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PEND HULU N
DefinisiTuberkulosis merupakan penyakit infeksi yang disebabkan
oleh bakteri Mycobacterium tuberculosis dengan gejalaumum batuk kronis.
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Prevalensi Penyakit Tb
TBC sbgglobal emergency(WHO, 1993)Menurut the Global Tuberculosis Burden Report 2011 yang diluncurkanWorld Health Organization, Indonesia menempati urutan keempat kasus Tb
tertinggi setelah China, India, dan Afrika Selatan.
Diperkirakan ada 450.000 kasus Tuberculosis baru di Indonesia di tahun
2011 dan sudah ada 65.000 orang yang mengalami kebal obat atau Multi-
Drugs Resistance (MDR)
Badan Kesehatan Dunia (WHO) memperkirakan prevalensi penyakit TBC di
Indonesia sebesar 786 per 100.000 penduduk, dengan 44% diantaranya BTApositif
95% ada di negara negara berkembang
75% penderita usia produktif (20-45 tahun)
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Tujuan Pengobatan
Pengobatan TB bertujuan untuk menyembuhkan
pasien, mencegah kematian, mencegah
kekambuhan, memutuskan rantai penularan dan
mencegah terjadinya resistensi kuman terhadap
OAT.
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Tuberculosis Pharmacologic activityMechanism of actionTherapeutic uses
Adverse effects
Pharmacologic activity
Mechanism of action
Therapeutic uses
Adverse effects
First-line drugs:
Isoniazid
rifampin
(INH)
pyrazinamide,ethambutol,streptomycin
Second-line drugs
Ethionamide, Amikacin, Ciprofloxacin, Ofloxacin,Capreomycin,Cycloserine.
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Classification of drugsAnti-tuberculosis drugs can be divided into two major
categories: base on their efficacies and toxicities
First-line drugs: good efficacy, less toxicity and beingwell tolerated for patients
Isoniazid (INH), rifampin, pyrazinamide,ethambutol, streptomycin.
Second-line drugs: usually used as alternatives to thefirst-line drug when drug resistance occurs or when a
particular therapy is required.
para-aminosalicylic acid, kanamycin, amikacin,capreomycin, ciprofloxacin, ethionamide.
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qIsoniazid (INH)
|It is the most active drug for the treatment
of tuberculosis
|After orally administered, well absorbed,widely distributed in body, including
cerebrospinal fluid. INH can also penetrate
into macrophages.
|Most INH is metabolized in the liver.
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qIsoniazid: Mechanism of action
probably related to the inhibition of synthesis
of mycolic acids, which are important and
characteristic components of mycobacterial
cell wall. As a result of the activity, tuberclebacilli lose their features of acid-resistance,
water-resistance and proliferating ability,
leading to death.
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qIsoniazid: Pharmacologic activity
n It is bactericidal for actively growingtubercle bacilli. But, for resting tuberclebacilli, it is bacteriostatic.
n Isoniazid is able to penetrate intophagocytic cells and thus is active againstboth extracellular and intracellularorganisms.
n This drug is not effective against atypicalmycobacteria.
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qClinical uses
JIsoniazid is the most widely used agent in
the treatment and prophylaxis of
tuberculosis.JIsoniazid is usually given by mouth but can
be given parenterally in the same dosage.
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qIsoniazid: Adverse effects
Allergic Reaction: fever,skin rash
Hepatotoxicity : Up to 20% of patients taking INHdevelop elevated serum amino transferase levels.
Severe hepatic injury occurs more frequentlyin patients over the age of 35, especially inthose who drink alcohol daily.
Isoniazid is discontinued if symptoms of
hepatitis develop or if the aminotransferaseactivity increases to more than three timesnormal.
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qIsoniazid: Adverse effects
Peripheral and CNS toxicity occur.
This toxicity probably results from an
increased excretion of pyridoxine induced by
isoniazid, which produces a pyridoxine
deficiency.
Peripheral neuritis, urinary retention, insomnia,
and psychotic episodes can occur.
Concurrent pyr idox ine admimistration with
INH prevents most of these complications.
