Flashcards in Pharm antimicrobials 2 Deck (57)
glycopeptide - cell wall synthesis inhibitor
binds rapidly and irreversibly to the D-alanyl-D-alanine group on the peptide side-chain of the membrane-bound precurosr; glycan chain extension, transpeptidation inhibited
vancomycin spectrum - why?
gram + only - molecule is HUUUUGGGGGEEEEE!!! can't get into gram -
vancomycin clinical uses
serious, multidrug-resistant organisms including MRSA, s epidermidis, enterococcus, clostridium difficile
vancomycin adverse effects
well tolerated in general but NOT trouble free (Nephrotoxicity, Ototoxicity, Thrombophlebitis and red man syndrome)
Red man driving a van down the intestine getting c diff
IV only - not absorbed orally
what is the advantage of vancomycin not being absorbed orally?
c difficile is in gut - it doesn't need to be absorbed to treat this
cell wall TOXIN - lipopetide
penetrates gram + cell wall forming a channel for subsequent leakage of intracellular ions
-insertion into the gram + cell membrane causing depolarization and ultimate cell death
gram + cocci only - used for VRE and VRSA (vancomycin resistant organisms)
what is daptomycin not used for? why?
pneumonia because it avidly binds to and is inactivated by surfactant
daptomycin side effects
myopathy and rabdomyolysis,
also eosinophilic pneumonia
what are the lipoglycopeptides (analogs of vancomycin)
dalbavancin, telavancin, oritavancin
binds to same target as vancomycin (D-alanyl-D-alanine group on peptide side-chain of the membrane-bound precursor)--> cell wall precursor and inhibits transglycosylation
similar to vancomycin (gram + only) but active against VRE and more anaerobe coverage
-vancins side effects
metallic taste, nausea, HA, nephrotoxicity, teratogenic (don't take if preggers)
also very very expensive
what is the half life of the -vancins? what is the longer half life due to?
telavancin - 7.5 hr
dalbavancin and oritavancin long (100+ hrs)
-due to lipophilic side chain that prolongs half life
are protein synthesis inhibitors bacteriocidal or bacteriostatic?
bacteriostatic EXCEPT aminoglycosides
30 S ribosomal subunit protein synthesis inhibitors
ATG = DNA = small
aminoglycosides, tetracyclines, glycylcyclines
50S ribosomal subunti protein synthesis inhibitors
COM = bigger and better!
clindamycin, oxazolidinones, macrolides
what are the aminoglycosides?
gentamicin, tobramycin, amikacin, streptomycin
bactericidal: irreversible inhibition of initiation complex through binding of the 30S subunti - can cause misreading of mRNA - also inhibits initiation
extremely effective against G- rods (esp enterics)
covers pseudomonas aeruginosa!!
what are aminoglycosides ineffective against? why?
anaerobes!! have O2 dependent uptake mechanism!!!
clinical use of aminoglycosides - what is it given with? why?
synergistic with cell-wall active agents for enterococcus infections (esp penicillins because they facilitate entry), cystic fibrosis (pseudomonas common infection)
aminoglycosides side effects
the MEAN GUY! (bacteriocidal)
-punch to the ear (ototoxicity)
-punch to the kidney (nephortoxicity)
-punch a pregnant woman (teratogen)
-knock them out (neuromuscular blockade)
which aminoglycoside is toxic and is typically only used topically for skin infections?
which aminoglycoside has the broadest spectrum?
what are the tetracyclines?
doxycycline, minocycline, tetracycline