Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Block 1.11 Lees Stuff > Targeting Cell Wall Part 2: B-lactams > Flashcards

Targeting Cell Wall Part 2: B-lactams Flashcards

1
Q

What are the four categories for the b-lactam antibiotics?

A
  1. Penicillins
  2. Cephalosporins
  3. Carbapenems
  4. Monobactams
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the MOA of the beta-lactams?

A

They will inhibit cell wall synthesis by binding to and inhibiting the bacterial transpeptidase (binds to PBP) this will cause the stopping of polmerization of the building blocks NAG/NAM peptidoglycan.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the mode of killing for the Beta-lactams and do they have a lot of drug interactions?

A

The mode of killing is TIME-DEPENDENT! (Meaning you need to keep this drugs on board for a longer time but do not have any concern about the concentration of the drug, Concentration-independent)

These drugs have very FEW drug-drug interactions (great drug to use and is generally very safe

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the pharmacokinetics of the beta-lactams?

A

They are oral, IV and IM (no topical)

They don’t have a very good oral bioavailability (less than 50%)

They are distributed well into many tissues (can accumulation into tissues

MOST are really eliminated from the host (reduce dose in renal impairment)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the ADRs for Beta-lactams?

A
  1. N/V diarrhea
  2. Dizzy / headache
  3. HYPERSENSITIVITY RXN!!! (You have to watch for cross sensitivity rxn with the b-lacs)
    • Stevens-Johns (you lose your skin)
    • Hapten (thing that will cause binding to T-cell to get rxn from IgE)
    • Need to get epi
  4. Super infections (such as CDAD)
  5. Hematologic toxicities ( myelosuppression, neutropenia and thrombocytopenia)
  6. Seizures
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the ways Gram negative will develop resistance

A
  1. Drug-modifying enzymes beta-lactamases
  2. Decrease in drug transport into the cell (less proins)
  3. Increase in drug export out of cell (more Efflux pumps)
  4. Changes in PBP so you don’t get binding
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the ways Gram positives develop resistance to beta - lactams?

A
  1. Change PBP

2. Drug modifying enzymes with B-lactamases
ONLY MSSA, MRSA, NOT Streptococcus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the major producers of Beta-lactamases

A

Gram positives: S. Aureus (MSSA, MRSA)

ALL GRAM NEGATIVES!!

Also gram negative anaerobes (bacteroids, b. Fragilis)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are the four classes of the Penicillins?

A
  1. Natural PCN (Pen V and Pen G)
  2. Aminopenicillins (Amoxicillin and Ampicillin)
  3. Beta-lacamase resistant PCN ( Nafcillin and Oxacillin)
  4. Broad-spectrum PCN ( Piperacillin)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is important to know about the Natural PCN?

A

It has a PO = Penicillin V
It’s used to treat strep throat

It’s IV form = Penicillin G which also comes as an IM

Pen G= is used for SYPHILIS!!!!! T. Pallidum!!!!
It can be given IV and you give it procaine and benzathine to help with the pain you might get from it

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is important to know about Aminopenicillin?

A

These are semi-synthetic drugs

PO = Amoxicillin and has good distribution

IV = Ampicillin which is given to treat LISTERIA!!!!!!!!! (Best drug for this)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is important to know about Beta-lactamase resistant PCN?

A

PO = Dicloxacillin - 2 cl added to make it oral of oxacillin

IV =
Nafcillin

Oxacillin= these are bulky and can not get thro proins so they are mostly used fro gram positive bacteria
**can be used for Staph!!

Oxacillin is also used along with methicillin t check is the staphylococcus is MRSA or ORSA

KNOW!!!!** these drugs can cause interstitial NEPHRITIS!!!!!!**

They have bulky side chains which makes them hard for lactemases to disrupt them

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is important to know about Broad - Spectrum PCN?

A

Only IV drug is Piperacillin

This is one that is small enough and can get thro proins which makes it a good choice to kill gram negative bacteria!!

It can be used for pseudomonas but resistance is starting to take effect!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Explain the bacteria coverage map for the Penicillins

A

Piperacillin = all the way to Pseudomonas and strep (broad spectrum)

Oxacillin and nefacillin = Can do to MSSA and very small amount of gram (-) -.5 coverage

Amoxicillin and Ampicillin = can do strep and gut bugs like E.coli

Pen V and Pen G = -0.5 into gram (-) and it can work for strep

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the first generation Cephalosporins?

