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SKRIPSI
NUVERA ARGIANTI
STUDI PENGGUNAAN KLORPROMAZIN
PADA PASIEN SKIZOFRENIA
(Penelitian Dilakukan di RSJ Dr. Radjiman
Wediodiningrat Lawang)
PROGRAM STUDI FARMASI
FAKULTAS ILMU KESEHATAN
UNIVERSITAS MUHAMMADIYAH MALANG
2018
ii
iii
iv
KATA PENGANTAR
Assalamualaikum Wr. Wb.
Puji syukur ke hadirat Allah SWT yang telah melimpahkan berkah, rahmat,
karunia dan hidayah ke hamba-Nya, karena dengan pertolongan-Nya skripsi yang
berjudul Studi Penggunaan Klorpromazin pada Pasien Skizofrenia
(Penelitian dilakukan pada Rumah Sakit Jiwa Dr. Radjiman Wediodiningrat
Lawang) dapat diselesaikan tepat waktu dan dengan sebaik-baiknya. Selanjutnya
penulis ingin mengucapkan terima kasih yang tidak terhingga kepada:
1. Orang tua Ibu Bahagia dan Bapak Muhammad Akhyar serta saudara Anisa
Lestari, Muhammad Habil Sauri Yahya, dan Muthia Latifah Cahyani yang
telah memberi motivasi dan doa terbesar saya untuk segera menyelesaikan
skripsi ini
2. Bapak Faqih Ruhyanudin, M. Kep., Sp. Kep. MB selaku dekan Fakultas Ilmu
Kesehatan Universitas Muhammadiyah Malang
3. Direktur dan staf Rumah Sakit Jiwa Dr. Radjiman Wediodingrat Lawang
yang telah membantu kelancaran penilitian skripsi hingga akhir.
4. Bapak Drs. Didik Hasmono, Apt., MS slaku pembimbing I yang telah banyak
meluangkan waktu untuk membimbing, mengarahkan, dan memberi
semangat, motivasi, serta menginspirasi penulis selama menempuh pendidikan
sampai terselesaikannya tugas akhir ini, semoga Allah selalu melimpahkan
kesehatan.
5. Ibu Dra. Lilik Yusetyani, Apt., Sp. FRS selaku Pembimbing II yang selalu
bersedia mengorbankan waktu untuk membimbing dan memberikan motivasi
serta selalu sabar dalam mengarahkan hingga tugas akhir ini dapat
diselesaikan dengan baik dan tepat waktu, semoga Allah selalu melimpahkan
kesehatan.
6. Ibu Hidajah Rachmawati, S.Si., Apt., Sp. FRS dan Ibu Ika Ratna Hidayati, S.
Farm., M. Sc., Apt selaku penguji I dan II yang telah banyak memberikan
kritikan dan saran demi terselesaikannya tugas akhir ini dengan sebaik-
baiknya, semoga Allah selalu melimpahkan kesehatan.
v
7. Seluruh jajaran prodi, dosen dan staf tata usaha Farmasi yang telah
memberikan dedikasi yang besar kepada penulis.
8. Kepada Santri Ningthias, Dwi Ridha Novianty, Winda Khairun Nasicha, Putri
Astutik, Rima Dwi Cahyani, Pangastutik Santikrama, Aldiala Apriliawati,
Muhammad Rivaldy Risnanda, Gading, Noval Yusup, dan teman-teman
lainnya yang tidak bisa saya sebutkan semuanya yang selalu memotivasi dan
sangat membantu dalam menyusun skiripsi ini.
9. Teman satu kelompok skripsi yang bertema Skizofrenia: Ririantika Dwi
Jiansari, Arina Rahayu, Noor Izzatil Faizah, Rahmat Akbar dan sesama
pejuang klinis lainnya yang telah berjuang bersama.
10. Terakhir, Seluruh teman-teman jurusan Farmasi angkatan 2014 yang telah
berjuang bersama penulis untuk menyelesaikan pendidikan di Program Studi
Farmasi.
