Download - ANTI MIKOBAKTERI
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DAN FK 111208 1
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DAN FK 111208 2
• Lambat berkembang
• Dormant
• Intrasel/ makrofag
• Membran kaya lipid
Sulit diobati
ResistenResisten
Sulit ditembus
KOMBINASI KOMBINASI dengan respon lambat
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DAN FK 111208 3
FAKTOR MEMPERSULIT FAKTOR MEMPERSULIT PENGOBATAN:PENGOBATAN:
1. Daya tahan hospes kurang
2. Daya bakterisid obat yang ada kurang
3. Timbul resistensi kuman
4. Efek samping obat
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DAN FK 111208 4
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DAN FK 111208 5
TUBERKULOSE (TBC)TUBERKULOSE (TBC)• ADALAH:ADALAH:
Psx inf kronis; plg sering tjd di paru (80%)
Ekstra paru: KGBKGB, ginjal, tulang, meningen
• PENYEBAB:PENYEBAB:
Mycobacterium tuberculosis, tahan asam
• GEJALA:GEJALA:
Batuk kronis (> 2 mgg), dahak berdarah, demam, keringat malam, sesak, nyeri dada, malaise, anoreksia, BB ↓, kontak (+)
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DAN FK 111208 6
TUBERKULOSTATIKTUBERKULOSTATIK• FIRST-LINE AGENTFIRST-LINE AGENT ::
IsoniazidIsoniazid : H : H
Rifampin Rifampin : R: R
PyrazinamidePyrazinamide : Z: Z
Ethambutol Ethambutol : E: E
StreptomysinStreptomysin : S: S
Resistensi/ Gagal respon/ Ef toksik
SECOND-LINE SECOND-LINE AGENTAGENT
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Dian Novita,dr
7
Dian Novita,dr
7
DRUGS USED IN TUBERCULOSIS
Dian Novita,dr
7
Isoniazid and rifampin are the two most active drugs
isoniazid-Rifampin combination administered for 9 months will cure 95–98% of cases of tuberculosis (susceptible strains)
Pyrazinamide + isoniazid-rifampin combination for the1st 2 months → therapy for 6 months without loss of efficacy
Ethambutol & Streptomycin → provide additional coverage if the isolate proves to be resistant to isoniazid, rifampin
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DAN FK 111208 8
DURASI Tx TUBERKULOSEDURASI Tx TUBERKULOSE
Regimen Durasi
Rifampin, isoniazid, pyrazinamide 6 bln
Rifampin, isoniazid 9 bln
Rifampin, ethambutol, pyrazinamide 6 bln
Rifampin, ethambutol 12 bln
Isoniazid, ethambutol 18 bln
Lainnya / (2nd line) >24 bulan
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DAN FK 111208 9
ISONIAZIDISONIAZID• Isonicotinyl hydrazide (INH)
• Antagonis kompetitif dalam reaksi yang dikatalisasi oleh pyridoxine (analog struktural)
• u/ basil tuberkel ekstrasel & intrasel
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DAN FK 111208 10
• F.KINETIK:F.KINETIK:
A:A: p.o, i.v; ↓: antasida (Al)
D: D: pleural, asitic fluid, CSF(inflamed)
M:M: di hepar
E:E: ren
• KEGUNAAN Kx:KEGUNAAN Kx:
– OAT plg penting (pd s’tiap regimen)
– u/ Profilaksis
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DAN FK 111208 11
RIFAMPINRIFAMPIN• F. KINETIK:F. KINETIK:
A:A: oral baik (ac)D:D: luas, termasuk BBB M:M: hepar E:E: bile
• INTERAKSI Ox:INTERAKSI Ox: enz inducermethadone, antikoagulan, antikonvulsan, kontrasepsi, kortikosteroid, digitoksin, propanolol, sulfonilurea, warfarin, cyclosporine, ketokonazole, chloramphenicol
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PYRAZINAMIDPYRAZINAMIDEE
KEGUNAAN Kx:KEGUNAAN Kx:
Efektif u/ pengobatan fase I (intensif)
Faktor ptg keberhasilan tx jangka pendek
DAN FK 111208
12
