Cell Wall Synthesis Inhibitors Flashcards
1
Q
allergenicity
A
-the ability of a substance to cause an allergy
2
Q
beta-lactam
A
- family of ATBs that inhibit transpeptidases (PBPs), activate autolytic enzymes in cell wall, are bactericidal and have time dependent action
- wide distribution, except CNS
- renal excretion, not metabolized (except nafcillin, imipenem)
- mostly effects gram+ aerobes
- resistance results mostly from B-lactamases/penicillinases
- adverse effects mainly allergy
3
Q
beta-lactamase (penicillinase)
A
- enzymes that breakdown B-lactam ATBs (except cephalosporins) inactivating them
- common mechanism of resistance against B-lactam ATBs
4
Q
beta-lactamase inhibitor
A
- prevent breakdown of B-lactam ATBs by B-lactamases
- have little ATB effect on there own but extend the range of B-lactam ATBs
5
Q
broad spectrum
A
-target many types of microbes both gram+ and gram- as well as other microorganisms (Rickettsia)
6
Q
cephalosporinase
A
-enzyme that inactivates cephalosporins and is a common mechanism of resistance against cephalosporins
7
Q
extended spectrum
A
-affects a variety of gram+ and gram- bacteria
8
Q
Gram Negative
A
-thin peptidoglycan layer sandwiched between an inner and outer cell membrane thus they are less dependent on peptidoglycan layer for survival and are generally harder to eradicate with ATBs
9
Q
Gram Positive
A
- have a thick peptidoglycan layer that forms cell wall outside of plasma membrane
- more dependent on this cell wall for survival and without it bacteria will lyse
10
Q
low-affinity penicillin-binding protein
A
-PBPs with a decrease binding affinity for ATBs and is a common mechanism of resistance to ATB therapy
11
Q
narrow specturm
A
- targets one specific type of bacteria, usually either gram positive or negative microbes
- optimal against specific organisms
- lower risk of superinfections
12
Q
penicillin binding protein
A
- enzyme responsible for synthesis of peptidoglycan which is important component of bacterial cell walls
- inhibition of PBPs leads to destruction of bacterial cell wall and lysis
13
Q
peptidoglycan layer
A
- major component of bacterial cell walls produced by PBPs
- inhibition of its synthesis (mechanism of many ATBs) leads to destruction of cell walls and bacterial cell lysis
14
Q
porin
A
-channel in bacterial cell membrane that functions as a channel that is permeable to select substances
15
Q
transpeptidase
A
-bacterial enzyme that cross-links the peptidoglycan chains to form rigid cell walls
16
Q
fosfomycin
A
Cell Wall Synthesis Inhibitor- non-B-Lactam
- Mechanism: structural analog of phosphoenol pyruvate (PEP), blocks step-1 PDG synthesis
- Pharmacokinetics: well absorbed and distributed, excreted unchanged in urine
- Broad spectrum with few adverse effects
- rapid resistance emerges from mult. dosing
- Uses: single dose oral treatment of uncomplicated UTIs
17
Q
D-cycloserine
A
Cell Wall Synthesis Inhibitor- non-B-Lactam
- Mechanism: structural analog of D-alanine, blocks step-2 in PDG synthesis
- Pharmacokinetics: oral, good CNS penetration, active form in urine
- broad spectrum, dose related CNS effects but reversible
- Uses: restricted second-line M. TB drug
18
Q
bacitracin
A
Cell Wall Synthesis Inhibitor- Non-B-Lactam
- Mechanism: depletes lipid carrier for PDG synthesis preventing its recycling
- TOPICAL application only
- narrow spectrum (gram+)
- severe nephrotoxicity
- Uses: skin and ophthalmologic infections; good in combo w/ polymyxin B (membrane inhibitor)
19
Q
vancomycin
A
Cell Wall Synthesis Inhibitor- Non-B-Lactam
- glycopeptide structure
- Mechanism: binds D-Ala-D-Ala terminus of pentapeptide; blocks PDG synthesis (step 4: transglycosylase and step 5: transpeptidation) by binding substrate; rapidly bactericidal for dividing bacterial cultures (except enterococci)
- Mostly IV administration (rarely oral, IM for intestinal)
- distribution through out body (CNS if meninges inflammed)
- narrow spectrum against Gram+ microbes and MRSA
- Resistance: VRE due to bacteria with diff. cell wall units with dec. binding affinity to vanco; VRSA, bacteria overexpresses D-Ala-D-Ala which binds up drug
- can cause Red Man Syndrome, ototoxicity and nephrotoxicity
- Reserved for serious Gram+ infections resistant to other less toxic drugs and MRSA
20
Q
daptomycin
A
Cell Membrane Agent
- Mechanism: novel cyclic lipopeptide which causes membrane depolarization (creates open pores in membrane in presence of Ca ??)
