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  • SKRIPSI

    DIMAS FAJAR AZIZ

    STUDI POLA PENGGUNAAN DIAZEPAM

    PADA PASIEN GANGGUAN BIPOLAR

    (Penelitian dilakukan di Rumah Sakit Jiwa

    Dr. Radjiman Wediodiningrat Lawang)

    PROGRRAM STUDI FARMASI

    FAKULTAS ILMU KESEHATAN

    UNIVERSITAS MUHAMMADIYAH MALANG

    2019

  • iv

    KATA PENGANTAR

    Bismillahirrahmanirrohim

    Assalamu’alaikum warohmatullahi wabarokatuh

    Puji syukur tercurahkan kepada Allah SWT, Tuhan semesta alam karena

    berkat rahmat serta ridloNya, penulis dapat menyelesaikan skripsi yang berjudul

    “STUDI POLA PENGGUNAAN DIAZEPAM PADA PASIEN GANGGUAN

    BIPOLAR”

    Skripsi ini diajukan untuk memenuhi syarat untuk mencapai gelar Sarjana

    farmasi pada Program Studi Farmasi Universitas Muhammadiyah Malang. Dalam

    penyusunan skripsi ini penulis tidak lepas dari peranan 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 yang memberikan rahmat, nikmat dan

    hidayahNya kepada umatnya, Rosulullah SAW, yang telah 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. Ibu Dian Ermawati, M.Farm., Apt selaku ketua program studi Farmasi

    Universitas Muhammadiyah Malang beserta jajarannya.

    4. Bapak Drs. Didik Hasmono, Apt., MS selaku pembimbing I yang selalu

    meluangkan waktu untuk membimbing, mengarahkan, memberikan motivasi

    serta menjadi inspirasi untuk menyelesaikan tugas akhir ini dengan baik,

    semoga Allah senantiasa memberikan rahmat dan kesehatan.

    5. Ibu Hidajah Rachmawati, S.Si., Apt., Sp. FRS selaku Pembimbing II yang

    selalu tegas, disiplin dan sabar membimbing serta mengarahkan hingga tugas

    akhir ini dapat terselesaikan dengan baik dan tepat waktu, semoga Allah

    senantiasa memberikan rahmat dan kesehatan.

  • v

    6. Ibu Dr. Lilik Yusetyani, Dra., Apt., Sp. FRS dan Ibu Firasti Agung N.S.,

    M.,Biotech., Apt. selaku penguji I dan II yang memberikan masukkan maupun

    saran dalam perbaikan naskah tugas akhir ini agar menjadi lebih baik lagi,

    semoga Allah senantiasa memberikan rahmat dan kesehatan.

    7. Kedua orang tuaku tercinta, Bapak H. Nur Azizi dan Ibu Hj. Fatimatuz Zahro’.,

    SE., yang selalu memberikan motivasi, doa, didikannya selama ini,

    pengorbanan, serta kerja kerasnya demi keberhasilan dan kesuksesan putranya.

    8. Direktur dan seluruh staf rumah sakit jiwa Dr. Radjiman Wediodiningrat

    Lawang yang sangat baik dan banyak membantu kelancaran penelitian skripsi

    ini.

    9. Tim bipolar dan seluruh teman pejuang klinis, khususnya Dini, Rizki, Amel,

    Andri, Juniarti, Aida, Shavira, Eliza dan Citra yang menjadi teman alarm untuk

    menyelesaikan tugas akhir dengan cepat dan tepat.

    10. Sahabat seperjuangan Aisyah, Dian, Syahrul, Dini, Sultan, Dwi N, Ersita dan

    Mutia atas kerja sama dan motivasinya. Sahabat-sahabatku Karir, Adam,

    Rizki, Rayhan, Lefi, Dika dan Bagas sudah menjadi sahabat yang baik selama

    4 tahun ini.

    11. Seluruh teman-teman Sianida 2015, khususnya Farmasi Bohay yang menjadi

    teman sejawat dalam perjuangan meraih Sarjana Farmasi. Terimakasih atas 4

    tahun yang kita lewati bersama didalam 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, doa dari kalian semua.

