Introduction to B-lactams

Question 1

What are the 4 major structural subclasses of B-lactams?

What is their common MOA?

Potent and Rapid?

However development of what is a major concern?

Answer 1

Question 2

Bacterial resistance

Current Problem Areas?

What gram (-) organisms are still a problem?

Answer 2

Question 3

Advantages of B-lactams?

4 things

Concerns of B lactams?

Clinical applications

Answer 3

Question 4

Which B-lactam is the most potent?

Why is this the case? What does that mean for the safety of the drug?

In general what type of antibiotics are less potent than the traditional 4-5 rings

Which B-lactam is the least potent? What does that mean with safety?

Answer 4

• Carbapenems most potent, most side effects most strained
• Cephs are in general less potent than B-lactams
• Monobactam is the least potent, it is the safest, least strained and least SEs

Question 5

Structural Featurs of Penicillins

4 points

Answer 5

Question 6

Instability of B-lactams to nucleophiles

What is formed?

Answer 6

Question 7

Degradation of penicillin in acid involves what carbon and what side chain?

Answer 7

Question 8

Enzymatic Hydrolytic products of Penicillins

What are the two products and what enzymes are involved in them?

Answer 8

Question 9

Drug interaction between B-lactam antibiotics and?

What does this lead to?

Answer 9

Question 10

Untoward Rxns to Penicillins

In general direct toxicity of Penicillins is?

Most common SE?

Caused by?

Spontaneous?

AS a general rule children are more or less likely ro have an allergic rxn?

IV or Oral less likely?

Answer 10

Question 11

Allergic Rxns in decreasing frequency

10

Answer 11

9) Anaphylaxis - Hitamine release from mast cells
10) Angioedema

Question 12

Cross allergies to penicillins?

Which meds are the most likely to have cross allergy?

Which ones are least?

Ocassionally with?

Answer 12

• Usually with other penicillins
• Ocassionally with cephs (5-8%)
• Imipenem (most) likely
• Aztrenam least likely

Question 13

Penicillin Allergy Slide

Answer 13

Question 14

Allergy testing

Skin tests

Useful only for?

What needs to be present?

What are the 2 tests?

Answer 14

Question 15

PPL test

Info

Answer 15

Question 16

MDM test

Answer 16

Question 17

MOA of Penicillins

Answer 17

• Irreversibly inhibits PBP enzymes responsible for processing the development of peptidoglycan layer of bacterial cell wall

Question 18

Penicillin Binding Proteins

Usually?

S. Aureus has how many? E coli.?

The PBPs vary in?

Lethal effect of antibacterial is due to?

Answer 18

• Several PBPs, S. Aureus- 4, E. Coli-5
• PBPs vary in their affinity for different B-lactam antibiotics
• Lethal due to binding

Question 19

PBPs of E. Coli anf their functions

PBP1a/1b

PBP-2

PBP-3

PBP4,5,6

Answer 19

Question 20

Where do penicillins cause cell wall destruction?

What indirect effect do they have?

What are the portions of the cell wall?

What cross linkes them together?

PBP binds to?

Answer 20

D-ala-Dala

Question 21

Mechanisms for cell wall cross linking and termination of cross-linking by PBPs

Path A

Path B

Answer 21

Question 22

Mechanism of transpeptidase Cross-linking and Inhibition by the Pens?

What portion of the transpeptidase binds to Pen initially? Attraction via what other portion?

Cool feature?

There is an ester link why isnt it degraded quickly?

Answer 22

Ester linkage is so much stronger due to steric hinderance block water from entering the active site

DOPE!!

Question 23

Bactericidal Action of B-lactams The overall pathway

Answer 23

Question 24

Bacterial resistanct to B-lactam

How common is it?

What are the four basic mechanisms for development of resistance?

What is the major cause for resistance though?

What do the enzymes do?

What are the 2 types of B-lactamases? What contains?

Answer 24

Contains Zinc

Question 25

Metallo lactamase is special because of? What are the 2 roles of this during hydrolysis?

Answer 25

Question 26

Gram Positive vs. Gram Negative What is generally present in gram negatives that make it difficult for drugs to get in?

Answer 26

Porins

Question 27

Gene Locations for B-lactamases The information for the production of B-lactamases is encoded in Chromosomes or Plasmids Chromosomes? Plasmids? Transduction? Conjugation? transposition? Transformation?

Answer 27

Question 28

Classifications of B-lactamases? Ambler classifications A-D based on?

Answer 28

Question 29

Ambler classifications Substrate Affinity and Selected Examples

Answer 29

Question 30

P. Aeruginosa? Increasingly? Why? Diminished? Loss or Modified?

Answer 30

* Increased resistance to B-lactams * Permeability of the Outer membrane bu B-lactams is abou t100-500 fold less than for E. Coli * Diminished Penetration through hydrophilic porins * Porins

Question 31

Activity of B-lactams is Dependent on?

Answer 31

* Ability to penetrate wall * Ability to bind to PBP * Sensitivity to beta-lactamases/amidase * Concentration of antibiotic * Presence of aoutlysin-inhibitor complex * Presence of Efflux systems, and other factors

Question 32

Strategies to overcome B-lactamase hydrolysis Preparation of B-lactamase ta

Answer 32

* Preparation of B-lactamase stable penicillins, cephalosporins, carbapenems, * Combination therapy with B-lactamase inhibitor