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Medical Pharmacology > Cell Wall Agents (Bactericidal) > Flashcards

Cell Wall Agents (Bactericidal) Flashcards

1
Q

what does the cell wall of gram negative bacteria look like

A

lipopolysaccharide and porins

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2
Q

what does cell wall of gram positive bacteria look like

A

murein (peptidoglycan outside)

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3
Q

how to build peptidoglycan

A

synthesis of murein monomers that are polymerized and crosslinked by transpeptidase

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4
Q

what are penicillin binding proteins

A

transpeptidases

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5
Q

what do PBP do

A

crosslink murein chains (to make peptidoglycan)

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6
Q

when do cell wall agents actually kill?

A

when cell walls are synthesizing

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7
Q

which drugs are inhibitors of murein monomer synthesis

A
  1. fosfomycin
  2. cycloserine
  3. bacitracin
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8
Q

MOA of fosfomycin

A

inhibits synthesis of UDP-NAM from UDP-NAG by inhibiting MurA

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9
Q

how does fosfomycin enter cell

A

via transporters for glycerophosphate or glucose 6 phosphate

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10
Q

what is fosfomycin used for

A

gram negative bacteria in urinary tract - single dose for uncomplicated lower UTI in women

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11
Q

what causes resistance to fosfomycin

A

mutations in transporters

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12
Q

what species does fosfomycin act against

A

e coli, klebsiella, serratia

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13
Q

MOA of bacitracin

A

interferes with dephosphorylation of bactoprenyl diphosphate, which is a bactoprenol lipid carrier necessary for murein monomer synthesis and export)

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14
Q

adverse effects of bacitracin

A

significant kidney, neuro and bone marrow toxicity so is not used systemically - only topically or GI tract

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15
Q

how is bacitracin used?

A

used to treat c diff or VRE in GI tract bc is not orally absorbed (stays in lumen)

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16
Q

which drugs are inhibitors of murein polymerization?

A
  1. vancomycin
  2. telavancin
  3. daptomycin
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17
Q

what kind of antibiotic is vancomycin

A

glycopeptide antibiotic

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18
Q

MOA of vancomycin

A

bind to D-Ala-D-Ala terminus of murein monomer unit, inhibiting peptidogylcan polymerization (blocks addition of murein units to growing polymer chain)

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19
Q

what is vancomycin effective against

A

gram positive ONLY rods and cocci including MRSA

orally for c diff

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20
Q

how is resistance against vancomycin occur

A

acquisition of DNA encoding enzymes that catalyze formation of D-Ala-D-lactate which is not bound by vancomycin, alter permeability

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21
Q

when is vancomycin used orally?

A

only for c diff (because not absorbed orally)

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22
Q

what is red man syndrome

A

flushing and itching that is due to vancomycin causing mast cell degranulation –> release of histamine

due to amount and rate of IV vancomycin infusion NOT IgE release or allergic reaction

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23
Q

ADE of vancomycin

A

nephrotoxic and ototoxic when given IV

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24
Q

which drugs bind to mast cells and cause degranulation?

A

vancomycin and morphine

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25
Q

when does red man syndrome occur

A

4-10min after start of vancomycin (or morphine) infusion or shortly after completion

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26
Q

how to monitor vancomycin levels

A

need to monitor the trough (level right before the next dose is due)

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27
Q

how is vancomycin cleared

A

renally

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28
Q

how does vancomycin have bactericidal activity

A

time dependent killing, bactericidal activity continues as long as plasma concentration is greater than minimum bactericidal concentration

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29
Q

what is daptomycin effective against

A

gram positive only

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30
Q

moa of daptomycin

A

bind to bacterial cell membrane, cause depolarization, disruption of functions and death

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31
Q

what is daptomycin used for

A
  1. MSSA/MRSA skin infections or bacteremia

2. right sided endocarditis

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32
Q

why can’t daptomycin be used for pneumonia?

A

is inactivated by pulmonary surfactant

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33
Q

ADE of daptomycin

A

myopathy (monitor CK) and nerve conduction deficits

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34
Q

how is daptomycin cleared

A

renally

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35
Q

what are the beta lactams?

A
  1. penicillins
  2. cephalosporins
  3. carbapenams
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36
Q

what is the general MOA of all beta lactams?

A

inhibit transpeptidases that mediate crosslinking because beta lactam ring is the structural analogue of terminal D-Ala-D-Ala

is bactericidal as long as cells are growing

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37
Q

what is D-Ala-D-ala

A

a substrate for one or more bacterial transpeptidases (penicillin binding protein)

beta lactam rings irreversibly bind to PCP

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38
Q

what are penicillin binding proteins?

A

transpeptidases that are responsible for synthesis of peptidoglycan wall (crosslink murein chains), and are the target of penicillin and cephalosporins

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39
Q

what determines beta lactam’s spectrum of activity?

A
  1. ability to enter periplasmic space

2. affinity for specific transpeptidases

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40
Q

what organisms are resistant to beta lactam drugs?

A

organisms that lack peptidoglycan cell walls – mycobacteria and protozoa

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41
Q

how do bacteria become resistant to beta lactam drugs?

