Block 4: Antibiotics- Inhibition Of Cell Wall Biosynthesis/membrane Potential

Front 1

Name two classes of drugs that inhibit cell wall biosynthesis and one class of drugs that inhibits membrane potential

Back 1

glycopeptide
beta lactams

lipopeptide antibiotics

Front 2

name two glycopeptide antibiotics

Back 2

vancomycin
teicoplanin

Front 3

glycopeptides are ___ against gram positive cocci and ___ against gram positive rods; they are ___ against gram negatives

Back 3

bacteriostatic- gram pos cocci
bactericidal- gram pos rods
non effective- gram negatives

Front 4

Where is vancomycin's site and mechanism of action

Back 4

binds D-ALA-D-ALA terminus of murine monomer
--> inhibits murine polymer synthesis by blocking attachment of repeating disaccharide subunits to pre-existing cell wall

Front 5

name four reasons/conditions to use vancomycin

Back 5

1. antibiotic resistant pseudomembranous colitis
2. antibiotic resistant staphylococcal enterocolitis
3. staph infection in beta-lactam sensitive patients- or when infection is resistant
4. strep infections in beta lactam sensitive patients, or when infection is resistant

Front 6

how do bugs become resistant to vancomycin

Back 6

acquire the ability to replace the terminal D-ala with D-lactate (acquire the van HAX gene)

Front 7

name three benefits of teicoplanin over vancomycin

Back 7

1. extened half-life
2. once daily dosing
3. no pain or tissue necrosis after IM injection

Front 8

beta lactams are type ___ antibiotics

Back 8

type 2:
bacteriocidal
time-dependent
no PAE

Front 9

name three classes of beta lactams

Back 9

1. penicillins
2. cephalosporins
3. carbapenems

Front 10

where do penicillins come from

Back 10

made by strains of the fungus penicillium

Front 11

what is the common structural feature of penicillins

Back 11

6-aminopenicillanic acid nucleus composed of a thiazolidine ring (pentagon) fused to a beta lactam ring (square)

Front 12

why are penicllins provided as their Na or K salts

Back 12

because they are strong acids, the salt improves their solubility

Front 13

where is the active center of penicillins, the site of action of penicillinases, and the site of formation of the major antigenic determinants of penicillins

Back 13

beta lactam ring

Front 14

name four things that changing the R-group can do to the penicillin molecule

Back 14

acid stability
sensitivity to penicllinase
antibacterial spectrum
potency

Front 15

penicillin MOA

Back 15

inhibit the formation of peptidoglycan crosslinks in the cell wall.

beta-lactam moiety of penicillin -> binds enzyme that links peptidoglycan molecules in the bacteria (prevents polymerization of subunits)->
prevents bacteria from multiplying by causing lysis when bacteria tries to divide

Front 16

Where is the site of action for penicillinase?
for amidase?

Back 16

penicillinase- between the C-N bond of the beta lactam ring
amidase- between the C-N bond of the C=O to the left of the lactam ring

Front 17

penicillin G is acid/base labile.
__ of an oral dose is absorbed
good distribution except ___
in renal failure, half life ___

Back 17

acid labile
1/3 absorbed
good distribution except CSF
renal failure- t1/2 INCREASES

Front 18

What plays a role in hypersensitivity to penicillin G- renal secretion of unmetabolized, yet active, drug or hepatic metabolites, although inactive?