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DAN FK 111208 13
ETHAMBUTOLETHAMBUTOL• Sukar resistensi kec R/ tunggal
• F.KINETIK:F.KINETIK:
A:A: baik
D:D: m’nembus BBB
E:E: 50 % urine (utuh), 20% feses (metabolit)
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DAN FK 111208 14
STREPTOMYCINSTREPTOMYCIN• Gol aminoglikosida
• F.KINETIK:F.KINETIK: A:A: Po <<, Pe >>
D: D: seluruh car ekstra sel, BBB (<)
E: E: ren (utuh)
• KEGUNAAN Kx:KEGUNAAN Kx:– u/ basil tuberkel ekstrasel
– u/ TBC berat
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DAN FK 111208 15
FDC (Fixed Dose Combination)FDC (Fixed Dose Combination)• 4 FDC: 75 mg H, 150 mg R, 400 mg Z, 275 mg E• 2 FDC: 150 mg H, 150 mg R
• Kategori I:Kategori I: px baru: BTA (+)/ BTA (-), Ro (+) 2RHZE/ 4R3H34 FDC;2bln 2FDC 3x/mgg;4bln
• Kategori II:Kategori II: kasus kambuh, gagal, putus berobat2RHZES/ RHZE/ 5R3H3E34FDC+S;2bln 4FDC;1bln 2FDC+E 3x/mgg;5bln
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DAN FK 111208 16
FDC FDC (Fixed Dose (Fixed Dose
Combination)Combination)
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Dian Novita,dr
17
17
17
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DAN FK 111208 18
EFEK SAMPINGEFEK SAMPINGEFEK SAMPINGEFEK SAMPING PENYEBABPENYEBAB TATALAKSANATATALAKSANA
MINOR MINOR TERUSKANTERUSKAN
G3 GIT R Sebelum tidur
Hiperuresemia Z, E Aspirin, Allopurinol
Neuropati perifer H (acetylator lmbt) Pyridoxine 25-50 mg/hr
Car tbh kemerahan R Advice
MAYOR MAYOR HENTIKANHENTIKAN
Alergi, urtikaria H,R,Z,E,S AH, observasi ketat
N VIII, nefrotoksik S Stop
Mual , muntah, H,R,Z Ikterik -, uji faal hati,
confus, ikterik Tx: hepatoprotektor
Neuritis retrobulber E (~dosis) Stop (KI:< 5 th)
Kelainan sistemik R Stop
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DAN FK 111208 19
KEADAAN KHUSUSKEADAAN KHUSUS• Bumil: aman, kecuali: streptomycin• KB hormonal dihindari (rifampin)• Gagal ginjal:
hindari aminoglycosida; ethambutol tx dg ox lain hendaknya dosis disesuaikan
• Kx hati: hindari pirazinamide• DM: hindari ethambutol; rifampin; kontrol gula
darah
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DAN FK 111208 20
PENYEBAB RESISTENSIPENYEBAB RESISTENSI• Pemakaian ox tunggal
• Panduan ox tdk adekuat
• Pemberian tidak teratur
• Fenomena “addition syndrome”
• Ox kombinasi dg p’campuran tdk baik
• Penyediaan ox tidak reguler
• Pemakaian ox cukup lama
• Pengetahuan px kurang
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DAN FK 111208 21
RESISTEN GANDA/ MDRRESISTEN GANDA/ MDR
• ADALAH:ADALAH: M.tuberculosis resisten thd Rifampin & INH ± OAT lain
Hidari: resistensi silang/ OAT dr gol sama
• Berikan RHZES sambil menunggu uji resistensi min 2 atau 3 OAT sensitif + ox lini2 (tx min 18 bl) INH seumur hidup
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DAN FK 111208 22
KLASIFIKASI OAT untuk MDR:KLASIFIKASI OAT untuk MDR:• Bakterisid:
– Aminoglycosida (inj): Streptomycin, Kanamycin, Amikacin, Capreomycin
– Thionamide: Ethionamide, Prothionamide– Pyrazinamide
• Bakterisid rendah: – Fluoroquinolone: Ofloxacin=Ciprofloxacin<
Levofloxacin<Moxifloxacin<Gatifloxacin
• Bakteriostatik:– Ethambutol, Cycloserine, PAS, Thioacetazone
• Unclear efficacy– Clofazimine, Amoxicillin/Clavulanate, Clarithromycin,
Linezolid
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DAN FK 111208 23
