroner

PNS

: Pegawai Negeri Sipil

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PROGRESS

: Perindopril Protection against Recurrent Stroke Study

RAAS

: Renin Angiotensin Aldosteron System

REGARDS

: Reasons for Geographic And Racial Differences in Stroke

RE-LY

: Randomized Evaluation of Long-Term Anticoagulant therapy

RISKESDAS

: Riset Kesehatan Dasar

RMK

: Rekam Medik Kesehatan

RSUD

: Rumah Sakit Umum Daerah

r-TPA

: Recombinant Tissue Plasminogen Activator

SAH

: Subarachnoid Hemorrage

SALSA

: Sacramento Area Latino Study on Aging

SHRsp

: Stroke-Prone Hypertensive Rats

SHS

: Study Strong Heart

SPARCL

: Stroke Prevention by Aggressive Reduction in Cholesterol

SSP

: Sistem Saraf Pusat

Syst-Eur

: The Systolic Hypertension in Europe

TD

: Tekanan Darah

TIA

: Transcient ischemic attack

TNI

: Tentara Nasional Indonesia

TOAST

: Trial of Organon 10172 in Acute Stroke Treatment

UK

: United Kingdom

UFG

: Universidade Federal de Goiás

UU SJSN

: Undang-UNdang Sistem Jaminan Sosial Nasional

VALUE

: Valsartan Antihypertensive Long-term Use Evaluation

WHO

: World Health Organization

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BAB I
PENDAHULUAN
1.1

Latar Belakang
Stroke adalah penyakit atau gangguan fungsional otak berupa kelumpuhan

saraf akibat terhambatnya aliran darah ke otak. Secara sederhana stroke
didefinisikan sebagai penyakit otak akibat terhentinya suplai darah ke otak karena
sumbatan (stroke iskemik) atau pendarahan (stroke hemoragik) (Junaidi, 2011).
Penghentian aliran darah