- bactericidal, IV admin with renal clearance
- Uses: narrow spectrum (gram+) used to treat VRE and MRSA
- Can cause myopathy
21
Q
cephalexin
A
Cell Wall Synthesis Inhibitor
- 1st generation cephalosporin
- acid stability
- broadest spectrum against gram+ cocci, effective against gram- bacilli
- better against gram +/S. aureus
- adverse effects: cutaneous allergy– NOT for patients with anaphylaxis to penicillin
22
Q
cefuroxime
A
Cell Wall Synthesis Inhibitor
- 2nd generation cephalosporin
- only group with significant activity against anaerobes
- adverse effects: cutaneous allergy (NOT for patients with anaphylaxis to penicillin), disulfiram-like reaction and bleeding disorder
23
Q
ceftriaxone
A
Cell Wall Synthesis Inhibitor
- 3rd generation cephalosporin
- resistance to beta-lactamases
- CNS penetration
- anti-pseduomonal and -pneumococcal, gram- infections (meningitis, pneumonia, gonorrhea)
- adverse effects: cutaneous allergy (NOT for patients with anaphylaxis to penicillin), disulfiram-like reaction, bleeding disorder, pseudomembranous colitis (CDAC)
24
Q
cefepime
A
Cell Wall Synthesis Inhibitor
- 4th generation cephalosporin
- resistance to beta-lactamases– usual for treating enterobacter & penicillin-resistant streptococci
- CNS penetration
- anti-pseudomonal
- adverse effects: cutaneous allergy (NOT for patients with anaphylaxis to penicillin), pseudomembranous colitis (CDAC)
25
imipenem
Cell Wall Synthesis Inhibitor
-carbapenem
-bind more efficiently with PBPs
-penetrate outer membrane of gram- bacteria
-BROADEST activity of all beta-lactam drugs
-resistant to degradation by most beta-lactamases, but induce those that inactivate pens/cephs
-active against extended-spectrum beta-lactamase producing organisms
-drug resistance d/t alteration of PBP-- carbapenemases (CRE)
-renal metabolism and inactivation
administer with cilastatin
-adverse effects: cross allergy to penicillin? rare effects-- GI, superinfections, neurotoxicity
-clinical use: 2nd line therapy for serious nosocomial infections
26
meropenem
Cell Wall Synthesis Inhibitor
- carbapenem
- bind more efficiently with PBP
- penetrate outer membrane of gram- bacteria
- BROADEST activity of all beta-lactam drugs
- resistant to degradation by most beta-lactmases, but induce those that inactivate pens/cephs
- active against extended-spectrum beta-lactamase producing organisms
- drug resistance d/t alteration of PBP
- adverse effects: cross allergy with penicillin? rare effects-- GI, superinfections, neurotoxicity
- clinical use: 2nd line therapy for serious nosocomial infections
27
cilastatin
```
inhibits dehydropeptidases (inactivates imipenem)
administer with imipenem
```
28
aztreonam
monobactam
- binds to PBPs
- relatively resistant to beta-lactamases
- IM or IV, drug penetrates inflamed CNS
- NO significant cross reaction with penicillin
- narrow spectrum: limited to gram- aerobes, including pseudomonas
- uses: gram- UTIs, lower RTIs, systemic infections
29
primaxin
imipenem + cilastatin
30
Penicillin G
PCN ATB
- beta lactame ATB
- t1/2
31
Penicillin V
PCN ATB
- beta lactame ATB
- t1/2
32
dicloxacillin
beta lactamase resistant PCN's
- most acid stable (can give PO but food affects absorption).
- Use: penicillinase-producing staphylococcus and streptococci
- resistance occurs 2/2 PBP with lower affinity for drugs.
- S/E: less than that with PCN's
33
oxacillin
beta lactamase resistant PCN's
- most acid stable (can give PO but food affects absorption).
- Use: penicillinase-producing staphylococcus and streptococci
- resistance occurs 2/2 PBP with lower affinity for drugs.
- S/E: less than that with PCN's
34
amoxicillin
```
Extended spectrum PCN's
-used with beta lactamase inhibitors (destroyed by beta lactamases).
-acid stable (can give PO).
+absorption better than ampicillin.
+absorption NOT affected by food
-t1/2 1.5' (dose BID-TID)
```
35
ampicillin
```
Extended spectrum PCN's
-used with beta lactamase inhibitors (destroyed by beta lactamases).
-acid stable (can give PO).
+absorption better than ampicillin.
+absorption NOT affected by food
-t1/2 1.5' (dose BID-TID)
```
36
ticarcillin (Timentin with clavulanate)
Carboxypenicillin ATB
- IV
- Used for pseudomonal infections
- rarely used alone
37
piperacillin
Ureidopenicillin ATB
- IV
- Used for pseudomonal infections and severe systemic infections caused by Klebsiella
- often combined with aminoglycosides to prevent resistance.
38
clavulanic acid
beta lactamase inhibitor
- irreversible inhibition of beta lactamase ("suicide substrates).
- Used in combinations because they are weak ATB's when given alone.
- Augmentin= clavulanic acid + amoxicillin
- Timentin= clavulanic acid + ticarcillin
39
sulbactam
beta lactamase inhibitor
- irreversible inhibition of beta lactamase ("suicide substrates).
- Used in combinations because they are weak ATB's when given alone.
- Augmentin= clavulanic acid + amoxicillin
- Timentin= clavulanic acid + ticarcillin
40
tazobactam
beta lactamase inhibitor
- irreversible inhibition of beta lactamase ("suicide substrates)
- Used in combinations because they are weak ATB's when given alone.
- Augmentin= clavulanic acid + amoxicillin
- Timentin= clavulanic acid + ticarcillin
