Cell Wall Drugs Flashcards
(99 cards)
1
Q
What are the groups of cell walls drugs
A
B-lactam
Non b-lactam
2
Q
What are the B-lactams
A
Penicillins
Cephalosporins
Carbapenems
Aztreonam
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
4
Q
Beta lactamaase inhibitors
A
Clavulanic acid
Sulbatram
Tazobactram
5
Q
4 ring structures
A
Beta lactam
6
Q
When you think beta lactams, what should you think
A
Penicillins and cephalosporins
7
Q
What are the beta lactams
A
Penicillins
Cephalosporins
Monobactam (aztreonam)
Carbapenems (imipenem)
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
9
Q
What is the first choice of Abx
A
Penicillin
10
Q
Types of penicillins
A
- natural penicillins (pen G)
- antistaphylococcal penicillins (nafcillin)
- amino penicillins (amoxicillin)
- antipseudomonal penicillins (piperacillin)
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
12
Q
What does penicillin bind to
A
penicillin binding protein (PBP)
13
Q
Enzyme that strengthens the bacterial cell wall
A
Transpeptidase
-penicillins bind these enzymes and prevent cross linking
14
Q
What enzyme lays down the building blocks to build the bacterial cell wall, elongates it
A
Transglycosylase
15
Q
What enzyme strengthens the bacterial cell wall, glues I️t together and cross links
A
transpeptidase
16
Q
Which enzyme do penicillins target (all B lactams actually)
A
Transpeptidase
-its the LATER step in cell wall synthesis
17
Q
What drug targets the enzyme involved in the earlier step of cell wall synthesis
A
Vancomycin
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
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
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
21
Q
Where are the beta lactamase enzymes located
A
On the surface of the cell wall just waiting for the beta lactams
22
Q
What is the only penicillin that can survive beta lactamase
A
Antistaphs (nafcillin)
-the rest get cleaved by beta lactamase
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
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
25
Combinations involving beta lactamase inhibitors
Clavulanic acid with amoxicillin
26
What drugs do not require renal adjustment in patients with renal failure?
- antistaph pens (nafcillin)
| - ceftriaxone
27
Resistance of beta lactams
- 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
28
Depot forms of beta lactams
Benzathine pen G is given IM asa depot form for slow release over time (beneficial for syphilis)
29
Benzathine pen g
Given IM as a depot form for slow release for syphilis
Increases half life
30
Excretion of beta lactams
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)
31
Excretion of antistaph pens
Excreted through both liver and kidney, dont need to adjust for renal failure
32
Adverse effects of penicillins
Hypersensitivity
- rash
- anaphylaxis
Cross linking reactions occur among the beta lactam antibiotics
GI problems
Low risk nephritis
33
How do you treat a patient that is allergic to penicillins
Their reaction determines how you treat them in the future
- if they have anaphylaxis, no structurally similar drugs can be used
- no beta lactams
34
Clinical uses of antistaph pen
- very narrow spectrum
- only kills staph
- MSSA
35
Clinical use of pen G
- narrow spectrum
- most streptococci
- treponema (syphilis)
36
Clinical use of aminopenicillins
- broad spectrum
- can target gram positive
- enteric gram negative
Amoxicillin
37
Clinical use of antipseudomonal penicillins (pipecillin)
- very broad spectrum
- pseudomonas
- gram + and -
- kills a lot of gram negatives
38
How do we treat treponema
- benzathine pen g
- slow release form of penicillin
- penicillin with long 1/2 life
- beta lactam with long 1/2 life
39
Do pens all kill gram negative?
No, all kill gram positive, but only broad spectrum kills gram negative
40
Order in which penicillins kill the most gram negatives from least to most
Antistaph
Pen G
Amoxicillin
Antipseudomonal
41
Antistaph kills
Staph
42
Pen G kills
Gram + cocci and treponema
43
Amoxicillin is good for
Gram + and some gram -
| Otitis media
44
Antipseudomonal pens kill
Pseudomonas and a lot of gram negative
| -broadest spectrum of all penicillins
45
Which penicillin has the broadest spectrum
Antipseudomonal drugs (pipercillin)
46
MRSA
- gram +
- resistance because it modifies the PBPs
- habe to target something other than the PBPs
- rules out all pens
- cephteraline and vancomycin
47
B lactam Abx that are closely related structurally and functionally to the penicillins, same MOA and same resistance mechanisms
Cephalosporins
48
First generation cephalosporins
Cephalexin
“Flexin Phirst”
49
Second gen cephalosporins
Cefaclor
50
Third gen cephalosporins
Cefotaxime
Ceftriaxone
“Tri”
“X”
51
Fourth gen cephalosporins
Cefepime
52
Fifth gen/other cephalosporins
Ceftaroline
53
MOA of cephalosporins
- bacteriocidal
- inactivate PBPs (transpeptidase)
- prevent cross linkage formation
54
Resistance of cephalosporins
- 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
Administration of cephalosporins
Most are given IV due to poor oral absorption
56
Distribution of cephalosporins
All distributed very well into body fluids except CSF, only get adequate levels int he CSF with 3rd gen cephalosporins
57
Elimination of cephalosporins
- kidney, need to adjust for renal failure
| - exception: ceftriaxone excreted through bile into the feces, good in patients with renal failure
58
What is the exception of the cephalosporin that does not get excreted by the kidneys
Ceftriaxone
59
Why is ceftriaxone contraindicated in kids
Because it is excreted through bile into the feces and can cause biliary sludging/obstruction in neonates
60
Tell me about ceftriaxone
- meningitis
- excreted through bile into feces
- dont give to neonates
Don’t tri axing neonates, only adults.