    Akhir kata, semoga skripsi ini memberikan manfaat untuk pengetahuan bagi

    farmasi klinis maupun pembaca. Penulis menyadari skripsi ini jauh dari sempurna.

    Oleh karena itu, kritik dan saran yang membangun sangat penulis harapkan.

    Wassalamu’alaikum Wr. Wb.

    Malang, 10 Juni 2019

    (Dimas Fajar Aziz)

  • x

    DAFTAR ISI

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

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

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

    RINGKASAN……………………………………………………………………vi

    ABSTRAK……………………………………………………………………...viii

    ABSTRACT .......................................................................................................... ix

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

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

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

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

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

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

    1.1. Latar belakang .................................................................................................. 1

    1.2 Rumusan Masalah ............................................................................................ 4

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

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

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

    2.1 Definisi Bipolar ................................................................................................ 5

    2.2 Klasifikasi Gangguan Bipolar .......................................................................... 6

    2.3 Epidemiologi Gangguan Bipolar ..................................................................... 6

    2.4 Etiologi Bipolar ................................................................................................ 7

    2.4.1 Faktor Biologis ....................................................................................... 7

    2.4.1.1 Faktor genetik .................................................................................. 7

    2.4.1.2 Faktor Biokimia ............................................................................... 8

    2.4.1.2.1 Serotonin .................................................................................. 8

    2.4.1.2.2 Dopamin .................................................................................. 9

    2.4.1.2.3 Norepinefrin........................................................................... 10

    2.4.1.2.4 Gangguan Neurotransmiter lainnya ....................................... 11

    2.4.2 Faktor Psikososial ................................................................................. 12

    2.4.2.1 Faktor Stres Lingkungan ............................................................... 12

    2.4.2.2 Faktor Personal .............................................................................. 13

    2.4.2.3 Faktor Psikodinamik pada Depresi dan Mania ............................. 13

    2.4.3 Faktor Lainnya dari Depresi ................................................................. 14

  • xi

    2.4.3.1 Faktor Kognitif .............................................................................. 14

    2.4.3.2 Faktor Hopelessness ...................................................................... 14

    2.5 Anatomi dan Fisiologi Gangguan Bipolar ..................................................... 14

    2.6 Patofisiologi Gangguan Bipolar ..................................................................... 17

    2.7 Manifestasi Klinis ........................................................................................... 19

    2.7.1 Major Depresive Disorder .................................................................... 20

    2.7.2 Manic Episode ...................................................................................... 20

    2.7.3 Hypomanic Episode .............................................................................. 20

    2.8 Diagnosis Bipolar ............................................................................................ 21

    2.8.1 Gangguan Bipolar 1 .............................................................................. 21

    2.8.2 Bipolar II Disorder ................................................................................ 25

    2.8.3 Cyclothymic Disorder ........................................................................... 28

    2.9 Penatalaksanaan Gangguan Bipolar ................................................................ 29

    2.9.1 Terapi Non Farmakologi ....................................................................... 29

    2.9.1.1 Psikoterapi ..................................................................................... 29

    2.9.1.2 Electroconvulsive Therapy ............................................................ 29

    2.9.2 Terapi Farmakologi ............................................................................... 30

    2.9.2.1 Fase Akut ....................................................................................... 31

    2.9.2.1.1 Mania dan Episode Campuran ............................................... 31

    2.9.2.1.2 Episode Depresi ..................................................................... 31

    2.9.2.1.3 Siklus Cepat ........................................................................... 32

