Pulmonary tuberculosis

(Indonesia)
3rd rank in the world
2

nd

rank cause of death

Higher lost of cases

Pulmonary remodelling
cases
Multi drug resistance
cases
Perception
Diagnosis

Pulmonary tuberculosis
(Indonesia)

* One new TB case / minute

* One new infectious TB case / 2 minutes
* One TB case died / 4 minutes

D
s i i ag
s
no

Pulmonary
tuberculosis
Suspected pulmonary
Tb
Pulmonary Tb
Post pulmonary Tb

KLINIS
Respiratorik : batuk > 2minggu,batuk darah,
sesak napas / nyeri dada
Sistemik : demam, malaise, keringat malam,
anoreksia, berat badan turun
Gejala TB ektra paru

Laboratoris : Mikrobiologi BTA (pasti)

Darah, Serum-imunologis (kead.
khusus), Deteksi DNA
Radiologis
TB aktif : infiltrat (berawan), kavitas, milier,efusi
TB inaktif : fibrotik, kalsifikasi, schwarte

Clinically
(+)
1 st Category
History (-)
Radiology
(+)
Laboratory
(-)
Suspected pulmonary
Tb
Clinically (+)
History (+)
Radiology(+
)
Laboratory(-

1 st Category

2 nd Category

Clinically (+)
Radiology
(+)
History (+)
Laboratory
(+)

Pulmonary Tb
Clinically (+)
Radiology
(+)
History ( - )
Laboratory
(+)

1 st Category

No treatment

Clinically (-)
Radiology (-) or
(+)
History (+)
Laboratory (-)

Post pulmonaryTb
Clinically ( +)
Radiology (+)
History (+)
Laboratory (-)

Symptomatic

THE PRINCIPAL ANTI TB DRUGS

H
R

: ISONIAZID
: RIFAMPICIN

: ETHAMBUTOL

: PYRAZINAMIDE

: STREPTOMYCIN

:THIOCETAZONE

KATEGORI I
2HRZE/4H3R3
2HRZE/4HR
2HRZE/6HE

KATEGORI II
2HRZS/HRZE/5H3R3E3
2HRZES/HRZE/5HRE

KATEGORI III
2HRZ/4H3R3
2HRZ/4HR
2HRZ/6HE

Penderita

baru TB-Paru BTA (+)

Tb-paru bta (-), Ro +, skt
berat
Tb ekstra-paru berat
Tb

paru kambuh (relaps)

Tb paru gagal (failure)
Pengobatan stl lalai (afterdefault)
Pend

baru BTA(-), Ro (+) lesi

minimal, skt ringan
Pdr ekstra paru
ringanlimfadenitis,
pl.eksv
unilateral, osteomielitis tb artritis
tb, nepritis tb

KRONIK
RHZES / SESUAI HASIL UJI
RESISTENSI (MINIMAL OAT YG
SENSITIF) + OBAT LINI 2
MINIMAL T/ 18 BLN
KATEGORI

IV

MDR TB
SESUAI UJI RESISTENSI + OAT
LINI 2 ATAU H SEUMUR HIDUP

Guideline of anti tb drugs

(tb control program in Indonesia,
based on WHO recommendation)
1 st Category

: ( 2 HRZE/ 4 HR )
( 2 HRZE/ 4 H3R3 )

(New cases, AFB + ,

AFB , Ro +, severe illness)

2 nd Category
(Relapse, failure, AFB + )

3 rd Category
(New cases, AFB - )

4 th Category
(Chronic tb)

: ( 2 HRZES + HRZE/ 5 H3R3E3 )

( 2 RHZES/ 5 RHE )
: ( 2 HRZ/ 4 H3R3 )
( 2 HRZ/ 4 HR)
: ( H long-life ? )

Lag phase :
Cessation of microbial metabolism
in period of time
Myc. tbc (72 hours )

Drug administration

Once a day

Three times a week

Pattern of Myc. tbc resistance

(Basic theory of multiple drugs adm.)
Rise & fall phenomena

Microbial Population

106

Time

POLITICAL
COMMITMENT

DIAGNOSTIC

DRUG - FDC

DOTS
DOTS
DOT

R.R

Fixed Dose
Combinations (FDCs)
Increase compliance
Reduce risk drug resistance
Lower cost
Less risk medication error
Minimize drug misuse of rifampicin
Simplified
RZH, World TB Day, 2003.

The Rationale for Using FDCs in TB Control

FDCs simplify the delivery of treatment

FDCs simplify drug supply management
WHO quality control network for FDCs provides easy
access to quality testing including bioavailability studies
Management of adverse reactions
FDCs may help prevent the emergence of drug resistance
Cost consideration
RZH, World TB Day, 2003.

Fixed Dose
Combinations (FDCs)

Not Combipacks, but 2,3 or 4 drugs

in one tablet

Main problem bioavailability of rifampicin

in several formulas

WHO standard formula for

bioavailability studies
RZH, World TB Day, 2003.

Bioavailability problem of rifampicin

solution
Good raw materials
Standard procedures quality of
pharmaceutical products
(Good Manufacturing Practice/GMP)
WHO-recommended laboratory network
(WHO & IUATLD only FDCs with proven
bioavailability)
Drug supply continuous & regular
(avoid expiry date influence bioavailability)
RZH, World TB Day, 2003.

