Part 2: Antimicrobials (Cell wall inhibitors)

Question 1

why is the peptidoglycan layer on bacteria cells a druggable target?

Answer 1

our cells dont have it

Question 2

penicillins and cephalosporins are both ___ type antibiotics

Answer 2

beta-lactam

Question 3

vancomycin is a ___ type antibiotic

Answer 3

glycopeptide

Question 4

beta-lactam and glycopeptide antibiotics target pathways involved in ____

Answer 4

making the rigid cell wall

Question 5

what happens to the bacteria when its cell wall is not properly formed?

Answer 5

get leaky, fill up with fluid and burst

Question 6

what is the most common glycopeptide antibiotic?

Answer 6

vancomycin

Question 7

which gram stain has the thick peptidogylcan layer?

Answer 7

+

Question 8

the cell wall of gram neg contains _____ that selectively allow molecules to enter the cell

Answer 8

pores

Question 9

t/f gram - still have a peptidoglycan layer, but it is thinner and surrounded by the outer envelope

Answer 9

t

Question 10

within the inner membrane of a gram - bacteria there are ___ that assemble the cell wall

Answer 10

enzymes

Question 11

the peptidogylcan layer of G- is between what other 2 layers?

Answer 11

1. outer envelope

2. inner cytoplasmic layer

Question 12

what is the role of bacterial transpeptidase?

Answer 12

one of the enzymes that crosslinks peptide subunits together to make the cell wall

Question 13

Penicillin binds to and inactivates the ____ enzyme

Answer 13

transpeptidase

Question 14

transpeptidase may also be called ___

Answer 14

penicillin binding protein (PBP)

Question 15

in order for penicillins to be effective, they must get to the transpeptidases in the ___ layer

Answer 15

cytoplasmic

Question 16

t/f to enter a gram - cell, penicillins must be transported in by ___

Answer 16

the membrane pores

Question 17

why are many penicillins only useful for gram +?

Answer 17

many are unable to cross the membrane of G-

Question 18

t/f some newer beta-lactam drugs facillitate the passage through G- pores

Answer 18

true

Question 19

what is the function of transglycosylase?

Answer 19

links sugar groups together

Question 20

what is the peptidoglycan wall made of?

Answer 20

cross-linked glycopeptides (sugars & aminoacids)

Question 21

to make the peptidoglycan cell wall, the bacteria builds gylcopeptides in the ___ and shuttles them into the ____ space

Answer 21

cytoplasm; periplasmic space

Question 22

what will happen to a G+ cell if we inhibit transpeptidase?

Answer 22

aminoacid cross-linking cannot occur and the wall will be weak

Question 23

Beta-lactams bind to transpeptidase in what way?

Answer 23

covalently (irreversibly)

Question 24

what part of the beta-lactam antibiotics binds to the transpeptidase?

Answer 24

beta-lactam 4 membered ring

Question 25

what makes the beta-lactam ring reactive?

Answer 25

strain of small ring

Question 26

what happens to the beta-lactam ring when it reacts with the transpeptidase?

Answer 26

it opens, relieving strain

Question 27

what is the main difference between penicillins and cephalosporins?

Answer 27

the second ring; cephalosporins have a 6 C ring, penicillins have a 5 C ring

Question 28

which are more stable, penicillins or cephalosproins? why?

Answer 28

cephalosporins bc the 6C ring is more stable than the 5C ring of penicillins

Question 29

which is more reactive, penicillins or cephalosporins? why?

Answer 29

penicillins; 5C ring

Question 30

bc penicillin is so reactive, what is it at risk of?

Answer 30

breakdown (ex: by reacting in the stomach with an H)

Question 31

if the beta-lactam ring is opened before it reaches the transpeptidase, what happens to it?

Answer 31

its now inactive

Question 32

t/f cephalosporins are less susceptible to inactivation at non-targets

Answer 32

t

Question 33

what environment may cause a penicillin to inactivate

Answer 33

acidic stomach

Question 34

some bacteria exhibit ____ enzymes that are able to break the beta lactam ring to inactivate them

Answer 34

beta lactamases

Question 35

t/f cephalosporins are less susceptible to beta lactamases

Answer 35

true

Question 36

what structural part of beta-lactam antibiotics influences the liklihood of being inactivated by a beta-lactamase?

Answer 36

R groups

Question 37

t/f some changes to the R group of a penicillin can help the stability in the stomach

Answer 37

t

Question 38

t/f some of the changes to the R groups on penicillins can impact activity on different bacteria

Answer 38

t

Question 39

what are the 2 oldest penicilins used clinically?

