B-Lactam Intro

Question 1

Why can’t beta lactams be completely synthetic?

Answer 1

we can’t make the base structure chemically, it must come from natural sources

Question 2

What are the four classes of beta lactams?

Answer 2

penicillins, cephalosporins, carbapenems, monobactams

Question 3

Are beta lactams time dependent or concentration dependent, and what is the predictive PK/PD parameter?

Answer 3

time dependent, time above the MIC (PK/PD parameter)

Question 4

Are beta lactams usually eliminated renally or hepatically?

Answer 4

renally

Question 5

What is the mechanism of action of beta lactams?

Answer 5

it binds to penicillin-binding proteins which inhibits transpeptidase in the bacterial cell wall from cross-linking the peptidoglycan (affects cell wall synthesis)

Question 6

What does it mean for a drug to be bactericidal?

Answer 6

it kills 99.9% of bacteria

Question 7

What adverse reaction can be caused by all beta lactams and is not related to dosage strength?

Answer 7

hypersensitivity reactions

Question 8

What are the two most serious hypersensitivity reactions?

Answer 8

acute interstitial nephritis (can lead to kidney failure), anaphylaxis

Question 9

Beta-lactams can also cause seizures, which means they are called ________ drugs

Answer 9

epileptogenic

Question 10

What is the most common reason why beta lactams cause seizures?

Answer 10

when the patient’s renal function changes (usually decreases) and the dose is not adjusted in time, the drug builds up in the blood and can cause the seizures

Question 11

What is the approximate percent cross-reactivity between penicillins and cephalosporins?

Answer 11

5-10%

Question 12

Which class of organisms are beta lactams NOT effective against?

Answer 12

atypical organisms (mycoplasma, chylamidia, etc)

Question 13

Which beta lactam was approved for MRSA treatment in 2010?

Answer 13

ceftaroline

Question 14

In what year did Alexander Fleming “discover” penicillin?

Answer 14

1929

Question 15

How long after Fleming’s work did it take before someone actually worked out the structure and properties of PCN and considered its clinical properties? Who were they?

Answer 15

10 years (1939), Florey and Chain

Question 16

When was resistance to PCN from S. aureus and E. coli observed and who observed it?

Answer 16

1942, Abraham and Chain

Question 17

In what year did it become possible to make semisynthetic penicillins?

Answer 17

1959

Question 18

Which part of 6-aminopenicillanic acid is the beta lactam part?

Answer 18

the square ring

Question 19

Which penicillin binding protein (PBP) is the most important and effective drug target?

Answer 19

PBP 2

Question 20

Are penicillin binding proteins enzymes?

Answer 20

yes

Question 21

What are three bacterial mechanisms that account for resistance to beta lactams?

Answer 21

destruction of antibiotic by beta-lactamases, failure to penetrate to penicillin binding protein target, low affinity binding of antibiotic to PBP

Question 22

How do beta-lactamases deactivate beta lactams?

Answer 22

break open the beta lactam ring

Question 23

Why is drug penetration to the penicillin binding protein mostly a problem in gram negative organisms?

Answer 23

the beta lactam gets “hung up” in the lipopolysaccharide of the cell wall

Question 24

What is the name of the penicilling binding protein that most commonly changes its shape to lower its affinity for beta lactam drugs?

Answer 24

PBP 2A

Question 25

What is vertical resistance transfer?

Answer 25

when the parent cell passes its resistant genes on to its daughter cells

Question 26

What is horizontal resistance transfer?

Answer 26

the passage of resistance from one species to another (usually through plasmids)

Question 27

What is constitutive resistance?

Answer 27

bacteria produces low levels of beta lactamase at all times

Question 28

What is inducible resistance?

Answer 28

bacteria produces a lot of beta lactamase only when needed

Question 29

Why are staphylococcal beta lactamases called penicillinases?

Answer 29

because they are mostly active against penicillins

Question 30

What are some characteristics of staphylococcal beta lactamases?

Answer 30

plasmid encoded, inducible, hydrolyzes (breaks open) penicillin before it reaches target PBPs

Question 31

What are two examples of antistaphylococcal penicillins?

Answer 31

methicillin, isoxazolyl

Question 32

Why can methicillin only by given IM or IV, not orally?

Answer 32

its beta lactam ring is broken open by stomach acid

Question 33

Where are gram negative beta lactamases strategically located, and why is this effective?

Answer 33

in the periplasmic space; it doesn’t cost very much energy to create enough beta lactamase to make a really high concentration in the space because it is so small, so very little beta lactamase needed

Question 34

gram negative beta lactamses can be coded on ____ or ______, and can be inducible or constitutive

Answer 34

plasmids, chromosomes

Question 35

Where did TEM-1 come from and what drug did it break down?

Answer 35

came from E. coli, broke down ampicillin

Question 36

What does ESBL stand for and what does it break down?

Answer 36

extended-spectrum beta lactamases, breaks down extended spectrum cephalosporins

Question 37

What are three constraints that porin channels (in gram negative cells) use to control what enters the cell?

Answer 37

size, structure, charge of molecule

Question 38

What are three mechanisms used to limit antibiotic concentrations in the periplasmic space?

Answer 38

exclusion of antibiotic by porins, destruction of antibiotic with beta lactamases, active transport of drug back across the membrane out of cell

Question 39

What PBP does MRSA have that changes its affinity for beta lactam antibiotics?

Answer 39

PBP2a

Question 40

What molecule is involved in crosslinking of peptidoglycan in the cell wall?

Answer 40

pentaglycine