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
inhibits 30S ribsome - blocks access of tRNA anticodon to its codon
gram + (s. pneumoniae, MRSA), very effective againast intracellular pathogens (mycoplasma, chlamydia, legionella, rickettsia) and mycobacteria
what does tetracycline treat?
"the diseases soldiers get"
chlamydia, yickettsia, borrelia, m pneumonia, acne, tick borne illness
how is doxycycline eliminated?
fecally - can be used in patients with renal failure
tetracycline drug interaction
ORAL forms are chelated with divalent cations - don't take with milk (Ca), antacids (Ca, Mg), iron supplements because they can inhibit drug absorption in gut
tetracyclines side effects
think of soldier in night vision goggles
GI distress (need to take with water and standing up);, discoloration of teeth and inhibition of bone growth in children, photosensitivity and hyperpigmentation
mechanism of resistance to tetracyclines
what is different about tigecycline (glycylcyclines)
9-glycl substitution enables it to overcomes two major types of resistance = efflux pumps and ribosomal protection
broad spectrum (covers tetracycline plus resistant organism) includes MRSA, VRE, enterobacteriaceae!!, anaerobes
what does tigecycline NOT have activity against?
tigecycline side effects
GI - significant nausea, vomiting, and diarrhea - transaminitis, increased mortality --> used in situations when alternative agents are not suitable
what are the macrolides?
azithromycin, clarithromycin, erythromycin
macrolides mechanism of action
inhibit protein synthesis by blocking translocation (macroSLIDES) bind to 50S subunit - bacteriostatic
atypical pneumonias (mycoplasma, chlamydia, legionalla), gram + cocci (strep in patients allergic to penicillin), B pertussis
macrolides side effects
well tolerated usually - MACRO: GI Motility issues, Arrhythmia with prolonged QT, Colestatic hepatitis, Rash, eOsinophilia
macrolides drug interaction
increases serum concentration of theophylline, oral anticoagulants
which macrolide has the least GI distress?
binds to 50S subunit "A site" --> blocks peptide transfer (translocation) - bacteriostatic
treats anaerobic infections ABOVE the diaphragm (bacteroides spp, clostridium perfringens)
also effective against invasive group A strep
which drug is used ABOVE the diaphragm for anaerobic infections? BELOW?
above = clindamycin
below = metronidazole
clindamycin side effects
pseudomembranous colitis (C difficile overgrowth) because everything else was killed off, fever, diarrhea
what are the oxazolidinones?
inhibit protein synthesis by binding to 50S subunit and preventing formation of initiation complex
gram + including MRSA and VRE
NO gram - and poor anaerobe
oxazolidinones side effects
severe side effects if used for 2+ weeks - HEMATOLOGIC toxicity (bone marrow suppression with thrombocytopenia), peripheral neuropathy, SEROTONIN SYNDROME
what drug interaction does oxazolidinones have?
Serotonin syndrome if used with MAOis and SSRIs