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.

v

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)

vii

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

xiii

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

69

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