Back 18

inactive hepatic metabolites

Front 19

how do you delay absorption of penicillin G from intramuscular sites

Back 19

add organic bases like procaine or benzathine

Front 20

what is the drug of choice of syphillis

Back 20

penicillin G + benzathine

Front 21

What does delaying absorption of penicillin G do to the maximum blood level achieved

Back 21

it is considerably lower for an equivalent dose

Front 22

how do you delay elimination of penicillin G

Back 22

administer probenecid- a competitive blocker of tubular secretion of organic acids

Front 23

most active of the penicillins against Gram positive bacteria (non-penicillinase producers), acid labile

Back 23

penicillin G

Front 24

acid stable penicillin form with better absorption after oral administration

Back 24

penicillin V

Front 25

name four mechanisms of beta-lactam resistance

Back 25

1. decreased affinity of penicillin binding proteins through mutation and recomb
2. decreased cell wall permeability
3. increased activity of penicillinases (beta-lactamases)
4. energy- dependent efflux pumps

Front 26

methicillin
nafcillin
cloxacillin

Back 26

penicillinase resistant penicillins

Front 27

name two bugs that make exocellular beta-lactamase

Back 27

staph aureus and s. epidermis

Front 28

is methacillin given orally

Back 28

no

Front 29

what is methicillin resistance related to

Back 29

failure to bind to penicillin binding proteins; organisms resistant are likely to be resistant to other penicillins and cephalosporins

Front 30

ampicillin
amoxicillin

Back 30

extended range penicillins

Front 31

how do ampicillin and amoxicillin increase spectrum

Back 31

better penetration of gram negative outer membrane and/or decreased susceptibility to gram negative penicillinases (but more susceptible to gram pos penicillinases)

Front 32

which is more completely absorbed after oral administration- amoxicillin or ampicillin

Back 32

amoxicillin

Front 33

name 6 bugs that ampicillin and amoxicillin are good for

Back 33

e. coli
p. mirabilis
h. influenza
salmonella
shigella
neisseria

Front 34

carbenicillin
ticarcillin

Back 34

anti-pseudomonal penicillins

Front 35

name three bugs that are susceptible to carbenicillin and ticarcillin

Back 35

p. aeruginosa
indole pos proteus
indole pos enterobacter

Front 36

name an N-acyl derivative anti-pseudomonal penicillin (ureidopenicillin)

Back 36

pipericillin

Front 37

amoxicillin plus clavulanate

Back 37

augmentin (add penicillin with a suicide inhibitor of beta-lactamase)

Front 38

ticarcillin plus clavulanate

Back 38

timentin (add penicillin with a suicide inhibitor of beta-lactamase)

Front 39

ampicillin plus sulbactam

Back 39

unasyn (add penicillin with a suicide inhibitor of beta-lactamase)

Front 40

pipericillin plus tazobactam

Back 40

Zosyn (add penicillin with a suicide inhibitor of beta-lactamase)

Front 41

is penicillin itself antigenic

Back 41

no- its polymers and metabolites can react with bacterial or tissue proteins to form antigenic conjugates

Front 42

what is the major class of metabolites which act as antigenic determinants of penicillin

Back 42

penicillinic acids

Front 43

name five adverse effects of penicillins

Back 43

1. allergic
2. diarrhea in kids
3. CV fluid overload
4. CNS effects in lg doses or renal failure
5. coag defects from inhibition of platelet activation and conversion of fibrinogen to fibrin

Front 44

does a negative skin test for penicillin hypersensitivity guarantee the absence of an anaphylactic response

Back 44

no- it only predicts 95% of IgE mediated hypersensitivity

Front 45

What is used to detect penicilloyl-specific IgE antibodies without skin testing

Back 45

Rast- radioimmunoassay testing

Front 46

cephalosporin MOA

new cephalosporins have a wider range of activity because of resistance to...

Back 46

type II bactericidal- time dependent, no PAE

gram negative penicillinases

Front 47

cefadroxil
cephalexin
cefazolin
cephadrine

Back 47

first generation (narrow spectrum) cephalosporin

Front 48

first generation cephalosporins have...
___ against gram pos's
___ against gram neg's
___ against methicillin-resistant S. aureus

Back 48

good activity- gram pos
moderate activity- gram neg
not effective- methicillin resistant S. aureus

Front 49

1st gen cephalosporins may not be drug of choice for active infection because they...
but may be drugs of choice for...

