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SKRIPSI
SARAH ALFIAH USMAN
STUDI PENGGUNAAN ANTIDIABETIK ORAL
PADA PASIEN DIABETES MELITUS TIPE 2
(Penelitian Dilakukan di RSUD dr. Abdoer Rahem Situbondo)
PROGRAM STUDI FARMASI
FAKULTAS ILMU KESEHATAN
UNIVERSITAS MUHAMMADIYAH MALANG
2017
iv
KATA PENGANTAR
Bismillahirrahmanirrohim
Assalamu’alaikum warohmatullahi wabarokatuh
Puji syukur tercurahkan kepada Allah SWT, Tuhan semesta alam karena
berkat rahmat serta ridhaNya, penulis dapat menyelesaikan skripsi yang berjudul
“STUDI PENGGUNAAN ANTIDIABETIK ORAL PADA PASIEN
DIABETES MELITUS TIPE 2 (Penelitian Dilakukan di RSUD dr. Abdoer
Rahem Situbondo)”
Skripsi ini diajukan untuk memenuhi syarat mencapai gelar Sarjana Farmasi
pada Program Studi Farmasi Universitas Muhammadiyah Malang. Dalam
penyusunan ini penulis tidak lepas dari peranan penting pembimbing dan bantuan
dari semua 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
hidayah kepada umatNya serta junjungan Nabi Muhammad SAW, yang
sudah menuntun kita menuju jalan yang lurus.
2 Bapak Yoyok Bekti Prasetyo, S.Kep, M.Kep., Sp.Kom. selaku Dekan
Fakultas Ilmu Kesehatan Universitas Muhammadiyah Malang yang telah
memberikan kesempatan kepada penulis untuk belajar di Fakultas Ilmu
Kesehatan Universitas Muhammadiyah Malang.
3 Bapak Drs. Didik Hasmono, Apt., Ms. Selaku dosen pembimbing I dan
Ibu Nailis Syifa’, S.Farm., M.Sc., Apt. selaku dosen pembimbing II yang
telah memberikan banyak arahan dan motivasi demi terselesaikannya
skripsi ini.
4 Ibu Hidajah Rachmawati, S.Si.,Apt.,Sp.FRS. selaku dosen penguji I dan
Ibu Dra. Lilik Yusetyani, Apt., Sp.FRS. selaku dosen penguji II yang telah
memberikan banyak saran dan masukan demi kesempurnaan skripsi ini.
5 Direktur RSUD dr. Abdoer Rahem Situbondo beserta jajarannya yang
telah memberikan kesempatan kepada penulis untuk melakukan penelitian
di RSUD dr. Abdoer Rahem Situbondo.
6 Staf pengawas Rekam Medis Kesehatan RSUD dr. Abdoer Rahem
Situbondo yang telah banyak membantu dalam proses pengambilan data
skripsi.
7 Kedua orang tuaku tercinta, Bapak Eki dan Ibu Yani, yang selalu
memberikan motivasi, doa dan didikannya selama ini, serta keluarga yang
selalu memberi semangat dalam kelangsungan pengerjaan skripsi ini.
8 Teman tersayang, Mahathir yang selalu ada dalam segala kondisi,
memberi dukungan dan bantuan hingga terselesaikan skripsi ini.
v
9 Teman seperjuangan skripsi, Aldi, Adel, Reni, Andin dan Cici atas
kerjasama dan motivasinya selama ini.
10 Sahabat-sahabatku tersayang, Kety, Irma, Selvin, Winda, Ijah, Didin yang
sudah menjadi sahabat terbaik selama lebih dari 3 tahun ini.
11 Untuk semua pihak yang belum disebutkan namanya, penulis mohon maaf
dan terima kasih sebesar-besarnya. Semua keberhasilan dalam
penyelesaian skripsi ini tidak luput dari bantuan dan doa kalian semua.
Jasa dari semua pihak yang telah banyak membantu dalam proses
penyelesaian skripsi ini, penulis hanya bisa mengucapkan terima kasih dan tidak
mampu membalas dengan apapun, semoga amalan kalian dapat imbalan dari Yang
Maha Kuasa Allah SWT. Penulis juga menyadari bahwa skripsi ini jauh dari
kesempurnaan, oleh karena itu penulis mengharapkan kritik dan saran yang
membangun dari pembaca demi kesempurnaan skripsi ini. Semoga haisl
penelitian ini dapat memberikan manfaat bagi pembaca dan penelitian
selanjutnya, aamiin.