61
Which cephalosporin can be used to treat meningitis in a neonate
Cefotaxime
Can’t use ceftriaxone in neonates because excreted through liver
62
Adverse effects of cephalosporins
- hypersensitivity: caution in individual allergic to penicillins
- can use in those with a mild rash reaction to penicillin
63
Is someone has a mild rash to penicillin what can you give them
Cephalosporins
64
If someone has anaphylaxis to penicillins what should you not give them
Avoid all beta lactams
65
Clinical uses for first generation cephalosporins (cephlexin)
- narrow spectrum
- most commonly used for surgical prophylaxis
- staph or strep
- MSSA
66
Clinical uses of second generation cephalosporins (cefaclor)
- broad spectrum
| - surgical prophylaxis of anaerobes such as bacteroides and clostridium
67
Which cephalosporin could be used to treat someone with an anaerobic infection
Second generation (cefaclor)
68
Clinical use of third generation cephalosporins (ceftriaxone and cephotaxine)
- 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
Clinical use of fourth generation cephalosporin (cefepime)
- very broad spectrum
- broadest of all cephalosporins
- most commonly used in hospital acquired infections but overkill for community acquired infections
70
Fifth generation (other) cephalosporins (ceftaroline)
- active against MRSA
- very narrow
- only ceph that kills MRSA
- can still bind the PBP
71
Which beta lactam kills MRSA
Ceftaroline
72
Which cephalosporins have the greatest susceptibility to beta lactamase?
1st and 2nd generation
73
Which cephalosporins have the least susceptibility to beta lactamase
4th and 5th generation are resistance
74
Generation 3 cephalosporins and beta lactamase
Some are cleaved and some are resistant
75
Carbapenems
Imipenem
| -first one developed
76
What is imipenem combined with and why?
Cilastatin, a dihydropeptidase inhibitor, which protects imipenem from being cleaved and forming a nephrotoxic metabolite
Other “penems” dont need this
77
Broadest spectrum beta lactams currently available
Penems
78
MOA of penems
Binds PBPs, transpeptidase
| -resistant to most beta lactamases
79
Therapeutic uses of penems
Empiric therapy, serious life threatening infection
80
Adverse effects of penems
- Hypersensitivity
| - seizures in patients with renal dysfunction
81
Why is impenem nephrotoxic
Because it forms toxic metabolites
82
How does cilastatin prevent impenem from being toxic
Prevents impenem from being cleaved and prevents toxic metabolite from forming
- not an abx!
- blocks dihydropeptidase
- not a statin!
83
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
Seizures
| -only if renal function decreases because that increases toxicity
84
How are monobactams (aztreonam) different than other beta lactams
Just one ring that is not fused to another ring
85
MOA of monobactams (aztreonam)
Same as penicillin
| -binds PBPs (transpeptidase)
86
Therapeutic use of monobactams (aztreonam)
No cross reactivity in patients allergic to penicillins because of the single ring structure \
Limited number of gram negative bac
87
Why is a monobactams (aztreonam) structure important
It’s just one ring, not connected to another one and this makes it have no cross reactivity in patients allergic to penicillins
88
How is monobactams (aztreonam s) given
IV
89
Is vancomycin a beta lactam
No
90
MOA of vancomycin
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
VRSA
Bacteria that changes the D-Ala to a D-lactate which prevents binding of vancomycin
92
Difference between vancomycin and Beta lactams MOA
- B lactams bind PBP (transpeptidase)
| - vancomycin bind D-ALa-D-ALa (inhibits transglycolase)
93
Drug of choice for hospital acquired MRSA
Vancomycin
94
Therapeutic use of vancomycin
- 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
How is vancomycin given
IV
| -adjust in renal failure
96
When is the only time you give vancomycin orally and why
C diff
| -want it to be in the gut
97
Adverse effects of vancomycin
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
Bacitracin
Used topically for gram + bacteria (staph on skin)
| -neosporin
99
Polymyxins
Used topically for gram negative bacteria
| -often combined with neomycin and bacitracin
