,INH ,PZA Part1 Antituberculous drugs ( ) First Line Drugs
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Second Line Drugs
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Isonizid ( INH) Isonizid ( ,INH) Isoniazid is the most active
drug for the treatment of tuberculosis caused by susceptible
strains. Isoniazid penetrates into macrophages and is active
against both extracellular and intracellular organisms. In vitro,
isoniazid inhibits most tubercle bacilli in a concentration of
0.025~0.05 g/mL or less and is bactericidal for actively growing
tubercle bacilli. It is less effective against atypical
mycobacterial species. Isonizid
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Pharmacokinetics Absorbtion: Isoniazid is readily absorbed from
the gastrointestinal tract. A 300-mg oral dose (5 mg/kg in
children) achieves peak plasma concentrations of 35 mcg/mL within
12 hours. Distribution: Isoniazid diffuses readily into all body
fluids and tissues. Metabolism: liver N-acetyltransferase(N ) rapid
acetylators -- hepatitis slow acetylators-- Peripheral neuropathy
Isonizid
rifampin( ) Antimicrobial activity: in vitro against
gram-positive and gram- negative cocci, some enteric bacteria,
mycobacteria, and chlamydia. Mechanism of action: bactericidal
inhibits DNA-dependent RNA polymerase Adverse effects:
hepatotoxicity. Resistance : rapidly. no crossresistance to other
classes of antimicrobial drugs cross-resistance to other rifamycin
derivatives, eg, rifabutin and rifapentine. Rifampin
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Pharmacokinetics Absorbtion: well absorbed after oral
administration excretion: mainly through the liver into bile
enterohepatic recirculation( ) bulk excreted as a deacylated
metabolite in feces a small amount in the urine. Distribution:
widely in body fluids and tissues. relatively highly protein-bound
adequate cerebrospinal fluid concentrations are achieved only in
the presence of meningeal inflammation. Rifampin
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Clinical Uses MYCOBACTERIAL INFECTIONS Rifampin, usually 600
mg/d (10 mg/kg/d) orally, must be administered with isoniazid or
other antituberculous drugs to patients with active tuberculosis to
prevent emergence of drug-resistant mycobacteria. Rifampin 600 mg
daily or twice weekly for 6 months also is effective in combination
with other agents in some atypical mycobacterial infections and in
leprosy. Rifampin, 600 mg daily for 4 months as a single drug, is
an alternative to isoniazid prophylaxis for patients with latent
tuberculosis only, who are unable to take isoniazid or who have had
exposure to a case of active tuberculosis caused by an
isoniazidresistant, rifampin- susceptible strain. OTHER INDICATIONS
prophylaxis meningococcal carriage 600 mg twice daily for 2 days
prophylaxis in Haemophilus influenzae type b ( )disease: 20 mg/kg/d
for 4 days, eradicate staphylococcal carriage: combination other
agents serious staphylococcal infections such as osteomyelitis ( )
prosthetic valve endocarditis( ) Rifampin
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Adverse Reactions harmless orange color : urine, sweat, tear,
and contact lenses (soft lenses may bepermanently stained).
Occasional adverse effects : rashes, thrombocytopenia( ), and
nephritis( ). cholestatic jaundice( ) and occasionally hepatitis.
flu-like syndrome : fever, chills( ), myalgias( ), anemia( ), and
thrombocytopenia and sometimes is associated with acute tubular
necrosis( ). Cytochrome P450 isoforms (CYPs 1A2, 2C9, 2C19, 2D6,
and 3A4) inducer : increases the elimination of numerous other
drugs including methadone( ), anticoagulants( ), cyclosporine( ),
some anticonvulsants, protease inhibitors, some nonnucleoside
reverse transcriptase inhibitors( ), contraceptives, and a host of
others. lower serum levels of these drugs. Rifampin
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Ethambutol( ), Mechanism of action: mycobacterial arabinosyl
transferases( ). Arabinosyl transferases are involved in the
polymerization reaction of arabinoglycan, an essential component of
the mycobacterial cell wall. Ethambutol
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Clinical Use Combination with isoniazid or rifampin. Ethambutol
hydrochloride, 1525 mg/kg, a single daily dose tuberculous
meningitis: higher dose 50 mg/kg twice-weekly Ethambutol