i

SKRIPSI

ROBIANA PRIHANDINI

STUDI PENGGUNAAN ISOSORBID DINITRAT

(ISDN) PADA PASIEN INFARK MIOKARD

AKUT DI RSUD SIDOARJO

PROGRAM STUDI FARMASI

FAKULTAS ILMU KESEHATAN

UNIVERSITAS MUHAMMADIYAH MALANG

2015

ii

Lembar Pengesahan

STUDI PENGGUNAAN ISOSORBID DINITRAT

(ISDN) PADA PASIEN INFARK MIOKARD AKUT DI

RSUD SIDOARJO

SKRIPSI

Dibuat untuk memenuhi syarat mencapai gelar Sarjana Farmasi pada

Program Studi Farmasi Fakultas Ilmu Kesehatan Universitas

Muhammadiyah Malang

2015

Oleh :

ROBIANA PRIHANDINI

201110410311137

Disetujui Oleh :

Pembimbing I Pembimbing II

Drs. Didik Hasmono, M.S., Apt Hidajah Rachmawati, S.Si., Apt., Sp.FRS

NIP. 1195809111986011001 NIP UMM. 11406090449

iii

Lembar Pengujian

STUDI PENGGUNAAN ISOSORBID DINITRAT

(ISDN) PADA PASIEN INFARK MIOKARD AKUT DI

RSUD SIDOARJO

SKRIPSI

Telah diuji dan dipertahankan di depan tim penguji

Pada tanggal 19 Agustus 2015

Oleh :

ROBIANA PRIHANDINI

201110410311137

Tim Penguji

Penguji I Penguji II

Drs. Didik Hasmono, M.S., Apt Hidajah Rachmawati, S.Si., Apt., Sp.FRS

NIP. 1195809111986011001 NIP UMM. 11406090449

Penguji III Penguji IV

Dra. Lilik Yusetyani, Apt., Sp. FRS Ika Ratna Hidayati, S.Farm., Apt., M.Sc

NIP UMM. 11407040450 NIP UMM. 11209070480

iv

KATA PENGANTAR

Puji syukur penulis panjatkan kehadirat Alloh SWT karena berkat rahmat

dan karunia-Nya, alhamdulillah penulis dapat menyelesaikan penyusunan skripsi

yang berjudul STUDI PENGGUNAAN ISOSORBID DINITRAT (ISDN)

PADA PASIEN INFARK MIOKARD AKUT DI RSUD SIDOARJO untuk

memenuhi satu persyaratan akademik dalam menyelesaikan Program Sarjana

Farmasi Fakultas Ilmu Kesehatan Universitas Muhammadiyah Malang.

Terselesaikannya skripsi ini tidak terlepas dari bantuan banyak pihak,

sehingga pada kesempatan ini dengan segala kerendahan hati dan penuh rasa

hormat bagi semua pihak yang telah memberikan bantuan moril maupun materiil

baik langsung maupun tidak langsung dalam penyusunan skripsi ini hingga

selesai, penulis meyampaikan terimakasih sebesar-besarnya kepada:

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

Kesehatan Universitas Muhammadiyah Malang.

2. Dr. Atok Irawan, Sp.P, selaku Direktur RSUD Sidoarjo yang telah

memberikan izin untuk melaksanakan penelitian di RSUD Sidoarjo.

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

Universitas Muhammadiyah Malang.

4. Drs. Didik Hasmono, M.S., Apt sebagai Pembimbing I dan Hidajah

Rachmawati, S.Si., Apt., Sp.FRS sebagai Pembimbing II yang bersedia

meluangkan waktu dengan tulus ikhlas dan penuh kesabaran memberikan

bimbingan, nasihat, dan arahan kepada saya.

5. Nailis Syifa’, S.Farm,. Apt,. M.Sc, Ika Ratna Hidayati, S.Farm., Apt., M.Sc

dan Dra.Lilik Yusetyani, Apt.,Sp.FRS sebagai Tim Penguji yang memberikan

kritik dan saran yang membangun terhadap skripsi yang saya kerjakan.

6. Program Studi Farmasi beserta seluruh staf pengajar Program Studi Farmasi

Universitas Muhammadiyah Malang

7. Heru prabowo, S.Farm., Apt sebagai Dosen Wali yang telah memberikan

bimbingan, arahan dan nasehat.

8. Sendi Lia Yunita, S.Farm., Apt., selaku Sekretaris Program Studi yang telah

melancarkan proses jalannya skripsi.

v

9. Teristimewa kepada orang tua saya tercinta ayah Adiwinarko dan bunda

Rochmiasih yang dengan penuh kasih sayang selalu mendoakan, memberikan

motivasi, semangat dan pengorbanannya baik segi moril maupun materiil.

