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Pharm Block 12 > Cell Wall Drugs > Flashcards

Cell Wall Drugs Flashcards

1
Q

What are the groups of cell walls drugs

A

B-lactam

Non b-lactam

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2
Q

What are the B-lactams

A

Penicillins
Cephalosporins
Carbapenems
Aztreonam

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3
Q

Why are beta lactamase inhibitors (BLI) often combined with beta lactam drugs

A

Beta lactamase cleaves the 4 ring structure of b lactams. It’ll help the b-lactams work better

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4
Q

Beta lactamaase inhibitors

A

Clavulanic acid
Sulbatram
Tazobactram

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5
Q

4 ring structures

A

Beta lactam

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6
Q

When you think beta lactams, what should you think

A

Penicillins and cephalosporins

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7
Q

What are the beta lactams

A

Penicillins
Cephalosporins
Monobactam (aztreonam)
Carbapenems (imipenem)

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8
Q

B lactamase inhibitors and beta lactams

A

Beta lactams have a 4 membered ring, and it must remain intact to work. BLI block the bacterial enzyme that breaks down the ring so that it can work

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9
Q

What is the first choice of Abx

A

Penicillin

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10
Q

Types of penicillins

A
  • natural penicillins (pen G)
  • antistaphylococcal penicillins (nafcillin)
  • amino penicillins (amoxicillin)
  • antipseudomonal penicillins (piperacillin)
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11
Q

MOA for all penicillins

A
  • bactericidal
  • active against rapidly growing organisms that synthesize a peptidoglycan cell wall
  • inactivate proteins present on bacterial cell membranes (penicillin binding proteins or PBPs) that are involved in synthesis of the cell wall. PBPs are transpeptidase enzymes
  • some PBPs catalyze cross-linkages between peptidoglycam chains
  • penicillins block this transpeptidase reaction and prevent the cross links essential for cell wall integrity
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12
Q

What does penicillin bind to

A

penicillin binding protein (PBP)

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13
Q

Enzyme that strengthens the bacterial cell wall

A

Transpeptidase

-penicillins bind these enzymes and prevent cross linking

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14
Q

What enzyme lays down the building blocks to build the bacterial cell wall, elongates it

A

Transglycosylase

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15
Q

What enzyme strengthens the bacterial cell wall, glues I️t together and cross links

A

transpeptidase

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16
Q

Which enzyme do penicillins target (all B lactams actually)

A

Transpeptidase

-its the LATER step in cell wall synthesis

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17
Q

What drug targets the enzyme involved in the earlier step of cell wall synthesis

A

Vancomycin

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18
Q

Gram +

A
  • Thick peptidoglycan
  • No outer membrane
  • vancomycin only kills gram + because it is too big to get through any pores in the gram negative bacteria

Ex. Staph aureus and strep

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19
Q

Gram negative

A
  • thin peptidoglycan
  • has an outer membrane with porins in it, which is one of the ways abx get into it
  • resistance to penicillins, combat this by making smaller drug
  • big drugs cant get in
  • the ones that only kill gram + are too big to get through the porins
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20
Q

Where are the PBPs that penicillins bind to on the cell wall

A

All the way under all of the layers of the cell wall

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21
Q

Where are the beta lactamase enzymes located

A

On the surface of the cell wall just waiting for the beta lactams

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22
Q

What is the only penicillin that can survive beta lactamase

A

Antistaphs (nafcillin)

-the rest get cleaved by beta lactamase

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23
Q

MOA of beta lactamase inhibitors

A

-irreversibly bind to a conserved region of the beta lactamase enzyme and alter the structure so it cant bind beta lactam ring

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24
Q

Is beta lactamase inhibitor synergistic with abx

A

No because it does nothing for killing the bacteria by itself
-example of expanding the spectrum, allows amoxicillin to kill organisms that produce beta lactamase

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25
Q

Combinations involving beta lactamase inhibitors

A

Clavulanic acid with amoxicillin

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26
Q

What drugs do not require renal adjustment in patients with renal failure?

A
  • antistaph pens (nafcillin)

- ceftriaxone

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27
Q

Resistance of beta lactams

A
  • natural resistance: organisms that lack cell wall are resistant
  • acquired resistance: 1,. Plasmid transfer of beta lactamase to the bacteria, 2. Decreased penetration of the drug through the outer cell membrane (porins) so it doesn’t reach the PBPs, 3. Modification of PBPs so that the drug doesn’t bind
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28
Q

Depot forms of beta lactams

A

Benzathine pen G is given IM asa depot form for slow release over time (beneficial for syphilis)

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29
Q

Benzathine pen g

A

Given IM as a depot form for slow release for syphilis

Increases half life

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30
Q

Excretion of beta lactams

A

Through the kidney (adjust doses in renal failure), the exception is the antistaph pens (nafcillin) which are secreted through both the biliary and renal routes (no adjustment in renal failure)