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qRifampin
Synthetic derivates of rifamycin B producedSterptomyces mediterranei
oral administration, well absorbed, widely
distributed in body, including sputum andtuberculotic caverna; adequate CSFconcentrations are achieved only in the
by
presence of meningeal inflammation.
most of the drug is excreted as a deacylatedmetabolite in feces and in the urine. half-life isabout 4 hours.
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qRifampin: Pharmacologic activity
n broad-spectrum
n It is active against G+cocci (including drug-
resistant S.aureus), some
mycobacteria
bacteria,
n It is bactericidalfor mycobacteria.
n It can kill organisms that are poorly accessible
to many other drugs, such as intracellularorganisms and those sequestered in abscesses
and lung cavities.
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qMechanism of rifampin
n RFP binds strongly to the-subunit ofDNA-dependent RNA polymerase and
thereby inhibits RNA synthesis.n Drug-resistance to RFP, due to target
mutations in RNA polymerase, occurs
readily.
n No cross-resistance to other classes ofantimicrobial drugs.
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Rifampin: Clinical uses
n Mycobacterial infections
It often uses in combination with other agents(Tuberculosis, rifampin) in order to preventemergence of drug-resistant mycobacteria.
n Leprosy
n Other infections
Rifampin can be used in a variety of gram-positive
coccal infections, especially the serious cases that
cannot be effectively treated with other drugs.
It is also used as prophylaxis for meningitis caused
highly penicillin-resistant strains of pneumococci.
by
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Rifampin: Adverse effects
v Urine, sweat, tears, and contact lenses maytake on an orange color because of rifampinadministration, this effect is harmless.
v Light-chain proteinuriaresponse may occur.
and impaired antibody
v Rifampin induces hepatic microsomal enzymesand therefore, affects the half-life of a number ofdrugs.
v When taken erratically in large doses, a febrileflu-like syndrome can occur.
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qTuberculosisFirst-line drugs: Pharmacologic activity
Mechanism of action
Therapeutic uses
Adverse effects
Isonizid (INH)
rifampinPharmacologic activity
Mechanism of actionTherapeutic uses
Adverse effects
pyrazinamide,ethambutol, streptomycin
Second-line drugs
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qEthambutoln Inhibits many strains of M. tuberculosis,bacteriostatic
n Well absorbed from the gut and widely distributedall body tissues and fluids.
n As with all antituberculotic drugs, resistance to
ethambutol emerges rapidly when the drug is usedalone.
n The most common serious adverse effect is dose-
in
related optic neuritis, causing loss of visual acuity and
red-green color-blindness, but are reversible.
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Pyrazinamide
n Pyrazinamide is
nicotinamide. At
pH 5.5 it inhibits
mycobacteria.
a pyrazine analogue of
neutral pH, it is inactive, but at
tubercle bacilli and some other
n Quickly absorbed after orally administered
n Widely distributed in body tissues,including
inflamed meninges.
n Excreted mainly by glomerular filtration
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PyrazinamideIt is used in combination with INH and RFP inmultiagent short-term therapy to exert its activityagainst residual intracellular organisms that maycause relapse.
Tubercle bacilli develop resistance topyrazinamide fairly readily, but no cross-
n
n
resistance with other antimycobacterial drug.
Liver damage is the most serious and commonadverse reactions. Therefore, liver function
studies should be performed before and duringtherapy.
n
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StreptomycinStreptomycin is the first antimicrobial drug used totreat tuberculosis. It is effective against most tubercle
bacilli, but its activity is weaker than that of INH andRFP.
Streptomycin penetrates into cells poorly, and drug-resistance is produced easily.At present, streptomycin is employed when aninjectable drug is needed or desirable, principally inindividuals with severe, possibly life-threateningforms of tuberculosis , and in treatment of infections
resistant to other drugs.It is always given together with other drugs to preventemergence of resistance.
v
v
v
v
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The second-line drugs
n The second-line drugs used for tuberculosis
infections when first-line drugs have been
discontinued owing to resistance or adverseeffects.
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qTuberculosisFirst-line drugs: Pharmacologic activity
Mechanism of action
Therapeutic uses
Adverse effects
Isonizid (INH)
rifampinPharmacologic activity
Mechanism of actionTherapeutic uses
Adverse effects
pyrazinamide,ethambutol, streptomycin
Second-line drugs
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