Serta adik-adik kesayangan Aqmarina Shabrina, Annisa Yumna Nabiilah, dan

M. Roziq Hanan, terimakasih atas doa dan dukungan kalian untuk saya.

10. Teman-teman klinis geng darjo tersayang: Dila, Mahiru, Lili, Roura, mbak

Sulis. Terimaksih atas bantuan yang selalu kalian berikan kepada saya dalam

menyelesaikan skripsi ini, menemani dalam segala kesusahan, kebingungan,

maupun kebahagiaan yang kita lalui.

11. Teman seperjuangan Khilmi Abdul Rahman. Terimakasih selalu ada untuk

saya, mengantar, mengajak, mengingatkan, memberi dorongan, dukungan,

canda dan tawa. Semoga kita tetap dapat saling menjaga dalam doa.

12. Teman-teman Farmasi C 2011: Anggi, Adel, Luluk, Sri, Irvan, Ilham, Izu,

Hasby, Inna, Shinta, Yuli, Rizqi, Arin, Resti, Wanda, Della, Fina, Adis, Putri,

Reza, Afnan dan teman-teman lainnya.

13. Sahabat terbaik yang saya miliki: Galih Nur Rendra Wijaya, Ridwana

Syafaati Rohmah, Rizki Sulis Sanjaya, Shinta Rosdiana Anggraini, Fitri Eko

Setyafani, Septi Aning Tyas Dwi Arti. Terimakasih telah memberikan doa,

dukungan dan motivasi terus menerus.

14. Serta semua pihak yang tidak bisa saya sebutkan satu persatu, terimakasih

telah membantu, memberikan dukungan, semangat, dan doa kepada saya.

Akhir kata, semoga Alloh SWT membalas kebaikan dan ketulusan semua

pihak yang telah membantu. Semoga skripsi ini dapat memberikan manfaat dan

kebaikan bagi banyak pihak serta bernilai ibadah dihadapan Alloh SWT. Aamiin.

Malang, 19 Agustus 2015

Robiana Prihandini

vi

DAFTAR ISI Halaman

HALAMAN JUDUL ................................................................................................ i

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

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

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

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

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

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

DAFTAR GAMBAR ........................................................................................... xiv

