Resp: Test 2 : 2. Bridges : Cell Wall Synthesis Inhibitors I & Ii

Front 1

Back 1

Front 2

type of drug: penicillin G

Back 2

Penicillins

beta-lactam

Front 3

type of drug: penicillin V

Back 3

Penicillins

beta-lactam

Front 4

type of drug: nafcillin

Back 4

Antistaphylococcal penicillins


beta-lactam

Front 5

type of drug: oxacillin

Back 5

Antistaphylococcal penicillins


beta-lactam

Front 6

type of drug: cloxacillin

Back 6

Antistaphylococcal penicillins


beta-lactam

Front 7

type of drug: dicloxacillin

Back 7

Antistaphylococcal penicillins


beta-lactam

Front 8

type of drug: methicillin

Back 8

Antistaphylococcal penicillins


beta-lactam

Front 9

type of drug: ampicillin

Back 9

Extended-spectrum penicillins


beta-lactam

Front 10

type of drug: amoxicillin

Back 10

Extended-spectrum penicillins

beta-lactam

Front 11

type of drug: ticarcillin

Back 11

Antipseudomonal penicillins

beta-lactam

Front 12

type of drug? piperacillin

Back 12

Antipseudomonal penicillins

Beta-lactams

Front 13

what are the 2 places on gram positive cell walls that we attack with antibiotics?

Back 13

peptidoglycan

peptide cross-links

Front 14

what is a major virulence factor in gram negative cell walls?

Back 14

beta lactamase

Front 15

the outer membrane of gram negative cell wall has what property?

Back 15

permeability barrier

Front 16

what is the important peptidoglycan structure on the gram positive bacteria?

Back 16

D-Ala D-Ala at the end

it is where vancomyosin binds

Front 17

what blocks the adding of 2 D-ala's to the end of the peptide chain of thecell wall for bacteria?

Back 17

Cycloserine prevents this from happening

Front 18

what is bactoprenol?

Back 18

it is responsible for carrying bacterial building blocks across the plasma membrane for cell wall synthesis

Front 19

what does vancomycin do?

****

Back 19

binds to the 2 d-ala's that attempt to put the building blocks into the cell wall of the bacteria

This prevents cross-linking & elongation of peptidoglycan (blocks transglycosylase)

Front 20

what does bacitracin do?

Back 20

prevents the recycling of bactoprenol (remember that bactoprenol is responsible for carrying bacterial building blocks across the plasma membrane for cell wall synthesis)

Front 21

what does transpeptidase do?

Back 21

builds amino acid cross link between building blocks of the bacterial cell wall

Front 22

how does penicillin work? (b-lactams)

Back 22

block transpeptidation step …block cross linking of peptidylglycan chains

penicllin looks like the alanine-alanine bridge, and uses up all the transpeptidase!

Front 23

what are the 3 basic steps of synthesis of bacterial cell wall? what blocks each stage?

Back 23

1: occurs in cytoplasm – provides building blocks (cycloserine blocks this)

2: : occurs as building blocks pass through the plasma membrane (vancomycin or bacitracin)

3:Occurs outside the plasma membrane and involves cross-linking of peptidylglycan strands (b-lactams)

Front 24

What do autolysins do?

Back 24

Look this up.. it was on slide 22

Front 25

are beta-lactam bactericidal or static?

Back 25

bactericidal

Front 26

are beta-lactams time or concentration dependent?

****

Back 26

Effect is directly proportional to amount of TIME the drug concentration at the site of infection is ABOVE the MIC of the organism

TIME DEPENDENT!

Front 27

What is essential for b-lactams to work (2)? functions?

*** gotta know this one

Back 27

1. intact beta-lactam ring is essential for binding to PBPs and antimicrobial activity

2. R side chain … determines spectrum of antibacterial activity and pharmacological properties (e.g., affinity for PBP, resistance to penicillinase, ability to penetrate G- outer membrane, resistance to stomach acid, PK)

Front 28

what is the difference between Pen G and Pen V?

Back 28

G: is acid labile … poor oral bioavailability

V: more stable in acid
so “better” oral availability
Remember: V is not IV

Front 29

what is the b-lactam bond?

Back 29

Front 30

Pen G is ____ spectrum

Back 30

narrow

Front 31

what does Pen G mostly treat?

****

Back 31

Gram Positives

note also treats: a few gram negatives (like Neisseriae meningococci)
some anaerobes and spirochetes (syphilis)

Front 32

what are some of the bugs with resistnace to penicillin G?

Back 32

> 90% of Staphylococcus a
~ 5 % of Streptococci
Most of Neisseria gonococci
Pen G no longer a DOC

Front 33

what are 3 areas that penicillin cannot treat infection in?

***

Back 33

prostate
ocular
CSF

Front 34

Can penicillin cross the BBB? Can it be used in Meningitis?