    2.9.2.2 Terapi pemeliharaan ................................................................. 32

    2.9.3 Obat Gangguan Bipolar ........................................................................ 33

    2.9.3.1 Mood Stabilizer ............................................................................. 33

    2.9.3.1.1 Litium .................................................................................... 33

    2.9.3.1.2 Valproat ................................................................................. 34

    2.9.3.1.3 Karbamazepin ........................................................................ 34

    2.9.3.1.4 Lamotrigin ............................................................................. 35

    2.9.3.2 Antidepresan .................................................................................. 35

    2.9.3.2.1 Indikasi .................................................................................. 36

    2.9.3.2.2 Klasifikasi .............................................................................. 36

    2.9.3.2.3 Golongan Obat Antidepresan ................................................ 38

    2.9.3.2.3.1 Selective Serotonin Re-uptake Inhibitor ........................ 38

    2.9.3.2.3.2 Fluoxetine ...................................................................... 38

    2.9.3.2.3.3 Sertraline ........................................................................ 39

    2.9.3.2.3.4 Siklik Antidepresan ........................................................ 39

  • xii

    2.9.3.2.3.5 Antagonis Serotonin ...................................................... 39

    2.9.3.3 Golongan Obat Antipsikotik ......................................................... 40

    2.9.3.3.1 Klozapin................................................................................. 41

    2.9.3.3.2 Klobazam ............................................................................... 41

    2.9.3.3.3 Quetiapin ............................................................................... 41

    2.9.3.3.4 Klorpromazin ......................................................................... 42

    2.9.3.3.5 Olanzapin ............................................................................... 43

    2.9.3.3.6 Risperidon .............................................................................. 43

    2.9.3.4 Ansiolitik ....................................................................................... 44

    2.9.3.4.1 Lorazepam ............................................................................. 44

    2.9.3.4.2 Alprazolam ............................................................................ 44

    2.9.3.4.3 Diazepam ............................................................................... 45

    2.9.3.4.3.1 Indikasi ........................................................................... 46

    2.9.3.4.3.2 Mekanisme Aksi ............................................................ 47

    2.9.3.4.3.3 Farmakokinetik .............................................................. 47

    2.9.3.4.3.4 Farmakodinamik ............................................................ 47

    2.9.3.4.3.5 Dosis Terapeutik ............................................................ 48

    2.9.3.4.3.6 Efek samping ................................................................. 48

    2.9.3.4.3.7 Interaksi Obat ................................................................. 49

    2.9.3.4.3.8 Sediaan Diazepam .......................................................... 49

    2.9.3.4.3.9 Penelitian Diazepam ...................................................... 49

    BAB III KERANGKA KONSEPTUAL ............................................................ 51

    BAB IV METODE PENELITIAN .................................................................... 53

    4.1 Rancangan Penelitian ..................................................................................... 53

    4.2 Populasi dan Sampel ...................................................................................... 53

    4.2.1 Populasi ................................................................................................ 53

    4.2.2 Sampel .................................................................................................. 53

    4.2.3 Kriteria Inklusi ...................................................................................... 53

    4.2.4 Kriteria Eksklusi ................................................................................... 53

    4.3 Bahan Penelitian ............................................................................................ 54

    4.4 Instrumen penelitian ....................................................................................... 54

    4.5 Tempat dan Waktu Penelitian ........................................................................ 54

    4.6 Metode pengumpulan data ............................................................................. 54

    4.7 Analisis Data .................................................................................................. 54

    4.8 Definisi Operasional ...................................................................................... 55

    BAB V HASIL PENELITIAN ........................................................................... 57