Wassalamu’alaikum warohmatullahi wabarokatuh
Malang, 22 Maret 2014
Penyusun
(Sarah Alfiah Usman)
x
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 I PENDAHULUAN ...................................................................................... 1
1.1 Latar Belakang .............................................................................................. 1
1.2 Rumusan Masalah ......................................................................................... 4
1.3 Tujuan Penelitian ........................................................................................... 4
1.3.1 Tujuan Umum .............................................................................................. 4
1.3.2 Tujuan Khusus ............................................................................................ 4
1.4 Manfaat Penelitian ......................................................................................... 4
BAB II TINJAUAN PUSTAKA ........................................................................... 6
2.1 Definisi Diabetes Melitus .............................................................................. 6
2.2 Anatomi dan Fisiologi Pankreas .................................................................... 6
2.2.1 Pankreas dan Pembentukan Insulin ........................................................... 7
2.2.2 Efek Insulin ................................................................................................... 8
2.3 Epidemiologi Diabetes Melitus ..................................................................... 9
2.4 Batasan dan Klasifikasi Diabetes Melitus ................................................... 11
2.4.1 Batasan Diabetes Melitus .......................................................................... 11
2.4.2 Klasifikasi Diabetes Melitus ..................................................................... 11
2.5 Etiologi dan Patofisiologi Diabetes Melitus ................................................ 12
2.5.1 Etiologi Diabetes Melitus .......................................................................... 12
2.5.2 Patofisiologi Diabetes Melitus ................................................................. 14
xi
2.6 Gejala Klinik Diabetes Melitus ................................................................... 16
2.7 Komplikasi Diabetes Melitus ..................................................................... 17
2.7.1 Hipoglikemia ............................................................................................. 17
2.7.2 Hiperglikemia ............................................................................................ 17
2.7.3 Komplikasi Makrovaskular ...................................................................... 18
2.7.4 Komplikasi Mikrovaskular....................................................................... 19
2.7.4.1 Diabetes Retinopati ...................................................................... 19
2.7.4.2 Diabetes Nefropati ....................................................................... 20
2.7.4.3 Diabetes Neuropati ...................................................................... 20
2.8 Diagnosis Diabetes Melitus ........................................................................ 21
2.9 Terapi Non Farmakologi Diabetes Melitus ................................................ 22
2.9.1 Pengaturan Diet ......................................................................................... 22
2.9.2 Olahraga ..................................................................................................... 23
2.10 Terapi Farmakologi Diabetes Melitus ....................................................... 23
2.10.1 Sulfonilurea ............................................................................................ 26
2.10.1.1 Farmakologi Sulfonilurea ..................................................... 26
2.10.1.2 Klasifikasi Sulfonilurea......................................................... 27
2.10.1.3 Farmakokinetika Sulfonilurea .............................................. 27
2.10.1.4 Efektivitas Sulfonilurea ........................................................ 27
2.10.1.5 Efek Samping Sulfonilurea ................................................... 28
2.10.2 Glinid....................................................................................................... 30
2.10.2.1 Farmakologi Glinid ................................................................ 31
2.10.2.2 Farmakokinetika Glinid ........................................................ 31
2.10.2.3 Efektivitas Glinid ................................................................... 31
2.10.2.4 Efek Samping Glinid ............................................................. 31
2.10.2.5 Interaksi Obat Glinid ............................................................. 32