Back 34

Do not readily cross BBB
… but … with inflamed meninges
Penicillins more easily enter the CSF
Therapeutic levels can be reached

Meningitis …
Penicillin may be used
Often used in combination with another antimicrobial

Front 35

Pen G has a short half-life, what can slow this process?

Back 35

Probenecid

blocks renal tubular secretion of penicillin

Front 36

if Pen G has a short half-life, how does it have a low/prolonged drug level?

Back 36

it is given with benzathine which gives a slow release from the injection site

Front 37

although Penicillin G has the lowest toxicity potential of all antimicrobials, what is the most common adverse effect?

Back 37

Allergic (hypersensitivity) Reactions

Front 38

what is a breakdown product of penicillin G? what is the importance of this?

Back 38

Penicilloic acid

acts as a hapten.... making a huge immune reaction....leading to penicillin allergy

Front 39

are diarrhea and GI intolerance allergic reactions of penicillin G?

Back 39

NO

but they do occur, just not allergic

Front 40

aside from allergic reactions, what is a possible major problem with use of penicllin G?

Back 40

Neurotoxicity

Most likely at high doses(intrathecal admin or renal failure)
Coma, seizures, hyper-reflexia

Front 41

what causes superinfections?

Back 41

loss of normal flora from use of broad spectrum agents

Front 42

what type of bacteria is generally resistant to penicillin g?

Back 42

Gram negative

Front 43

What is the most common resistance component to penicillin G?

***

Back 43

Penicillinase production


(beta lactamase)

Front 44

why does penicillin not affect mycoplasma?

Back 44

NO CELL WELL (and that is the mech of action for penicillin

Front 45

What happens in MRSA?

Back 45

Beta-lactams can’t bind to target because transpeptidases are mutated

Front 46

how do beta lactamases work?

Back 46

break the beta lactam bond on the beta lactam ring

Front 47

what type of b-lactamases give resistance? what do they give resistance to?

***

Back 47

Plasmid encoded

mediate resistance to penicillins and 1st & 2nd generation cephalosporins

Front 48

what are extended spectrum b-lactamases? where are these seen in most commonly (2)?

**

Back 48

can hydrolyze penicillins AND CEPHALOSPORINS (all generations!)
--this is bad!

In gram negative bacteria: most commonly Klebsiella and e coli

Front 49

what are the antistaphylococcal penicillins? 4

Back 49

Oxacillin
Nafcillin
Cloxacillin
Dicloxacillin

Front 50

what are the b-lactamase resistant penicllins?

Back 50

Antistaphylococcal penicillins:

Oxacillin
Nafcillin
Cloxacillin
Dicloxacillin

Front 51

will antistaphylococcal agents work against MRSA?

Back 51

NO

PBP (drug target) is altered in MRSA ...  … and the drugs can’t bind!!

Front 52

oxacillin causes what side-effect?

Back 52

hepatotoxicity

Front 53

what are the 2 extended spectrum penicillins?

Back 53

ampicillin
amoxicillin

Front 54

what would you want to use for gram negatives (e coli, n. meningitidis)? note: these would NOT work on beta-lactamase bugs

Back 54

Extended spectrum penicillins: Ampicillin & Amoxicillin

Not effective against beta-lactamase producers


(3rd and 4th gen cephalosporins work against gram neg and would work against beta-lactamase bugs)

Front 55

what is the only oral pen that food does not interfere with absorption?

Back 55

Amoxicillin

Front 56

Ampicillin & Amoxicillin spectrum of activity?

***

Back 56

similar to Pen G (gram +) and extends to:

H influenzae
E. coli
Listeria sp.
Proteus
Salmonella

HELPS

Front 57

clinical uses fro ampicillin and amoxicillin?

***

Back 57

Sinusitis,
otitis,
UTIs,
pneumonia

(SOUP)

Front 58

what do you normally use with ampicillin?

Back 58

Ampicillin is frequently used (synergistic) with an

AMINOGLYCOSIDE

(gentamicin) for broad range coverage in serious infections

Front 59

DOC for Listeria meningitis

Back 59

Ampicillin

Front 60

why do you use a bactericidal drug in meningitis?

Back 60

no immune response in spinal column!

Front 61

what are the Antipseudomonal penicillins?

Back 61

ticarcillin

piperacillin

Front 62

spectrum of activity for ticarcillin and piperacillin?

Back 62

Pen G (gram pos) + HELPS + Pseudomonas, Klebseilla, and Serratia

Front 63

ticarcillin and piperacillin are used with what?

Back 63

in combination with an aminoglycoside

Front 64

what has the broadest spectrum of the penecillins?

Back 64

Piperacillin

Front 65

sodium overload is a potential with what penicillin drug?

Back 65

Antipseudomonal penicillins (Ticarcillin & Piperacillin)

Front 66

do beta lactamase inhibitors have antimicrobial activity?