  • xiii

    5.1 Data Demografi Pasien Gangguan Bipolar ..................................................... 57

    5.1.1 Distribusi Berdasarkan Jenis Kelamin .................................................. 57

    5.1.2 Distribusi Berdasarkan Usia Pasien ...................................................... 58

    5.1.3 Distribusi Berdasarkan Status Pasien ................................................... 59

    5.2 Diagnosa Pasien Gangguan Bipolar ................................................................ 59

    5.3 Lama Pasien Gangguan Bipolar Masuk Rumah Sakit .................................... 60

    5.4 Keluhan Utama Pasien Gangguan Bipolar ...................................................... 61

    5.5 Pola Penggunaan Terapi Diazepam Pasien Rawat Jalan................................. 62

    5.5.1 Pola Penggunaan Terapi Kombinasi Dizepam ..................................... 62

    5.5.2 Pola Pergantian (Switching) Terapi Diazepam per-oral ....................... 64

    5.5.3 Lama Pemeberian Terapi Diazepam per-oral ....................................... 64

    5.6 Pola Penggunaan Terapi Diazepam Pasien Rawat Inap .................................. 65

    5.6.1 Pola Penggunaan Terapi Tiga Kombinasi Diazepam ........................... 65

    5.6.2 Pola Penggunaan Terapi Empat Kombinasi Diazepam ........................ 66

    5.6.3 Pola Penggunaan Terapi Lima Kombinasi Diazepam .......................... 68

    5.6.4 Pola Penggunaan Terapi Enam Kombinasi Diazepam ......................... 69

    5.6.5 Pola Pergantian (Switching) Terapi Diazepam intramuscular .............. 70

    5.6.6 Lama Pemberian Terapi Diazepam intramuscular ............................... 74

    5.7 Perbandingan Siklus Tidur Pasien Gangguan Bipolar ketika Masuk Rumah

    Sakit dengan Kondisi Klinis Sekarang .......................................................... 74

    5.8 Kondisi Klinis Sekarang dari Pasien Gangguan Bipolar yang Diterapi dengan

    Diazepam ....................................................................................................... 76

    BAB VI PEMBAHASAN .................................................................................... 77

    BAB VII KESIMPULAN ................................................................................... 93

    7.1 Kesimpulan ..................................................................................................... 93

    7.2 Saran ................................................................................................................ 93

    DAFTAR PUSTAKA .......................................................................................... 94

  • xiv

    DAFTAR TABEL

    Halaman

    Table II.1 Tingkat prevalensi seumur hidup gangguan depresi ............................. 7

    Table II.2 Struktur Otak yang Terlibat dalam Respon Emosi ............................. 15

    Table II.3 Klasifikasi obat antidepresan .............................................................. 28

    Table II.4 Sediaan Diazepam ............................................................................... 40

    Table V.1 Distribusi jenis kelamin ...................................................................... 58

    Table V.2 Distribusi Usia .................................................................................... 58

    Table V.3 Distribusi Status .................................................................................. 59

    Table V.4 Diagnosa .............................................................................................. 59

    Table V.5 Lama Pasien Masuk Rumah Sakit ....................................................... 61

    Table V.6 Keluhan Utama Pasien ........................................................................ 61

    Table V.7 Pola Penggunaan Terapi Pasien Rawat Jalan ...................................... 62

    Table V.8 Pola Penggunaan Terapi Kombinasi Pasien Rawat Jalan ................... 63

    Table V.9 Pola Switch Terapi Diazepam Pasien Rawat Jalan ............................. 64

    Table V.10 Lama Pemberian Terapi Diazepam Pasien Rawat Jalan ................... 64

    Table V.11 Pola Penggunaan Terapi Pasien Rawat Inap ..................................... 65

    Table V.12 Pola Penggunaan Terapi Kombinasi 3 Obat Pasien Rawat Inap ....... 66

    Table V.13 Pola Penggunaan Terapi Kombinasi 4 Obat Pasien Rawat Inap ....... 66

    Table V.14 Pola Penggunaan Terapi Kombinasi 5 Obat Pasien Rawat Inap ....... 68

    Table V.15 Pola Penggunaan Terapi Kombinasi 6 Obat Pasien Rawat Inap ....... 69

    Table V.16 Pola Switch Terapi Diazepam Pasien Rawat Inap ............................ 70

    Table V.17 Lama PemberianTerapi Diazepam Pasien Rawat Inap ..................... 74

    Table V.18 Efek Pemberian Siklus Tidur Pasien ................................................. 74

    Table V.19 Kondisi Klinis Sekarang Pasien Gangguan Bipolar .......................... 76

  • xv

    DAFTAR GAMBAR

    Halaman

    Gambar 2.1 Siklus suasana hati pasien bipolar ..................................................... 5

    Gambar 2.2 Model transmisi genetik penularan gangguan bipolar ....................... 8

    Gambar 2.3 Proyeksi dopaminergik utama dalam CNS ...................................... 10

    Gambar 2.4 Mekanisme Patofisiologi GABA ..................................................... 12

