Flashcards in Pharm antimicrobials 2 Deck (57):
1
vancomycin class
glycopeptide - cell wall synthesis inhibitor
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vancomycin mechanism
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
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vancomycin spectrum - why?
gram + only - molecule is HUUUUGGGGGEEEEE!!! can't get into gram -
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vancomycin clinical uses
serious, multidrug-resistant organisms including MRSA, s epidermidis, enterococcus, clostridium difficile
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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
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vancomycin administration
IV only - not absorbed orally
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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
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daptomycin class
cell wall TOXIN - lipopetide
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daptomycin mechanism
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
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daptomycin spectrum
gram + cocci only - used for VRE and VRSA (vancomycin resistant organisms)
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what is daptomycin not used for? why?
pneumonia because it avidly binds to and is inactivated by surfactant
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daptomycin side effects
myopathy and rabdomyolysis,
also eosinophilic pneumonia
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what are the lipoglycopeptides (analogs of vancomycin)
-vancins
dalbavancin, telavancin, oritavancin
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-vancins mechanism
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
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-vancins spectrum
similar to vancomycin (gram + only) but active against VRE and more anaerobe coverage
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-vancins side effects
metallic taste, nausea, HA, nephrotoxicity, teratogenic (don't take if preggers)
also very very expensive
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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
18
are protein synthesis inhibitors bacteriocidal or bacteriostatic?
bacteriostatic EXCEPT aminoglycosides
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30 S ribosomal subunit protein synthesis inhibitors
ATG = DNA = small
aminoglycosides, tetracyclines, glycylcyclines
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50S ribosomal subunti protein synthesis inhibitors
COM = bigger and better!
clindamycin, oxazolidinones, macrolides
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what are the aminoglycosides?
gentamicin, tobramycin, amikacin, streptomycin
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aminoglycoside mechanism
bactericidal: irreversible inhibition of initiation complex through binding of the 30S subunti - can cause misreading of mRNA - also inhibits initiation
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aminoglycoside spectrum
extremely effective against G- rods (esp enterics)
covers pseudomonas aeruginosa!!
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what are aminoglycosides ineffective against? why?
anaerobes!! have O2 dependent uptake mechanism!!!
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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)
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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)
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which aminoglycoside is toxic and is typically only used topically for skin infections?
neomycin
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which aminoglycoside has the broadest spectrum?
amikacin
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what are the tetracyclines?
-cycline
doxycycline, minocycline, tetracycline
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tetracycline mechanism
inhibits 30S ribsome - blocks access of tRNA anticodon to its codon
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tetracycline spectrum
gram + (s. pneumoniae, MRSA), very effective againast intracellular pathogens (mycoplasma, chlamydia, legionella, rickettsia) and mycobacteria
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what does tetracycline treat?
"the diseases soldiers get"
chlamydia, yickettsia, borrelia, m pneumonia, acne, tick borne illness
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how is doxycycline eliminated?
fecally - can be used in patients with renal failure
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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
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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
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mechanism of resistance to tetracyclines
efflux pump!
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tigecycline class
glycylcycline
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what is different about tigecycline (glycylcyclines)
9-glycl substitution enables it to overcomes two major types of resistance = efflux pumps and ribosomal protection
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tigecycline spectrum
broad spectrum (covers tetracycline plus resistant organism) includes MRSA, VRE, enterobacteriaceae!!, anaerobes
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what does tigecycline NOT have activity against?
pseudomonas
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tigecycline side effects
GI - significant nausea, vomiting, and diarrhea - transaminitis, increased mortality --> used in situations when alternative agents are not suitable
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what are the macrolides?
-THROMYCINs
azithromycin, clarithromycin, erythromycin
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macrolides mechanism of action
inhibit protein synthesis by blocking translocation (macroSLIDES) bind to 50S subunit - bacteriostatic
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macrolides spectrum
atypical pneumonias (mycoplasma, chlamydia, legionalla), gram + cocci (strep in patients allergic to penicillin), B pertussis
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macrolides side effects
well tolerated usually - MACRO: GI Motility issues, Arrhythmia with prolonged QT, Colestatic hepatitis, Rash, eOsinophilia
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macrolides drug interaction
increases serum concentration of theophylline, oral anticoagulants
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which macrolide has the least GI distress?
erythromycin
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clindamycin mechanism
binds to 50S subunit "A site" --> blocks peptide transfer (translocation) - bacteriostatic
49
clindamycin spectrum
treats anaerobic infections ABOVE the diaphragm (bacteroides spp, clostridium perfringens)
also effective against invasive group A strep
50
which drug is used ABOVE the diaphragm for anaerobic infections? BELOW?
above = clindamycin
below = metronidazole
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clindamycin side effects
pseudomembranous colitis (C difficile overgrowth) because everything else was killed off, fever, diarrhea
52
what are the oxazolidinones?
-ZOLID
linezolid, tedizolid
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oxazolidinones mechanism
inhibit protein synthesis by binding to 50S subunit and preventing formation of initiation complex
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oxazolidinones spectrum
gram + including MRSA and VRE
NO gram - and poor anaerobe
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oxazolidinones side effects
severe side effects if used for 2+ weeks - HEMATOLOGIC toxicity (bone marrow suppression with thrombocytopenia), peripheral neuropathy, SEROTONIN SYNDROME
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what drug interaction does oxazolidinones have?
Serotonin syndrome if used with MAOis and SSRIs
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