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74 Cards in this Set
- Front
- Back
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What is the standard treatment for TB (first 8 wks, then 8-26 wks)?
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first 8 wks: INH, rifampin, ethambutol, pyrazinamide; wks 8-26: INH + rif
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Describe rif and INH drug resistance in TB?
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rif resistance is 1x10*-8, while INH is 1x10*-6. multiply them when used as combined therapy= 1x10*-14.... a very low incidence of resistance!
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Which of the 4 std. TB drugs is bacteriostatic during growth phase?
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ethambutol
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Which of the 4 std. TB drugs is bacteriostatic during stationary/intracellular phase?
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INH, and ethambutol
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What is the MOA of INH?
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disrupt mycolic acid synthesis
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How is INH activated (from prodrug)?
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by the mycobacteria! ezymes that require NAD
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What are 3 mechanisms of resistance to INH of mycobacterium?
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loss of INH-activating enzymes, overexpression/mutation of mycolic acid synthesis enzymes
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Which minority group is the "fast acetylators" of INH?
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Asians
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What are the 2 major AE's of INH?
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Hepatic (inc. liver enzymes, jaundice, hepatitis), neurologic (peripheral neuritis, convulsions)
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Why is hepatotoxicity a problem in slow acetylators of INH?
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only about 65% of INH is excreted as N-acetyl-INH (opposed to 90%), which leaves them w/ increased exposure to N-Acetylhydrazine
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what is the active form of INH?
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4-dizenyl carbonyl pyridine
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Why is neuropathy a risk for "slow acetylators" of INH?
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pyridoxal-5-phosphate (vit b 6) is depleted by INH... vit b 6 is a cofactor for many enzymes in NT synthesis
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INH. broad or narrow spectrum antibiotic?
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narrow (to m. tuberculosis)
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Rifampin (RIF): narrow or broad spectrum?
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broad spectrum
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What is the MOA of RIF?
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inhibits DNA-dependent-RNA polymerase in bacteria. it is BACTERICIDAL
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What is a unique bactericidal qualitiy of RIF?
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inhibits DNA-dependent-RNA polymerase in bacteria. it is BACTERICIDAL
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What is a unique bactericidal qualitiy of RIF?
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it has high intracellular penetration (especially during continuation treatment)
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Common AE of RIF?
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stains things red/orange (contacts, urine)
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What is an important drug interaction of RIF? What are its implications in certain pts?
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it is a strong INDUCER of CYP450... so inc metabolism of other drugs....
1. if you are on BC plan on getting pregnant lest you find alternate routes of protection 2. on warfarin? extra-clearance and inc. risk of thrombosis 3. HIV treatments also effected |
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What should an HIV pt. take for TB if they are on HIV treatment drugs?
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substitute rifabutin for rifampin
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Pyrazinamide (PZA). narrow or broad spectrum?
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narrow (kills TB at ACIDIC pH)
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What is the MOA of PZA?
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beats me. it does get activated by the bacteria.
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Whate are 2 common toxicity problems of PZA?
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frequently hepatotoxic & renal toxic (gout results)
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which TB drug is the "sterilizing agent" and why?
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PZA b/c it gets intracellular at slays them at an acidic pH
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Ethambutol (EMB). narrow or broad spectrum?
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narrow
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What is the MOA of EMB?
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inhibits arabinosyl transferases & cell wall synthesis
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Two major AE's of EMB?
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visual (optic neuritis, color disturbance) and renal (gout)
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How does EMB and PZA cause gout?
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blocks tubular secretion, subsequently enhancing urate retention
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What should you NEVER do in TB treatment
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add a single 2nd line drug to a failed treatment regimen
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What are the 6 second line TB drugs and their MOA's? good luck
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see his slide. like i'm typing all that out
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true or false. If TB pt. is pregnant, withhold treatment until delivery.
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FALSE. active tb must be treated. however, in the US, PZA is not recommended
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If pt. has HIV. which treatment should you start first, TB or HIV?
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TB
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MOA of penicillins?
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cell-wall inhibitors
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Core antipsuedomonals?
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beta-lactams and aminoglycosides
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Anti-pseudomonals static or cidal?
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bactericidal
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MOA of aminoglycoside tobramycin
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protein synth inhibitor: 30S
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Toxicities of penicillins and cephalosporins?
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diarrhea and colitis
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Unique MOA of anti-pseudomonals?
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pass through porins, bind PBPs and subsequently disrupt cell wall integritiy
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Why is Tobramycin distinctively bactericidal against pseudomonas?
