Penicillins & Cephalosporins

Question 1

beta lactams target ______ by interfering with ______

Answer 1

cell wall synthesis, transpeptidase

Question 2

bacterial cell wall is a cross-linked polymer called _______ which allows a bacteria to maintain its shape despite the internal pressure caused by ______

Answer 2

peptidoglycan, osmotic pressure differences

Question 3

if the peptidoglycan fails to _____, the cell wall will lose its strength which results in cell lysis

Answer 3

crosslink

Question 4

the cross linking reaction is catalyzed by a class of transpeptidases known as ________

Answer 4

penicillin binding proteins (PBPs)

Question 5

a critical part of the cross linking process is the recognition of the ________ sequence of the NAMA peptide side chain by the PBP

Answer 5

D-Ala-D-Ala

Question 6

beta lactams mimic the structure of the _______ link and bind to the active site of _____, disrupting the cross-linking process

Answer 6

D-Ala-D-Ala, PBPs

Question 7

the ____ of the beta lactam ring is unusually reactive due to ring strain

Answer 7

amide

Question 8

beta lactams acylate the _____ group on the serine residue of PBP active site in an irreversible manner

Answer 8

hydroxyl

Question 9

what is the “secondary” mechanism of beta lactams that cannot occur without the primary mechanism

Answer 9

the bacteria detect a “defect” in its cell wall so it produces more peptidoglycan. in doing so, it produces autolysin, which is an enzyme produced by the bacteria to remove damaged cell wall for repair (slices off its own cell wall)

Question 10

what are 3 mechanisms of bacterial resistance

Answer 10

efflux pumps, beta lactamases, mutation at genes that control PBP production

Question 11

how do beta lactamases render beta lactams useless

Answer 11

they hydrolyze the amide bond of the beta lactam ring

Question 12

beta lactams can easily penetrate _____ bacteria

Answer 12

gram positive

Question 13

the outer membrane of ____ bacteria makes diffusion of beta lactams to the site of activity challenging

Answer 13

gram negative

Question 14

any bacteria which lack ____ will not be affected by beta lactams

Answer 14

peptidoglycan

Question 15

why are beta lactams relatively non toxic

Answer 15

they target PBPs exclusively, human cell membranes don’t have PBPs

Question 16

penicillin __ is not orally active due to gut acidity

Answer 16

G

Question 17

penicillin __ is orally viable and acid stable because of an added oxygen

Answer 17

VK

Question 18

caution with high potassium/ESRD for which natural penicillin

Answer 18

VK

Question 19

what was oral penicillin historically used for

Answer 19

dental prophylaxis in patients w/ prosthetic heart valves

Question 20

when is oral penicillin actually used now

Answer 20

dental infections (soft tissue impacted molar), IM for syphilis, IV for susceptible severe streptococcal infections

Question 21

______ are enzymes that hydrolyze the beta lactam ring, deactivating the drug

Answer 21

beta lactamases

Question 22

beta lactamases can be present in both gram positive and negative bacteria, but they are a significant focal point in _____

Answer 22

gram negative, particularly those causing nosocomial infections

Question 23

________ penicillins have a notable large R group which can block the beta-lactamases which hydrolyze the beta lactam ring

Answer 23

anti-staphylococcal

Question 24

what are the oral anti-staphylococcal penicillins

Answer 24

cloxacillin, dicloxacillin

Question 25

what are the IV anti-staphylococcal penicillins

Answer 25

oxacillin, nafcillin

Question 26

what is the downside to anti-staphylococcal penicillins

Answer 26

due to the bulky side group, they have difficulty penetrating the cell membrane and are less effective against gram negative bacteria (no clinically relevant activity)

Question 27

staphylococcus produces _____

Answer 27

penicillinase (beta lactamase)

Question 28

Pen VK/G activity against staphylococci

Answer 28

extremely limited

Question 29

Pen VK/G activity against streptococci

Answer 29

good activity against some: pyogenes is always susceptible, pneumoniae is mostly susceptible

Question 30

anti-staphylococcal penicillin activity against staphylococcus

Answer 30

excellent activity against MSSA, no activity against MRSA

Question 31

anti-staphylococcal penicillin activity against streptococci

Answer 31

little to no activity

Question 32

_________ have more hydrophilic groups, allowing the drug to penetrate into gram negative bacteria via the outer membrane porins

Answer 32

aminopenicillins

Question 33

downside to aminopenicillins

Answer 33

without the bulky R group of the anti-staphylococcal PCNs, they are once again susceptible to attack by beta lactamases

