Bismillahirrohmaanirrohiim

Asyhadu anlaa ilaaha illalloh

wa asyhadu anna Muhammadan rasuululloh

Rodliitu billahi robbaa
wa bil-islaami diinaa
wa bi Muhammadin nabiyyaw wa rosuulaa

Robbii zidni ilmaa
warzuqnii fahmaa
Aamiin....
Doa belajar
Wiwik Kusumawati, MD, Master of Health
Science
Lecturer of Pharmacology (1996 to now)
Lecturer of Medical Education (2004 to now)
Vice Dean for academic affair (2004 to 2007)
Coordinator of Pharmacology Dept (1996 to
2002)
Coordinator of Medical Education Unit (2004 to
2010)
PhD Cand. of Medical Education of Faculty of
Medicine Gadjah Mada University, Yogyakarta
(2007 now)
Magister of Health Sciences from Faculty of
Medicine of Gadjah Mada University,
Yogyakarta (1997 2000)
Medical Doctor from Faculty of Medicine of
Airlangga University, Surabaya (1985 1991)
General Practitioner (PTT doctor) at Ende,
Flores, NTT (1992 1995)

By
Wiwik Kusumawati

Tuberculosis Infection
?
Pulmonary tuberculosis
7.5 to10.2 million new cases of tbc (WHO)
2.5 to 3.5 million tuberculosis death
Develop and developing countries
Immunodeficiency virus (HIV) infection
Up 80 % tbc px are HIV positive
3.5 million, dual infection
Reactivation dormant infection
Pulmonary tuberculosis
Prompt diagnosis and effective treatment
General symptoms
Weight loss, malaise, fevers
Respiratory symptoms
Cough, sputum and haemoptysis

Resistance of M. tuberculosis
Spontaneous mutation
Improperly prescribed therapy
Erratic drug ingestion
Inadequate dosage
Incomplete therapy
Lack of compliance by px
Resistance of M. tuberculosis
MDR : INH and Rifampicin
XDR : + Fluoroquinolone + 1 injection
drug
Primary
Secondary
Distribution of Primary MDR
Compliance ?
DIRECTLY OBSERVE THERAPY
Patient compliance
Health care
CLASS ROUTE MAJOR INDICATION
Isoniazid PO Primary
Rifampin IV, PO Primary
Streptomycin IM Primary
Ethambutol PO Primary
Pyrazinamide PO Primary CNS or
secondary
Capreomycin IM Secondary or atypical
Kanamycin IM Secondary
Cycloserine PO Secondary
Ethionamide PO Secondary or atypical
Aminosalicylic acid PO Secondary
Clofazimine PO Atypical in HIV px
Rifabutin PO Atypical in HIV px
INH & Rifampin
Tuberculocidal for both extracellular intracellular
organism
Streptomycin
Tuberculocidal for extracellular organism only
Pyrazinamide
Tuberculocidal for intracellular organism
Ethambutol, p-aminosalicylic acid &
ethionamide
Tuberculostatic
Bactericidal cell wall synthesis
Combination
Active infection
Secondary chemoprophylaxis should be given with
2 or more effective drugs
Should never be used as a single to treat
active tbc
Single agent (monotherapy)
Primary chemoprophylaxis
PO: well and rapidly absorbed
Peak concentration 1 to 2 hours
The distribution is extensive
3 to 5 mg/kg/day 20 mg/kg/day
Metabolism by acetylation and hydroxylation
Slow acetylators (Scandinavia, North Africa)
adverse effects
Rapid acetylators (Japan, Escimo) intermittent
regimen
No influence both the effect of therapy and side
effect if INH given everyday
Side effect
Peripheral neuropathy 10 mg/day of
pyridoxine
Induced hepatic injury
A first-line bactericidal anti-tuberculosis
Inhibits RNA-polymerase
Combination with pyrazinamide : persisters
PO, IV
PO : well and completely absorbtion (empty
stomach)
Peak concentration 2 to 4 hours
Combination with INH not influence absorbtion
Distribution is extensive, protein
(albumin) binding 80%
Red-brown colouration of body fluid
Metabolism deacetylation active
metabolite
Excretion : biliary and renal (30%)
Resistant rifampicine rifabutine
Dose 450 600 mg/day (adult); 10 20 mg/kg
BW/day (children)
Side effect
Rash, fever, nausea, vomiting
Flu like syndrome
Hepatotoxic hepatitis
Enzyme hepatic inducer (increase metabolism
of oral contraception, corticosteroid,
hypoglycemic agent, vitamine D)
PAS inhibits absorbtion of rifampicine
Rifampicine + INH (slow acetlators)

Bactericidal to mycobacteria multiplying
intracellularly at low pH level
The first 2 months of a treatment regimen
Reduce later relaps rates
A shorter duration of therapy
PO : well absorbed
Penetrates well in CSF
Nausea, flushing, arthralgia, hepatotoxic
reactions
An aminoglycoside
Extracellular bacteria
Single drug no effective
Must be given by injection (IM)
Widely distributions doesnt cross well
into CSF
30 % protein binding
90 % drugs excreted via urine
Dose
20 mg/kg BW maximally 1 gram/day
Side effect
Neurotoxic and nephrotoxic
8 cranial nerve damage, vestibular
toxicity, rash
Caution
Pregnancy, elderly, renal disease, etc
An essentially bacteriostatic
Inhibits mycobacterial cell wall synthesis
PO : well absorbed (75% to 80 %)
Doesnt cross BBB
Excretion : unchanged in the urine
Dose 15 mg/kg BW/day
Side effect
Retrobulbar neuritis (bilateral)
Rash, fever, Increasing blood uric acid,
etc

At least 3 drugs
INH, Rifampicin, Pyrazinamide
For at least 8 weeks sensitivity
established


Rifampicin and INH
Further 4 months
2HRZ/4HR 6 months
2EHR/7HR 9 month
Rifampicin not included : 18 months

Monitoring adverse effect and efficacy of
drugs
Monitoring up to 1 year after a regimen
completely
Treatment during pregnancy
INH, Ethambutol, Rifampicin (safely)
INH, Pyrazinamide, Rifampicin (poorly tolerated)
Ethionamide is contra indication
Streptomycin is best avoided
Treatment in renal disease
Rifampicin (normal dose)
Other drugs (reduced dose)
Pyrazinamide precipitate gout
Streptomycin if essential
Ethambutol is best avoided in renal failure (GFR 50
ml/min or 3 L/h)
Treatment in liver disease
INH, rifampicin, ethionamide and pyrazinamide can
all be hapatotoxic
Ethambutol, Streptomycin, INH
Regular liver function monitoring
Treatment in children
Standard initial regimen
INH, rifampicin and pyrazinamide
if 2 drugs regimen (INH and rifampicin) : 9 months
Ethambutol is best avoided
Averys Drug Treatment 4
th
edition
(Trevor & Nicholas) : 1047 1054
Clinical Pharmacology, Basic Principles
in Therapeutics (Melmon and Morellis) :
711 712

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