Antimycobacterial agents Flashcards
what is the shape of mycobacteria?
rod
what is incorporated into the cell wall of mycobacteria?
mycolic acids
what is the gram stain of mycobacteria?
poor gram stain, or not at all
what is the stain used for mycobacteria?
acid fast
which bacterial organism is stained using an acid fast stain?
mycobacterium
where do mycobacteria replicate?
macrophages
what is the route of transmission for m. tuberculosis?
respiratory droplets
what type of organism is present in patients with latent TB infection?
inactive, contained tubercle bacilli
what type of organism is present in patients with TB disease?
actie, multiplying tubercle bacilli
what organisms are included in m. avium complex (MAC)?
m. avium
m. intracellulare
what can MAC cause?
pulmonary disease in immuno-competent individuals, and disseminated disease in AIDS patients
what is the route of transmission for MAC?
ingestion of contaminated food and water
respiratory droplets
what is the most active drug used in the treatment of TB (active and latent)?
isoniazid
isoniazid shares structural similarity with what vitamin?
B6 (pyridoxine)
what is the MOA of isoniazid?
inhibits synthesis of mycolic acid - covalently binds with at least two proteins involved in mycolic acid synthesis
what are the two mechanisms of resistance in isoniazid therapy?
mutation in Kat G gene - lack of prodrug activation
overexpression of Inh A protein - cannot inhibit mycolic acid synthesis
what is essential in active TB treatment?
at least two antiTB agents always be used
how is isoniazid absorbed?
GI tract
what are the adverse effects of isoniazid?
hepatitis
peripheral neuropathy
what is the first line treatment for active TB?
rifampin
rifampin is also effective against what other organisms?
gram positive
gram negative
chlamydia
what is the MOA of rifampin?
inhibits RNA synthesis
binds to bacterial DNA dependent RNA pol
penetrates most tissues, and phagocytic cells
what is the mechanism of resistance for rifampin?
point mutations in bacterial RNA pol gene
how is rifampin absorbed?
GI tract
what are the adverse reactions to rifampin?
GI
nervous system - headache, dizziness, fatigue
hepatitis
harmless, red-orange urine, feces, sweat, tears, saliva
what are the important drug interactions of rifampin?
strong inducer of cyp450s - increases elimination of many drugs and drug classes
in HIV patients rifampin should be replaced by what drug? why?
rifabutin
less potent inducer of cyp450 enzymes
rifabutin should replace rifampin in treatment of TB for what population?
HIV
what is pyrazinamide?
used in multidrug regimen in treating active TB
what is the proposed MOA of pyrazinamide?
inhibition of mycolic acid synthesis
what is the mechanism of resistance for pyrazinamide?
mutation in pyrazinamidase enzyme
what are the adverse reactions to pyrazinamide?
hepatotoxicity
hyperuricemia
what drug is used in combination therapy for active TB and m. avium infection?
ethambutol
what is the MOA of ethambutol?
inhibits arabinosyl transferases (mycobacterial cell wall synthesis)
what is the MOR of ethambutol?
point mutations in genes encoding arabinosyl transferase
what are the adverse reactions of ethambutol?
retrobulbar neuritis
hyperuricemia
what is the indication for streptomycin in TB therapy?
TB caused by strains resistant to other first line drugs
what is the MOA of streptomycin?
interferes with bacterial protein synthesis
streptomycin is effective against which TB organisms?
m. tubuerculosis
MAC species
what is the MOR of streptomycin?
point mutations in ribosomal proteins
what are the adverse reactions of streptomycin?
ototoxic
nephrotoxic
what is the MOA of rifabutin?
inhibition of RNA polymerases
rifabutin is more effective against what organisms?
MAC organisms
what is the combination therapy for MAC organisms?
macrolide (clarithromycin, azithromycin)
rifampin (or rifamycin)
ethambutol
streptomycin
what is the combination therapy for MAC disseminated disease?
macrolide (clarithromycin, azithromycin)
rifampin (or rifamycin)
ethambutol
what is the treatment for prophylaxis in HIV patients?
clarithromycin or azithromycin
what is the treatment for leprosy?
dapsone
clofazimine
rifampin
dapsone is a structural analog of what compound?
PABA
what is the MOA of dapsone?
competitive inhibitor of folate synthesis