PILOT PROJECT 2008 PILOT PROJECT 2008 DOTS PLUS INDONESIADOTS PLUS INDONESIA
1. Kanamycin (K) inj bac-cide
2. Cycloserine (Cs) oral bac-statik
3. Ethionamide (Eto) oral bac-cide
4. Levofloxacin (Lfx) oral
5. Pyrazinamide (Z) oral bac-cide
6. Ethambutol (E) oral bac-statik
66 K-Lfx-Eto-Cs-Z-E /K-Lfx-Eto-Cs-Z-E /12-1812-18 Lfx-Eto-Cs-Z-ELfx-Eto-Cs-Z-E
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DAN FK 111208 24
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DAN FK 111208 25
KUSTAKUSTA• LEPRA = MORBUS HANSENLEPRA = MORBUS HANSEN
• ADALAH:ADALAH:
Psx inf kronis yg menyerang saraf tepi, kulit, nasal, mucosa, dan mata
slow–growing intercellular bacillus
Masa inkubasi 2 -10 th (s/ 20 th)
• PENYEBAB:PENYEBAB: Mycobacterium leprae
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DAN FK 111208 26
KLASIFIKASI WHOKLASIFIKASI WHO
Cardinal SignCardinal Sign PB PB (Paucibacillary)(Paucibacillary)
MB MB (Multibacillary)(Multibacillary)
BercakBercak 1-51-5 > 5> 5
Lesi saraf tepiLesi saraf tepi 1 saraf1 saraf > 1 saraf> 1 saraf
Sediaan apusSediaan apus BTA (-)BTA (-) BTA (+)BTA (+)
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DAN FK 111208 27
SULFONE SULFONE • Diamino Diphenyl Sulfone (DDS) atau Dapsone
• Tab putih 50 mg, 100 mg
• Bakteriostatik
• KINETIK:KINETIK:
A:A: baik; t ½: 1-2 hr
D:D: luas; ditimbun di kulit (inf >>), ot, hepar, ren trace (+) stlh tx 3 mgg
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DAN FK 111208 28
CLOFAZIMINECLOFAZIMINE• Atau LAMPRENELAMPRENE; Turunan phenazine • Kapsul coklat 50 mg, 100 mg• Resisten/ tidak toleran terhadap sulfone• Bakteriostatik
• F.KINETIK:F.KINETIK:A:A: bervariasi; t ½ sampai 2 bulanD:D: ditimbun dijaringan retikuloendotelial & kulit
• Sbg antireaksi (antiinflamasi) m’cegah ENL
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DAN FK 111208 29
OFLOXACINOFLOXACIN• Turunan Fluoroquinolone
MINOCYCLINEMINOCYCLINE• Turunan Tetracycline
CLARITHROMYCIN CLARITHROMYCIN • Golongan Macrolide
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DAN FK 111208 30
THALIDOMIDETHALIDOMIDE
• Sbg pengganti Clofazimine (krn ES pigmentasi)
• Tdk digunakan: cepat timbul resistensi, > toksik
ETHIONAMIDEETHIONAMIDE
• Tx ENL
• Tdk digunakan: teratogenik
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DAN FK 111208 31
• Pausi Basiler (PB):Pausi Basiler (PB): 6 blister 6-9 bulan Di depan petugas; bulanan: RMP 600 mg & DDS 100 mg
Di rumah; harian: DDS 100 mg
• Multi Basiler (MB):Multi Basiler (MB): 12 blister 12-18 bulanDi depan petugas; bulanan:
RMP 600 mg; Clofazimine 300 mg; DDS 100 mgDi rumah; harian: Clofazimine 50 mg (1 mg/kgBB/hr);
DDS 100 mg (1-2 mg/kgBB/hr)
KEADAAN KHUSUSKEADAAN KHUSUS• Bumil: aman• Px TB: RMP sesuai dosis TB
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DAN FK 111208 32
EFEK SAMPINGEFEK SAMPING MINOR MINOR TERUSKAN TERUSKAN
EFEK SAMPINGEFEK SAMPING PENYEBABPENYEBAB TATALAKSANATATALAKSANA
Kulit merah, coklat hitam clofazimine Advice
Gangguan GIT dapsone, clofazimine
durante/post coenam
Hemolisis, Methemoglobnemia
dapsone Fe,
asam folat
MAYOR MAYOR HENTIKAN HENTIKAN EFEK SAMPINGEFEK SAMPING PENYEBABPENYEBAB TATALAKSANATATALAKSANA
Alergi, urtikaria,
ENL (Eritema Nodosum Leprosum)
dapsone PB: ganti dg clofazimine
MB: tanpa dapsone
Tx: Prednison
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DAN FK 111208 33
what
why where
how
who
TERIMA KASIHTERIMA KASIH