10.19 Antibiotics II – Flashcards
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| Which ribosome has the E, P, and A sites? |
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| large ribosomal subunit |
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| Whata re the three ways antibiotics can inhibit bacterial ribosome function? |
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| initiation, elongation, misreading |
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| Drugs that act on bacterial ribosomes often have what kind of effect on eukaryotic host? |
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| mitochondrial toxicity |
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| Describe the characteristics you must take into consideration when administering aminoglycosides. |
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| concentration dependent killing, post antibiotic effect, follow drug levels, peak= effectiveness, trough = accumulation (renal excretion) |
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| What is the spectrum of aminoglycosides? |
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| gram - rods NOT anaerobes gram + cocci in combination |
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| What is the spectrum of streptomycin? |
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| M. tuberculosis, F. tularenis, Yersinis pestis combination for enterococcus |
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| What are the uses of streptomycin? |
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| TB, Single agent, combination |
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| What is the spectrum of gentamycin and tobramycin? |
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| GNR not anaerobes, pseudomonas, combination |
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| What is the spectrum of amikacin? |
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| resistant GNR |
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| What are the uses of gentamicin and tobramycin? |
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| blood strem UT, combinations, NOT anaerobic |
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| How do bacteria develop resistance to aminoglycosides? |
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| enzyme modification, altered ribosomal target, decreased permeability, efflux pump |
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| What are the otoxocity symptoms that can be caused by aminoglycosides? When do these symptoms occur? How? |
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| auditory and vestibular, idiosyncratic and dose dependent, binds NMDA receptors, reactive oxygen species, mitochondrial toxicity (genetic predisposition--> necrosis or apoptosis |
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| At what doses do you get nephrotoxicity from aminoglycoside agents? |
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| dose dependent and length dependent; sometimes idiosyncratic |
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| How do aminoglycosides cause nephrotoxicity? |
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| filtered and binding to proximal tubules, binds megalin, alterations in calcium channels, necrosis or apoptosis due to cationic nature (calcium dependent) |
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| What is the spectrum of linezolid? |
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| gram positive, especially resistant ones, good lung penetration |
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| Is resistance developing to linezolid? |
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| ribosome target modification is seen with long-term use |
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| What are the mjoar side effects of linezolid? |
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| hematologic, neuropathy, and serotonin syndrome |
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| What are the special characteristics of tetracyclines and glycocyclines? |
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| long acting (doxycycline, minocycline, tigecycline), reversible binding to ribosome, binds metals (teeth, bones), captures photons, broad spectrum activity |
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| How do organisms become resistant to tetracycline? |
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| efflux pump, ribosome protection (molecules taht have homology for ribosomal proteins, promotes dissociation), modification of molecule (oxidation Tet[x]), modification of ribosome target |
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| What is the spectrum of tetracycline? |
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| broad spectrum, lots of resistance |
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| What are the characteristics of tetracycline dosing? |
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| frequent dosing |
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| What is the spectrum of doxycycline? |
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| broad spectrum, intracellular bacteria |
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| How do you give tetracycline? |
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| PO |
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| How do you give doxycycline? |
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| IV/PO |
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| What are the characteristics of doxycycline dosing? |
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| BID |
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| How do you give minocycline? |
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| IV/PO |
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| What is the spectrum of minocycline? |
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| intracellular bacteria and staphylococcus |
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| What are the dosing characteristics of minocycline? |
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| BID |
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| How do you give tigecycline? |
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| IV |
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| What is the spectrum of tigecycline? |
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| broad spectrum, much less resistance, NOT pseudomonas |
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| What are the characteristics of tigecycline dosing? |
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| BID dosing, binds ribosome more tightly |
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| How does chloramphenicol work? |
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| binds 50S; block A site |
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| What is the spectrum of chloramphenicol? |
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| broad spectrum, resistance growing |
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| What are the side effects of chloramphenicol? |
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| dose-dependent anemia (reversible), and aplastic anemia (irreversible) ** rarely used in this country but frequently in third world (cheap) |
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| How do bacteria become resistant to choloramphenicol? |
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| chloramphenicol acetyl transferase |
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| How do macrolide/azalide/ketolides work? |
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| reversible binding to ribosomes based on intracellular concentration |
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| What is the spectrum of macrolide/azalide/ketolide? |
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| broad spectrum but resistance common among gram - organisms and increasing in gram + organisms |
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| Which antibiotic that targets bacterial protein synthesis is also anti inflammatory? |
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| macrolide/azalide/ketolide |
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| What are the side effects of macrolide/azalide/ketolide? |
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| GI, hearing loss (reversible) |
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| What are the mechanisms of resistance against macrolide/ketolide/azalide? |
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| efflux pumps, altered binding sites (methylation= inducible or constitutive), alteration of tunnel morphology |
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| How do you give erythromycin? |
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| IV/PO |
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| What is the spectrum of erythromycin? |
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| respiratory gram +, helicobacter/campylobacter jejuni, mycoplasma, chlamydia, legionella |
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| What are the dosing characteristics of erythromycin? |
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| QID dosing, GI upset frequent, motilin analogue, resistance increasing |
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| What is the spectrum of clarithromycin? |
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| respiratory gram +, helicobacter/campy, mycoplasma, chlamydia, legionella + atypical mycobacteria (LESS RESISTANCE THAN ERYTHROMYCIN) |
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| What are the characteristics of clarithryomycin dosing? |
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| BID dosing |
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| How do you give clarithrymycin? |
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| PO |
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| How do you give azithromycin? |
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| IV/PO |
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| What is the spectrum of azithromycin? |
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| respiratory gram +, helicobacter/campy, mycoplasma, chlamydia, legionella |
