Antimicrobial agents Flashcards
what do cidal vs. static AMs do
cidal - act on cell wall, membrane or DNA
static - inhib protein synthesis
when were majority of AMs invented
40s and 50s
naming for penicillin
-cillin
naming for cephalosporins
Ceph- or cef-
naming for carbapenems
- penem
naming for fluoroquinilones
-floxacin
naming for macrolides
-thromycin
naming for aminoglycocides
-micin or mycin
what is ideal AM
- kills infection
- safe
- no SE
- ignores bystanders
- no resitance
- cheap
what type of agent do you need it neutropenic
cidal - satics won’t kill
how is cell wall held together
NAG and NAM sugars with a d-ALA d-ALA cross link
what is the d-ALA crosslink called
transpeditidase - penicillin binding protein -PBP
what are the 3 b-lactam AMs
- penicillin
- cepahlosporins
- carbapenems
what is major toxicity of B-lactams
allergy
what gives a B-lactam a wider spectrum
longer and more complex side chains
what is MOA of B-lactams
irreversibly bind to transpeptidase and prevent peptidoglycan cross-linking
3 main mech of resistance
- drug inactivation or modification
- alteration of target site
- reduced drug accumulation at target site
what is uncommon resistance
alteration of metabolic pathways
what is B-lactam resistance
B-lactamase - cleaves the B-lactam rings so it can’t bind to the PBP site
what ABs are used to counter B-lactamases
clavulanic and tazobactam - inhib B-lactamases - not actually AM themselves
what 2 AM classes are naturally resistant to B-lactamases
cephalosporin and carbapenem - especially extended spectrum - many side chains
what are ESBLs
extended spectrum B-lactamases - resistance that has further developed
what are useful against ESBL
carbapenems
what is MOA of MRSAs
changes in the PBP so that the B-lactams can’t bind - due to SCCmecA genes
what is main drug of choice for streps
penicillin - amoxicillin (oral) ampicillin (IV)
what do most cephalosporins cover well
most Gr+ and Gr-, but not anaerobes
what cephalosporins is good for anaerobes
3rd gen
what is broadest spectrum B-lactams
carbapenems, but not many available
how to test for penicillin alergy
skin test to rule out Type 1 sensitivity
what is chance of cephalosporin allergy if allergic to penicilin
5%
MOA of vancomycin
Binds directly to d-ALA and prevents peptidoglycan crosslinking
what is vancomycin able to target
Gr+ - can’t bind Gr- because of large size
what is vancomycin problems
weak AM and not well tolerated so dosing is an issue
2 mechs of resisitance to vancomycin
VISA - Vanco Intermediate susceptable SA - thickened cell wall so can’t get in as well
VRSA - Vanco Resisitant SA - alteration of d-ALA to d-LAC to prevent binding
what is responsible for DNA supercoiling
DNA gyrase (topoisomerase 2) - introduces negative supercoiling
what does topoisomerase 4 do?
similar to DNA gyrase, but does not cause DNA towrap around itself
where do topoisomerase 2 and 4 work
2 (gyrase) works ahead of the fork and 4 works after the fork
what is the most overused AM
fluroquinolones (FQs)
what is FQ MOA
- DNA are separated when supercoiling and create a pocket
- FQ binds in pocket and stabilizes
- prevents uncoiling
- broken bits of DNA are repaired in a disorganized manner
what are Gr - and + targets in FQs
+ topoisomerase 4
- DNA gyrase
what causes moderate restance to FQ
mutation in primary target (topoismoerase)
what causes high level resistance in FQ
second mutation in the target
what are 3 mech of FQ resistance
- altered target (above)
- efflux pumps push out FQ
- altered porin (Gr- only) that don’t allow FQ in
what is MOA of sulfonamides and trimethoprim
block folate synthesis at 2 sites which is needed for DNA production - static, with a touch of cidal
where does bacterial protein synthesis occur
ribosome - has a large 50S subunit and smaller 30S subunit
5 classes of protein syn inhibitors
- aminoglycosides
- macrolides
- clindamycin
- tetracyclins
- oxazolidinones
what is major problems with aminoglycosides
nephro and ototoxicity
MOA of aminoglycosides
- bind to 30S subunit
- also bind to outer membrane and displace Mg and Ca
- leaky cell
- cidal and static
mechanisms of resistance in aminoglycosides
- in safe doses can’t cross Gr+ wall
- modification of drug by bact enzymes so can’t cross wall
- modify the ribosome to prevent binding
MOA of macrolides and clindamycin
bind to 50S subunit and are cidal
MOA of resistance in macrolides and clindamycin
modification of 23S subunit to prevent binding
what is MOA of tetracyline
bind to 30S subunit and are static
use of tetracyline
active against a wide variety of bact and MRSA
what class is linzolid
oxazolidinone
MOA of linzolid
bind to 50S subunit and are static
what is range of linzolid
very active agains + and no -
MOA of metronidazole (-flagel)
in bact it accepts electrons and causes free radicals - cidal
range of metronizaole
anaerobes only
3 main classes of anti fungals
- polyenes
- azoles
- echinocandins
MOA of polyenes
amphoceterin B binds to ergosterol in membrane and causes leaks
what is prob with polyenes
also binds cholesterol
- fever, rigors
- nephrotoxitiy
2 ways to avoid polyene toxiticy
- slow infusion
2. bind with liposomes - expensive
MOA of azoles
inhib enzyme which converts lanosterol to ergosterol
- altered membrane and slowed growth
major issue with azoles
CYP450 inhibitor
what is mech of resistance in azoles
the usual suspects
MOA of echinocandins
inhib. 1,3-B glucan synthase and therefore inhib cell wall formation- fungal version of B-lactams