A

PO = Cephalexin (Keflex)

IV = Cefazolin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the second generation cephalosporins?

A

PO = Cefuroxime axetil (Ceftin)

IV = Cefuroxime

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are the cephamycins?

A

IV =

Cefoxitin

Cefotetan

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are the 3rd generation cephalosporins?

A

PO =

Cefdinir (Omnicef)

Cefpodoxime proxetil (Vantin)

IV =

Ceftriaxone

Cefotaxime

Ceftazidime

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are the fourth generation cephalosporins?

A

IV=

Cefipime

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are the 5h generation cephalosporins?

A

IV=

Ceftaroline fosamil

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are the new agents for cephalosporins?

A

IV

Ceftazidime - Avibactam (used to disrupt beta-lactamase and restore function of the cephalosporins

Ceftolozane - tazobactam

22
Q

What are the structure-activity relationships when it comes to the cephalosporins?

A
  1. The C4 MUST have a caroxylic acid
    • an ester will promote more oral absorption
  2. On C7 having a group here will affect stability and spectrum
    • Having an IMINOMETHOXY or OXYIMINE which will promote activity against the beta-lactamases and stabilize the drug
  3. Have an R group on C3 will effect activity and stability
23
Q

What is something that cephalosporins groups can promote (The 7-me tho you and the MTT groups)?

A

This can lead to hypoprothrombinemia ( make it easier to bleed/bruise)

This can lead to a disulfiram reaction ( severe “hangover” flushing headache and such

Which drug has the MTT group and what does it cause?
Cefotetan and it messes with VKORK and can lead to an increase in bleeding
**main reason this drug isn’t used

24
Q

What is unique about 3G cephalosporins that’s allows them to kill gram negative bacteria?

A

They all have an iminomethoxy group which will allow them to kill the gram negative

25
Q

What is something that is on newer cephalosporins that allows them to kill gram positives?

A

Only one has this ability is ceftaroline fosamil

Will allow it to work with MRSA but DOES NOT work for gram negatives

26
Q

What cephalosporins have CNS penetration?

A

Ceftriaxone

Cefepime

27
Q

What bacteria do the cephalosporins NOT work for?

A

No activity against enterococcus, anaerobes or Listeria

Cephamycins can be used for anaerobes (cefotetan, cefoxitin)

Listeria you must must Ampicillin

28
Q

What are some of the unique properties that go along with ceftriaxone?

A
  1. Biliary sludge (gal bladder can get clogged up)
  2. Can not use in neonates (28 days or younger) due to the sludge effect
  3. Really good effect all on types of bacteria but not Pseudomonas or Acinetobacter
  4. Can be good for CNS penetration
29
Q

Explain the bacteria coverage map for Cephalosporins

A

First gen = -1 (gut, e. Coli) to MSSA infections

2nd gen = Some hemaophia (respiratory, watch for resistance) to some gram (+) 0.5 **this is normally used for kids

3rd gen = up to SCE and strep (ceftazidine can work this as well as but to Pseudomonas but resistance is a problem)

4th gen= Cefepine can work from MSSA to Pseudomonas

5th gen= can cover MRSA to e. Coli (gut)

Cefoxitin and cefotetan can over B. Fragilis

30
Q

What are the carbapenems ?

A

DIM-E (All IV)

These have activities against Pseudomonas and Acinetobacter

Doripenem

Imipenem - cilastatin

Meropenem

No Pseudomonas or Acinetobacter activity

Ertapenem

**these also have activities against MSSA, streptococci and gram (-) bacteria anaerobes

31
Q

What is the Monobactams ?

A

Aztreonam ( IV only)

This is only good for gram negatives and works much like colistin in terms off coverage but less side effects

32
Q

What are important things to know about the carbapenems?

A
  1. They cover a lot of bacteria but we must reserve them for MDR bacteria so that they don’t get resistance to them and we lose our ability to use these drugs
  2. Works for all gram (-) and has the lowest MIC against Pseudomonas
33
Q

What are the important things when it comes to the carbapenems and chemistry?

A
  1. The carbon atom on the C-1 position which will add it to be more stable against dihydropeptidase I (DHP-I) which is responsible for breaking down the drug (this is found in the human kidney brush border enzymes)
  2. The carbapenems MUST HAVE TRANS CONFIGURATION of the eta-lactam ring at C-5 and C-6
34
Q

Which carbapenem does not have the C1 methyl and what is done to overcome?