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passes through cell membrane to directly inhibit protein synth
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Weakness of narrow spectrum agents?
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cannot traverse porins or cell membrane
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Why can piperacillin readily traverse porins?
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very hydrophillic and ionizable (lots of hydroxide ions)
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What is a distinctive advantage of cefepime?
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4th gen quaternary amine that is always ionized
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What is the common IV regimen for Psuedomonas?
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tobramycin combine w/ piperacillin and cefepime
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While not synergistic, why are aminioglycosides and beta-lactams bomined (though given staggered) against pseudomonas?
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may prevent multi-drug resistance
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Describe how efficacy of tobramycin is measured (characteristic)? Therefore, how should it be administered
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concentration-dependent efficacy; given as single daily dose which also reduces risk of toxicities
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Describe how efficacy of anti-pseud beta-lactams are measured (characteristic)? Therefore, how should it be administered
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time-dependent killing: given as slow infusion every 6 hours
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What provides greatest resistance to anti-pseudomonals?
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less porins, altered PBPs in the case of some pens and cephs, and finally enzymatic modifications
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What is a mucoid phenotype?
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production in the lung (mucous, etc.) favors chronic infection
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What commonly hinders eradication of pseudomonas?
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colonies and biofilms
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Common trifecta of drugs to prevent chronic pseudomonal infection?
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aerosol tobramycin, oral azithromyicin, and aerosoal dornase (dna nuclease)
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MOA of azithromycin?
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binds 50S ribosome
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Where does oral azithromycin concentrate?
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in the lung! (concentrates in the sputum)... can alter the bacterial phenotype
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What is the sum action of the combination therapy of CF infections?
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supress airway destruction by eliminated infection and subsequently inflammation and junk
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When is colistin selected?
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in severe case of MDR pseudomal infections
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If staph is penicillin resistant and meth resistant, what do you give?
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vancomycin
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if staph is vanco resistant, what do you give?
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linezolid (a bacteriostatic)
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What do you give a staph that is pen. resistant, and meth. sensitive? the staph is MSSA
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beta-lactams (staph is often acommpanying pseudomas infection in cases of CF); specific drugs: ticarcillin, and piperacillin
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What two combo regimens can be given to CF patients with staph and pseudomonal infection?
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ticarcillin-clavulanate or pipercillin-tazobactam
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Burholderia infection, what do you give?
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combo of sulfmethoxazole-trimethoprim
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4 common organisms found infecting CF patients
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s. aureus, p. aeruginosa, burkholderia cepacia, stentrophomonas maltophilia (in decreasing incidence)
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beta lactams MOA versus tobramycin?
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piperacillin, ticarcillin, ceftazidime, and cefapime all bind to PBPs and disrupt cell wall integrity while tobra, an aminoglycoside, inhibits the 30S ribosome
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True or False. all penicillins, cephalosporins, and aminoglycosides are hydrophillic and can traverse porins
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FALSE. some penicillins (pipercillin), some cephs (cefepime), and all aminoglycosides
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What is an example drug regimen common for treatment of psuedomonal infection?
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tobramycin combined w/ piperacillin, cefepime, and imipenem-cilastin
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P. aeruginosa infection, but it is tobramycin-resistant. what do you give?
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amikacin
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What is the best time/concentration approach for treatment w/ tobramycin?
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short exposure to high levels (conc-dep. killing). aka single daily dose
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What defines the safety of tobramycin?
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the trough (below through threshold > 12 hours is safer)
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What defines the efficacy of penicillins?
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time above MIC (time-dep. killing)
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combination of aerosol tobramycin/dnanuclease and oral azithromycin helps do what?
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suppress chronic infection in CF pts.
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What treatment method must be employed to thwart antagonism of purulent sputum to aminoglycoside activity?
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raise the aminoglycoside content in the sputum to 25X the MIC
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Pt has MDR P. aeruginosa. what is the only therapeutic option? What is its MOA?
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colistin (iv). binds LPS
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What is the MOA of vancomycin?
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inhibits cell wall synthesis by blocking linear elongation via transglycosylase-inhibition, NOT PBP's
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What is the MOA of linezolid?
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binds 50S of ribosome and disrupts peptidyl transferase center, especially in mitochondrial ribosomes
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What is a major possible clearance/toxicity problem of linezolid?
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MAO interaction
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What do clavulanate and tazobactam do?
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inhibit beta-lactamase
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