Antimicrobial Drugs: Detailed Notes

Ideal Antimicrobial Characteristics

• Doesn't promote antimicrobial resistance.
• Accessible price.
• Doesn't cause secondary effects like allergies.

Antimicrobial Drugs Definition

• Substances that kill microbes.

Semi-Synthetic Drugs Definition

• Chemically modified drugs, partially natural and partially synthetic.

Origin of Antibiotics

• From bacteria and fungi.
• Examples:
  • Streptomyces.
  • Bacillus.
  • Penicillium.
  • Clostridium.

Spectrum of Antimicrobial Drugs

• Narrow:
  • Limited effect, affects a small range of microbes (1-2).
• Broad:
  • Greater effect, kills a wide range of microbes.

Negative Impact of Broad-Spectrum Antimicrobials

• Can kill both good and bad bacteria.

Classification of Drug Action (Five Classifications)

• Cell Wall Inhibitors
• Cell Membrane
• Protein Synthesis (30S and 50S Ribosomes)
• mRNA and DNA

Cell Wall Inhibitors

• Target: Cell wall, specifically peptidoglycan.

Beta Lactams

• Natural:
  • Penicillin: Attacks peptidoglycan.
    • Penicillin G: Injectable, used for syphilis.
    • Penicillin V: Oral, used for oropharyngeal infections.
• Semi-synthetic:
  • Amoxicillin: Resistant to stomach acids.
    • Clinically used to treat otitis media and streptococcal pharyngitis.
    • Effective against gram-positive bacteria.
  • Methicillin: Created against MRSA but discontinued in the US due to resistance.

Cephalosporins

• Another type of beta-lactam.
• Five generations:
  • First Gen: Cephalothin, cefaclor.
  • Fifth Gen: Ceftaroline - used to treat MRSA.
• Mode of action: Block Penicillin-Binding Proteins (PBPs), which are enzymes.

Non-Beta Lactams

• Vancomycin:
  • Interferes with alanine amino acids and cross-bridge formation in cell walls.
  • Effective against MRSA and used pre-surgery.
  • Ineffective against Gram-negative bacteria (due to size; cannot penetrate the cell wall).
  • Targets the peptide part of peptidoglycan.
• Isoniazid:
  • Blocks the production of enzyme for mycolic acid.
  • Used for tuberculosis.
• Ethambutol:
  • Interferes with the integration of mycolic acid.
  • Also used for tuberculosis.
• Isoniazid vs. Ethambutol:
  • Both target mycolic acid in tuberculosis treatment.
  • Isoniazid blocks production.
  • Ethambutol interferes with integration.

Cell Membrane

• Target: Cell membrane.
• Mode of action: Disrupts the cell membrane.
• Example: Polymyxin.
  • Topical use only (e.g., Neosporin, Polysporin) due to toxicity if ingested.
  • Five types: A, B, C, D, and E; type B is the most common.
  • Cell membrane is not a good antibiotic target because we also have it.

Protein Synthesis Inhibitors (30S and 50S Ribosomes)

• Targets: Ribosomes (30S and 50S subunits).
• 30S Subunit: Bottom.
• 50S Subunit: Top.

30S Inhibitors

• Aminoglycosides:
  • Mode of action: Change the shape of the 30S ribosome.
  • Broad spectrum.
  • First antimicrobial discovered: Streptomycin (toxic).
  • Newer aminoglycosides: Tobramycin (inhaler) and amikacin.
    • Used against tuberculosis, Pseudomonas, Gram-negative bacteria, and bone infections.
  • Advantage: Can act synergistically with other antimicrobials (e.g., in tuberculosis cocktail).
  • Disadvantage: Ototoxicity (dizziness and headache).
• Tetracycline:
  • Mode of action: Blocks the docking site for tRNA on the bacterial ribosome.
  • Examples: Tetracycline, doxycycline (for Lyme disease), minocycline.
  • Effective against:
    • Intracellular parasites (Chlamydia, Rickettsia – Rocky Mountain spotted fever).
    • MRSA.
    • Pneumonia.
  • Side effects/Disadvantages:
    • Permanent discoloration of teeth in children/young adults.
    • Inactive when taken with calcium or iron.
    • Cannot take during pregnancy.
    • May cause liver issues.

50S Inhibitors

• Mode of action: Blocks the formation of peptide bonds.
• Chloramphenicol:
  • Used for Salmonella, typhoid fever, and pink eye (backup drug for severe infections).
  • Side effects:
    • Reversible anemia.
    • Aplastic anemia (irreversible and fatal).
    • Contraindicated during breastfeeding.
• Macrolides:
  • Mode of action: Prevent the movement of the ribosome along mRNA.
  • Examples:
    • Erythromycin (natural).
    • Azithromycin (Z-Pak - semi-synthetic, synergy of antibiotics for 5 days).
    • Clarithromycin (semi-synthetic).
  • Clinical Use: Common cold, Streptococcus, staphylococcus, Enterocetral, respiratory chlamydia.
  • Recommended for patients with penicillin allergies.
  • Advantage of Azithromycin: Short regimen (5 days), long half-life (68 hours).
  • Disadvantage: Diarrhea.
  • Chlamydia trachomatis: Can be transmitted vertically (mother to child) and cause corneal ulcers/blindness in newborns; treated with ointment/drops.

Metabolic Pathway Inhibitors (Anti-Metabolites)

• Mode of action: Interfere with metabolic pathways.
• Analogs of PABA or vitamin B.
• Sulfonamides:
  • Analog to PABA.
  • Example: Sulfamethoxazole.
  • Used against protozoal infections.
• Trimethoprim:
  • Analogous to dihydrofolic acid.
  • Prescribed in combination with sulfonamides.
• How They Interfere: Sulfonamides block the enzyme that uses PABA, while trimethoprim blocks the enzyme that uses dihydrofolic acid, preventing vitamin B synthesis.
• Clinical Use of TMP (Trimethoprim):
  • P: Pneumonia.
  • G: Gastrointestinal tract infections.
  • U: Urinary tract infections.

Nucleic Acid Inhibitors (DNA and RNA)

• DNA Inhibitors: Block DNA synthesis.
  • Fluoroquinolones (synthetic):
    • Examples: Ciprofloxacin, levofloxacin, ofloxacin, norfloxacin.
    • Clinical Use:
      • Multi-resistant Pseudomonas aeruginosa.
      • GI tract infections (Shigella, E. coli, Salmonella).
      • Drug-resistant pneumococci.
      • Ciprofloxacin is used as prevention against anthrax.
    • Ciprofloxacin side effects: Tendon rupture, central nervous system toxicity, impaired cartilage development; not prescribed for people under 18 years old. Cannot take these drugs with vitamins.
• RNA Inhibitors: Block RNA synthesis.
  • Rifampin:
    • Mode of action: Blocks the synthesis of mRNA by targeting RNA polymerase.
    • Side effect: Red-orange urine and body fluids.
    • Used in tuberculosis cocktail.
    • Components of tuberculosis cocktail (RIPE):
      • R: Rifampin.
      • I: Isoniazid.
      • S: Streptomycin.
      • E: Ethambutol.