Antibiotic Classes of Protein Synthesis Inhibitors

Study Notes

Antibiotic Classes of Protein Synthesis Inhibitors

Tetracyclines
- Tetracycline: Low potency; moderate GI absorption; significant gastrointestinal side effects; low phototoxicity risk.
- Minocycline: High potency; complete absorption; minimal GI side effects; higher phototoxicity risk than tetracycline.
- Doxycycline: Similar to minocycline but safer for patients with renal failure due to biliary excretion.
Aminoglycosides
- Amikacin: Effective against gentamicin-resistant strains.
- Gentamicin: Prototype aminoglycoside; most commonly prescribed.
- Kanamycin: Highly nephrotoxic; rarely used.
- Neomycin: Primarily used topically or for gut sterilization.
- Streptomycin: Used for specific zoonotic infections and as a second-line treatment for tuberculosis.
- Tobramycin: Specifically effective against Pseudomonas aeruginosa; often combined with anti-pseudomonal beta-lactam antibiotics.
Macrolides and Related Antibiotics
- Macrolides:
  - Erythromycin: Associated with risk of cardiac arrest.
  - Clarithromycin: A derivative with improved dosing frequency and lower GI side effects.
  - Azithromycin: Considered safest for use during pregnancy.
  - Clindamycin: Primarily used for anaerobic infections and specific skin conditions.
  - Fidaxomicin: Effective for C. difficile infections.
- Oxazolidinones:
  - Linezolid: Bacteriostatic with potential bactericidal effects; used for resistant Gram-positive infections.
- Miscellaneous:
  - Chloramphenicol: Broad-spectrum but with notable side effects; inhibits bacterial protein synthesis.
  - Streptogramins: Combination agents effective against resistant strains.

Mechanisms of Action

Tetracyclines
- Enter the bacterial cytoplasm and bind to the 30S ribosomal subunit; inhibit protein synthesis, resulting in bacteriostatic effects.
Aminoglycosides
- Passive diffusion through bacterial outer membrane via porins; require active transport across the inner membrane in aerobic conditions.
- Bind to the 30S ribosomal subunit, leading to misreading of mRNA and irreversible bactericidal effects; effective only against Gram-negative aerobic bacteria.
Macrolides and Related Antibiotics
- Macrolides:
  - Bacteriostatic; inhibit translocation and peptide elongation by binding to the P site of the 50S ribosomal subunit.
- Oxazolidinones (Linezolid):
  - Interfere with the formation of the translation initiation complex by binding to the 23S component of the 50S subunit.
- Chloramphenicol:
  - Inhibits peptidyl transferase, which transfers amino acids between ribosomal sites.

Antibiotic Resistance Mechanisms

Tetracyclines
- Bacterial resistance through efflux pumps specific to tetracyclines.
Aminoglycosides
- Resistance mechanisms include enzymatic modifications that modify the drug or binding site, such as N-acetylation, O-adenylation, and O-phosphorylation.
- Resistance varies within aminoglycoside family (e.g., amikacin can act when gentamicin cannot).
- Gram-positive bacteria show intrinsic resistance owing to their thick peptidoglycan layers, preventing drug diffusion.
Macrolides and Related Antibiotics
- Resistance can occur through ribosomal methylation (erm genes) and efflux pumps conferring resistance against macrolides.
- Chloramphenicol can be inactivated by acetyltransferases.
- Streptogramins capable of inactivating drugs via efflux mechanisms due to acetyltransferases.

Description

Test your knowledge on the different classes of protein synthesis inhibitors, focusing on their characteristics and specific examples. This quiz covers tetracyclines, aminoglycosides, and macrolides, presenting critical information about their usage and properties. Perfect for students in microbiology or pharmacology courses.