2.10.2.6 Dosis dan Cara Pemberian Glinid ....................................... 32
2.10.3 Biguanid ................................................................................................. 33
2.10.3.1 Farmakologi Biguanid ........................................................... 33
2.10.3.2 Farmakokinetika Biguanid ................................................... 33
2.10.3.3 Efektivitas Biguanid .............................................................. 34
2.10.3.4 Efek Samping Biguanid ........................................................ 34
xii
2.10.3.5 Interaksi Obat Biguanid ........................................................ 34
2.10.3.6 Dosis dan Cara Pemberian Biguanid ................................... 34
2.10.4 Thiazolidenidion ..................................................................................... 35
2.10.4.1 Farmakologi Thiazolidenidion .............................................. 36
2.10.4.2 Farmakokinetika Thiazolidenidion ....................................... 36
2.10.4.3 Efektivitas Thiazolidenidion ................................................. 36
2.10.4.4 Efek Samping Thiazolidenidion ........................................... 37
2.10.4.5 Interaksi Obat Thiazolidenidion ........................................... 37
2.10.4.6 Dosis dan Cara Pemberian Thiazolidenidion ...................... 37
2.10.5 Penghambat Glukosidase α ................................................................... 38
2.10.5.1 Farmakologi Penghambat Glukosidase α ............................. 39
2.10.5.2 Farmakokinetik Penghambat Glukosidase α ....................... 39
2.10.5.3 Efektivitas Penghambat Glukosidase α ................................ 39
2.10.5.4 Efek Samping Penghambat Glukosidase α .......................... 40
2.10.5.5 Dosis dan Cara Pemberian Penghambat Glukosidase α ..... 40
2.10.6 Penghambat DPP-IV .............................................................................. 40
2.10.6.1 Farmakologi Penghambat DPP-IV ....................................... 41
2.10.6.2 Farmakokinetik Penghambat DPP-IV ................................. 41
2.10.6.3 Efektivitas Penghambat DPP-IV .......................................... 41
2.10.6.4 Interaksi Obat Golongan Penghambat DPP-IV .................. 42
2.10.6.5 Efek Samping Penghambat DPP-IV .................................... 42
2.10.6.6 Dosis dan Pemberian Penghambat DPP-IV ........................ 42
2.10.7 Insulin ...................................................................................................... 44
2.10.7.1 Farmakokinetik Insulin .......................................................... 44
2.10.7.2 Dosis dan Aturan Pakai Insulin ............................................ 45
2.10.7.3 Efek Samping Insulin ............................................................. 45
2.10.7.4 Perhatian pada Penggunaan Insulin ...................................... 46
2.10.7.5 Interaksi Obat Insulin ............................................................. 46
2.11 Farmakoterapi Penderita Diabetes Melitus Tipe 2 .................................... 47
2.11.1 Penatalaksanaan Diabetes Melitus Tipe 2 .......................................... 47
2.11.2 Terapi Inisial .......................................................................................... 48
2.11.3 Terapi Kombinasi (2 Obat) .................................................................. 49
xiii
2.11.4 Terapi Kombinasi (3 Obat) .................................................................. 50
BAB III KERANGKA KONSEPTUAL ............................................................ 51
3.1 Kerangka Konseptual .................................................................................. 52
3.2 Kerangka Operasional ................................................................................. 53
BAB IV METODE PENELITIAN .................................................................... 54
4.1 Rancangan Penelitian .................................................................................. 54
4.2 Populasi dan Sampel ................................................................................... 54
4.3 Bahan Penelitian .......................................................................................... 55
4.4 Instrumen Penelitian .................................................................................... 55
4.5 Tempat dan Waktu Penelitian ..................................................................... 55
4.6 Definisi Operasional .................................................................................... 55
4.7 Metode Pengumpulan Data.......................................................................... 56
4.8 Analisis Data ................................................................................................ 57