Question 34

the hydrophilic groups of aminopenicillins also allow for greater absorption in the ____

Answer 34

GI tract

Question 35

aminopenicillins are the drugs of choice for _____

Answer 35

enterococcus and listeria

Question 36

acronym for aminopenicillin activity

Answer 36

HELPS: hemophilus, enterococcus, listeria, proteus, salmonella/shigella

Question 37

PO frequency of administration for ampicillin

Answer 37

4x/day

Question 38

PO frequency of administration for amoxicillin

Answer 38

3x/day

Question 39

which aminopenicillin is more bioavailable

Answer 39

amoxicillin, less frequency of diarrhea too

Question 40

ampicillin with regards to food?

Answer 40

should be administered PO on an empty stomach, food decreases absorption and peak plasma concentration

Question 41

amoxicillin with regards to food?

Answer 41

may be taken without regards to meal

Question 42

what are the IV beta lactamase inhibitors

Answer 42

sulbactam, tazobactam

Question 43

what is the PO beta lactamase inhibitor

Answer 43

clavulanic acid

Question 44

what are the first generation cephalosporins

Answer 44

cefazolin, cephalothin, cephalexin, cefadroxil

Question 45

which first generation cephalosporins are PO

Answer 45

cephalexin, cefadroxil

Question 46

what is the spectrum of activity for first generation cephalosporins

Answer 46

excellent against MSSA and streptococci, no activity against enterococcus, limited activity against gram negative, no activity against gram negative obligate anaerobes in the gut

Question 47

first generation cephalosporins are excreted by the _____ unmetabolized

Answer 47

kidney

Question 48

dose adjustments for first generation cephalosporins are made for patients with _____

Answer 48

poor kidney function

Question 49

what are the second generation cephalosporins

Answer 49

cefaclor, cefuroxime, cefprozil

Question 50

what second generation cephalosporins are PO

Answer 50

cefaclor, cefuroxime, cefprozil

Question 51

what second generation cephalosporins are IV

Answer 51

cefuroxime

Question 52

spectrum of activity for second generation cephalosporins

Answer 52

slightly less potent against gram positive, increased activity against gram negatives

Question 53

given the spectrum of first generation cephalosporins, what are they good for

Answer 53

skin and skin structure infections, clean surgical procedures

Question 54

given the spectrum of second generation cephalosporins, what are they good for

Answer 54

URTIs (bacterial sinusitis, otitis media), UTIs

Question 55

the PO form of cefuroxime is a ____ that increases absorption by increasing lipophilicity

Answer 55

prodrug

Question 56

______ possess a methoxy group at the 7-alpha position of the cephem ring instead of a carboxylic acid

Answer 56

cephamycins

Question 57

what are the cephamycins

Answer 57

cefoxitin and cefotetan

Question 58

cefoxitin and cefotetan possess ______ activity whereas other 2nd generation cephalosporins do not

Answer 58

gram-negative obligate anaerobic

Question 59

_______ contains an N-methylthiotetrazole side chain (NMTT or 1-MTT) that can lead to inhibition of vitamin K epoxide reductase and increase prothrombin times and risk for bleed

Answer 59

cefotetan

Question 60

if the cephamycins have anaerobic activity why are they not used in the setting of active infection where obligate anaerobes are present

Answer 60

due to resistance. so they are used for peri-operative prophylaxis

Question 61

what are the third generation cephalosporins

Answer 61

cefotaxime, ceftriaxone, ceftazidime, cefpodoxime, cefixime, ceftibuten, cefdinir, cefditoren

Question 62

spectrum for third generation cephalosporins

Answer 62

broad spectrum gram negative

Question 63

the third generation cephalosporins are mostly excreted by the kidney except for ______ which undergoes enterohepatic recycling

Answer 63

ceftriaxone

Question 64

therapeutic uses for third generation cephalosporins in the community

Answer 64

otitis media (recurrent/frequent), URTI

Question 65

cefpodoxime PO form is a ______ that increases absorption by increasing lipophilicity

Answer 65

prodrug

Question 66

bioavailability of cefpodoxime proxetil is ____

Answer 66

50%

Question 67

what is different about ceftazidime

Answer 67

gram negative coverage includes pseudomonas aeruginosa

Question 68

what is pseudomonas aeruginosa

Answer 68

nosocomial pathogen typically causing infections in hospitalized patients