Back 49

don't penetrate CSF

surgical prophylaxis

Front 50

cefotetan
cefoxitin
cefuroxime
cefuroxime axetil
carbacephem

Back 50

second generation (increased activity against gram neg, decreased activity against gram pos) cephalosporins

Front 51

good activity against B. fragilis, and anaerobic organisms

Back 51

cefotetan

Front 52

similar spectrum of action to cefotetan; both used for prophylaxis during intra-abdominal surgery

Back 52

cefoxitin

Front 53

effective against h. influenzae and k. penumoniae; used to treat community acquired pneumonia

Back 53

cefuroxime

Front 54

orally active prodrug axetil form of cefuroxime

Back 54

cefuroxime axetil

Front 55

cephalosporin derivative with spectrum of activity comparable to that of cefaclor or amoxicillin/clavulanate

Back 55

carbacephem

Front 56

cefotaxime
cefpodoxime
ceftazidime
ceftriaxone

Back 56

3rd gen (good penetration to CNS) cephalosporin

Front 57

high activity against many gram negative enteric bacteria

Back 57

cefotaxime

Front 58

orally active with wide spectrum of action; useful for URTI and UTI

Back 58

cefpodoxime

Front 59

indicated primarily for multidrug resistant gram negative infections; particularly those caused by pseudomonas

Back 59

ceftazidime

Front 60

similar spectrum to cefotaxime, 8 hr serum half life instead of 1 hr, drug of choice for n. gonorrhea and b. burgdorferi with CNS involvement

Back 60

ceftriaxone

Front 61

cefepime

Back 61

4th generation cephalosporin

Front 62

similar to ceftazidime in activity against pseudomonas and other gram negative organisms;
better than 3rd generation cephalosporins against gram pos organisms because of its resistance to chromosomally-encoded beta-lactamase; orally active

Back 62

cefepime

Front 63

name 6 adverse effects of cephalosporins

Back 63

1. diarrhea and GI upset
2. vit K def
3. nephrotoxicity
4. suprainfection
5. hypersensitivity reax
6. disulfiram-alcohol reax

Front 64

imipenem
meropenem
ertapenem
monobactam

Back 64

carbapenems (also beta-lactam antibiotics --> type II bactericidal, time-dependent; no PAE)

Front 65

extremely broad anti-bacterial spectrum;
resistant to beta-lactamase
not resistant to metallo-beta-lactamase
cross-allergenicity with penicillin

Back 65

imipenem

Front 66

imipenem with cilastatin

Back 66

primaxin- because imipenem alone is rapidly hydrolyzed by renal tubule dipeptidase

Front 67

structurally related to imipenem, but less susceptible to hydrolysis by renal tubule dipeptidase

Back 67

meropenem

Front 68

longer plasma half life than meropenem -> permitting once-daily dosing

Back 68

ertapenem

Front 69

excellent activity against gram neg
poor activity against gram pos
little cross-allergenicity with other beta-lactam drugs

Back 69

monobactam

Front 70

daptomycin

Back 70

lipopeptide antibiotic- inhibits cell membrane potential

Front 71

used for tx of complicated skin infections by aerobic, gram pos's

Back 71

daptomycin

Front 72

daptomycin MOA

Back 72

bactericidal type I
concentration dependent, significant PAE

binds to bacterial membranes and forms channels in a calcium-dependent manner leading to rapid membrane depolarization -> inhibiting protein, DNA, and RNA synthesis

Front 73

bactericidal against vancomycin resistant enterococci

Back 73

daptomycin

Front 74

how do you give daptomycin and does it cross the BBB

Back 74

injection only

no

Front 75

how do bugs get daptomycin resistance

Back 75

so far, they haven't

Front 76

combinations of beta lactams with inhbitors of bacterial beta lactamases, such as ___ improves the effectiveness of the antibiotic

Back 76

clavulanate

Front 77

imipenem, a broad-spectrum antibiotic, is rapidly degraded by the renal ___, however, a related carbapenem, ___, is resistant to this degradation

Back 77

renal tubule dipeptidase

meropenem