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31
Q

Excretion of antistaph pens

A

Excreted through both liver and kidney, dont need to adjust for renal failure

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32
Q

Adverse effects of penicillins

A

Hypersensitivity

  • rash
  • anaphylaxis

Cross linking reactions occur among the beta lactam antibiotics

GI problems
Low risk nephritis

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33
Q

How do you treat a patient that is allergic to penicillins

A

Their reaction determines how you treat them in the future

  • if they have anaphylaxis, no structurally similar drugs can be used
  • no beta lactams
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34
Q

Clinical uses of antistaph pen

A
  • very narrow spectrum
  • only kills staph
  • MSSA
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35
Q

Clinical use of pen G

A
  • narrow spectrum
  • most streptococci
  • treponema (syphilis)
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36
Q

Clinical use of aminopenicillins

A
  • broad spectrum
  • can target gram positive
  • enteric gram negative

Amoxicillin

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37
Q

Clinical use of antipseudomonal penicillins (pipecillin)

A
  • very broad spectrum
  • pseudomonas
  • gram + and -
  • kills a lot of gram negatives
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38
Q

How do we treat treponema

A
  • benzathine pen g
  • slow release form of penicillin
  • penicillin with long 1/2 life
  • beta lactam with long 1/2 life
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39
Q

Do pens all kill gram negative?

A

No, all kill gram positive, but only broad spectrum kills gram negative

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40
Q

Order in which penicillins kill the most gram negatives from least to most

A

Antistaph
Pen G
Amoxicillin
Antipseudomonal

41
Q

Antistaph kills

A

Staph

42
Q

Pen G kills

A

Gram + cocci and treponema

43
Q

Amoxicillin is good for

A

Gram + and some gram -

Otitis media

44
Q

Antipseudomonal pens kill

A

Pseudomonas and a lot of gram negative

-broadest spectrum of all penicillins

45
Q

Which penicillin has the broadest spectrum

A

Antipseudomonal drugs (pipercillin)

46
Q

MRSA

A
  • gram +
  • resistance because it modifies the PBPs
  • habe to target something other than the PBPs
  • rules out all pens
  • cephteraline and vancomycin
47
Q

B lactam Abx that are closely related structurally and functionally to the penicillins, same MOA and same resistance mechanisms

A

Cephalosporins

48
Q

First generation cephalosporins

A

Cephalexin

“Flexin Phirst”

49
Q

Second gen cephalosporins

A

Cefaclor

50
Q

Third gen cephalosporins

A

Cefotaxime
Ceftriaxone

“Tri”
“X”

51
Q

Fourth gen cephalosporins

A

Cefepime

52
Q

Fifth gen/other cephalosporins

A

Ceftaroline

53
Q

MOA of cephalosporins

A
  • bacteriocidal
  • inactivate PBPs (transpeptidase)
  • prevent cross linkage formation
54
Q

Resistance of cephalosporins

A
  • natural resistance: no cell wall
  • acquired resistance: 1) plasmid reansfer of beta lactamase, 2) decreased penetration of drug through porins 3) modification of PBPs so drug doesn’t bind
55
Q

Administration of cephalosporins

A

Most are given IV due to poor oral absorption

56
Q

Distribution of cephalosporins

A

All distributed very well into body fluids except CSF, only get adequate levels int he CSF with 3rd gen cephalosporins

57
Q

Elimination of cephalosporins

A
  • kidney, need to adjust for renal failure

- exception: ceftriaxone excreted through bile into the feces, good in patients with renal failure

58
Q

What is the exception of the cephalosporin that does not get excreted by the kidneys

A

Ceftriaxone

59
Q

Why is ceftriaxone contraindicated in kids

A

Because it is excreted through bile into the feces and can cause biliary sludging/obstruction in neonates

60
Q

Tell me about ceftriaxone

A
  • meningitis
  • excreted through bile into feces
  • dont give to neonates

Don’t tri axing neonates, only adults.

