SKRIPSI

ALISHA AZIZAH

STUDI PENGGUNAAN AMLODIPINE PADA PASIEN

STROKE ISKEMIK

(Penelitian di Rumah Sakit Umum Daerah Sidoarjo)

PROGRAM STUDI FARMASI

FAKULTAS ILMU KESEHATAN

UNIVERSITAS MUHAMMADIYAH MALANG

2017

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KATA PENGANTAR

Bismillahirohmanirrohim

Assalamu’alaikum warohmatullahi wabarokatuh

Puji syukur atas segala nikmat Allah SWT karena berkat rahmat serta

ridhonya penulis dapat menyelesaikan penulisan skripsi yang berjudul “STUDI

PENGGUNAAN AMLODIPINE PADA PASIEN STROKE ISKEMIK

(Penelitian di Rumah Sakit Umum Daerah Sidoarjo)” sebagai persyaratan

dalam memperoleh gelar Sarjana Farmasi pada Program Studi Farmasi Fakultas

Ilmu Kesehatan Universitas Muhammadiyah Malang.

Penulis menyadari bahwa penulisan skripsi ini tidak mungkin akan

terwujud apabila tidak ada bantuan dan bimbingan yang ikhlas dari berbagai pihak

sehingga tidak lupa penulis menyampaikan rasa terima kasih yang tulus kepada:

1. Bapak Yoyok Bekti Prasetyo, S.Kep., M.Kep., Sp.Kom. selaku Dekan

Fakultas Ilmu Kesehatan yang telah memberikan kesempatan kepada

penulis untuk menempuh pendidikan di Fakultas Ilmu Kesehatan UMM.

2. Ibu Nailis Syifa’, S.Farm., Apt., M.Sc. selaku Ketua Program Studi Farmasi

Universitas Muhammadiyah Malang yang telah memberikan motivasi dan

kesempatan kepada penulis untuk belajar di Program Studi Farmasi UMM.

3. drg. Syaf Satriawarman, Sp. Pros selaku Direktur RSUD Sidoarjo beserta

jajarannya yang telah memberikan kesempatan pada penulis untuk

melakukan penelitian di Rumah Sakit tersebut.

4. Bapak Drs. Didik Hasmono, Apt., MS., selaku pembimbing I dan Ibu Nailis

Syifa’, S.Farm., Apt., M.Sc. selaku pembimbing II yang di sela kesibukan

telah bersedia meluangkan waktu untuk membimbing dan mengarahkan

demi kesempurnaan skripsi ini.

5. Ibu Hidajah Rachmawati, S.Si., Apt., Sp.FRS., dan Ibu Dra. Lilik

Yusetyani, Apt., Sp.FRS., selaku dosen penguji yang telah memberikan

banyak masukan demi kesempurnaan skripsi ini.

6. Bapak Ahmad Shobrun Jamil, S.Si., MP selaku dosen wali yang bersedia

menerima konsultasi dan memberikan dukungan moral kepada penulis.

7. Bapak Andri Tilaqza, S.Farm., M.Farm., Apt, selaku kepala biro skripsi dan

Alfian Hadi selaku staf biro skripsi yang dengan sabar membimbing,

memberikan informasi dan dukungan kepada penulis.

8. Bapak Ibu Dosen dan staf tata usaha Program Studi Farmasi yang telah

banyak berjasa sehingga penulis dapat menyelesaikan pendidikan sarjana.

9. Ibu Yani Aryanti Abdurrajak, SH. yang selalu menjadi motivasi terbesar

bagi penulis, yang selalu mencintai, memaafkan, mendukung dan

mendo’akan penulis. Terimakasih telah berusaha bertahan hingga saat ini.

10. Bapak Ahmad yang telah memberikan pelajaran aqidah dan akhlak terbaik

bagi penulis.

11. Adik-adik kecil tersayang Aviva Azizah, Arzaqi Ayarwati Fatwa Aziza dan

Aisya Nur Ahya Aziza yang selalu membahagiakan, mendukung dan

mendo’akan penulis.

12. Keluarga besar Abdurrajak Kassan yang telah menyayangi, mendukung dan

mendo’akan yang terbaik untuk penulis.

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13. Teman-teman seperjuangan skripsi: Imas, Lia, Reni, Reza, Raisa, ifa, tya,

ulifah, Naniek, Manggi, Nita, Rizka, Dede, Amel, Revi, Kurnia, Asma, Baiq

yang telah berbagi dalam segala hal serta memberi motivasi kepada penulis.

14. Isna Maulidyah Chalimy yang telah menjadi saudara terbaik selama hampir

empat tahun terakhir.