    Gambar 2.5 Ilustrasi daerah otak utama .............................................................. 14

    Gambar 2.6 Amygdala & Hipocampus .............................................................. 15

    Gambar 2.7 Dorsolateral Prefrontal Cortex ......................................................... 16

    Gambar 2.8 Anterior Cingulate & Subgenual Anterior Cingulate ...................... 16

    Gambar 2.9 Jalur serotonin dan dopamin dalam otak ......................................... 17

    Gambar 2.10 Perubahan fungsional otak pada orang dengan bipolar ................. 18

    Gambar 2.11 Kondisi Normal & Kondisi Inflamasi Peripheral Saraf Glial ........ 18

    Gambar 2.12 Struktur kimia Asam Valproat ....................................................... 34

    Gambar 2.13 Struktur kimia Karbamazepin ........................................................ 35

    Gambar 2.14 Struktur kimia Lamotrigin ............................................................. 35

    Gambar 2.15 Struktur kimia Fluoxetin ................................................................ 30

    Gambar 2.16 Struktur kimia Traxodon................................................................ 31

    Gambar 2.17 Struktur kimia Nefaxodon ............................................................. 31

    Gambar 2.18 Struktur kimia Klozapin ................................................................ 32

    Gambar 2.19 Struktur kimia Quetiapin ............................................................... 33

    Gambar 2.20 Struktur kimia Klorpromazin ......................................................... 34

    Gambar 2.21 Struktur kimia Olanzapin ............................................................... 34

    Gambar 2.22 Struktur kimia Lorazepam ............................................................. 35

    Gambar 2.23 Struktur kimia Alprazolam ............................................................ 36

    Gambar 2.24 Struktur kimia Diazepam ............................................................... 45

    Gambar 3.1 Skema kerangka konseptual ............................................................ 41

    Gambar 3.2 Skema kerangka operasional ........................................................... 42

    Gambar 5.1 Skema inklusi dan eksklusi……...…………………………………57

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  • xvi

    DAFTAR LAMPIRAN

    LAMPIRAN 1 : Daftar Riwayat Hidup ............................................................ 99

    LAMPIRAN 2 : Surat Pernyataan .................................................................. 100

    LAMPIRAN 3 ; Surat Keterangan Selesai Penelitian ................................... 101

    LAMPIRAN 4 : Surat Laik Etik...................................................................... 102

    LAMPIRAN 5 : Lembar Pengumpul Data ..................................................... 103

  • xvii

    DAFTAR SINGKATAN

    APA : American Psychiatric Association

    BDNF : Brain Derived Neurotrophic Factor

    BDZ : Benzodiazepin

    BPJS : Badan Penyelenggara Jaminan Sosial

    CBT : Cognitif Based Therapy

    CNS : Central Nervous System

    CSF : Cerebrospinal Fluid

    DSM : Diagnostic and Stastical Manual of Bipolar Disorder

    D2 : Dopamin 2

    D-M-I : Depression Mania Well Interval

    DZ : Diazepam

    ECT : Electro Convulsive Therapy

    EEG : Elektroensefalogram

    FDA : Food Drug Association

    GABA : Gamma Amino Butyrac Acid

    GAD : Glutamat dekarboksilase

    GCS : Glasgow Coma Scale

    GDNF : Glial Cell Line-Derived Neurotrophic Factor

    H1 : Histamin1

    KRS : Keluar Rumah Sakit

    LPD : Lembar Pengumpul Data

    MAO : Mono Amin Oksidase

    MRI : Magnetic Resonance Imaging

    MRS : Masuk Rumah Sakit

  • xviii

    NIMH : National Institute of Mental Health

    OCD : Obsessive Compulsive Disorder

    PET : Positron Emission Tomographic

    PTSD : Post traumatic stress disorder

    REM : Rapid Eye Movement

    RISKESDAS : Riset Kesehatan Dasar

    RMK : Rekam Medik Kesehatan

    RR : Respiratory Rate

    TD : Tekanan Darah

    SSP : Sistem Saraf Pusat

  • 94

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