BAB V HASIL PENELITIAN ........................................................................... 58
5.1 Data Demografi Pasien ................................................................................ 59
5.1.1 Jenis Kelamin .............................................................................................. 59
5.1.2 Usia .............................................................................................................. 59
5.1.3 Status Pasien ............................................................................................... 60
5.2 Faktor Resiko .............................................................................................. 60
5.3 Penggunaan Antidiabetik Oral .................................................................... 61
5.4 Pola Pergantian Obat Antidiabetes .............................................................. 63
5.5 Terapi Selain OAD ...................................................................................... 65
5.6 Lama Mendapatkan Terapi Antidiabetik Oral ............................................. 66
5.7 Lama Masuk Rumah Sakit .......................................................................... 66
5.8 Kondisi Keluar Rumah Sakit ....................................................................... 66
BAB VI PEMBAHASAN .................................................................................... 67
BAB VII KESIMPULAN DAN SARAN ........................................................... 94
7.1 Kesimpulan .................................................................................................. 94
7.2 Saran ............................................................................................................ 94
DAFTAR PUSTAKA .......................................................................................... 96
Lampiran-Lampiran ......................................................................................... 100
xiv
DAFTAR GAMBAR
Gambar Halaman
Gambar 2.1 Organ Pankreas ................................................................................... 6
Gambar 2.2 Pulau Langerhans ................................................................................ 8
Gambar 2.3 GLUT 4 protein transporter (a) dan GLUT 4 ke membran sel (b). ... 9
Gambar 2.4 Patogenesis Diabetes Tipe 2 .............................................................. 13
Gambar 2.5 Mekanisme Resistensi Insulin pada Diabetes Melitus Tipe 2 ........... 15
Gambar 2.6 Algoritma Penatalaksanaan Diabetes Melitus Tipe 2 ....................... 25
Gambar 2.7 Struktur Kimia Obat Antidiabetik Golongan Sulfonilurea ............... 26
Gambar 2.8 Struktur Kimia Repaglinid ................................................................ 30
Gambar 2.9 Struktur Kimia Nateglinid ................................................................. 31
Gambar 2.10 Struktur Kimia Metformin .............................................................. 33
Gambar 2.11 Struktur Kimia Pioglitazone ............................................................ 35
Gambar 2.12 Struktur Kimia Risoglitazone .......................................................... 35
Gambar 2.13 Struktur Kimia Acarbose ................................................................. 38
Gambar 2.14 Struktur Kimia Maglitol .................................................................. 38
Gambar 2.15 Struktur Kimia Sitagliptin ............................................................... 40
Gambar 2.16 Struktur Kimia Vidagliptin ............................................................. 41
Gambar 5.1 Skema Inklusi dan Eksklusi Penelitian pada Pasien DM Tipe 2…....58
xv
DAFTAR TABEL
Tabel Halaman
Tabel II.1 Target Pelaksanaan Diabetes Melitus................................................... 24
Tabel II.2 Farmakokinetik Beberapa Sediaan Sulfonilurea .................................. 28
Tabel II.3 Obat-obat yang Berinteraksi dengan Sulfonilurea ............................... 28
Tabel II.4 Obat Hipoglikemik Oral Golongan Sulfonilurea ................................. 29
Tabel II.5 Obat Hipoglikemik Oral Golongan Glinid ........................................... 32
Tabel II.6 Obat Hipoglikemik Oral Golongan Biguanida ..................................... 35
Tabel II.7 Obat Hipoglikemik Oral Golongan Tiazolidindion.............................. 38
Tabel II.8 Obat Hipoglikemik Oral Golongan Inhibitor α-Glukosidase ............... 40
Tabel II.9 Obat Oral Antidiabetik ......................................................................... 43
Tabel V.1 Jenis Kelamin Pasien DM Tipe 2………………………………….….59
Tabel V.2 Usia Pasien DM Tipe 2 ........................................................................ 59
Tabel V.3 Status Pasien DM Tipe 2 ...................................................................... 60
