Antibiotic drug classes & mechanisms Flashcards
What are the possible reasons for adverse reactions to antibiotics?
Membrane interacting antibiotics may interact with patient membranes at high concentrations
Breakdown and release of bacterial components can cause a reaction
What are narrow vs broad spectrum antibiotics?
Narrow spectrum
- Targets narrow group of bacteria (i.e. either Gram positive or Gram negative)
Broad spectrum
- Targets Gram +ve & –ve bacteria
What is a bacteriocidal antibiotic?
Kills the organism
Example penicillin’s, cephalosporin’s
What is a bacteriostatic antibiotic?
Drugs that temporarily inhibit the growth of an organism (i.e. reversible if removed).
E.g. Tetracycline’s, Chloramphenicol
rely on host systems to reduce & remove bacteria that are not growing
- not very effective in immuno-compromised patients
What is the MIC of an antibiotic?
(minimum inhibitory concentration):
concentration required at site of infection to achieve bacterial inhibition.
What is the MBC of an antibiotic?
(minimum bactericidal concentration):
concentration required at site of infection to kill the bacteria
What is concentration dependant killing?
where drug has to be at or above critical concentration to have an impact. It relates to getting enough of the drug bound to enough to the targets in the bacteria to have an effect.
What are the main antibiotic targets of action?
Inhibition of protein synthesis
Inhibition of cell membrane function
Inhibition of cell wall synthesis
Interference with other pathways
Inhibition of DNA dependent RNA polymerase
Disruption of DNA structure
Give examples of antibiotics that inhibit protein synthesis
Chloramphenicol
Lincosamides
Macrolides
Amino glycosides
Pleuromutilin
Tetracyclines
Nitrofurans
Give examples of antibiotics that inhibit cell membrane function
Polypeptides
Antimicrobial peptides
Give examples of antibiotics that inhibit cell wall synthesis
B-lactam antibiotics
Vancomycin
Bacitracin
Give examples of antibiotics that inhibit DNA dependant RNA polymerase
Rifampicins
Give examples of antibiotics that disrupt DNA structure
Nitroimidazoles
Metronidazole
What is peptidoglycan
unique to bacteria (good target)
polymer of sugars & amino acids that forms mesh-like cell wall
The polysaccharide chains cross linked by interlinking peptides
How do beta-lactam antibiotics target the bacterial cell wall (peptidoglycan)?
Inhibit transpeptidase (Penicillin-Binding Protein), preventing peptide cross-link formation in peptidoglycan
Result: Weakened cell wall & bacterial lysis due to osmotic pressure.
How does penicillin resistance develop in bacteria?
Production of beta-lactamase enzymes that break beta-lactam ring
Methicillin-resistant strains have altered PBP due to mec gene, making them resistant to beta-lactams
What are cephalosporins, and how are they classified?
Cephalosporins are beta-lactam antibiotics divided into 5 generations based on their spectrum of activity:
1st Gen: Effective against Gram-+ve bacteria, moderate against Gram- -ve
2nd Gen: Targets both Gram-+ve (less effective) & Gram- -ve
3rd Gen: Broad-spectrum, reserved for critical cases.
4th Gen: Even broader spectrum, used sparingly due to resistance concerns.
5th Gen: Effective against MRSA, used only in critical human cases.
What is the role of methicillin in combating beta-lactamase-producing bacteria?
Methicillin is resistant to beta-lactamase enzymes, but resistance can develop due to altered PBPs
What are examples of antibiotics that inhibit protein synthesis?
30S subunit inhibitors:
- Tetracyclines: Block tRNA attachment.
- Aminoglycosides: Cause irreversible inhibition of protein synthesis.
50S subunit inhibitors:
- Macrolides: Block translocation
- Chloramphenicol: Prevent peptide bond formation.
- Lincosamides: Similar to macrolides but with a different spectrum.
What is the mechanism of action for ribosome-targeting antibiotics?
These antibiotics bind to specific sites on ribosomal RNA or ribosomal proteins within 30S or 50S subunits, physically blocking ribosome’s function & inhibiting protein synthesis.
How can bacteria develop resistance to ribosome-targeting antibiotics?
Mutations in ribosomal RNA or ribosomal proteins alter binding sites, reducing antibiotic efficacy
These modifications increase MIC required for effectiveness, leading to resistance.
How do Quinolones work?
Inhibit DNA gyrase & topoisomerase, disrupting DNA supercoiling & replication
Spectrum: Broad, effective against Gram- -ve & some Gram- +ve bacteria.
What is the mechanism and common use of TMPS (sulphonamides and trimethoprim)?
TMPS is synergistic combination targeting 2 points in same metabolic pathway, inhibiting folic acid synthesis in bacteria.
Competitive inhibitors
It is effective due to its dual mechanism of action.
What is the mechanism of action for nitroimidazoles?
produce reactive reduction products that interact with & damage bacterial DNA, leading to bacterial death.
How does Rifampicin work?
Inhibits DNA dependent RNA polymerase => blocks initiation of protein synthesis
What are cationic antimicrobial peptides, and how do they work?
Disrupt bacterial membranes by interacting with lipids.
Often used topically in dermatology (e.g., ear infections).
Why do antimicrobial peptides (AMPs) not harm eukaryotic cells?
Eukaryotic cell membranes contain zwitterionic phospholipids & cholesterol, which are absent in bacteria.
These components provide intrinsic resistance to AMPs.
How does the site of infection influence antibiotic activity?
Anaerobic conditions: Nitroimidazoles are activated.
Aerobic conditions: Aminoglycosides require oxygen for uptake.
Why are nitroimidazoles effective under anaerobic conditions?
Nitroimidazoles require anaerobic conditions to be reduced to their active form by anaerobic bacteria
Once activated, they interact with and damage bacterial DNA.
Why are aminoglycosides less effective under anaerobic conditions?
Aminoglycosides rely on aerobic electron transport chain to enter bacterial cells
In anaerobic conditions, bacteria downregulate part of transport chain, reducing aminoglycoside uptake.
What is the key factor for time-dependent antibiotics?
most important factor is time serum concentration remains above Minimum Inhibitory Concentration (MIC)
Increasing concentrations above MIC doesn’t enhance killing
e.g. Beta-lactams, macrolides
What is the key factor for concentration-dependent antibiotics?
most significant factor is achieving high peak concentration at binding site
Killing increases with higher concentrations
e.g. Aminoglycosides, fluoroquinolones