Back 66

not intrinsically they potentiate the effect of the anti-biotics

Front 67

how do Beta lactamase inhibitors work?

Back 67

Binds to B-lactamase and inactivates the enzyme
Because they look like a penicillin
Suicide inhibitors
Binding is irreversible

Front 68

as you shift from 1-4 generation cephalosporins, what happens? (3)

Back 68

increasing activity against Gram negative (decreasing against gram pos)

Increasing resistance to B-lactamases

Increasing ability to cross BBB

Front 69

what class of cephalosporin can you use to treat meningitis?

Back 69

3rd and 4th... able to cross the BBB

Note: penecillin can work b/c you have enough "leakiness" for it to fit in

Front 70

Cephalexin is what kind of drug?

Back 70

1st Generation

Cephalosporins

Front 71

Cefazolin is what kind of drug?

Back 71

1st Generation

Cephalosporins

Front 72

Cefoxitin is what kind of drug?

Back 72

2nd Generation


Cephalosporins

Front 73

Cefaclor is what kind of drug?

Back 73

2nd Generation


Cephalosporins

Front 74

Cefprozil is what kind of drug?

Back 74

2nd Generation


Cephalosporins

Front 75

Ceftriaxone is what kind of drug?

Back 75

3rd Generation

Cephalosporins

Front 76

Ceftazidime is what kind of drug?

Back 76

3rd Generation

Cephalosporins

Front 77

Cefotaxime is what kind of drug?

Back 77

3rd Generation

Cephalosporins

Front 78

Cefdinir is what kind of drug?

Back 78

3rd Generation

Cephalosporins

Front 79

Cefepime is what kind of drug?

Back 79

4th Generation

Cephalosporins

Front 80

specturm of activity for cephalosporins?

Back 80

… generally like ampicillin (G+ & HELPS) ... but varies with generation

Front 81

cephalosporin: bactericidal or static?

Back 81

bactericidal

Front 82

what are the 2 resistances to cephalosporins?

Back 82

Penicillinases and cephalosporinases

Front 83

In general … cephs are more resistant to breakdown by what enzymes?

Back 83

Penicillinases and cephalosporinases

Klebsiella, E Coli, Pseudomonas, Enterobacter, (ESBL can breakdown penicillins & cephs)

Front 84

what is an adverse effect of cephalosporins? 2

Back 84

ALLERGIC reactions

superinfection

Front 85

2 major clinical indications of cephalosporins?

Back 85

Can be useful alternative for penicillin allergic patients (if mildly allergic)

Frequently used for surgical prophylaxis (especially 1st generation)

Front 86

order gram positive coverage for the different generations of cephalosporins

Back 86

1>2>3

Front 87

order gram negative coverage for the different generations of cephalosporins

Back 87

3>2>1

Front 88

Resistance to beta lactamases increases from ___ to ___ generation

Back 88

increases from 1st to 4th generation

Front 89

Hypoprothrombinemia is a side-effect of what? what is it?

Back 89

Cephalosporins

Coagulation abnormalities
Disturbs synthesis of vitamin K-dependent clotting factors

Front 90

Alcohol intolerance is a side-effect of what? what is it?

Back 90

Cephalosporins

disulfiram-like reaction--

Disulfiram is an agent that inhibits alcohol dehydrogenase, causing an increase of acetaldehyde, the agent that causes hangovers

Front 91

what causes the adverse side effects of cephalosporins? what drugs is it in?

***

Back 91

Due to methylthiotetrazole (MTT) group

Cefotetan (2nd generation)
Cefoperazone (3rd generation)

Front 92

primary use for 1st generation cephalosporins? Specific drug?

****

Back 92

Prophylaxis of surgical procedures

(cefazolin)

Front 93

primary clinical use for 2nd generation cephalosporins? 4

***

Back 93

UTIs,
soft tissue infections, 
bone infections,
surgical prophylaxis

SUBS

Front 94

primary use for 3rd generation cephalosporin?

Back 94

Nosocomial G- infections ... often in combination with AGs

Front 95

1st gen cephalosporins are active against?

Back 95

G+  plus Proteus, E. coli, Klebsiella

(Pen G + PEcK)

Front 96

Cefazolin used for

Back 96

surgical prophylaxis

Front 97

Cefoxitin Cefaclor Cefprozil

are what drugs

Back 97

2nd Generation

cephalosporin

Front 98

spectrum of coverage for 2nd gen cephalosporins?

Back 98

G+ + H. influenza, Enterobacter, Neisseria, Proteus, E. coli, Klebsiella

(G+ HEN PEcK)

Front 99

what is primarily used to treat sinusitis, bronchitis, otitis media
lower respiratory tract infections ?

Back 99

2nd gen cephalosporins

Front 100

Allergic reactions
Blood dyscrasias (anemia, eosinophilia)
Pseudomembranous colitis

are side effects of what?

Back 100

2nd Generation Cephalosporins