Part 2: Antimicrobials (Cell wall inhibitors) Flashcards
why is the peptidoglycan layer on bacteria cells a druggable target?
our cells dont have it
penicillins and cephalosporins are both ___ type antibiotics
beta-lactam
vancomycin is a ___ type antibiotic
glycopeptide
beta-lactam and glycopeptide antibiotics target pathways involved in ____
making the rigid cell wall
what happens to the bacteria when its cell wall is not properly formed?
get leaky, fill up with fluid and burst
what is the most common glycopeptide antibiotic?
vancomycin
which gram stain has the thick peptidogylcan layer?
+
the cell wall of gram neg contains _____ that selectively allow molecules to enter the cell
pores
t/f gram - still have a peptidoglycan layer, but it is thinner and surrounded by the outer envelope
t
within the inner membrane of a gram - bacteria there are ___ that assemble the cell wall
enzymes
the peptidogylcan layer of G- is between what other 2 layers?
- outer envelope
2. inner cytoplasmic layer
what is the role of bacterial transpeptidase?
one of the enzymes that crosslinks peptide subunits together to make the cell wall
Penicillin binds to and inactivates the ____ enzyme
transpeptidase
transpeptidase may also be called ___
penicillin binding protein (PBP)
in order for penicillins to be effective, they must get to the transpeptidases in the ___ layer
cytoplasmic
t/f to enter a gram - cell, penicillins must be transported in by ___
the membrane pores
why are many penicillins only useful for gram +?
many are unable to cross the membrane of G-
t/f some newer beta-lactam drugs facillitate the passage through G- pores
true
what is the function of transglycosylase?
links sugar groups together
what is the peptidoglycan wall made of?
cross-linked glycopeptides (sugars & aminoacids)
to make the peptidoglycan cell wall, the bacteria builds gylcopeptides in the ___ and shuttles them into the ____ space
cytoplasm; periplasmic space
what will happen to a G+ cell if we inhibit transpeptidase?
aminoacid cross-linking cannot occur and the wall will be weak
Beta-lactams bind to transpeptidase in what way?
covalently (irreversibly)
what part of the beta-lactam antibiotics binds to the transpeptidase?
beta-lactam 4 membered ring
what makes the beta-lactam ring reactive?
strain of small ring
what happens to the beta-lactam ring when it reacts with the transpeptidase?
it opens, relieving strain
what is the main difference between penicillins and cephalosporins?
the second ring; cephalosporins have a 6 C ring, penicillins have a 5 C ring
which are more stable, penicillins or cephalosproins? why?
cephalosporins bc the 6C ring is more stable than the 5C ring of penicillins
which is more reactive, penicillins or cephalosporins? why?
penicillins; 5C ring
bc penicillin is so reactive, what is it at risk of?
breakdown (ex: by reacting in the stomach with an H)
if the beta-lactam ring is opened before it reaches the transpeptidase, what happens to it?
its now inactive
t/f cephalosporins are less susceptible to inactivation at non-targets
t
what environment may cause a penicillin to inactivate
acidic stomach
some bacteria exhibit ____ enzymes that are able to break the beta lactam ring to inactivate them
beta lactamases
t/f cephalosporins are less susceptible to beta lactamases
true
what structural part of beta-lactam antibiotics influences the liklihood of being inactivated by a beta-lactamase?
R groups
t/f some changes to the R group of a penicillin can help the stability in the stomach
t
t/f some of the changes to the R groups on penicillins can impact activity on different bacteria
t
what are the 2 oldest penicilins used clinically?
G and V
what is the function of the R group on Pen V?
makes it more stable in the acidic environment of the stomach
Pen V is given as what doasge form?
oral
Pen G is given as what dosage form?
IM or IV
Pen G and Pen V have ___ spectrum and are active against ___
narrow; subset of G+
t/f Pen V and Pen G are easily broken down by beta-lactamases
t
ampicillin and amoxicillin have R groups that do what?
- make more stable in acidic environemnt
2. extend activity to some G-
ampicillin and amoxicillin are ____ spectrum
extended
how do the R groups of ampicillin and amoxicillin allow them to act against some G-?
facillitate crossing the pores
t/f ampicillin and amoxicillin are still susceptible to beta-lactamases inside the bacteria
true
what is the purpose of adding clavulanic acid with beta-lactam antibiotics?
beta-lactamase inhibitor
how does clavulanic acid inactive beta-lactamases?
they also have a B-lactam ring, so B-lactamases target them rather than the antibiotic (and bind covalently, so enzyme cant be used again)
does clavulanic acid have any antibiotic activity on its own?
no; bc it does not bind to transpeptidase
cephalosporins are separated into “generations” based on what 2 factors?
- time of development
2. R group modifications that give different spectrums of activity
cephalexin is a ___ gen cephalosporin
1st
__ generation cephalosporins are similar to penicillins
1st
1st generation ceph. are active primarily against Gram ___
+
are 1st gen ceph. susceptible to beta-lactamses?
yes
as the generations of ceph. get higher, the R groups have made these drugs ____ (more or less) active against G-
more
how do the R groups of gen 2-4 ceph make them able to target some G-?
makes them able to cross the outer envelope
are gen 2-4 ceph less susceptible to beta lactamases?
yes
ceftazidime is a ___ generation ceph.
3rd
3rd gen ceph are ____ spectrum
broad
which gen of ceph are typically used empirically?
3rd
cefuroxime is a ___ ge ceph and is mostly active against ___
2nd; G+, some G-
cefepime is a ___ gen ceph. and active against__
4th; mostly G-, some G+
what makes antibiotics generally very safe with low risk of ADRs?
they act on non-human targets
penicillin allergy is mediated by IG__
E
t/f there can be cross-allergies between penicillins and cephaolosporins
t
if someone is allergic to penicillin, is it certain that they will be allergic to cephalosporins?
no
t/f in some extraordinary circumstances, desensitization therapy can be given to reduce penicillin allergies
t
vacomycin acts by preventing the ___ of peptidoglycan by binding to the ___
cross-linking; bacterial peptide chain
vancomycin has a large structure, which part is most importnat?
peptide chain region in the middle
the peptide backbone of vancomycin forms ___ bonds with the bacerial peptide chains of peptidoglycan subunitis
H
which bacterial peptide does the peptide backbone of vancomycin bind to?
D-Ala-D-Ala
how does vancomycin prevent transpeptidases from bringing bacterial peptide togther and linking them?
H bond to peptide back bone make the rest of the vancomycin molecule folds over the bacterial peptide
how can bacteria make themselves resistant to vancomycin?
replace one of the 2 alanines that bind to vanco into a lactate, meaning only 4 H bonds rather than 5 can be made to vanco, so the interaction is much weaker, allowing transpeptidase to still be able to link the peptide into the wall
the loss of 1 H bond due to vancomycin resistance makes the drug ____x weaker
1000
is vancomycin resistance very common?
not really; but moreso in hospitals
what is a disadvantage of the large size of vancomycin?
too large to fit through pores of G-
how must vancomycin be given to treat systemic infections? why?
IV; it is too big to get absorbed from the GI tract
in what situation would vancomycin be given orally?
to treat a GI infection, like C. dif (can give high dose to target, because it wont be absorbed systemically)
