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61 Cards in this Set
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drugs used in TB
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isoniazid (INH), rifampin, ethambutol, pyrazinamide, streptomycin
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isoniazid is a structural congener of what?
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pyridoxine (B6)
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mechanism of action of isoniazid?
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inhibition of mycolic acids, characteristic components of mycobacterial cell walls
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what occurs if isoniazid is used alone?
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rapid resistance
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mutations of what genes results in resistance to isoniazid?
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deletion of katG gene for catalase-peroxidase involved in bioactivation of INH
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deletion of katG gene results in what?
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codes for catalase-peroxidase involved in bioactivation of INH so become resistant if don't have it
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deletion of inhA gene results in what?
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resistance to INH b/c deletion of gene that encodes the "target enzyme", an acyl carrier protein reductase
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INH is active against which bacteria?
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bactericidal for actively growing tubercle bacilli, less effective against dormant organisms
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liver metabolism of INH?
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via acetylation and under genetic control
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how does INH work?
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absorbed orally and penetrates cells to act on intracellular mycobacteria
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half life of INH in "fast acetylators" and "slow acetylators"
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fast- 60-90 minutes
slow- 3-4 hours |
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which population contains highest fast acetylators?
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Asians origin including Native American
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clinical use of INH?
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single most important drug used in TB and is component of most drug combination regimens
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toxicity of INH?
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neurotoxic effects: peripheral neuritis, restlessness, muscle twitching, insomnia
Hemolysis if patient has glucose-6-phosphate deficiency hepatotoxicity |
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what can be used to treat neurotoxic effects of INH?
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pyridoxine (B6)
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rifampin is a derivative what drug?
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rifamycin
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rifampin is used for treatment of what?
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bactericidal against M. tuburculosis
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MOA of rifampin?
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inhibits DNA-dependent RNA polymerase encoded by rpo gene
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metabolism of rifampin?
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undergoes enterohepatic cyclin and partially metabolized by the liver. produces orange colored metabolites
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when can rifampin be used as a sole drug?
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in latent TB when INH-intolerant patient or in close contacts of patients with INH-resistant strains
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rifampin and vancomycin in combination is used for treatment of what?
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infections due to resistant staph (MRSA) or pneumococci (PRSP)
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what drug causes light chain proteinuria and can impair antibody responses
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rifampin
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side effects of rifampin?
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skin rashes, thrombocytopenia, nephritis, liver dysfunction
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if given less than twice weekly, what effects may rifampin cause?
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flulike syndrome and anemia
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effect of rifampin on liver?
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strongly induces liver drug metabolizing enzymes and enhances elimination rate of many drugs
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what drug is used over rifampin that has less drug interactions and equally effective as antimycobacterial agent?
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rifabutin
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when is rifabutin preferred over rifampin?
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for treatment of tuberculosis or other mycobacterial infections in AIDS patients
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MOA of ethambucol?
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inhibits arabinosyl transferases (encoded by embCAB operon)
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what is arabinosyl transferases involved in?
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the synthesis of arabinogalactan, a component of mycobacterial cell walls
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how does resistance occur to ethambutol?
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mutations in emb gene if drug is used alone
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clinical use of ehtambutol?
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tuberculosis, in combination with other drugs
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which drug causes dose-dependent visual disturbances?
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ethambutol
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adverse effects of ethambutol?
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dose-dependent visual disturbances including red-green color blindness, optic neuritis, possible retinal damage
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MOA of pyrazinamide?
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bacteriostatic, requires metabolic conversion via pyrazinamides (encoded by pncA gene) present in M. tuberculosis
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how does resistance to pyrazinamide occur?
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mutations in gene that encodes enzymes involved in bioactivation of pyrazinamide, and by increased efflux
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which drug has minimal cross resistance with other antimycobacterial drugs?
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pyrazinamide
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40% of patients using this drug develop nongouty polyarthralgia
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pyrazinamide
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which drug should be avoided during pregnancy?
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pyrazinamide
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toxicity of pyrazinamide?
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nongouty polyarthragia, hyperuricemia, myalgia, GI irritation, maculopapular rash, hepatic dysfunction, porphyria, photosensitivity reactions
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when is streptomycin used?
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treatment of life threatening TB, including meningitis, miliary dissemination, and severe organ TB
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drug used for treatment of TB suspected to be caused by streptomycin-resistant or multi-drug resistant mycobacterial strains
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amikacin
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which two fluoroquinolones are used as second line therapy for treatment of M. tuberculosis resistant to first line therapy?
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ciprofloxacin and ofloxacin
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which drug is a congener of INH?
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ethionamide
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toxicities of ethionamide?
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severe GI irritation and adverse neurologic effects at doses needed to achieve effective plasma levels
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drug rarely used due to ototoxicity and renal dysfunction?
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capreomycin
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drug with limited use b/c peripheral neuropathy and CNS dysfunction?
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cycloserine
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standard drug regimen for TB
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initial 3 drug regimen of INH, rifampin, and pyrazinamide. discontinue pyrazinamide after 2 months (if HIV negative) and use 2 drug regimen for following 4 months
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alternative regimen for TB
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INH, rifampin for 9 months, or INH + ethambutol for 18 months
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when treating TB, if resistance to INH >4%, what drugs should be included in the regimen?
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ethambutol or streptomycin
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TB resistant only to INH should be treated with what drugs?
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treated for 6 months with rifampin + pyrazinamide, ethambutol or streptomycin
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treatment of MAC infections?
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combination of drugs, consisting of azithromycin or clarithromycin with ethambutol and rifabutin
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which drugs are used for prophylaxis for MAC in patients with CD4 count < 50/microL
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clarithromycin or azithromycin with or without rifabutin
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drug regimen for leprosy?
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combinations of dapsone with rifampin (or rifabutin) plus or minus clofazimine
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which drug is a phenazine dye that may interact with DNA, causes GI irritation and skin discoloration ranging from red-brown to nearly black?
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clofazimine
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what is clofazimine?
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it is a phenazine used in combination for treatment of leprosy
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what is the most active drug against M leprae?
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dapsone, a sulfone
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MOA of sulfones?
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involve inhibition of folic acid synthesis
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dapsone should be used in combination with which other drugs?
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rifampin or clofazimine or both b/c of increasing resistance
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adverse effects of dapsone?
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GI irritation, fever, skin rash, methemoglobinemia, hemolysis if glucose-6-dehydrogenase deficient
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which drug is a respiratory form of dapsone?
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acedapsone
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acedapsone is used for treatment of what?
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leprosy, and alternative drug for pneumocysitis jiroveci pneumonia in AIDS patients
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