Doa belajar

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....

CURRICULUM VITAE

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)

CURRICULUM VITAE
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)

ANTITUBERCULOSI
S DRUGS
By
Wiwik Kusumawati

INTRODUCTION

Tuberculosis Infection

INTRODUCTION

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

INTRODUCTION

Tbc infection in Indonesia?

Population
Hygiene and sanitation
Status of immunity
Status of economy

CASE
A 54 years old man bring to the hospital with
cough more than 3 weeks, fever, and
decreasing of appetite after taking history and
conducting clinical examination, the doctor do
laboratory test (sputum test). Laboratory result
revealed mycobactterium tbc positive and the
doctor prescribe antituberculosis drugs.

Pulmonary T uberculosis
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

Distribution of
Secondary MDR

MAJOR PROBLEM?
Compliance ?

DOTS
DIRECTLY OBSERVE THERAPY
Five component of DOTS

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

DRUGS
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

DRUGS (INH)
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

DRUGS (INH)

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

DRUGS (INH)
Side effect
Peripheral neuropathy 10 mg/day of
pyridoxine
Induced hepatic injury

DRUGS (Rifampicine)
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

DRUGS (Rifampicine)
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

DRUGS (Rifampicine)
Dose 450 600 mg/day (adult); 10 20 mg/kg
BW/day (children)
Side effect
Rash, fever, nausea, vomiting
Flu like syndrome
Hepatotoxic hepatitis

DRUGS (Rifampicine)
Enzyme hepatic inducer (increase metabolism
of oral contraception, corticosteroid,
hypoglycemic agent, vitamine D)
PAS inhibits absorbtion of rifampicine
Rifampicine + INH (slow acetlators)

DRUGS (Pyrazinamide)
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

STREPTOMYCIN
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

STREPTOMYCIN
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

ETHAMBUTOL

An essentially bacteriostatic
Inhibits mycobacterial cell wall synthesis
PO : well absorbed (75% to 80 %)
Doesnt cross BBB
Excretion : unchanged in the urine

ETHAMBUTOL

Dose 15 mg/kg BW/day

Side effect
Retrobulbar neuritis (bilateral)
Rash, fever, Increasing blood uric acid,
etc

INITIAL TREATMENT

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

CONTINUATION
TREATMENT

Rifampicin and INH

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

MONITORING
Monitoring adverse effect and efficacy of
drugs
Monitoring up to 1 year after a regimen
completely

CASE
A 44 years old woman suffering from tbc
infection and also A type of hepatitis infection.
Health care provider give this patient
rifampicine, INH, pyrazinamide as
antituberculosis drugs for 2 months in intensive
phase

SPECIFIC CONDITION
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)

SPECIFIC CONDITION
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

Refferences
Averys Drug Treatment 4th edition
(Trevor & Nicholas) : 1047 1054
Clinical Pharmacology, Basic Principles
in Therapeutics (Melmon and Morellis) :
711 712

Doa penutup majelis

Subhaanakallohumma
wabihamdika
asyhadu anlaa illaaha illa anta
astaghfiruka wa atuubu ilaika