15. Jumadi yang telah mendukung, mendo’akan dan memberikan banyak

pelajaran yang tidak mungkin di dapatkan penulis dari orang lain.

16. Teman-teman seperjuangan dari Bulungan, Naniek, Niar, Amel, Eci, Revi,

Dita yang telah banyak memberikan bantuan dan dukungan bagi penulis.

17. Teman-teman seperjuangan Farmasi angkatan 2013 semuanya tanpa

terkecuali yang bersama-sama berjuang meraih gelar sarjana.

18. Semua pihak yang tidak dapat disebutkan satu persatu, terima kasih atas

bantuan dan dukungannya selama penulis menyelesaikan skripsi ini.

Penulis menyadari bahwa skripsi ini jauh dari sempurna, oleh karena itu

penulis mengharapkan kritik dan saran yang membangun. Semoga penulisan

skripsi ini dapat bermanfaat bagi penelitian berikutnya, aamiin.

Wassalamu’alaikum warohmatullahi wabarokatuh

Malang, 14 Juni 2017

Penyusun

(Alisha Azizah)

vi

RINGKASAN

Stroke merupakan penurunan onset syaraf fokal secara mendadak yang

berlangsung setidaknya 24 jam dan diduga berasal dari pembuluh darah. Stroke

bisa berupa iskemik (87%) dan hemoragik (17%). Stroke di perkirakan

menyebabkan 134.000 kematian tiap tahunnya dan merupakan penyebab utama

kematian ketiga di banyak negara, setelah penyakit jantung dan kanker.

Pasien stroke mengalami defisit neurologis, menyebabkan gangguan motorik,

psikologis atau perilaku, dimana gejala paling khas adalah hemiparesis, hilang

sensasi wajah, kesulitan bicara dan kehilangan penglihatan sesisi. Penyebab utama

stroke iskemik kebanyakan adalah aterosklerosis yang dapat pecah dan

menyebabkan paparan kolagen, agregasi platelet dan terbentuknya thrombus. Plak

tersebut dapat menyebabkan oklusi lokal bergerak dalam pembuluh darah dan

menyumbat pembuluh darah otak (emboli).

Terapi utama untuk pasien dengan stroke iskemik meliputi neuroprotektor,

antiplatelet, antikoagulan dan antitrombolitik. Terapi untuk menurunkan tekanan

darah di rekomendasikan setelah periode akut (pada 7 hari pertama). Penurunan

tekanan darah pada pasien stroke iskemik berpotensi menurunkan resiko

terjadinya edema otak, resiko hemoragik dan kerusakan vascular lebih lanjut.

CCB (Calcium Channels Blocker) atau antagonis kalsium bekerja dengan

mengikat kanal L-type dan dengan menghalangi masuknya Ca2+

ke dalam sel,

menyebabkan terjadinya relaksasi pada arteriol otot polos dan mengurangi

resistensi perifer dan menyebabkan penurunan tekanan darah. Amlodipine

merupakan CCB yang paling sering diresepkan karena memiliki waktu paruh

yang panjang, bioavaibilitas tinggi dan lama kerja obat yang panjang yang

memungkinkan untuk dosis pemberian sekali dalam sehari. Selain itu amlodipine

dapat meningkatkan produksi asam nitrat endotel, menghambat poliferasi sel otot

polos dan aktivitas antioksidan yang tidak dimiliki oleh obat-obat golongan CCB

lainnya. Amlodipine juga terbukti dapat mengurangi stroke fatal maupun non

fatal.

Tujuan dari penelitian ini adalah untuk mengetahui profil penggunaan

amlodipine yang diterima pasien stroke iskemik terkait dosis, rute interval

pemberian, frekuensi dan lama penggunaan terapi yang dikaitkan dengan data

klinik dan data laboratorium pasien di Rumah Sakit Umum Daerah Sidoarjo.

Penelitian ini bersifat observasional karena peneliti tidak memberikan

perlakuan kepada sampel. Rancangan penelitian dilakukan secara deskriptif

dimana penelitian ini dimaksudkan untuk mendeskripsikan profil penggunaan

amlodipine dengan metode retrospektif. Kriteria inklusi meliputi pasien rawat

inap dengan diagnosis stroke iskemik di Rumah Sakit Umum Daerah Sidoarjo

dengan data Rekam Medik Kesehatan (RMK) meliputi data terapi obat

amlodipine dan obat lain yang menyertai periode 1 Januari 2016 – 30 Juni 2016.

Hasil penelitian didapatkan 38 data RMK sebagai sampel penelitian dari

313 populasi. Angka kejadian stroke iskemik lebih besar pada laki-laki sebanyak

23 pasien (59%) dibandingkan dengan perempuan yaitu sebanyak 15 pasien

(41%). Untuk kelompok usia yang paling banyak terkena stroke iskemik adalah

kelompok usia 60-69 tahun dengan dengan jumlah pasien laki-laki sebanyak 8

(21%) pasien dan perempuan 7 pasien (19%) dengan total 15 pasien (40%).

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Penggunaan amlodipine tunggal sebanyak 24 pasien (45%) paling banyak

diberikan dengan dosis (1x5mg) PO yaitu 10 pasien (42%). Penggunaan

kombinasi amlodipine sebanyak 29 pasien (55%), dengan penggunaan amlodipine

kombinasi dua sebanyak 23 pasien (44%) dan kombinasi tiga sebanyak 6 pasien

(11%). Untuk penggunaan amlodipine kombinasi dua terbanyak yaitu kombinasi

amlodipine (1x10mg) PO dan valsartan (1x80mg) PO sebanyak 5 pasien (22%).

Penggunaan amlodipine dengan pergantian (switch) sebanyak 24 pasien dengan

penggunaan switch terbanyak pada Nicardipine (0,5µg/KgBB/menit) IV di ganti

dengan kombinasi amlodipine (1x5mg) PO dan Valsartan (1x80mg) PO sebanyak

2 pasien (12%). Penggunaan dosis, rute pemberian, interval pemberian, frekuensi

pemberian, serta lama pemberian amlodipine yang diberikan pada pasien stroke

iskemik di RSUD Sidoarjo sudah sesuai menurut beberapa literatur yang ada.

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DAFTAR ISI

LEMBAR PENGESAHAN .................................................................................. ii

LEMBAR PENGUJIAN ...................................................................................... iii

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

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

ABSTRACT ........................................................................................................ viii

ABSTRAK ............................................................................................................ ix

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

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

DAFTAR GAMBAR ............................................................................................ xv

DAFTAR LAMPIRAN ...................................................................................... xvi

DAFTAR SINGKATAN ................................................................................... xvii

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

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

1. 2 Perumusan Masalah .................................................................................. 3

1.3 Tujuan Penelitian ...................................................................................... 3

1.3.1 Tujuan Umum .................................................................................. 3

1.3.2 Tujuan Khusus ................................................................................. 3

1.4 Manfaat Penelitian .................................................................................... 5

1.4.1 Bagi Peneliti .................................................................................... 5

1.4.2 Bagi Rumah Sakit ............................................................................ 5

BAB II TINJAUAN PUSTAKA ............................................................................ 6

2.1 Definisi Stroke .......................................................................................... 6

2.2 Epidemiologi Stroke ................................................................................. 6

2.3 Etiologi Stroke .......................................................................................... 9

2.3.1 Etiologi Stroke Iskemik ................................................................... 9

2.3.2 Etiologi Stroke Hemoragik ............................................................ 10

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2.4 Patofisiologi Stroke ................................................................................. 11

2.4.1 Patofisiologi Stroke Iskemik ......................................................... 11

2.4.2 Patofisiologi Stroke Hemoragik .................................................... 13

2.5 Faktor Resiko .......................................................................................... 13

2.5.1 Faktor yang tidak dapat Dimodifikasi ........................................... 14

2.5.1.1 Usia .................................................................................... 14

2.5.1.2 Jenis Kelamin..................................................................... 14

2.5.1.3 Ras ..................................................................................... 14

2.5.1.4 Faktor Genetik ................................................................... 15

2.5.2 Faktor yang dapat Dimodifikasi .................................................... 15

2.5.2.1 Hipertensi .......................................................................... 15

2.5.2.2Merokok ............................................................................. 16

2.5.2.3 Diabetes ............................................................................. 16

2.5.2.4 Dislipidemia ....................................................................... 17

2.6 Gejala dan Tanda Stroke ......................................................................... 17

2.7 Penatalaksanaan Terapi Stroke ............................................................... 18

2.8. Terapi Khusus Stroke Iskemik ................................................................ 18

2.8.1 Trombolitik .................................................................................... 19

2.8.1.2 Altaplase ............................................................................ 19

2.8.1.2 Streptokinase...................................................................... 21

2.8.1.3 Tenecteplase ...................................................................... 21

2.8.2 Antiplatelet .................................................................................... 22

2.8.2.1 Aspirin ............................................................................... 22

2.8.2.2 Kombinasi Aspirin-Clopidogrel ........................................ 22

2.8.2.3 Citostazol ........................................................................... 23

2.8.2.4 Clopidogrel ........................................................................ 23

2.8.2.5 Dipyridamole ..................................................................... 23

2.8.3 Antikoagulan ................................................................................. 23

2.8.3.3 Dabigatran.......................................................................... 25

2.8.4 Neuroprotektan .............................................................................. 25

2.8.4.1 Citicoline ........................................................................... 25

2.8.4.2 Piracetam ........................................................................... 25

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2.8.5 Antidislipidemia ........................................................................... 26

