Pulmonary tuberculosis

(Indonesia)
•2rd 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

 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 (+) 1 st Category
•Radiology(+)
•Laboratory(-)
 • Clinically (+)
2 nd Category
• Radiology (+)
• History (+)
• Laboratory (+)

Pulmonary Tb

• Clinically (+)
• Radiology (+) 1 st Category
• History ( - )
• Laboratory (+)
 •Clinically (-)
No treatment •Radiology (-) or (+)
•History (+)
•Laboratory (-)

Post pulmonaryTb

•Clinically ( +)
•Radiology (+) Symptomatic
•History (+)
•Laboratory (-)
THE PRINCIPAL ANTI TB DRUGS

H : ISONIAZID
R : RIFAMPICIN
E : ETHAMBUTOL
Z : PYRAZINAMIDE

S : STREPTOMYCIN
T :THIOCETAZONE
 KATEGORI I Penderita baru TB-Paru BTA (+)
Tb-paru bta (-), Ro” +, skt berat
2HRZE/4H3R3
Tb ekstra-paru berat
2HRZE/4HR
2HRZE/6HE

 KATEGORI II Tb paru kambuh (relaps)

Tb paru gagal (failure)
2HRZS/HRZE/5H3R3E3
Pengobatan stl lalai (after-
2HRZES/HRZE/5HRE
default)
 KATEGORI III Pend baru BTA(-), Ro (+) lesi minimal,
skt ringan
2HRZ/4H3R3 Pdr ekstra paru ringanlimfadenitis,

2HRZ/4HR pl.eksv unilateral, osteomielitis tb artritis

2HRZ/6HE 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 : ( 2 HRZES + HRZE/ 5 H3R3E3 )

(Relapse, failure, AFB + ) ( 2 RHZES/ 5 RHE )

3 rd Category : ( 2 HRZ/ 4 H3R3 )

(New cases, AFB - ) ( 2 HRZ/ 4 HR)

4 th Category : ( H long-life ? )
(Chronic tb)
“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.)
106
Rise & fall phenomena

+ + + + +
Time
 POLITICAL
COMMITMENT

DIAGNOSTIC DRUG - FDC

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 R (150 mg) + H ( 75 mg) + Z (400 mg) + E (275 mg)
RHZ R (150 mg) + H ( 75 mg) + Z (400 mg)
R ( 60 mg) + H ( 30 mg) + Z (150 mg)  paed. use
RH R (300 mg) + H (150 mg)
R (150 mg) + H ( 75 mg)
R ( 60 mg) + H ( 30 mg)  paed. use
EH H (150 mg) + H (400 mg)

Drug Drug strengths for use 3 times a week

RHZ R (150 mg) + H (150 mg) + Z (500 mg)
RH R (150 mg) + H (150 mg)
R ( 60 mg) + H ( 60 mg)  paed. use
(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)

R : * 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 Tatalaksana
penyebab

Minor OAT diteruskan

Tidak makan, mual, Rifampisin Obat diminum malam

sakit perut sebelum tidur

Nyeri dada Pyrazinamid Beri aspirin/Allopurinol

Kesemutan s/d rasa INH Beri vit.B6 1x100 mg/hari

terbakar diikaki

Warna kemerahan Rifampisin Beri penjelasan, tidak perlu

pada air seni diberi apa2
Mayor Hentikan obat

Gatal dan kemerahan pada kulit Semua jenis Beri anti histamin dan
OAT evaluasi ketat
Tuli Streptomisin Streptomisin stop

Gangguan keseimbangan (vertigo & Streptomisin Streptomisin stop

nistagmus

Hepatitis imbas obat Sebagian besasr Hentikan semua OAT

OAT sampai iktertik hilang dan
boleh diberikan
hepatoproktektor
Muntah&cofusion (susp. Drug Sebagian besasr Hentikan semua OAT dan
induce) OAT lakukan uji fungsi hati

Gangguan penglihatan Etambutol Hentikan etambutol

Kelainan sistemik, termasuk, syok Rifampisin Hentikan rifampisin

dan purpura
 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

S : Only parenterally, because it cannot cross

lipid membranes, excreted unchanged in
the urine

E : ± 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)
R : Bactericidal for slow-growing intracellular
bacteria, inhibits DNA-dependent
RNA polymerase, synergistically with H to
kill extracellular organism
E : Bacteriostatic, inhibits bacterial RNA synth.

Z : Bactericidal for intracellular bacteria

S : 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

R : Absorbed in the intestine & reduced by concurrent

food, rapidly eliminated in bile, enters entero-
hepatic circ. & deacetylation to an active
metabolite, > 30 % excreted in active form in the
urine
 Doses of anti tb drugs
(tb control program in Indonesia,
based on WHO recommendation)
1 st Category
Intensive : H 300 mg , R 450 mg, Z 1500 mg, E 750 mg
phase
Intermittent : H 600 mg , R 450 mg
phase
2 nd Category

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

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

phase

Intermittent : H 600 mg , R 450 mg

phase
 Paduan OAT yang paling aman untuk pasien
TB dengan gagal ginjal adalah 2HRZ/4HR.
 Paduan OAT yang dianjurkan untuk pasien TB
dengan kelainan hati yaitu 2RHES/6RH atau
2HES/10HE.
 Pencegahan terhadap penyakit TB dapat
dilakukan dengan hidup sehat dengan makan
makanan bergizi dan teratur, istirahat yang
cukup, olah raga teratur, hindari rokok,
minuman beralkohol, obat bius, hindari stress.
 Kemudian untuk mencegah terjadinya
penularan TB, maka para pasien TB
diharapkan menutup mulut saat batuk dan
tidak meludah di sembarang tempat. Usaha
pencegahan lainnya yaitu dengan melakukan
imunisasi BCG (Bacillus Calmette-Guerin) yang
akan memberikan kekebalan aktif pada
penyakit TB. Selain itu menjaga daya tahan
tubuh juga penting dalam mengantisipasi
penyakit TB. Dengan daya tahan tubuh yang
kuat maka tidak mudah untuk terserang
infeksi oportunistik (TB).