41: antimycobacterial Flashcards
KatG gene mutation results in resistance to?
isoniazid
mycolic acid synthesis inhibition is MoA of?
isoniazid
1st line drugs for M TB? (4)
isoniazid
rifampin
pyrazinamide
ethambutol
RoA of Isoniazid
oral or parenteral (IM)
If isoniazid resistance is observed what can we use?
rifampin
which 1st line mycobacterial drugs has bacteriostatic action?
ethambutol
INH prophylaxis is given to?
in person with positive tuberculin skin test who meets the criteria:
- HIV +
- recently infected
- X ray shows nonprogressive TB
- illicit injected drug use
- DM
- immunosuppression
which drug is activated by mycobacterial catalase-peroxidase
isoniazid
isoniazid is active against which mycobacteria?
M tb
M kansasii
which antimycobacterial drugs are metabolized by acetylation? (2)
isoniazid
dapsone
vitamin B6 deficiency is observed as adverse effect of ? (2)
isoniazid
dapsone
peripheral neuritis in isoniazid is more likely seen in which phenotype ?
slow acetylators
to prevent peripheral neuritis we can supplement?
vitamin B6 - pyridoxine
RoA of rifampin
oral , IV
MoA of ethambutol
Inhibit arabinosyl transferase and synthesis of arabinogalactan for cell wall.
resistance to ethambutol is gained by mutations in:
arabinosyl transferase.
adverse effect of ethambutol?
Optic neuritis, Impaired red-green color discrimination.
Hyperuricemia; GOUT.
Hepatitis and thrombocytopenia.
contraindication for ethambutol?
children too young to asses visual acuity
ethambutol is active against which mycobacteria?
M tb
MAI
treatment regimen for MAI?
Treatment: azithro/clarithromycin + ethambutol +/- rifabutin
incase if resistance to rifampin we use?
rifabutin
which antimycobacterial agent is more rapidly bactericidal than others, and has sterilizing effect?
pyrazinamide
which agent is a nicotinamide derivative?
pyrazinamide
2 known mechanisms of action of pyrazinamide
- inhibition of fatty acid syntesis
2. inhibits ribosomal translation of mRNA
inhibition of ribosomal mRNA , mechanism of pyrazinamide helps it to kill _____ TB?
dormant (nongrowing)
RoA of pyrazinamide
oral
mutation of which enzyme results in resistance to pyrazinamide?
pyrazinamidase
adverse effects of pyrazinamide
Arthralgia. Hyperuricemia gout. Hematologic toxicity. Hepatitis increase in serum iron concentration.
pyrazinamide is bactericidal or bacteriostatic?
bactericidal
which first line mycobacterial is broad spectrum?
rifampin
rifampin is active against which Mycobacteria?
M tb
MAI
M kansasii
M leprae
MoA of rifampin
: binds to B-subunit (of DNA dependent RNA polymerase) → inhibits DNA transcription and RNA synthesis
clinical indications of rifampin? (
- TB
- leprosy
- TB meningitis
- prophylaxis (INH alternative, exposure to H influenza , prevent meningococcal disease)
- eliminate staphylococcal carriage
- treat staph infections: endocarditis
- occasionally: legionella pneumophila
which drug is used in treatment of lepromatous leprosy but not for tuberculoid leprosy?
clofazimine
regimen for leprosy? (3)
dapsone + clofazimine + rifampin
resistance to rifampin is gained by which mechanism?
decreased affinity of RNA polymerase to drug
reddish orange to brown discoloration of saliva, tears, urine is adverse effect of?
rifampin
- also causes permenant staining of contact lenses
which 1st line antimycobacterial agent causes hepatotoxicity and nephrotoxicity?
rifampin
- hepatitis
- cholestatic jaundice
- acute intersitial nephritis
- light-chain proteinuria
rifampins drug interactions are:
Macrolides - Benzodiazepines - Calcium channel blocker
Digoxin - Estrogens - Sulfonylureas - Theophylline
Warfarin
long acting rifamycin derivative is called?
rifapentine
highly lipophillic derivative of rifamycin? (take with food to avoid irritation)
rifabutin
if HIV patient is on protease inhibitor, which drug is preffered to use in MTB regiment?
rifabutin
TB aminoglycosides are?
amikacin
kanamycin
streptomycin
which aminoglycoside for M TB treatment is contraindicated in pregnant women?
streptomycin
ROA of M tb aminoglycosides?
parenteral
which aminoglycoside is more active than streptomycin?
amikacin
MoA of Bedaquiline?
acts by blocking proton pump for ATP synthase in M tb
bedaquiline is approved for treating?
MDR TB
which antimycobacterial agent prolongs QT interval? and what should u consider doing before taking drug?
bedaquiline
perform ECG before taking drug
sulfones MoA?
same as sulfonazmide: inhibit dehydropteorate synthase –> inhibits folic acid synthesis
dapsone belongs to which class of drugs?
sulfones
in patient with G6PDH deficiency which drug can cause an adverse effect?
dapsone, can cause hemolytic anemia
adverse effects of dapsone ? (7)
- gi disturbance
- peripheral neuropathy
- optic neuritis, blurred vision
- proteinuria, nephrotic syndrome
- lupus erythematous-like syndrome
- hematologic toxicity
- G6PDH def –> hemolytic anemia
which antibiotic has antimycobacterial and antiinflammatory effects?
clofazimine
clofazimine is bacteriostatic against which mycobacteria and bacteriocidal against which?
bacteriostatic –> M leprae
bactericidal –> M tb
remember: is also acitive against MAI
half life of clodazimine?
70 days
if i say phenazine dye, what comes to ur mind?
clofazimine
photosensitivity and hepatitis, also discoloration of body secretions are adverse effects of?
clofazimine
clinical indications of clofazmine?
- lepromatous leprosy (used with dapsone and rifampin)
2. erythema nodosum leprosum - due to its inflammatory effects
which drug was banned due to phocomelia in offsprings of women who took drug during pregnancy?
thalidomide
which drug has orphan status?
thalidomide
which antimycobacterial drug is also used for legionella pneumophila ?
rifampin
for treatment of prosthetic valve endocarditis we use rifampin in combination with?
gentamicin / vancomycin
rifampin is used in prevention of meningococcal disease , but the preffered drugs for this are?
ceftriaxone / ciprofloxacin
