Do’a 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
 Dr.dr. Wiwik Kusumawati, MKes
 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)
 Chair of Interprofessional Education (2012 to
now)
CURRICULUM VITAE
 PhD in Medical Education of Faculty of
Medicine Gadjah Mada University, Yogyakarta
(2014)
 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)
ANTITUBERCULOSIS
DRUGS
By
Wiwik Kusumawati
Physician Competence

 Pulmonary TB without complication (level

of competence : 4)
 Pulmonary TB with HIV (level of
competence : 3A)
 Multi Drug Resistance (MDR) TB/AFB
(level of competence : 2)
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
Pulmonary TBC in
Indonesia (2010)
 Incidence: 189 per 100.000 (343)
 Prevalence: 285 per 100.000 (443)
 Mortality: 27 per 100.000 (92)
 New cases 430.000/year
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 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
Distribution of Secondary
MDR
MDR in Indonesia

 Central Java (2006)

 Primary MDR 1,8%
 Secondary MDR 16,7%
MAJOR PROBLEM?

Compliance ?
DOT’S
 DIRECTLY OBSERVE THERAPY
 Five component of DOTS
1. Political will of goverment and stakeholders
2. TBC diagnose by microscopic examination
3. Treatment and monitoring
4. Quality and availability of drugs
5. Recording and reporting
 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 – doesn’t 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 %)
 Doesn’t 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
CATEGORY 1

 2HRZE/4H3R3
 2HRZE/4HR
 2HRZE/6HE
CATEGORY 2

 2HRZES/HRZE/5H3R3E3
 2HRZES/HRZE/5HRE
CATEGORY 3

 2HRZ/4H3R3
 2HRZ/4HR
 2HRZ/6HE
MONITORING

 Monitoring adverse effect and efficacy of

drugs
 Monitoring up to 1 year after a regimen
completely
FOLLOW UP (AFB +)

 Sputum BTA (AFB) examination

 At the end of 2nd month; 3rd month; 5th
month and the end of treatment
 Recover /cure
 Sputum BTA (AFB) become negative at
the end of 2nd month or 3rd month or 5th
month and the end of treatment
FOLLOW UP (AFB -)
 Sputum BTA (AFB) examination
 At the end of 2nd month; 5th month and
the end of treatment
 Complete
 Sputum BTA (AFB) remain negative at
the end of 2nd month; or 5th month and
the end of treatment
 Fail
 Sputum BTA (AFB) become +
Target
 Case detection rate 70% population
(BTA/AFB +)
 Cure rate more than and equal 85%
 DO less than 15%
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

 Avery’s Drug Treatment 4th edition

(Trevor & Nicholas) : 1047 – 1054
 Clinical Pharmacology, Basic Principles
in Therapeutics (Melmon and Morelli’s) :
711 – 712
 Do’a penutup majelis

Subhaanakallohumma
wabihamdika
asyhadu anlaa illaaha illa anta
astaghfiruka wa atuubu ilaika