A

Imipenem-cilastatin

It has the cilastatin attached to it which is an inhibitor of DHP-1 so it does not get broken down

35
Q

What a major drug to drug interaction that you need to watch out for when using the carbapenems?

A

VALPROIC ACID!!!

Carbapenems will reduce VPA levels and you can increase you chance of having a seizure

36
Q

How do carbapenems do when it comes to bacteria producing beta-lactamases?

A

They are good and these drugs are resistant against a lot of beta-lactamases

**Some drugs create carbapenemases which is able to inactivate the carbapenems

EX: Klebsiella pneumonia carbapenamases (KPC)

Carbapenem-resistant enterobacteriacae (CRE), Morganella, proteus

37
Q

What is one of the big upsides when it comes to using aztreonam?

A

Has very little cross-reactivity with beta-lactams

**Very safe to use in pts who have PCN-allergic rxn ( anaphylaxis from PCN)

***these only treat Gram negative bacteria

Pseudomonas (P. Aeruginosa) and Acinetobacter (A. Baumannii

38
Q

Explain the bacteria coverage map for aztreonam and the carbapenems

A

Azetrenom = all gram negative aerobes (no gram (+))

Dori, imipen, meropenem = MSSA to Pseudomonas

Ertepenmem = MSSA to SCE

All carbapenems can kill b. Fragillis

39
Q

Which bacteria create beta-lactamases?

A

Staphylococcus (MSSA)

All gram negatives

Bacteroides fragilis ( B. Fragilis)

40
Q

What kind of beta-lactamase does MSSA produce and what can we use in order to over come this?

A

Penicilinase

Can use resistant penicillins such as oxacillin, Nafcillin (these are large so they are resistant)

Can use beta-lactamase inhibitors such as Clavulanic acid, tazobactam and sulbactam

41
Q

What kind of beta-lactamase does gram negatives create?

A

AmpC-type (less likely to be inhibited by clavulanic acid etc… these also create cephalosporinases (break down cephalosporins

Extended spectrum beta-lactamase (ESBL) these will block a lot of cephalosporins
**will have to use carbapenems (last resort)

42
Q

What do we use so that we can overcome beta-lactimase on Bacteroides fragilis

A

We can use Clavulanic acid, tazobactam and sulbactam

This will allow augmentin to kill it

43
Q

What are Suicide substrates?

A

These are Clavulanic acid, tazobactam and sulbactam

They will bind to beta-lactamase which will shut it down

  • **adverse effects
    1. Very bad diarrhea (you kill off a lot of the bacteria in your gut using this)
    2. Increased risk of C. Diff
44
Q

What beta-lactamase inhibitors have the same structure as the beta-lactam?

A
  1. Clavulanic acid
  2. Tazobactam
  3. Sulbactam
45
Q

What is important about avibactam?

A

It is broad spectrum and will help activity against all the type of beta-lactamases EXPECT NDM-1

46
Q

What is important to note about Vabrbactam?

A

Used with carbapenems to help over come carbapenmases KPC

47
Q

What is important to know about sulbactam?

A

It enhances the beta-lactams activity against acinetobacter

48
Q

What beta-lactamase inhibitor do you add to amoxicillin and what extra activity does it give to amoxicillin?

A

You would add clavulanic acid and t gives it added activity towards MSSA and Bacterodies (b. Fragillis) gram (-) anaerobe

49
Q

What beta-lactamase would you add to ampicillin and how does it improve the coverage for ampicillin?

A

Sulbactam

Gives MSSA and bacteriodes (b. Fragillis )

50
Q

What beta-lactamase inhibitor do you add to Piperacillin and what extra coverage does it add?

A

You add tazobactam and it adds MSSA and bacteriodies (b. Fragillis)

51
Q

What beta-lactamase inhibitor do you add to cefazidime and how does it increase its activity?

A

You add acibactam and it will enhances the effectiveness and give to CRE and KPC

52
Q

What beta-lactamase do you add to meropenem and how does it enhance if effects ?

A

You add vaborbactam, which enhances the effects of carbapenems and helps protect them from being broken down

***vaborbactam only gets added to carbapenems

Block 1.11 Lees Stuff (5 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions