Antibiotics and Bacterial Inhibition Study Notes

Study Notes on Antibiotics and Bacterial Inhibition

General Introduction

  • It is important to start early when studying antibiotics.

  • Aim not to procrastinate as memorization of material is required.

Antibiotics Affecting Cell Wall Formation

Beta-Lactam Antibiotics

  • Penicillin and Cephalosporins: Both have a beta-lactam ring structure, which is crucial for their function.

  • Carbapenem: Represents a mixture of penicillin and cephalosporin; also contains a beta-lactam ring.

Vancomycin

  • Mechanism: Inhibits the removal of the terminal alanine in bacterial cell wall synthesis.

  • Historical Use: Previously considered a "drug of last resort," now replaced by other medications as resistance has developed (e.g., vancomycin-resistant enterococci).

  • Etymology: The term "entero" indicates intestinal origin, relevant to enterococci which are present in intestines.

Gram-positive vs. Gram-negative Bacteria

  • Enterobacter (Gram-negative) and Enterococci (Gram-positive).

Metabolic Antagonists

Mechanism of Action

  • Metabolic antagonists, specifically anti metabolites, resemble the true substrate of enzymes but are not functionally identical.

  • Example: PABA (p-aminobenzoic acid) serves as a precursor to folic acid.

  • Sulfonamides (Sulfa drugs): Structurally similar to PABA, they compete for binding to the enzyme responsible for folic acid synthesis but do not allow the formation of the product.

Key Concepts

  • Inhibition Process: The presence of sulfa drugs inhibits the addition of side groups necessary for folic acid formation.

  • Static vs. Cidal: Metabolic antagonists are generally bacteriostatic, meaning they inhibit growth without killing bacteria.

Interaction Dynamics

  • The binding interactions with both PABA and sulfa are temporary and non-covalent, allowing for competitive inhibition based on concentration ratios.

  • When more sulfa drug is present than PABA, the likelihood of the enzyme binding to PABA is reduced.

Role of the Immune System

  • The goal of this inhibition is to allow the immune system to take over and eliminate the bacteria.

Selection for Antibiotic Treatments

  • Bactrim: A combination therapy utilizing both sulfa and trimethoprim to enhance efficacy.

  • Synergism: Using multiple antibiotics together offers a lower chance for microbial resistance as it necessitates multiple mutations.

  • Side Effects: Includes abdominal pain and photosensitivity (e.g., wear sunglasses).

Protein Synthesis Inhibitors

Overview

  • Translation: The process by which ribosomes synthesize proteins from mRNA; essential for normal cell function.

  • Ribosomes differ between prokaryotic (bacterial) and eukaryotic cells:

    • 70S Ribosome (bacteria): Comprised of 30S (small) + 50S (large) subunits.

    • 80S Ribosome (eukaryotes): Comprised of 40S (small) + 60S (large) subunits.

Aminoglycosides

  • Mechanism: Bind to the 30S subunit, inhibit protein synthesis.

  • Examples: Streptomycin, Kenamycin, Neomycin (true antibiotics from Streptomyces); Gentamicin (another true antibiotic).

  • Side Effects: Potential for nephrotoxicity (renal damage).

Tetracyclines

  • Structure: Characterized by four rings (hence the prefix