Akhir kata, penulis mohon maaf atas kekurangan dan ketidaksempurnaan
penulisan skripsi dan dengan senang hati menerima kritik dan saran yang
membangun. Semoga skripsi ini bermanfaat dalam mengembangkan ilmu
pengetahuan bidang farmasi klinis bagi penulis maupun pembaca.
Wassalamualaikum Wr. Wb.
Malang, 6 Juni 2018
Nuvera Argianti
ix
DAFTAR ISI
KATA PENGANTAR .......................................................................................... iv
RINGKASAN ....................................................................................................... vi
ABSTRAK ........................................................................................................... vii
DAFTAR ISI ......................................................................................................... ix
DAFTAR GAMBAR .......................................................................................... xiv
DAFTAR TABEL................................................................................................ 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 Skizofrenia ................................................................................................ 5
2.1.1 Definisi .............................................................................................. 5
2.1.2 Epidemiologi ..................................................................................... 5
2.1.3 Etiologi .............................................................................................. 7
2.1.3.1 Faktor Genetik ............................................................................... 8
2.1.3.2 Faktor Lingkungan ........................................................................ 9
2.1.3.3 Perubahan Neuroanatomis ............................................................. 9
2.1.3.4 Perubahan Sirkuit Fungsional pada Skizofrenia............................ 9
2.1.3.5 Gangguan Transmisi Sinaptik Pada Skizofrenia ........................... 9
2.1.3.6 Sitokin pada Skizofrenia.............................................................. 10
2.1.3.7 Hipotesis Serotonin Terhadap Skiofrenia .................................... 10
2.1.3.8 Hipotesis Dopamin Terhadap Skizofrenia................................... 10
2.1.4 Klasifikasi Skizofrenia .................................................................... 11
2.1.4.1 Skizofrenia Tipe Paranoid ........................................................... 11
2.1.4.2 Skizofrenia Tipe Tidak Terorganisir (Hebefrenik)...................... 12
2.1.4.3 Skizofrenia Tipe Katatonik.......................................................... 12
x
2.1.4.4 Skizofrenia Tipe Tidak Berdiferensiasi ....................................... 12
2.1.4.5 Skizofrenia Tipe Residual ........................................................... 12
2.1.5 Patofisiologi Skizofrenia ................................................................. 13
2.1.6 Gejala dan Gambaran Klinis ........................................................... 16
2.1.6.1 Gejala Positif ............................................................................... 16
2.1.6.2 Gejala Negatif .............................................................................. 16
2.1.6.3 Gejala Kognitif ............................................................................ 17
2.1.7 Diagnosis ......................................................................................... 17
2.1.7.1 Kriteria A ..................................................................................... 18
2.1.7.2 Kriteria B ..................................................................................... 18
2.1.7.3 Kriteria C ..................................................................................... 18
2.1.7.4 Kriteria D ..................................................................................... 18
2.1.7.5 Kriteria E ..................................................................................... 19
2.1.7.6 Kriteria F ..................................................................................... 19
2.2 Terapi Skizofrenia .................................................................................. 19
2.2.1 Tujuan Terapi Skizofrenia............................................................... 19
2.2.2 Prinsip Umum Terapi Skizofrenia .................................................. 19
2.2.2.1 Terapi Awal ................................................................................. 19
2.2.2.2 Terapi Stabilisasi ......................................................................... 20
2.2.2.3 Terapi Pemeliharaan .................................................................... 20