A

produce beta lactamases that clip the beta lactam ring so it cannot bind to transpeptidase

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42
Q

how is beta lactam resistance transferred

A

encoded on DNA plasmids from 1 bacteria to the other

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43
Q

how are antistaphylococcal penicillins helpful against resistance?

A

have steric hinderence to beta lactamases that are produced by staph

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44
Q

what is added to beta lactams to help with resistance?

A

beta lactamase inhibitors added to prevent beta lactamase catalyzed degradation of penicillin

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45
Q

what drugs prevent beta lactamase from degrading the drugs?

A

cephalosporins and carbapenams because of steric hinderance – but extended spectrum beta lactamase and carbapenemases have emerged to resist

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46
Q

how are bacteria beta lactam resistant

A

have alterations in or acquisition of PBP, but most drugs are active against multiple transpeptidases so the bacteria would have to mutate ALL PBP to be fully resistant

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47
Q

what are gram positive bacteria inherently resistant to?

A

aztreonam

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48
Q

what are enterococci inherently resistant to

A

cephalosporins

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49
Q

how is MRSA so resistant to everything

A

has altered ALL of its PBP so it has inherent resistance to beta lactams

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50
Q

what is MRSA NOT resistant to

A

ceftaroline

51
Q

how to gram negative bacteria become beta lactam resistant

A

they alter their porins

52
Q

how do intracellular bacteria have resistance

A

mammalian cells lack beta lactam uptake mechanism

53
Q

which are the beta lactamase inhibitors

A
  1. clavulanic acid
  2. sulbactam
  3. tazobactam
54
Q

MOA beta lactamase inhibitors

A

resemble beta lactam molecules so the bacteria recognize them and cleave them instead of the “real drug”

55
Q

what is amoxicillin/clavulanate

A

beta lactamase inhibitor - augmentin

56
Q

what is augmentin used for

A
  1. acute otitis media where beta lactamase positive strains are likely
  2. URI
  3. UTI
  4. soft tissue when caused by beta lactamase + strain (MSSA)
57
Q

why is it hard to kill bacteria attached to implanted devices (biofilms)?

A

because beta lactams are most active in the logarithmic phase (takes out walls as they are produced)

58
Q

what if a pt has an IgE mediated reaction

A

do not use other beta lactams because there could be cross reactivity

59
Q

what if a pt has type IV hypersensitivity

A

can use other beta lactams

60
Q

beta lactam ADE

A
  1. type I or IV hypersensitivity
  2. interstitial nephritis
  3. rash
  4. eosinophilia
  5. serum sickness (drug fever)
  6. hemolysis (lupus)
61
Q

what ADE occurs at high doses or in renal impaired pt?

A

seizures because beta lactams are GABA antagonists

62
Q

how is ceftriaxone cleared

A

lipophilic so ceftriaxone is highly bound to albumin. it can displace bilirubin from albumin binding to sites in neonates (causing hyperbilirubinemia)

63
Q

why is ceftriaxone contraindicated in neonates

A

can displace bilirubin from albumin binding to sites in neonates – hyperbilirubinemia

64
Q

why is impienem dangerous

A

high high risk of seizures bc GABA antagonist

65
Q

how are most beta lactams cleared?

A

renally cleared except ceftriaxone

66
Q

what does penicillin have greatest activity

A

gram + and gram - cocci, non beta lactamase producing anaerobes

67
Q

what are antistaphylococcal penicillins effective against

A

staph and strep

NOT enterococci, anaerobic and gram negative cocci and rods

68
Q

what are extended spectrum penicillins effective against

A

greatest activity against gram + and gram - cocci and non beta lactamase producing anaerobes, improved activity against gram - organisms

69
Q

what is the drug of choice for syphillis

A

penicillin

70
Q

what is penicillin G or V effective against

A

NOT USED IN STAPH

strep, syphilis, g+ anaerobes except bacteriodes or c diff, neisseria, spirochetes

71
Q

half life of penicillin

A

30-90min

72
Q

when can pregnant women take penicillin?

A

if they have T palladium – is super effective against t pallidium

73
Q

which are the aminopenicillins

A

ampicillin and amoxicillin

74
Q

spectrum that aminopenicillins cover

A

non beta lactamase producing neisseria, escherichia, haemophilus, enterococci, listeria, h pylori, klebsiella

75
Q

what if add beta lactamase to aminopenicillin?

A

cover h influenzae and enterobacteriaceae

76
Q

what are aminopenicillins first line for?

A

acute otitis media, neonatal meningitis (with gentamicin), uncomplicated enterococcal or proteus mirabilis UTI, dental prophylaxis

77
Q

what are the penicillinase-resistant penicillins

A
  1. oxacillin
  2. nafcillin
  3. cloxacillin
  4. methicillin
78
Q

what are the penicillinase resistant penicillins against

A

antistaphylococcal – for confirmed staph infections – endocarditis, osteomyelitis, skin/soft tissue, pneumo

also for strep bacteria

79
Q

what does naficillin cover

A

gram + only

80
Q

which are the antipseudomonal penicillins?

