Antimycobacterial agents Flashcards
non-tuberculous mycpbacteria
M. avium
M. intracellulare
primary drugs used in TB
Isoniazid
Rifampicin
Pyrazinamide
Ethambutol
most active TB drugs
Isoniazid and rifampicin
Isoniazid and rifampicin
Initial intensive phase of tx is recommended for the first __ months
2
how many active agents should be used to treat active TB to prevent emergence of resistance during therapy
at least 2
primary tx tb
2 months of HRZE and
4 months of HR
maximum dose of H
300mg/day
Max dose of rifampicin
600mg/day
category 1
for pulmonary and extrapulmonary meninges, bones or joints
2 HRZE
4 HR
Category 1a
for extrapulmonary TB of meninges, bones, and joints
2 HRZE
10 HR
max 1 yr
Category 2
for retx of confirmed rifampicin-sensitive pulmonary and extra-PTB except meninges, bones or joints
2HRZES
1HRE
5HRE
for retreatment of confirmed rifampicin-sensitive extra-PTB of meninges, bones, or joints
2HRZES
1HRE
9HRE
most active drug for the tx of TB caused by susceptible strains
isoniazid
sim struc: pyridoxine
isoniazid inhibits most tubercle bacilli at a concentration of __
0.2 mcg/mL
isoniazid MOA
inh synth of mycolic acids
bactericidal
Isoniazid resistance
overexpression of inhA
mutation or deletion of the katG gene
overexpression of ahpC
mutations in kasA
isoniazid is readily absorbed from GIT optimally on an _____
empty stomach
rapid acetylators (inh)
<1-hour half life
slow acetylators (INH)
around 3 hours
sleeping tb
latent tb
diagnosis: PPD or interferon gamma release assay or positive IgA test for TB.
dosage for latent TB
INH 300mg/day or 900mg twice weekly (9 months; ph: 6 months)
isoniazid immunologic rxn
fever and skin rashes
SLE
Direct toxicity
hepatitis (most common major toxic effect)
10-20% of patients given doses are greater than 5mg/kg/d, but it is frequently seen with the standard 300mg adult dose (INH)
peripheral neuropathy
neuropathy is reversed by
pyridoxine b6 10mg/d (25-50mg/day)
antibiotic produced by Amycolaptosis rifamycinica
Rifampin (S. mediterranei)
rifampicin is active in vitro against
gram +
some gram - (neisseria and haemophilus)
mycobacteria
Chlamydiae
Rifampin MOA
binds to the B subunit of bacterial DNA-dependent RNA polymerase and thereby inhibits RNA synthesis
Rifampin resistance
mutations in rpoB
rifampin is excreted mainly through the____
liver and bile
Latent tb
-single agent alternative to isoniazid dosage is ______
600mg/day for 4 months
dosage meningococcal carriage elimination
600mg BID x 2 days
H. influenzae type b disease prophylaxis
600mg OD x 4 days
AE of rifampin
harmless orange color urine, sweat and tears
Rashes, thrombocytopenia, and nephritis
cholestatic jaundice and occasionally hepatitis
synthetic water-soluble, heat-stable compound
Ethambutol
the dextro isomer of the structure is dispensed as
dihydrochloride salt
ethambutol MOA
inh mycobacterial arabinosyl transferases, which are encoded by the embCAB operon
ethambutol resistance
Due to the mutations resulting in overexpression of emb gene products or within the embB structural gene
accumulates in renal failure, the dose should be reduced to 3x weekly if creatinine clearance is less than 30mL/min
Ethambutol
most common serious AE of ethambutol
retrobulbar neuritis (x visual acuity and red-green color blindness)
relative of nicotinamide, and it is only used for treatment of tuberculosis
Pyrazinamide
active form of pyrazinamide
Pyrazinoic acid
pyrazinamide resistance
due to impaired uptake of pyrazinamide or mutations in pncA that impair conversion of PZA to its active form
important front-line drug used in conjunction with isoniazid and rifampin in short-course regimens as a “sterilizing agent” active against residual intracellular organisms that may cause relapse
Pyrazinamide
AE pyrazinamide
Hepatotoxicity Hyperuricemia Nausea Vomiting Drug fever Photosensitivity
2nd line TB
streptomycin
streptomycin resistance
point mutation rpsL (s12) gene or rrs gene (16s)
streptomycin AE
Ototoxic
Nephrotoxicity
MAC
M avium
M intracellulare
recommended for initial therapy of lepromatous leprosy
dapsone
dapsone may also be used to prevent and treat ______ in aids patients
Pneumocystis jirovecii pneumonia
AE dapsone
Hemolysis
Methemoglobinemia
Erythema nodosum leprosum
highly effective drug in leprosy
rifampin 600mg daily
phenazine dye used in the tx of multibacillary leprosy
clofazimine
common dosage of clofamizine
100-200mg/day orally
most prominent adverse effect of clofamizine is
discoloration of the skin and conjunctivae