2.2.3 Terapi Non Farmakologi ................................................................ 20
2.2.3.1 Terapi ECT (Electroconvulsive).................................................. 21
2.2.3.2 Terapi Perilaku Kognitif untuk Orang dengan Skizofrenia ......... 22
2.2.3.3 Pendekatan Berbasis Keluarga untuk Pasien Skizofrenia ........... 22
2.2.3.4 Rehabilitasi dalam skizofrenia .................................................... 23
2.2.4 Terapi Farmakologi ......................................................................... 24
2.2.4.1 Algoritma dan Guidline terapi ..................................................... 24
2.2.4.2 Antipsikotik ................................................................................. 25
2.2.4.2.1 Klorpromazin ......................................................................... 28
2.2.4.2.2 Flufenazin .............................................................................. 28
2.2.4.2.3 Haloperidol ............................................................................ 28
2.2.4.2.4 Perfenazin .............................................................................. 29
xi
2.2.4.2.5 Aripiprazole ........................................................................... 29
2.2.4.2.6 Asenapin ................................................................................ 29
2.2.4.2.7 Klozapin ................................................................................. 29
2.2.4.2.8 Olanzapin ............................................................................... 30
2.2.4.2.9 Risperidon .............................................................................. 30
2.2.4.2.10 Quetiapin .............................................................................. 30
2.2.4.3 Penstabil Mood (mood stabilizer) ............................................... 31
2.2.4.3.1 Lithium ................................................................................... 32
2.2.4.3.2 Karbamazepin ........................................................................ 32
2.2.4.3.3 Divalproex Na ........................................................................ 32
2.2.4.3.4 Asam Valproat ....................................................................... 32
2.2.4.3.5 Lamotrigine ............................................................................ 33
2.2.4.4 Antidepresan ................................................................................ 33
2.2.4.4.1 Antidepresan SSRI ................................................................. 36
2.2.4.4.2 Antidepresan SNRI ................................................................ 37
2.2.4.4.3 Antidepresan 5-HT Receptor Modulators .............................. 37
2.2.4.4.4 Antidepresan Trisiklik ........................................................... 37
2.2.4.4.5 Antidepresan Monoamine Oxidase Inhibitors (MAOi) ......... 37
2.2.4.5 Antianxietas ................................................................................. 38
2.2.4.5.1 Alprazolam ............................................................................. 39
2.2.4.5.2 Diazepam ............................................................................... 39
2.2.4.5.3 Lorazepam.............................................................................. 39
2.2.4.5.4 Nitrazepam ............................................................................. 39
2.2.4.5.5 Midazolam ............................................................................. 39
2.3 Tinjauan Klorpromazin .......................................................................... 40
2.3.1 Efek Farmakologis .......................................................................... 40
2.3.2 Mekanisme Kerja ............................................................................ 40
2.3.3 Farmakokinetik ............................................................................... 47
2.3.4 Dosis ................................................................................................ 48
2.3.5 Efek Samping .................................................................................. 48
2.3.6 Interaksi ........................................................................................... 48
2.3.7 Sediaan Klorpromazin di Indonesia ................................................ 48
xii
BAB III KERANGKA KONSEPTUAL ............................................................ 49
3.1 Kerangka Konseptual ............................................................................. 49
3.2 Kerangka Operasional ............................................................................ 50
