Penicillin Flashcards
What are the differences between Gram-(+) and Gram-(–) bacteria regarding drug penetration?
Gram-(+): Drugs can penetrate the outer layers of the cell wall effectively.
Gram-(–): The outer membrane excludes drugs, but some drugs still get through the porins.
How is the distribution of beta-lactamases different in Gram-(+) and Gram-(–) bacteria?
Gram-(+): Beta-lactamases are excreted through the cell wall to the external environment; they must be produced in larger quantities.
Gram-(–): Beta-lactamases are confined to the periplasmic space.
What is the peptidoglycan thickness in Gram-(+) and Gram-(–) bacteria?
Gram-(+): Thick peptidoglycan.
Gram-(–): Thin peptidoglycan.
How many membranes are present in the cell wall of Gram-(+) and Gram-(–) bacteria?
Gram-(+): One bacterial membrane.
Gram-(–): Two membranes - outer membrane and inner membrane.
What is the peptidoglycan content in Gram-(+) and Gram-(–) bacteria?
Gram-(+): the DAP residue is replaced by an L-lysine residue (COOH of DAP is replaced by an H)
Gram-(–): the peptidoglycan contains a meso-diaminopimelic acid residue (DAP)
How does peptidoglycan bridging differ in Gram-(+) and Gram-(–) bacteria?
Gram-(+): The bridge exists between the L-Lys strand and the terminal D-Ala of the second molecule.
Gram-(–): Peptidoglycan is cross-linked by a bridge between the DAP residue of one strand and the terminal D-Ala of another.
What is the role of transpeptidase in bacterial cell wall strength?
Transpeptidase cross-links peptidoglycan strands, which is necessary to confer strength to the bacterial cell wall to prevent lysis.
How does transpeptidase function in cross-linking peptidoglycan?
Transpeptidase has a serine residue in its active site that carries out a nucleophilic attack on the amide carbonyl, forming a tetrahedral intermediate and linking peptidoglycan strands.
What is the mechanism of action of penicillins?
Penicillin is a beta lactam-antibiotic; beta-lactam MOA: Penicillin inhibits transpeptidases that glue peptidoglycan strands together by cross-linking, inhibiting bacterial cell wall synthesis, which kills the bacteria.
How do beta-lactam antibiotics inactivate transpeptidase?
Beta-lactam antibiotics acylate the transpeptidase Ser residue, forming a stable product that inhibits peptidoglycan cross-linking, leading to cell lysis and death.
What structural feature of beta-lactams allows them to mimic D-Ala-D-Ala?
The structures of beta-lactams resemble the D-Ala-D-Ala fragment, allowing them to ‘fool’ transpeptidase into thinking they are the D-Ala-D-Ala fragment.
What are common bacterial resistance mechanisms toward penicillins?
Resistance may result from decreased drug uptake, mutations in penicillin-binding proteins, or the presence of efflux pumps. A common mechanism is the induction of beta-lactamases that hydrolyze the beta-lactam moiety. The beta-lactamases form hydrolyzed penicillin (penicillin that is broken down, so it’s inactive as an antibiotic)
How does penicillin allergenicity occur?
Beta-lactam antibiotics act as haptens, acylating host cell proteins and raising antibodies that lead to allergic reactions.
What happens to penicillins under acidic conditions?
Under acidic conditions, Pen G degrades to benzylpenicillenic acid, benzylpenillic acid, and benzylpenicilloic acid, making it unstable for oral administration.
What happens to penicillins under basic conditions?
hydroxyl group attacks carbonyl to form a penicilloic acid.
What is the main chemical feature of penicillins that confers resistance to acidic degradation?
The presence of a phenoxymethyl group attached to the beta-lactam ring in penicillin V provides resistance to degradation under acidic conditions, allowing it to be taken orally. This modification stabilizes the molecule against hydrolysis in acidic environments. So, pen V is more stable to hydrolysis in the stomach than pen G because the electronegativity of the ether oxygen decreases the nucleophilicity of the amide carbonyl
What conditions promote penicillin degradation?
Heavy metal ions catalyze penicillin degradation reactions.
How does lipophilicity of penicillins affect their serum protein binding?
As CLogP increases, it is more lipophilic. Penicillins with more lipophilic side chains are more highly protein bound.