DAFTAR TABEL .................................................................................................. xv

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

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

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

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

1.2 Rumusan Masalah ............................................................................................ 3

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

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

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

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

BAB 2 TINJAUAN PUSTAKA .............................................................................. 5

2.1 Definisi Infark Miokard Akut .......................................................................... 5

2.2 Epidemiologi Infark Miokard Akut ................................................................. 5

2.3 Etiologi Infark Miokard Akut .......................................................................... 6

2.3.1 Klasifikasi IMA Berdasarkan Jenis Penyebabnya ................................... 6

2.3.1.1 Infark Miokard Tipe 1 ...................................................................... 6

2.3.1.2 Infark Miokard Tipe 2 ...................................................................... 7

2.3.1.3 Infark Miokard Tipe 3 ...................................................................... 7

2.3.1.4 Infark Miokard Tipe 4 ...................................................................... 7

2.3.1.5 Infark Miokard Tipe 5 ...................................................................... 7

2.3.2 Faktor Risiko ............................................................................................ 7

2.4 Patogenesis Infark Miokard Akut .................................................................... 9

2.5 Patofisiologi Infark Miokard Akut ................................................................ 12

vii

2.6 Manifestasi Klinis .......................................................................................... 13

2.6.1 Nyeri Dada ............................................................................................. 14

2.6.2 Bradikardi dan Takikardi ....................................................................... 14

2.6.3 Perubahan Elektrokardiografi (EKG) .................................................... 15

2.6.4 Peningkatan Serum Biomarker Jantung ................................................. 15

2.7 Diagnosis Infark Miokard Akut ..................................................................... 16

2.7.1 Elektrokardiogram (EKG)...................................................................... 17

2.7.2 Tes Laboratorium ................................................................................... 17

2.7.3 Cardiac Imaging ..................................................................................... 17

2.7.4 Serum Biomarker ................................................................................... 18

2.7.4.1 Creatinin Kinase (CK) .................................................................... 19

2.7.4.2 Serum Troponin .............................................................................. 20

2.7.4.3 Myoglobin ...................................................................................... 21

2.7.4.4 Serum Glutamic Oxalo-acetic Transaminase (SGOT) ................... 21

2.7.4.5 Serum Lactate Dehydrogenase (SLDH) ......................................... 21

2.8 Komplikasi Infark Miokard Akut .................................................................. 21

2.9 Penatalaksanaan Infark Miokard Akut .......................................................... 23

2.9.1 Oksigen .................................................................................................. 24

2.9.2 Antiplatelet ............................................................................................. 24

2.9.2.1 Aspirin ............................................................................................ 25

2.9.2.2 Klopidogrel ..................................................................................... 25

2.9.3 Beta Bloker ............................................................................................ 26

2.9.4 ACE Inhibitor ......................................................................................... 27

2.9.5 Calcium Chanel Blocker (CCB) ............................................................ 27

2.9.6 Analgesik. .............................................................................................. 28

2.9.7 Nitrat. ..................................................................................................... 28

2.10 Penggunaan Isosorbid Dinitrat (ISDN) sebagai Terapi

Farmakologis IMA........................................................................................ 30

BAB 3 KERANGKA KONSEPTUAL .................................................................. 33

3.1 Uraian Kerangka Konseptual ......................................................................... 33

3.2 Bagan Alir Kerangka Konseptual .................................................................. 35

3.3 Kerangka Operasional Terapi pada Pasien IMA ........................................... 36

viii

BAB 4 METODE PENELITIAN........................................................................... 37

4.1 Rancangan Penelitian ..................................................................................... 37

4.2 Populasi dan Sampel ...................................................................................... 37

4.2.1 Populasi .................................................................................................. 37

4.2.2 Sampel. ................................................................................................... 37

4.2.3 Kriteria Data Inklusi............................................................................... 37

4.2.4 Kriteria Data Eksklusi. ........................................................................... 37

4.3 Bahan Penelitian ............................................................................................ 38

4.4 Instrumen Penelitian ...................................................................................... 38

4.5 Tempat dan Waktu Penelitian ........................................................................ 38

4.6 Definisi Operasional ...................................................................................... 38

4.7. Metode Pengumpulan Data ........................................................................... 39

4.8. Analisis Data ................................................................................................. 39

BAB 5 HASIL PENELITIAN ............................................................................... 41

5.1 Data Demografi ............................................................................................. 42

5.1.1 Jenis Kelamin ......................................................................................... 42

5.1.2 Usia Pasien ............................................................................................. 42

5.1.3 Status Pasien .......................................................................................... 43

5.2 Faktor Risiko ................................................................................................. 43

5.3 Penggunaan Obat pada Pasien Infark Miokard Akut .................................... 44

5.4 Penggunaan Vasodilator Nitrat pada Pasien Infark Miokard Akut ............... 46

5.5 Pola Penggunaan ISDN pada Pasien IMA ..................................................... 46

5.5.1 Pola Penggunaan ISDN .......................................................................... 46

5.5.2 Penggunaan ISDN Tunggal ................................................................... 47

5.5.3 Terapi ISDN Tunggal dengan Pergantian .............................................. 47

5.5.4 Terapi Kombinasi ISDN dengan Satu Antihipertensi ............................ 47

5.5.5 Terapi Kombinasi ISDN dengan Dua Antihipertensi ............................ 47

5.5.6 Terapi Kombinasi ISDN dengan Tiga Antihipertensi............................ 49

5.5.7 Terapi Kombinasi ISDN dengan Empat Antihipertensi ........................ 50

5.6 Lama Penggunaan Isosorbid Dinitrat ............................................................ 50

5.7 Lama Perawatan ............................................................................................. 50

5.8 Kondisi Keluar Rumah Sakit ......................................................................... 51

ix

BAB 6 PEMBAHASAN ........................................................................................ 52

BAB 7 KESIMPULAN DAN SARAN ................................................................. 64

7.1 Kesimpulan .................................................................................................... 64

7.2 Saran .............................................................................................................. 64

DAFTAR PUSTAKA ............................................................................................ 65

LAMPIRAN ........................................................................................................... 70

x

DAFTAR GAMBAR

Gambar Halaman

2.1 Jantung dan Gambaran Pembuluh Darah dengan Plak Aterosklorosis ......... 10

2.2 Perbedaan aliran darah normal dan yg mengalami aterosklerosis............... .. 11

2.3 Perubahan EKG pada IMA ............................................................................ 15

2.4 Kenaikan Biomarker Jantung setelah IMA .................................................... 16

2.5 Biomarker Jantung pada IMA ....................................................................... 20

2.6 Rumus Struktur Isosorbid Dinitrat ................................................................. 30

3.1 Kerangka Konseptual ..................................................................................... 35

3.2 Kerangka Operasional ................................................................................... 36

5.1 Skema Kriteria Inklusi dan Eksklusi Penelitian pada Pasien Infark

Miokard Akut................................................................................................ 41