Tabel V.4 Faktor Resiko DM Tipe 2 .................................................................... 60
Tabel V.5 Pola Penggunaan Terapi OAD ............................................................. 61
Tabel V.6 Penggunaan OAD Tunggal pada Pasien DM Tipe 2 ........................... 61
Tabel V.7 Penggunaan Kombinasi 2 OAD pada Pasien DM Tipe 2 .................... 62
Tabel V.8 Penggunaan Kombinasi 3 OAD pada Pasien DM Tipe 2 .................... 63
Tabel V.9 Pola Pergantian Obat Antidiabetes pada Pasien DM Tipe 2 ................ 64
Tabel V.10 Terapi Selain OAD pada Pasien DM Tipe 2 ...................................... 65
Tabel V.11 Lama Mendapatkan Terapi OAD pada Pasien DM Tipe 2 ................ 66
Tabel V.12 Lama MRS Pasien DM Tipe 2 ........................................................... 66
Tabel V.13 Kondisi KRS Pasien DM Tipe 2 ........................................................ 66
xvi
DAFTAR LAMPIRAN
Lampiran Halaman
Lampiran 1 Daftar Riwayat Hidup ...................................................................... 100
Lampiran 2 Surat Pernyataan .............................................................................. 101
Lampiran 3 Rencana Jadwal Penelitian .............................................................. 102
Lampiran 4 Rencana Anggaran Biaya ................................................................ 103
Lampiran 5 Ethical Clearence ............................................................................ 104
Lampiran 6 Tabel Nilai Normal Data Klinik dan Data Laboratorium ................ 105
Lampiran 7 Tabel Pengumpulan Data................................................................. 106
Lampiran 8 Tabel Data Induk ............................................................................. 111
xvii
DAFTAR SINGKATAN
1. α : Alfa
2. β : Beta
3. γ : Gamma
4. ACE : Angiotensin-Converting Enzyme
5. ADA : American Diabetes Association
6. AGIs : Alpha Glucosidase Inhibitors
7. AMP : Activated Protein Kinase
8. ARB : Angiotensin Receptor Blocker
9. ATN : Acute Tubular Necrosis
10. ATP : Adenosin Trifosfat
11. BMI : Body Mass Index
12. BP : Blood Pressure
13. BPJS : Badan Penyelenggara Jaminan Sosial
14. BPOM : Badan Pengawasan Obat-obatan dan Makan
15. BPPV : Benign Paroxysmal Positional Vertigo
16. DCCT : Diabetes Control and Complications Trial
17. CHF : Congestive Heart Failure
18. DKA : Diabetic Ketoacidosis
19. dL : Desiliter
20. DM : Diabetes Mellitus
21. CPI : C-Peptide Index
22. DPP-4 : Dipeptidyl Peptidase-4
23. DRPs : Drug Related Problems
24. FPG : Fasting Plasma Glucose
25. g : Gram
26. GDA : Gula Darah Acak
27. GDP : Glukosa Darah Puasa
28. GD2PP : Glukosa Darah 2 jam Post Prandial
29. GFM : Glomerular Filtration Membrane
30. GFR : Glomerulus Filtration Rate
31. GI : Gastrointestinal
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32. GIP : Gastric Inhibitory Polypeptide
33. GLP-1 : Glukagon Like Peptide-1
34. GLUT 4 : Glucose Transporter 4
35. HDL : High Density Lipoprotein
36. HMW : High Molecular Weight
37. H2RAs : Histamine-2-Receptor Antagonist
38. IDF : International Diabetes Federation
39. IFG : Impared Fasting Glucose
40. IGT : Impared Glucose Tolerance
41. IL-6 : Interleucin-6
42. ISK : Infeksi Saluran Kemih
43. KRS : Keluar Rumah Sakit
44. L : Liter
45. LDL : Low Density Lipoprotein
46. LPD : Lembar Pengumpulan Data
47. MAO : Monoamine Oxidase
48. mEq : miliequivalent
49. mg : Miligram
50. mL : Mililiter
51. mmHg : Milimeter Hydrargyrum/Milimeter Raksa
52. MRS : Masuk Rumah Sakit
53. NEFAs : Non Esterifi Fatty Acids
54. NGSP : National Glycohemoglobin Standardization Program
55. NIDDM : Non-Insulin Dependent Diabetes Mellitus
56. OAD : Oral Antidiabetik
57. OHO : Obat Hipoglikemik Oral
58. PAI-1 : Plasminogen Activator Inhibitor-1
59. pH : pangkat Hidrogen
60. PKV : Penyakit Kardiovaskuler
61. PPAR-γ : Peroxisomen Proliferator Activated Reseptor gamma
62. PPI : Proton Pump Inhibitor
63. PPPG : Post Prandial Plasma Glucose
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64. RA : Ringer Acetate
65. RISKESDAS : Riset Kesehatan Dasar
66. RL : Ringer Lactat
67. RMK : Rekam Medis Kesehatan
68. RR : Respiration Rate
69. SPM : Standar Pelayanan Minimal
70. SUIT : Secretory Unit of Islet in Transplantation
71. SUR : Sulfonilurea
72. TD : Tekanan Darah
73. TG : Trigliserida
74. TGT : Toleransi Glukosa Terganggu
75. TNF-α : Tumor Necrosis Factor-α
76. TTGO : Tes Toleransi Glukosa Oral
77. TTH : Tension Type Headache
78. TZD : Tiazolidinedion
79. UKPDS : United Kingdom Prospective Diabetes Study
80. USFDA : United States Food and Drug Administration
81. VAT : Visceral Adipose Tissue
82. VEGF : Vascular Endothelial Growth Factor
83. VLDL : Very Low Density Lipoprotein
84. WHO : World Health Organization
96
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