Introduction to B-lactams Flashcards
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?
Bacterial resistance
Current Problem Areas?
What gram (-) organisms are still a problem?
Advantages of B-lactams?
4 things
Concerns of B lactams?
Clinical applications
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?
- 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
Structural Featurs of Penicillins
4 points
Instability of B-lactams to nucleophiles
What is formed?
Degradation of penicillin in acid involves what carbon and what side chain?
Enzymatic Hydrolytic products of Penicillins
What are the two products and what enzymes are involved in them?
Drug interaction between B-lactam antibiotics and?
What does this lead to?
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?
Allergic Rxns in decreasing frequency
10
9) Anaphylaxis - Hitamine release from mast cells
10) Angioedema
Cross allergies to penicillins?
Which meds are the most likely to have cross allergy?
Which ones are least?
Ocassionally with?
- Usually with other penicillins
- Ocassionally with cephs (5-8%)
- Imipenem (most) likely
- Aztrenam least likely
Penicillin Allergy Slide
Allergy testing
Skin tests
Useful only for?
What needs to be present?
What are the 2 tests?
PPL test
Info
MDM test
MOA of Penicillins
- Irreversibly inhibits PBP enzymes responsible for processing the development of peptidoglycan layer of bacterial cell wall
Penicillin Binding Proteins
Usually?
S. Aureus has how many? E coli.?
The PBPs vary in?
Lethal effect of antibacterial is due to?
- Several PBPs, S. Aureus- 4, E. Coli-5
- PBPs vary in their affinity for different B-lactam antibiotics
- Lethal due to binding
PBPs of E. Coli anf their functions
PBP1a/1b
PBP-2
PBP-3
PBP4,5,6
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?
D-ala-Dala
Mechanisms for cell wall cross linking and termination of cross-linking by PBPs
Path A
Path B
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?
Ester linkage is so much stronger due to steric hinderance block water from entering the active site
DOPE!!
Bactericidal Action of B-lactams The overall pathway
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?
Contains Zinc
Metallo lactamase is special because of?
What are the 2 roles of this during hydrolysis?
Gram Positive vs. Gram Negative
What is generally present in gram negatives that make it difficult for drugs to get in?
Porins
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?
Classifications of B-lactamases?
Ambler classifications
A-D
based on?
Ambler classifications
Substrate Affinity and Selected Examples
P. Aeruginosa? Increasingly?
Why? Diminished?
Loss or Modified?
- 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
Activity of B-lactams is Dependent on?
- 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
Strategies to overcome B-lactamase hydrolysis
Preparation of B-lactamase ta
- Preparation of B-lactamase stable penicillins, cephalosporins, carbapenems,
- Combination therapy with B-lactamase inhibitor
