1-20 Mechanisms of Action of Antibiotics Flashcards
What is the difference between bacteriostatic and bacteriocidal agents?
Bacteriostatic agents inhibit the growth and/or reproduction of the infecting agent without killing it. They are dependent on the host’s immune system.
Bacteriocidal agents cause irreversible damage to or kill the infecting agent. They act independently of the host’s immune system.
Some antimicrobials may be bacteriostatic at low concentrations and bacteriocidal at high concentrations (Minimal Inhibitory Concentration [MIC] and Minimal Bacteriocidal Concentration [MBC]).
What are the five mechanisms of action by which antibiotics inhibit or kill bacteria, and what are some examples of each?
- Inference with cell wall synthesis: β-lactams, glycopeptides
- Interference with protein synthesis: aminoglycosides, linezolid, macrolids, lincosamides, chloramphenicol, tetracyclines, furanes
- Interference with cytoplasmic membrane function: polymyxins, bacitracin, anti-fungals
- Interference with nucleic acid synthesis: quinolones, fluoroquinolones, metronidazole (DNA); rifampin, bacitracin (RNA)
- Interference with metabolic pathway: sulfonamides, trimethoprim
What is antimicrobial inhibition of cell wall synthesis?
Interference with peptidoglycan synthesis and murein assembly.
The two major classes of these inhibitors are the β-lactams and glycopeptides, which are bacteriocidal.
This is the most common mechanism of action for antibiotics, and the largest class.
What are the mechanism of action of β-lactams?
β-lactams are bacteriocidal inhibitors of cell wall synthesis. They disrupt peptidoglycan cross-linking by mimicking the normal D-alanyl-D-alanine binding residues.
What are the major classes of β-lactams?
- Penicillins
- Cephalosporins: categorized by different generations, each of which has increased spectra of activity and resistance to destruction by β-lactamase
- Monobactams: active against aerobic Gram(-) bacilli
- Carbapenems: active against virtually all pathogenic organisms and resistant to destruction by extended spectrum β-lactamases
What are glycopeptides?
Glycopeptides are bacteriocidal inhibitors of cell wall synthesis. They prevent the cross-linkage of peptidoglycan sheets by binding to penicillin binding proteins (PBPs) and cleaving the terminal D-Ala residue. They are effective against Gram(+) organisms only.
ex) Vancomycin
What is the mechanism of action for antimicrobial inhibition of protein synthesis?
Antimicrobial agents that inhibit protein synthesis can do so in one of several ways:
- Interfere with the formation of the 30S initiation complex
- Interfere with the formation of the 70S ribosome (by the 30S initiation complex and 50S ribosome)
- Block the elongation process (AA assembly –> polypeptide)
What are the major classes of protein synthesis inhibitors?
- Aminoglycosides
- Macrolids
- Tetracyclines
- Linezolid
- Lincosamides
- Chloramphenicol
- Furanes
What are aminoglycosides?
Aminoglycosides are bacteriocidal inhibitors of protein synthesis. They bind to the 30S ribosome, changing its shape and causing a misreading of mRNA.
ex) gentamycin, tobramycin, amikacin, streptomycin
What are macrolids?
Macrolids are bacteriostatic inhibitors of protein synthesis. They bind to the 50S subunit of the bacterial ribosome, blocking the exit of the growing peptide chain.
ex) erythromycin, azithromycin, clarithromycin
What are tetracyclines?
Tetracyclines are bacteriostatic inhibitors of protein synthesis. They inhibit codon-anticodon interaction. They can inhibit eukaryotic protein synthesis, but they preferentially bind to bacterial ribosomes.
ex) tetracycline, minocycline, doxycycline, demeclocycline, tigecycline
Which inhibitors of nucleic acid synthesis interfere with DNA, and how do they do it?
- Quinolones/fluoroquinolones: Inhibit DNA gyrases/topoisomerases required for supercoiling. ex) ciprofloxacin, levofloxacin, norfloxacin
- Metronidazole: Disrupts DNA with cytotoxic metabolic products.
Both are bacteriocidal.
Which inhibitors of nucleic acid synthesis interfere with RNA, and how do they do it?
- Rifampin: binds to DNA-dependent RNA polymerase, inhibiting initiation of RNA synthesis.
- Bacitracin: inhibits transcription.
Both are bacteriocidal.
What are some examples of antimicrobial agents that interfere with metabolic pathways, and how do they do it?
- Sulfonamides: prevents folic acid synthesis by competing with p-aminobenzoic acid (PABA).
- Trimethoprim: also prevents folic acid synthesis, but by inhibit dihydrofolate reductase.
Both are bacteriostatic, but can be used in combination bacteriocidally.