BAB IV METODE PENELITIAN .................................................................... 51
4.1 Rancangan Penelitian ............................................................................. 51
4.2 Populasi dan Sampel............................................................................... 51
4.3 Bahan Penelitian ..................................................................................... 51
4.4 Instrumen Penelitian ............................................................................... 52
4.5 Tempat dan Waktu Penelitian ................................................................ 52
4.6 Definisi Operasional ............................................................................... 52
4.7 Metode Pengumpulan Data .................................................................... 53
4.8 Analisis Data .......................................................................................... 53
BAB V HASIL PENELITIAN ........................................................................... 54
5.1 Data Demografi ...................................................................................... 54
5.1.1 Distribusi Berdasarkan Jenis Kelamin Pasien ................................. 54
5.1.2 Distribusi Berdasarkan Usia Pasien ................................................ 55
5.1.3 Distribusi Berdasarkan Berat Badan Pasien .................................... 55
5.1.4 Distribusi Berdasarkan Status Pasien .............................................. 56
5.2 Diagnosis Jenis Skizofrenia .................................................................... 56
5.3 Pola Penggunaan Terapi Pada Pasien Skizofrenia ................................. 57
5.4 Pola Penggunaan Terapi Pada Pasien ..................................................... 59
5.4.1 Pola Penggunaan Terapi Tunggal Pasien Rawat Jalan ................... 59
5.4.2 Pola Penggunaan Terapi 2 Kombinsi Pasien Rawat Jalan .............. 59
5.4.3 Pola Penggunaan Terapi 3 Kombinsi Pasien Rawat Jalan .............. 61
5.4.4 Pola Penggunaan Terapi 4 Kombinsi Pasien Rawat Jalan .............. 64
5.4.5 Pola Penggunaan Terapi 2 Kombinsi Pasien Rawat Inap ............... 66
5.4.6 Pola Penggunaan Terapi 4 Kombinsi Pasien Rawat Inap ............... 67
5.5 Pola Pergantian Terapi Klorpromazin pada Pasien Skizofrenia............. 68
5.5.1 Pola Pergantian Terapi Klorpromazin Pasien Rawat Jalan ............. 68
5.5.2 Pola Pergantian Terapi Klorpromazin Pasien Rawat Inap .............. 73
5.6 Lama Pemberian Terapi Obat Klorpromazin ......................................... 75
5.6.1 Lama pemberian Terapi Obat Klorpromazin Rawat Jalan .............. 75
xiii
5.6.2 Lama pemberian Terapi Obat Klorpromazin Rawat Inap ............... 75
BAB VI PEMBAHASAN .................................................................................... 76
BAB VII KESIMPULAN DAN SARAN ........................................................... 87
7.1 Kesimpulan ............................................................................................. 87
7.2 Saran ....................................................................................................... 87
DAFTAR PUSTAKA .......................................................................................... 88
LAMPIRAN ......................................................................................................... 95
xiv
DAFTAR GAMBAR
Gambar 2.1. DALY Skizofrenia menurut WHO ................................................... 6
Gambar 2.2. Jalur dopaminergik pada otak manusia ........................................... 13
Gambar 2.3. Aktivitas Hiperdopaminergik di Jalur Mesolimbik ......................... 14
Gambar2.4. Aktivitas Hipodopaminergik di jalur Mesokorteks ......................... 15
Gambar 2.5. Algoritma penggunaan obat Antipsikosis pada Skizofrenia ........... 24
Gambar 2.6. Struktur kimia antipsikosis generasi pertama.................................. 26
Gambar 2.7. Struktur kimia antipsikosis generasi kedua ..................................... 26
Gambar 2.8. Mekanisme Kerja Klorpromazin ..................................................... 40
Gambar 2.9. Mekanisme Klorpromazin Pada Jalur Mesolimbik ......................... 41
Gambar 2.10.Mekanisme Klorpromazin Pada Jalur Mesokorteks........................ 42
Gambar 2.11.Mekanisme Klorpromazin Pada Jalur Nigrostriatal ........................ 43
Gambar 2.12.Mekanisme Klorpromazin menyebabkan Tardive dyskinesia ........ 44
Gambar 2.13.Mekanisme Klorpromazin Pada Jalur Tuberoinfundibular ............. 44
Gambar 2.14.Klorpromazin Pada Berbagai Reseptor ........................................... 45