61
Q

Which cephalosporin can be used to treat meningitis in a neonate

A

Cefotaxime

Can’t use ceftriaxone in neonates because excreted through liver

62
Q

Adverse effects of cephalosporins

A
  • hypersensitivity: caution in individual allergic to penicillins
  • can use in those with a mild rash reaction to penicillin
63
Q

Is someone has a mild rash to penicillin what can you give them

A

Cephalosporins

64
Q

If someone has anaphylaxis to penicillins what should you not give them

A

Avoid all beta lactams

65
Q

Clinical uses for first generation cephalosporins (cephlexin)

A
  • narrow spectrum
  • most commonly used for surgical prophylaxis
  • staph or strep
  • MSSA
66
Q

Clinical uses of second generation cephalosporins (cefaclor)

A
  • broad spectrum

- surgical prophylaxis of anaerobes such as bacteroides and clostridium

67
Q

Which cephalosporin could be used to treat someone with an anaerobic infection

A

Second generation (cefaclor)

68
Q

Clinical use of third generation cephalosporins (ceftriaxone and cephotaxine)

A
  • very broad spectrum
  • greater gram negative activity
  • meningitis (caused by neissera or strep pneumonia, use either drug)
  • gonorrhea (ceftriaxone)

Ax to the head for meningitis, ax to the crotch for gonorhea

69
Q

Clinical use of fourth generation cephalosporin (cefepime)

A
  • very broad spectrum
  • broadest of all cephalosporins
  • most commonly used in hospital acquired infections but overkill for community acquired infections
70
Q

Fifth generation (other) cephalosporins (ceftaroline)

A
  • active against MRSA
  • very narrow
  • only ceph that kills MRSA
  • can still bind the PBP
71
Q

Which beta lactam kills MRSA

A

Ceftaroline

72
Q

Which cephalosporins have the greatest susceptibility to beta lactamase?

A

1st and 2nd generation

73
Q

Which cephalosporins have the least susceptibility to beta lactamase

A

4th and 5th generation are resistance

74
Q

Generation 3 cephalosporins and beta lactamase

A

Some are cleaved and some are resistant

75
Q

Carbapenems

A

Imipenem

-first one developed

76
Q

What is imipenem combined with and why?

A

Cilastatin, a dihydropeptidase inhibitor, which protects imipenem from being cleaved and forming a nephrotoxic metabolite

Other “penems” dont need this

77
Q

Broadest spectrum beta lactams currently available

A

Penems

78
Q

MOA of penems

A

Binds PBPs, transpeptidase

-resistant to most beta lactamases

79
Q

Therapeutic uses of penems

A

Empiric therapy, serious life threatening infection

80
Q

Adverse effects of penems

A
  • Hypersensitivity

- seizures in patients with renal dysfunction

81
Q

Why is impenem nephrotoxic

A

Because it forms toxic metabolites

82
Q

How does cilastatin prevent impenem from being toxic

A

Prevents impenem from being cleaved and prevents toxic metabolite from forming

  • not an abx!
  • blocks dihydropeptidase
  • not a statin!
83
Q

If someone has a serious life threatening infection and placed on impenem that has normal kidney infection, but later develops renal failure, what is the patient at risk of

A

Seizures

-only if renal function decreases because that increases toxicity

84
Q

How are monobactams (aztreonam) different than other beta lactams

A

Just one ring that is not fused to another ring

85
Q

MOA of monobactams (aztreonam)

A

Same as penicillin

-binds PBPs (transpeptidase)

86
Q

Therapeutic use of monobactams (aztreonam)

A

No cross reactivity in patients allergic to penicillins because of the single ring structure \

Limited number of gram negative bac

87
Q

Why is a monobactams (aztreonam) structure important

A

It’s just one ring, not connected to another one and this makes it have no cross reactivity in patients allergic to penicillins

88
Q

How is monobactams (aztreonam s) given

A

IV

89
Q

Is vancomycin a beta lactam

A

No

90
Q

MOA of vancomycin

A

Inhibits cell wall synthesis at an earlier step than that inhibited by beta lactam Abx. Prevents peptidoglycan elongation by binding to the D-Ala-D-Ala terminal and inhibiting transglycosylase

91
Q

VRSA

A

Bacteria that changes the D-Ala to a D-lactate which prevents binding of vancomycin

92
Q

Difference between vancomycin and Beta lactams MOA

A
  • B lactams bind PBP (transpeptidase)

- vancomycin bind D-ALa-D-ALa (inhibits transglycolase)

93
Q

Drug of choice for hospital acquired MRSA

A

Vancomycin

94
Q

Therapeutic use of vancomycin

A
  • drug of choice for hospital acquired MRSA
  • serious gram + infections in patients allergic to beta lactams
  • treats C diff that does not respond to the first choice (metronidazole)
95
Q

How is vancomycin given

A

IV

-adjust in renal failure

96
Q

When is the only time you give vancomycin orally and why

A

C diff

-want it to be in the gut

97
Q

Adverse effects of vancomycin

A

Red man syndrome

  • histamine mediated flushing of upper body
  • not a true allergy and does not preclude further use
  • occurs if infused too quickly
  • infuse over 1 hour
98
Q

Bacitracin

A

Used topically for gram + bacteria (staph on skin)

-neosporin

99
Q

Polymyxins

A

Used topically for gram negative bacteria

-often combined with neomycin and bacitracin

Pharm Block 12 (7 decks)

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