A

ticarcillin

piperacillin

81
Q

what has the broadest spectrum of penicillins

A

piperacillin when combined with tazobactam

82
Q

what is the spectrum of antipseudomonal penicillins

A

staph aureus, coag negative strep, strep pneumo, strep species, h influenzae, moraxella catarrhalis, neisseria meningititis, neisseria gonorrheae, e coli, klebsiella, pseudomonas, enterobactericeae, bacteriodes

83
Q

what can cause MSSA

A

beta lactamases

84
Q

what can cause MRSA

A

is inherently resistant

85
Q

how is amoxicillin absorbed?

A

extensively absorbed PO so not good for shigella or salmonella

86
Q

are penicillins safe for pregnancy?

A

generally

87
Q

most common resistance to penicillins

A

inactivation by beta lactamase

88
Q

how do pneumococci and enterococci have resistance to penicillins

A

modification of target PBP

89
Q

how do gram - have resistance to penicillins?

A

impaired penetration of drug to target PBP and increased antibiotic efflux

90
Q

what are cephalosporins NOT effective against

A
  1. listeria monocytogenes
  2. atypical pathogens in pneumonia like mycoplasma or chlamydia
  3. MRSA except 5th gen
  4. enterococci

“LAME”

91
Q

what are cephalosporins susceptable to

A

ESBL but not most “wimpy” beta lactamases

92
Q

what are 1st gen cephalosporins effective against

A

gram +

some gram -

93
Q

2nd gen cephs effective against

A

better gram -
less gram+
some anaerobes

94
Q

3rd gen cephs effective against

A

better gram - than the 2nd
some anaerobes
less + than 1st

95
Q

4th gen cephs effective against

A

better gram -
some anaerobes
less +
PSEUDOMONAS

96
Q

5th gen cephs effective against

A

better gram -
some anaerobes
less +
MRSA

97
Q

which are the 1st gen cephalosporins

A
  1. cephalexin
  2. cefazolin

don’t let the LEXicon FAZe you, 1st gen are the only ones with a PH

98
Q

1st gen ceph effective against

A

gram + plus PEcK

proteus
e coli
klebsiella

UTI caused by these plus saprophyticus

99
Q

2nd gen cephalosporins

A 
cefprozil 
cefotetan
cefoxitin
cefuroxime 
cefaclor

she nearly FPROZ going through the TETons so she wore her FOX FUR FACe

100
Q

what do 2nd cephs cover

A

gram + plus HENPEcK

haemophilus, enterobacter, neisseria, proteus, e coli, klebsiella

101
Q

what 2nd gen may cover bacteroides fragilis? for abd or gyn surgeries

A

cefotetan and cefoxitin

tetans have foxes

102
Q

what are cefuroxime/cefprozil used for

A

lymes, acute otitis media, URI

103
Q

what are the 3rd gen cephalosporins

A

cefdinir
ceftriaxone
cefazidime
cefotaxime

104
Q

what are 3rd gen cephs effective against

A

enterobacteriaceae, neisseria, h influenzae, pneumococci

105
Q

which 3rd gen are helpful against pneumococci

A

ceftriaxone

cefotaxime

106
Q

what 3rd gen ceph is used for pseudomonas

A

ceftaxidime

107
Q

what is a 4th gen ceph

A

cefepime

108
Q

what does cefepime cover

A

broad spectrum including PSEUDOMONAS

109
Q

what is a 5th gen ceph

A

ceftaroline

110
Q

what does ceftaroline cover

A

like ceftriaxone (pneumo-CAP) that covers MRSA

111
Q

what are the carbapenams

A
  1. imipenem/cilastatin
  2. ertapenem
  3. doripenem
  4. meropenem
112
Q

what are carbapenams not effective against

A

atypical pneumonia, legionella, MRSA, or carbapenamase producing strains

113
Q

what are carbapenams effective against

A

ESBL gram - (but not carbapenamase +), PSEUDOMONAS, actinobacter, anaerobes

114
Q

what is added to imipenem and why

A

cilastatin to prevent deactivation by dipeptidases in the renal brush borders – the inactivation results in low urinary concentration

115
Q

adverse effects carbapenams

A

seizures (imipenem)

116
Q

what is the monobactam

A

aztreonam

117
Q

what is aztreonam safe in

A

safe even in severe beta lactam allergy (except ceftazidime bc has identical side chain)

118
Q

profile of aztreonam

A

aerobic gram -, including PSEUDOMONAS

119
Q

what to do if type I hypersensitivity to penicillin, cephalosporin, carbapenam?

A

avoid other classes (can use aztreonam) unless benefit outweighs risk

120
Q

what to do if type IV hypersensitivity to beta lactams?

A

just switch to different class

121
Q

use of cell wall agents in neonates

A

ceftriaxone may displace bilirubin so don’t use it, don’t give IV calcium with it

122
Q

what cell wall agents are safe in pregnancy

A

vancomyin and beta lactams general safe

123
Q

what are cephalosporins not effective against?

A

enterococcus, MRSA, listeria, atypical pneumonia

Medical Pharmacology (13 decks)

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