Gambar 2.15.Mekanisme Klorpromazin Pada Reseptor Kolinergik ................... 45
Gambar 2.16.Hubungan timbal balik dopamin dan asetilkolin............................. 46
Gambar 2.17.Dopamin, asetilkolin, dan antagonis D2 ......................................... 46
Gambar 2.18 Antagonis D2 dan agen antikolinergik ............................................ 47
Gambar 3.1. Skema Kerangka Konseptual ........................................................... 49
Gambar 3.2 Skema Kerangka Operasional .......................................................... 50
xv
DAFTAR TABEL
Tabel II.1. Prevalensi Gangguan Jiwa Berat Menurut Provinsi Indonesia 2013 .... 7
Tabel II.2.Obat-obat Antipsikotik berdasar golongan/kelas dan dosisnya ........... 25
Tabel II.3. Farmakokinetik obat antipsikotik FGA dan SGA ............................... 27
Tabel II.4. Efek samping obat antipsikotik FGA dan SGA .................................. 27
Tabel II.5. Dosis dan pemakaian klinik mood stabilizer ....................................... 31
Tabel II.6.Golongan obat Antidepresan dan dosis pemakaiannya ........................ 33
Tabel II.7.Profil Farmakokinetik Antidepresan .................................................... 35
Tabel II.8.Golongan obat Antiansietas (Benzodiazepin) ...................................... 38
Tabel II.9.Farmakokinetik agen Antiansietas Benzodiazepin ............................... 38
Tabel V.1 Distribusi Jenis Kelamin Pasien ........................................................... 54
Tabel V.2 Distribusi Berdasarkan Usia Pasien ..................................................... 55
Tabel V.3 Berat Badan Pasien Skizofrenia dengan Terapi Klorpromazin ............ 55
Tabel V.5 Distribusi Berdasarkan Status Pasien ................................................... 56
Tabel V.6 Distribusi Diagnosa Skizofrenia .......................................................... 56
Tabel V.7 Pola Penggunaan Terapi Pada Pasien Rawat Jalan Skizofrenia ........... 57
Tabel V.8 Persen Pola Penggunaan Terapi Pasien Rawat Jalan Skizofrenia ........ 57
Tabel V.9 Pola Penggunaan Terapi Pasien Rawat Inap Skizofrenia .................... 58
Tabel V.10 Persen Pola Penggunaan Terapi Pasien Rawat Jalan Skizofrenia ...... 59
Tabel V.11 Pola Penggunaan Terapi Tunggal Pasien Rawat Jalan ...................... 59
Tabel V.12 Pola Penggunaan Terapi 2 Kombinasi Pasien Rawat Jalan ............... 59
Tabel V.13 Pola Penggunaan Terapi 3 Kombinasi Pasien Rawat Jalan ............... 61
Tabel V.14 Pola Penggunaan Terapi 4 Kombinasi Pasien Rawat Jalan ............... 64
Tabel V.15 Pola Penggunaan Terapi 2 Kombinasi Pasien Rawat Inap ................ 66
Tabel V.16 Pola Penggunaan Terapi 4 Kombinasi Pasien Rawat Inap ................ 67
Tabel V.17 Pola Pergantian Terapi Klorpromazin Pasien Rawat Jalan ................ 68
Tabel V.18 Pola Pergantian Terapi Klorpromazin Pasien Rawat Inap ................. 73
Tabel V.19 Lama Pemberian Terapi Klorpromazin pada Saat Rawat Jalan ......... 75
Tabel V.20 Lama Pemberian Terapi Klorpromazin pada Saat Rawat Inap .......... 75
xvi
DAFTAR LAMPIRAN
Lampiran 1: Daftar Riwayat Hidup....................................................................... 95
Lampiran 2: Surat Tugas ....................................................................................... 96
Lampiran 3: Surat Keterangan Selesai Penelitian ................................................. 97
Lampiran 4: Surat Ethical Clearence .................................................................... 98
Lampiran 5: Surat Hasil Plagiasi Naskah.............................................................. 99
Lampiran 6: Surat Pernyataan ............................................................................. 102
xvii
DAFTAR SINGKATAN
5-HT : Serotonin
ADL : Activities of Daily Living
ALT : Alanine Transminase
AST : Aspartate Transaminase
Ca2+
: Kalsium
CBT : Cognitive Behavioural Therapy
CT Scan : Computerized Tomographic Scan
DA : Dopamin
DSM : Diagnostic and Statistical Manual
ECT : Electro Convulsive Therapy
EPSP : Excitatory Postsynaptic Potential
GABA : Gamma Aminobutyric Acid
K+ : Kalium
LPD : Lembar Pengumpul Data
LSD : Lysergic Acid Diethylamide
mg : miligram
MRI : Magnetic Resonance Imaging
MRS : Magnetic Resonance Spectroscopy
NMDA : N-metil-d-aspartat
PFC : Pre Frontal Cortex
Riskesdas : Riset Kesehatan Dasar
RMK : Rekam Medik Kesehatan
RSJ : Rumah Sakit Jiwa
RTA : Reality Testing Ability
SNRI : Selective Norepinephrine Reuptake Inhibitor
SSP : Sistem Saraf Pusat
SSRI :Selective Serotonin Reuptake Inhibitor
TCA : Tricyclic Antidepressants
WHO : World Health Organization
88
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