2.8.5.1 Statin .................................................................................. 26

2.8.5.2 Niacin ................................................................................. 26

2.8.6 Antihipertensi ................................................................................ 26

2.8.6.1 Angiotensin-Converting Enzyme Inhibitors ...................... 28

2.8.6.2 Angiotensin receptor Blocker ............................................ 29

2.8.6.3 Diuretik .............................................................................. 29

2.8.6.4 Calcium Channel Blockers ................................................ 30

2.8.6.4.1 Non Dihydropiridin ............................................. 32

2.8.6.4.1.1 Verapamil ....................................... 33

2.8.6.4.1.2 Diltiazem ........................................ 33

2.8.6.4.2 Dihydropiridin ..................................................... 34

2.8.6.4.2.1 Amlodipine ..................................... 34

2.8.6.4.2.2 Nifedipine ....................................... 36

2.8.6.4.2.3 Nikardipin....................................... 37

2.8.6.4.2.4 Nimodipin....................................... 37

2.9. Amlodipine pada Stroke Iskemik............................................................ 38

BAB III KERANGKA PENELITIAN ............................................................... 41

3.1 Kerangka Konseptual .............................................................................. 41

3.2 Kerangka Operasional ............................................................................. 42

BAB IV METODE PENELITIAN ..................................................................... 43

4.1 Rancangan Penelitian .............................................................................. 43

4.2 Populasi dan Sampel ............................................................................... 43

4.2.1 Populasi ......................................................................................... 43

4.2.2 Sampel ........................................................................................... 43

4.2.3 Kriteria Data Inklusi ...................................................................... 43

4.2.4 Kriteria Data Eksklusi ................................................................... 43

4.3 Bahan Penelitian ..................................................................................... 44

4.4 Instrumen Penelitian ............................................................................... 44

4.5 Tempat dan Waktu Penelitian ................................................................. 44

4.6 Definisi Operasional ............................................................................... 44

4.7 Metode Pengumpulan Data ..................................................................... 45

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4.8 Analisa Data ............................................................................................ 45

