K44 - Farmakologi Obat Anti-TB.pptx
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Transcript of K44 - Farmakologi Obat Anti-TB.pptx
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Rozaimah Zain Hamid
Tri Widyawati
Dr. Hasanul Arifin
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Mycobacterium
Bakteri tahan asam (BTA)
Penyebab penyakit tuberkulosis (Mycobacterium tuberculosis)
Penyebab penyakit leprosi /penyakit Hansen
(Mycobacterium leprae)
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Masalah pada penggunaanobat antituberkulosis (OAT)
Pertumbuhan yang cepat bakteri ekstraselular (H, R)
Pertumbuhan yang lambat bakteri intraselular di dalam makrofag (Z)
Bakteri yang berada di dalam granuloma kaseosa (R)
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Masalah pada penggunaanobat antituberkulosis (OAT)
Resitensi kuman terhadap OAT
Kondisi dorman memerlukan terapi jangka lama
Toksisitas OAT
Kepatuhan pasien terhadap regimen pengobatan
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Antimycobacterium TB
Lini pertama: Isoniazid / INH (H)
Rifampicin (R)
Ethambutol (E)
Pyrazinamide (Z) Streptomycin (S)
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Antimycobacterium TB
Lini kedua: Amikacin
Capreomycin Cycloserine Ethionamide
Fluoroquinolone Kanamycin
p-aminosalicylic acid
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Antimycobacterium TB
Lini kedua: Efektivitas < lini pertama E.S.O > lini pertamaToleransinya < lini pertama morbiditas biaya pengobatan Frekwensi pemberian > lini pertama adherensi <
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Antimycobacterium TB
Lini kedua:
Resisten terhadap OAT lini pertama
Gagal dengan terapi konvensional
Pertimbangan terhadap efek toksik OAT lini pertama
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Isoniazid / INH (H)
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Isoniazid / INH
Bakterisid (terutama untuk bakteri di ekstraselular
yang sedang tumbuh dengan cepat)
Tersebar dengan cepat ke seluruh jaringan, mempenetrasi sel bakteri &
dapat melintasi sawar darah otak
Mengganggu sintesa dinding sel, sintesa asam nukleat,
metabolisme lipid bakteri
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Isoniazid / INH
Di metabolisme di hepar melalui reaksi acetylasi
Golongan acetylator cepat:T ½ : ≤1,5 jam
orang Asia, Jepang & Eskimo(kegagalan pada terapi intermiten)
Diberikan peroral
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Hepatitis Neuropati periferal
‘SLE-like rash’ Gangguan mental
Reaksi hypersensitivitas
Efek samping isoniazid / INH(H)
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Rifampicin (R)
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Rifampicin (R)
Bakterisid (bakteri gram (+) & ( - ),
M.tuberculosis intraselular & sinergistik dengan INH untuk bakteri ekstraselular
Diabsorpsi di usus & tersebar ke seluruh jaringan
Menghambat ‘DNA-dependent RNA polymerase’ bakteri
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Rifampicin (R)
Di metabolisme melalui reaksi deacetylasi
Menginduksi sistem enzim metabolisme aktivitas obat yang
dimetabolisme di hepar(methadone, coumarin, estrogen, kontrasepsi oral,
agen hipoglisemik & digoxin)
Dieliminasi dengan cepat ke dalam empedu & mengalami sirkulasi enterohepatik
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Hepatitis Trombositopenia
Ikterus Gangguan saluran cerna
Reaksi demam Warna jingga pada urin, air mata
& lensa kontak
Efek samping rifampicin(R)
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Ethambutol (E)
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Bakteriostatik
Ethambutol (E)
Menghambat sintesa RNA bakteri
80 % diabsorpsi di saluran cerna & tersebar ke seluruh jaringan & cairan tubuh termasuk cairan cerebrospinal & paru-paru
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Ethambutol (E)
Di metabolisme di hepar
50 % diekskresi dalam bentuk utuh melalui urin
20 % diekskresi dalam bentuk utuh melalui feses
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Efek samping ethambutol(E)
Neuritis optik retrobulber (hilang sensasi warna merah & hijau)
Hypersensitivitas
Hyperuricemia
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Pyrazinamide (Z)
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Pyrazinamide (Z)
Bakterisid dalam makrofag yang berada dalam lingkungan asam &
membasmi bakteri intraseluler, sinergistik dengan INH membasmi bakteri
ekstraseluler
Diabsorpsi di saluran cerna & sebagian besar diekskresi dalam
bentuk utuh melalui filtrasi glomerulus
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Efek samping pyrazinamide(Z)
Hepatitis
Demam karena obat
Hyperuricemiamenghambat ekskresi renal asam urat
penyakit gout
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Streptomycin (S)
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Streptomycin (S)
Terutama terhadap bakteri ekstraseluler
Hanya dapat diberikan secara parenteral
Menghambat ikatan pada subunit 30S ribosom bakteri
menghambat sintesa protein
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Efek samping streptomycin(S)
Ototoksisitas yang menetap
Gangguan vestibular / keseimbangan
Nefrotoksisitas
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DASAR TEORI TERAPI KOMBINASI
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106
Waktu
Pola resistensi Mycobacterium tuberculosis P
op
ula
si k
um
an
(Dasar teori terapi kombinasi)
++ + + +
“Rise & fall phenomena”
sensitif
resisten
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INTERMITEN TERAPIOBAT ANTI TB
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‘Lag phase’ Terhentinya metabolisme kuman
pada periode waktu tertentu
Mycobacterium tuberculosis (72 jam )
Sekali / hari Sekali / 2 atau 3 hari
Pemberian OAT
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INTERAKSIOBAT ANTI TB
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INTERAKSI OBAT ANTI TB
Pemberian bersamaan dengan phenytoin
Kadar kedua obat dalam darah
Kombinasi dengan pyrazinamide (Z)
Pengobatan TB yang lebih baik
Isoniazide (H)
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Induksi sistem enzim hepatik
Rifampicin (R)
ekskresi urin, kadar plasma gejala putus obat methadone
eliminasi antikoagulan, kontrasepsi
kadar ketoconazole, cyclosporine, chloramphenicol dalam serum
INTERAKSI OBAT ANTI TB
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‘DIRECT OBSERVED THERAPY SHORTCOURSE’ / (‘DOTS’)
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Meningkatkan kepatuhan minum obat(‘compliance’)
‘DIRECT OBSERVED THERAPY SHORTCOURSE’ / (‘DOTS’)
Keberhasilan terapi
Pengawas Minum Obat (PMO)
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KOMBINASI DOSIS TETAPOBAT ANTI TB
(‘FIXED DOSE COMBINATIONS’/ (‘FDCs’)
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Bukan ‘Combipacks’, tetapi 2,3 atau 4 obat dalam satu tablet
Problem utama bioavailabiliti of rifampicin pada beberapa formula
WHO formula standard untuk kajian bioavailabiliti
Kombinasi Dosis TetapFixed Dose Combinations (FDCs)
Kombinasi Dosis TetapFixed Dose Combinations (FDCs)
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Problem bioavailabiliti rifampicin
solusi
Bahan baku yang baik Prosedur standard:
Cara Pembuatan Obat yang Baik (‘Good Manufacturing Practice/GMP’)
Jaringan pengawasan kualitas obat FDCs oleh WHO
(kajian bioavailabiliti)
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