Recommended FDCs for

anti-tuberculosis drugs
Drug

Drug strengths for daily use

RHZE
RHZ

EH

R (150 mg) + H ( 75 mg) + Z (400 mg) + E (275 mg)

R (150 mg) + H ( 75 mg) + Z (400 mg)
R ( 60 mg) + H ( 30 mg) + Z (150 mg) paed. use
R (300 mg) + H (150 mg)
R (150 mg) + H ( 75 mg)
R ( 60 mg) + H ( 30 mg) paed. use
H (150 mg) + H (400 mg)

Drug

Drug strengths for use 3 times a week

RHZ
RH

R (150 mg) + H (150 mg) + Z (500 mg)

R (150 mg) + H (150 mg)
R ( 60 mg) + H ( 60 mg) paed. use

RH

(WHO Bulletin, 2001)

RZH, World TB Day, 2003.

DRUG INTERACTION ANTI TB DRUGS

H

: * Concurrent adm. with phenytoin : blood level

of both drugs
* Combination with Z : preferred tb treatment
( reduced the duration of therapy)

: * Induced the hepatic enzyme metabolizing

system : the action of methadone, coumarin
anticoagulants, estrogens, oral hypogycemic
agents, oral contraceptives, digoxin

ADVERSE EFFECTS
OF ANTI TB DRUGS
H : Hepatitis, peripheral neuropathy, SLE-like rash,
mental disorder, hypersensitivity
R : Hepatitis, thrombocytopenia, jaundice, g.i.t dis,
febrile reaction, orange staining of urine, tears &
contact lenses
E : Retro bulbair optic neuritis (loss of red-green),
hypersensitivity, hyperuricemia
Z : Hepatitis, hyperuricemia (dapat menyebabkan
serangan arthritis gout).
S : Ototoxicity, vestibular dis, nephrotoxicity

Efek samping

Kemungkinan
penyebab

Minor

Tatalaksana

OAT diteruskan

Tidak makan, mual,

sakit perut

Rifampisin

Obat diminum malam

sebelum tidur

Nyeri dada

Pyrazinamid

Beri aspirin/Allopurinol

Kesemutan s/d rasa

terbakar diikaki

INH

Beri vit.B6 1x100

mg/hari

Warna kemerahan
pada air seni

Rifampisin

Beri penjelasan, tidak

perlu diberi apa2

Mayor

Hentikan obat

Gatal dan kemerahan pada kulit

Semua jenis
OAT

Beri anti histamin dan

evaluasi ketat

Tuli

Streptomisin

Streptomisin stop

Gangguan keseimbangan
(vertigo & nistagmus

Streptomisin

Streptomisin stop

Hepatitis imbas obat

Sebagian
besasr OAT

Hentikan semua OAT

sampai iktertik hilang
dan boleh diberikan
hepatoproktektor

Muntah&cofusion (susp. Drug

induce)

Sebagian
besasr OAT

Hentikan semua OAT

dan lakukan uji fungsi
hati

Gangguan penglihatan

Etambutol

Hentikan etambutol

Kelainan sistemik, termasuk,

syok dan purpura

Rifampisin

Hentikan rifampisin

FDCs recommended in the 1999

WHO Model List of Essential Drugs

RHZE (tablet)
- 150 mg + 75 mg + 400 mg + 275 mg (daily)
RHZ (tablet)
- 60 mg + 30 mg + 150 mg for pediatric use (daily)
RH (tablet)
- 60 mg + 30 mg for pediatric use (daily)
- 60 mg + 60 mg for pediatric use (intermittent
3 times weekly)

PHARMACOKINETICS OF
ANTI TB DRUGS
Z

: Absorbed orally, mostly excreted unchanged

by GFR

: Only parenterally, because it cannot cross

lipid membranes, excreted unchanged in
the urine

: 80 % absorbed from gi.t irrespective of food

consumption, distr. into most fluids & tissues
(CSF & lung), partially metabolized in the liver,
15 % metabolized drug & 50 % of unchanged
drug (urine), 20 % unchanged (feces)

MECHANISM OF ACTION/ PHARMACODYNAMIC OF

ANTI TB DRUGS
H

: Bactericidal for rapidly growing extracellular

bacteria, affects cell wall synthesis,
lipid metabolism, nucleic acid synthesis
(standard preventive therapy for TB)

: Bactericidal for slow-growing intracellular

bacteria, inhibits DNA-dependent
RNA polymerase, synergistically with H to
kill extracellular organism

: Bacteriostatic, inhibits bacterial RNA synth.

: Bactericidal for intracellular bacteria

: Inhibits protein synthesis & 30 S ribosomal

binding

PHARMACOKINETICS OF
ANTI TB DRUGS
H

: Rapid distr. to all tissues, penetrates into cells,

cross the blood-brain barrier, metabolized by
acetylation

: Absorbed in the intestine & reduced by concurrent

food, rapidly eliminated in bile, enters entero-

Doses of anti tb drugs

(tb control program in Indonesia,
based on WHO recommendation)
1 st Category

Intensive
phase

: H 300 mg , R 450 mg, Z 1500 mg, E 750 mg

Intermittent : H 600 mg , R 450 mg

phase
2 nd Category

Intensive
phase

: H 300 mg , R 450 mg, Z 1500 mg, E 750 mg

S 750 mg

Intermittent : H 600 mg , R 450 mg

phase

Doses of anti tb drugs

(tb control program in Indonesia,
based on WHO recommendation)
3 rd Category

Intensive
phase

: H 300 mg , R 450 mg, Z 1500 mg,

Intermittent : H 600 mg , R 450 mg

phase