materi 4 anti tbc

7/25/2019 Materi 4 Anti TBC

1/31

PEND HULU N

DefinisiTuberkulosis merupakan penyakit infeksi yang disebabkan

oleh bakteri Mycobacterium tuberculosis dengan gejalaumum batuk kronis.


2/31

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)


3/31

Tujuan Pengobatan

Pengobatan TB bertujuan untuk menyembuhkan

pasien, mencegah kematian, mencegah

kekambuhan, memutuskan rantai penularan dan

mencegah terjadinya resistensi kuman terhadap

OAT.


4/31


5/31


6/31


7/31


8/31

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.


9/31


10/31

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.


11/31

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.


12/31

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.


13/31

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.


14/31

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.


15/31

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.


16/31

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.


17/31

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.


18/31

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.


19/31

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.


20/31

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


21/31

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.


22/31

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


23/31

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.


24/31

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


25/31

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


26/31

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


27/31

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.


28/31

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


29/31


30/31


31/31

materi 4 anti tbc

Documents