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| What are the characteristics of azithromycin dosing? |
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| single dose STD perscription; daily dosing; long half-life |
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| How do you give telithromycin? |
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| PO |
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| What is the spectrum of telithromycin? |
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| same as azithromycin (respiratory pathogens) |
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| What are the dosing characteristics of telithromycin? |
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| daily dosing, resists efflux, does not induce erm |
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| How does clindamycin work? |
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| binds in same area as macrolides on a ribosome and turns off toxin production |
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| What is the spectrum of clindamycin? |
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| gram +, anaerobic (increasing resistance) |
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| How are bacteria resistant to clindamycin? |
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| clindamycin is resistant to the bacterial efflux pump but NOT to the alteration of ribosome target (inducible erm) |
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| What are the possible side effects of clindamycin? |
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| C. difficile colitis |
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| Name a type of antibiotic used in animal feeds? |
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| quino/dalpopristin |
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| Is there an IV formulation of streptogramins? |
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| yes |
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| What is the spectrum of streptogramins? |
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| gram +, especially resistant ones (NOT E. faecalis) |
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| Describe resistance to streptogramins? |
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| efflux, modification of drug, modification of ribosome |
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| What are the side effects of streptogramins? |
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| myalgia, arthralgia |
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| Ribosome modification of a bacteria can cause multiple resistance to which types of antibiotics? |
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| macrolides, lincosamides, and streptogramins |
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| How do quinolones work? |
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| inhibit topoisomerase and gyrase |
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| How does rifampin work? |
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| inhibits the dissociation of RNA polymerase from sigma factor |
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| How do sulfa and trimethoprim work? |
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| inhibit the synthesis of folic acid |
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| What must you take into account when giving flouroquinolones? |
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| concentration dependent, spectrum and toxicity depends on side groups |
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| How do you give flouroquinolones? |
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| IV/PO formulation |
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| Why are flouroquinolones so popular? |
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| inexpensive, good tissue penetration |
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| What are the major side effects of flouroquinolones? |
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| tendon rupture, bone deformities (use care with children), QT prolongation |
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| How are bacteria able to become resistent to flouroquinolones? |
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| mutations of target enzymes |
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| How do you give ciprofloxacin? |
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| IV/PO |
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| What is teh spectrum of ciprofloxacin? |
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| gram neg organisms including pseudomonas B. anthracis, STDs NOT syphilis |
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| What is the most potent antibiotic against GNR? |
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| ciprofloxacin |
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| How often do you give cipro? |
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| BID |
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| How is ciprofloxacin excreted from the body? |
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| urinary |
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| How do you give Levofloxaxin? |
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| IV/PO |
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| What is the spectrum of levofloxaxin? |
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| gram negative |
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| How is levovloxaxin excreted? |
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| urinary excretion |
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| How often do you give levofloxacin? |
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| daily or BID |
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| How do you give moxifloxacin? |
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| IV/PO |
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| What is the spectrum of moxifloxacin? |
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| more potent against G+, less potent against G-, more anaerobes (oral) |
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| How often do you give moxifloxacin? |
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| daily |
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| Which flouroquinolone has less urinary excretion? |
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| moxifloxacin |
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| How does trimethroprim-sulfa work? |
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| two step inhibition: 1) inhibit generation of folinic acid 2) necessary for metabolism |
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| What is the spectrum of trimethoprim sulfa? |
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| broad aerobic (not strep/not pseudomonas), pneumocystis jiroveci |
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| What are the side effects of trimethoprim-sulfa? |
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| rash including phototoxicity, erythema multiforme to TEN, renal toxicity/hepatitis, hyperkalemia |
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| Which bacteria is exhibiting increasing resistance to trimethoprim-sulfa? |
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| e coli |
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| What enzyme is inhibited by sulfa, PAS, and Dapsone? |
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| dihydro-pterorate synthetase (converts PABA + Dihydro-Pteridine into Dihydropterorate) |
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| What enzyme is inhibited by trimethoprim? |
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| dihydro-folic acid reductase (dihydrofolic acid into tetrahydro-folic acid) |
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| What is the spectrum of rifampin? |
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| broad spectrum (staph and mycobacteria) |
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| How does resistance against rifampin occur? |
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| occurs rapidly if used as a single agent due to enzyme mutation |
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| What are the side effects of rifampin? |
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| hepatitis, orange secretions/urine, induction of P450 |
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| What is the spectrum of metronidazole? |
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| anaerobes, C. difficile, amoebae (trichomonas, giardia, entamoeba) |
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| How do you give metronidazole? |
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| oral/IV |
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| T/F Metronidazole has poor tissue penetration |
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| false, has good penetration |
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| What are the side effects of metronidazole? |
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| antabuse reaction, neuropathy, dysgeusia (metallic taste), black urine |
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| What is the mechanism of nitrofurantoin? |
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| unclear; msut be reduced by an enzyme for activity |
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| What is the spectrum of nitrofurantoin? |
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| (lower UTI infections), many gram -, (not proteus, not pseudomonas), enterococcus |
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| What are the side effects of nitrofurantoin? |
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| pulmonary infiltrates/fibrosis, eosinophilia |
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| How do you give mupirocin? |
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| topically |
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| What is the spectrum of mupirocin? |
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| gram positive esp. Staph |
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| How does mupirocin work? |
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| binds tRNA-isoleu |