BAB V HASIL PENELITIAN ............................................................................ 47

5.1 Karakteristik Subyek Penelitian .............................................................. 48

5.1.1 Jenis Kelamin ................................................................................ 48

5.1.2 Usia ................................................................................................ 48

5.1.3 Status Penjaminan Biaya Pengobatan Pasien ................................ 48

5.2 Faktor Resiko Pasien Terdiagnosis Stroke Iskemik................................ 48

5.3 Klasifikasi Stroke Iskemik ...................................................................... 49

5.4 Penyakit Penyerta Pasien Terdiagnosis Stroke Iskemik ......................... 49

5.5 Terapi Selain Amlodipine pada Pasien Stroke Iskemik .......................... 49

5.6 Terapi antihipertensi pada Pasien Stroke Iskemik .................................. 50

5.6.1 Profil Penggunaan Terapi Amlodipine .......................................... 50

5.6.2 Profil Penggunaan Terapi Amlodipine Tunggal............................ 50

5.6.3 Profil Penggunaan Terapi Amlodipine Kombinasi II .................... 51

5.6.4 Profil Penggunaan Terapi Amlodipine Kombinasi III .................. 51

5.6.5 Profil Penggunaan Terapi Amlodipine dengan Pergantian ............ 52

5.7 Lama Penggunaan Terapi Amlodipine ................................................... 54

5.8 Lama Masuk Rumah Sakit (MRS) .......................................................... 54

5.9 Kondisi KRS ........................................................................................... 55

BAB VI PEMBAHASAN ..................................................................................... 56

BAB VII KESIMPULAN DAN SARAN ............................................................ 71

7.1 Kesimpulan ............................................................................................. 71

7.2 Saran ....................................................................................................... 71

DAFTAR PUSTAKA ........................................................................................... 72

LAMPIRAN .......................................................................................................... 81

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DAFTAR TABEL

Tabel

II. 1 Tanda dan Gejala Stroke ............................................................................... 18

II. 2 Kriteria Inklusi dan Eksklusi Penggunaan Altaplase .................................... 20

II. 3 Perbandingan Profil Farmakokinetika Obat Golongan CCB ........................ 31

II. 4 Sediaan Amlodipine di Indonesia .................................................................. 35

V. 1 Persentase distribusi jenis kelamin pasien .................................................... 48

V. 2 Status penjaminan biaya pengobatan pasien ................................................. 48

V. 3 Status penjaminan biaya pengobatan pasien ................................................. 48

V. 4 Persentase distribusi faktor resiko pasien stroke iskemik ............................. 48

V. 5 Persentase distribusi klasifikasi stroke iskemik pada pasien ........................ 49

V. 6 Penyakit Penyerta Pasien Stroke Iskemik ..................................................... 49

V. 7 Terapi pada Pasien Stroke Iskemik ............................................................... 49

V. 8 Profil Penggunaan Terapi Amlodipine .......................................................... 50

V. 9 Profil Penggunaan Terapi Amlodipine Tunggal ........................................... 50

V. 10 Profil Penggunaan Terapi Amlodipine Kombinasi II ................................. 51

V. 11 Profil Penggunaan Terapi Amlodipine Kombinasi III ................................ 51

V. 12 Profil penggunaan terapi amlodipine dengan pergantian (Switch) .............. 52

V. 13 Lama Penggunaan Terapi Amlodipine pada Pasien Stroke Iskemik .......... 54

V. 14 Lama MRS pasien stroke iskemik ............................................................... 54

V. 15 Kondisi KRS pasien stroke iskemik ............................................................ 55

xv

DAFTAR GAMBAR

Gambar

2. 1 Klasifikasi Stroke ............................................................................................. 8

2. 2 Etiologi Stroke ................................................................................................ 9

2. 3 Etiologi Stroke Iskemik ................................................................................... 9

2. 4 Etiologi Stroke Hemoragik ............................................................................ 10

2. 5 Tatalaksana Terapi Antihipertensi pada Pasien Stroke Akut ......................... 28

2. 6 Struktur Kimia Verapamil .............................................................................. 32

2. 7 Struktur Kimia Diltiazem .............................................................................. 33

2. 8 Struktur Kimia Amlodipine ........................................................................... 34

2. 9 Struktur Kimia Nifedipine.............................................................................. 36

2. 10 Struktur Kimia Nikardipine ......................................................................... 37

xvi

DAFTAR LAMPIRAN

Lampiran

1 Daftar Riwayat Hidup ......................................................................................... 81

2 Surat Pernyataan.................................................................................................. 82

3 Keterangan Kelaikan Etik (Ethical Clearance) .................................................. 83

4 Surat Jawaban Ijin Penelitian .............................................................................. 84

5 Nota Dinas ........................................................................................................... 85

6 Daftar Nilai Normal Data Klinik dan Data Laboratorium .................................. 86

7 Lembar Pengumpulan Data Pasien ..................................................................... 88

8 Tabel Data Induk ................................................................................................. 94

xvii

DAFTAR SINGKATAN

ACCES = Acute Candesartan Cilexetil Therapy in Stroke

ACEi = Angiotensin-converting Enzyme Inhibitor

AHA = American Heart Association

ALLHAT = Antihipertensive and Lipid Lowering Treatment to

Prevent Heart Attack Trial

ARB = Angiotensin Receptor Blocker

ASA = American Stroke Association

ASCOT-BPLA = Anglo-Scandinavian Cardiac Outcomes Trial Blood

Pressure-Lowering Arm of the Anglo

ATP = Adenosina trifosfat

CAMELOT = Comparison of Amlodipine versus Enalapril to

Limit Occurences of Thrombosis

CASE-J = Candesartan Antihypertensive Survival Evaluation in

Japan

CCB = Calcium Channel Blockers

CVA = Cerebrovascular Accident

DBP = Diastole Blood Pressure

FDA = Food and Drug Association

GDS = Gula Darah Sesaat

HDL = High Density Lipid

ICH = Intracerebral Hemorrhage

IDNT = Irbesartan Diabetic Nephropathy Trial

IMA = Infark Miokard Akut

LDL = Low Density Lipid

LMWH = Low Molecule Weight Heparin

PERDOSSI = Persatuan Dokter Saraf Seluruh Indonesia

PRoFESS = Prevention Regimen for Effectively Avoiding Second

Strokes

RISKESDAS = Riset Kesehatan Dasar

xviii

SBP = Sytole Blood Pressure

SSP = Sistem Saraf Pusat

TDD = Tekanan Darah Diastolik

TDS = Tekanan Darah Sistolik

TIA = Transient Ischemic Attack

VALUE = Valsartan Antihypertensive Long-term Use Evaluation

72

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