Anti-Mycobacterial Agents Flashcards
Mycobacteria important characteristics (4)
MYCOLIC ACID in cell wall
ACID FAST STAINING
INTRACELLULAR - replicate in macrophages
Generally SLOW GROWING
Latent TB
INACTIVE, non replicating tubercle bacilli
NORMAL CXR
NEGATIVE SPUTUM SMEARS/CULTURES
Not infectious - not a case of TB
Active TB
ACTIVELY replicating tubercle bacilli
ABNORMAL CXR
SMEARS AND SPUTUM POSITIVE
SYMPTOMS POSITIVE
Mycobacterium avium COMPLEX
M avium
M intracellulare
through contaminated food or water
may be disseminated
typically associated with IMMUNOCOMPROMISED
Active TB Recommended regimen
Initial phase - Rifampin, Isoniazid, Pyrazinamide, Ethambutol (RIPE) daily for 8 weeks
Continuation phase - Isoniazid and RIfampin daily for 18 weeks (or could do twice weekly)
Latent TB typical drug?
Isoniazid
6 or 9 month regimens
Isoniazid MOA
delivered as?
Use for TB?
INHIBITS MYCOLIC ACID SYNTHESIS
pro-drug - activated by bacteria
both latent and active infections
Resistance to Isoniazid associated with? (2)
mutations in Kat G gene
Overexpression of Inh A protein
Two major adverse effects with isoniazid?
Hepatitis
Peripheral neuropathy
Rifamycins MOA
inhibits RNA synthesis
BINDS BACTERIAL DNA-DEPENDENT RNA POLYMERASE
bactericidal for mycobacteria
Rifampin resistance associated with
point mutations in bacterial RNA polymerase
Rifampin adverse effects
GI disturbances
Neurological
hepatitis
Harmless red-orange color of urine, sweat, feces, etc.
Rifampin effect on cytochrome p450
Drug-drug interactions?
What can be substituted?
INDUCER
INCREASES METABOLISM OF ANTI-RETROVIRALS
Rifabutin
Pyrazinamide MOA
Used almost exclusively in?
not really known - inhibition of mycolic acid synthesis
pro-drug converted to active form by bacteria
COMBINATION THERAPY
Pyrazinamide resistance?
pyrazinamidase enzyme mutations
Pyrazinamide adverse effects (2)
Hepatotoxicity
HYPERURICEMIA - can lead to gout
Ethambutol MOA
Resistance?
always given?
inhibits ARABINOSYL TRANSFERASES - mycobacterial cell wall synthesis
point mutations in arabinosyl transferase enzymes
in COMBINATION THERAPY
Ethambutol adverse reactions (2)
Retrobulbar neuritis
Hyperuricemia
Streptomycin type of antibiotic?
Adverse effects?
AMINOGLYCOSIDE ANTIBIOTIC
OTOTOXICITY
NEPHROTIC
Rifabutin use?
vs rifampin?
commonly substituted for rifampin
greater activity against MAC than rifampin
MAC regimen?
Macrolide
Rifampin or other rifamycin
Ethambutol
sometimes streptomycin
Leprosy Treatment Regimen
Dapsone
Clofazimine
Rifampin
therapy lasts for years
Clofazimine
bactericidal dye
discoloration of the skin