Answer 39

G and V

Question 40

what is the function of the R group on Pen V?

Answer 40

makes it more stable in the acidic environment of the stomach

Question 41

Pen V is given as what doasge form?

Answer 41

oral

Question 42

Pen G is given as what dosage form?

Answer 42

IM or IV

Question 43

Pen G and Pen V have ___ spectrum and are active against ___

Answer 43

narrow; subset of G+

Question 44

t/f Pen V and Pen G are easily broken down by beta-lactamases

Answer 44

t

Question 45

ampicillin and amoxicillin have R groups that do what?

Answer 45

1. make more stable in acidic environemnt | 2. extend activity to some G-

Question 46

ampicillin and amoxicillin are ____ spectrum

Answer 46

extended

Question 47

how do the R groups of ampicillin and amoxicillin allow them to act against some G-?

Answer 47

facillitate crossing the pores

Question 48

t/f ampicillin and amoxicillin are still susceptible to beta-lactamases inside the bacteria

Answer 48

true

Question 49

what is the purpose of adding clavulanic acid with beta-lactam antibiotics?

Answer 49

beta-lactamase inhibitor

Question 50

how does clavulanic acid inactive beta-lactamases?

Answer 50

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)

Question 51

does clavulanic acid have any antibiotic activity on its own?

Answer 51

no; bc it does not bind to transpeptidase

Question 52

cephalosporins are separated into "generations" based on what 2 factors?

Answer 52

1. time of development | 2. R group modifications that give different spectrums of activity

Question 53

cephalexin is a ___ gen cephalosporin

Answer 53

1st

Question 54

__ generation cephalosporins are similar to penicillins

Answer 54

1st

Question 55

1st generation ceph. are active primarily against Gram ___

Answer 55

+

Question 56

are 1st gen ceph. susceptible to beta-lactamses?

Answer 56

yes

Question 57

as the generations of ceph. get higher, the R groups have made these drugs ____ (more or less) active against G-

Answer 57

more

Question 58

how do the R groups of gen 2-4 ceph make them able to target some G-?

Answer 58

makes them able to cross the outer envelope

Question 59

are gen 2-4 ceph less susceptible to beta lactamases?

Answer 59

yes

Question 60

ceftazidime is a ___ generation ceph.

Answer 60

3rd

Question 61

3rd gen ceph are ____ spectrum

Answer 61

broad

Question 62

which gen of ceph are typically used empirically?

Answer 62

3rd

Question 63

cefuroxime is a ___ ge ceph and is mostly active against ___

Answer 63

2nd; G+, some G-

Question 64

cefepime is a ___ gen ceph. and active against__

Answer 64

4th; mostly G-, some G+

Question 65

what makes antibiotics generally very safe with low risk of ADRs?

Answer 65

they act on non-human targets

Question 66

penicillin allergy is mediated by IG__

Answer 66

E

Question 67

t/f there can be cross-allergies between penicillins and cephaolosporins

Answer 67

t

Question 68

if someone is allergic to penicillin, is it certain that they will be allergic to cephalosporins?

Answer 68

no

Question 69

t/f in some extraordinary circumstances, desensitization therapy can be given to reduce penicillin allergies

Answer 69

t

Question 70

vacomycin acts by preventing the ___ of peptidoglycan by binding to the ___

Answer 70

cross-linking; bacterial peptide chain

Question 71

vancomycin has a large structure, which part is most importnat?

Answer 71

peptide chain region in the middle

Question 72

the peptide backbone of vancomycin forms ___ bonds with the bacerial peptide chains of peptidoglycan subunitis

Answer 72

H

Question 73

which bacterial peptide does the peptide backbone of vancomycin bind to?

Answer 73

D-Ala-D-Ala

Question 74

how does vancomycin prevent transpeptidases from bringing bacterial peptide togther and linking them?

Answer 74

H bond to peptide back bone make the rest of the vancomycin molecule folds over the bacterial peptide

Question 75

how can bacteria make themselves resistant to vancomycin?

Answer 75

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

Question 76

the loss of 1 H bond due to vancomycin resistance makes the drug ____x weaker

Answer 76

1000

Question 77

is vancomycin resistance very common?

Answer 77

not really; but moreso in hospitals

Question 78

what is a disadvantage of the large size of vancomycin?

Answer 78

too large to fit through pores of G-

Question 79

how must vancomycin be given to treat systemic infections? why?

Answer 79

IV; it is too big to get absorbed from the GI tract

Question 80

in what situation would vancomycin be given orally?

Answer 80

to treat a GI infection, like C. dif (can give high dose to target, because it wont be absorbed systemically)