5.2 Jenis Kelamin Pasien Infark Miokard Akut dengan Terapi ISDN ................ 42

5.3 Usia Pasien Infark Miokard Akut dengan Terapi ISDN ................................ 42

5.4 Status Pasien Infark Miokard Akut dengan Terapi ISDN ............................. 43

5.5 Diagram Distribusi Kondisi 38 Pasien Infark Miokard Akut saat KRS

di RSUD Sidoarjo ......................................................................................... 51

xi

DAFTAR TABEL

Tabel Halaman

II.1 Sediaan Isosorbid Dinitrat ............................................................................. 32

V.1 Faktor Risiko Infark Miokard Akut .............................................................. 43

V.2 Pola Penggunaan Terapi Infark Miokard Akut tanpa ISDN ......................... 44

V.3 Pola Penggunaan Terapi Penyerta pada 38 Pasien Infark Miokard Akut

di RSUD Sidoarjo ......................................................................................... 45

V.4 Tabel Penggunaan Vasodilator Nitrat ........................................................... 46

V.5 Pola Penggunaan ISDN pada Pasien IMA .................................................... 46

V.6 Pola Penggunaan ISDN Tunggal tanpa Pergantian ...................................... 47

V.7 Pola Penggunaan ISDN dengan Pergantian .................................................. 47

V.8 Pola Penggunaan Kombinasi ISDN dengan Satu Antihipertensi ................. 47

V.9 Pola Penggunaan Kombinasi ISDN dengan Dua Antihipertensi .................. 47

V.10 Pola Penggunaan Kombinasi ISDN dengan Tiga Antihipertensi ............... 49

V.11 Pola Penggunaan Kombinasi ISDN dengan Empat Antihipertensi ............ 50

V.10 Lama Perawatan Pasien Infark Miokard Akut dengan Terapi ISDN ......... 50

xii

DAFTAR LAMPIRAN

Lampiran Halaman

1 Daftar Riwayat Hidup ....................................................................................... 67

2 Surat Pernyataan Bebas Plagiasi ...................................................................... 68

3 Keteranga Kelayakan Etik ................................................................................ 69

4 Daftar Nilai Normal Data Laboratorium .......................................................... 71

5 Lembar Pengumpul Data .................................................................................. 72

xiii

DAFTAR SINGKATAN

ACC : American College of Cardiology

ACEI : Angiotensin Converting Enzyme Inhibitor

ACS : Acute Coronary Syndrome

ACTH : Adrenocorticotropic Hormone

ADH : Anti Diuretic Hormone

ADP : Adenosine Di Phosphate

AHA : American Heart Association

ALDH2 : Aldehide Dehydrogenase-2

ALDH3 : Aldehide Dehydrogenase-3

aPTT : Activated Partial Thromboplastine Time

ARB : Angiotensin Receptor Blocker

ATP : Adenosine Tri Phosphate

CABG : Coronary Artery Bypass Grafting

CCB : Calcium Channel Blocker

cGMP : Cyclase Guanylyl Mono Phosphate

CK : Creatine Kinase

CKMB : Creatine Kinase Myocard Band

COX 2 : Cyclo-Oxygenase 2

cTnC : Serum Troponin C

cTnI : Serum Troponin I

cTnT : Serum Troponin T

CVD : Cardiovascular Disease

EKG : Elektrokardiogram

ESC : European Society of Cardiology

GC : Guanylyl cyclase

HIT : Heparin Induced Thrombocytopenia

IL-1 : Interleukin 1

IMA : Infark Miokard Akut

LBBB : Left Bundle Branch Block

LD : Laktat Dehidrogenase

LMWH : Low Molecule Weight Heparin

LV : Left Ventricular

MLC : Myosin Light Chain

MLCK : Myosin Light Chain Kinase

NO : Nitrat Oksida

Non Q MI : Non Q Wave Myocardial Infarction

NSAID : Non Steroid Anti Inflammation Drug

NSTEMI : Non ST Elevation Myocardial Infarction

PCI : Percutaneous Coronary Intervention

PJK : Penyakit Jantung Koroner

Q MI : Q Wave Myocardial Infarction

RISKESDAS : Riset Kesehatan Dasar

rPa : Reteplase

RV : Right Ventricular

SA : Sino Atrial

xiv

SGOT : Serum Glutamic Oxalo-Acetic Transaminase

SLDH : Serum Laktat Dehidrogenase

STEMI : ST Elevation Myocardial Infarction

TNF : Tumour Necrosis Factor

TNK-tPa : Tenekplase

tPa : Alteplase

TPR : Total Peripheral Resistency

UA : Unstable Angina

UFH : UnFractionated Heparin

WHO : World Health Organization

xv

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