Antimicrobial+drug unit 11

Antimicrobial Drugs for BIO2100

Modes of Action of Anti-Bacterial Drugs

Inhibition of Cell-Wall Biosynthesis

• Beta lactams:

  • Penicillins: Effective against a broad range of Gram-positive and some Gram-negative bacteria; disrupts peptidoglycan layer in bacterial cell wall.

  • Cephalosporins: Have a broader spectrum than penicillins; classified into generations (1st-5th) with varying effectiveness against different bacteria.

  • Monobactams: Primarily effective against Gram-negative bacteria; Aztreonam is a notable example.

  • Carbapenems: Broad-spectrum agents effective against a wide array of bacteria, utilized for severe infections; include Imipenem and Meropenem.

• Glycopeptides:

  • Vancomycin: Effective against Gram-positive bacteria, especially MRSA; binds to the D-Ala-D-Ala terminus of peptidoglycan precursors, inhibiting cell wall synthesis.

  • Bacitracin: Effective for localized skin infections, inhibits the transport of peptidoglycan precursors.

Inhibition of Protein Synthesis (Translation)

• Inhibits Prokaryotic Ribosomes:

  • Tetracycline (e.g., Doxycycline): Binds to the 30S ribosomal subunit, inhibiting tRNA binding; side effects include phototoxicity and discoloration of teeth due to chelation with calcium.

  • Aminoglycosides:

    • Gentamicin: Treats serious infections caused by Gram-negative bacteria.

    • Neomycin: Often used topically, as it is nephrotoxic when used systemically.

    • Streptomycin: First-line treatment for tuberculosis.

  • Macrolides:

    • Erythromycin: Effective against atypical pneumonia and some Gram-positive bacteria; side effects may include gastrointestinal upset.

    • Chloramphenicol: Broad-spectrum; used in severe infections and for bacterial meningitis; side effect includes aplastic anemia.

Inhibition of Nucleic Acid Synthesis

• DNA Synthesis Inhibitors:

  • Fluoroquinolones (e.g., Ciprofloxacin, Nalidixic Acid): Inhibit bacterial DNA gyrase and topoisomerase IV, leading to DNA strand breakage.

• RNA Synthesis Inhibitors:

  • Rifamycin, Rifampin: Primarily used for tuberculosis; inhibits bacterial RNA polymerase.

Inhibitors of Plasma Membranes

• Polymyxin B, Colistin: Effective against Gram-negative bacteria; disrupt membrane integrity. Associated with nephrotoxicity and neurotoxicity.

• Daptomycin: Effective against Gram-positive bacteria; disrupts membrane potential; used against MRSA infections.

Inhibitors of Crucial Enzymes or Metabolic Pathways

• Sulfonamides (Sulfamethoxazole), Trimethoprim: Combined often as TMP-SMX; inhibits folic acid synthesis, essential for nucleic acid synthesis.

• Antimycobacterial Agents:

  • Izoniazid: Inhibits mycolic acid synthesis, critical for mycobacterial cell walls; side effects include hepatotoxicity and neurotoxicity.

  • Ethambutol: Inhibits incorporation of mycolic acid into the cell wall.

Antifungal Drugs

Ergosterol Synthesis Inhibitors

• Miconazole, Ketoconazole, Fluconazole: Interfere with ergosterol synthesis, essential component of fungal cell membranes; effective against various fungal infections.

• Nystatin: Used topically for fungal infections, particularly Candida; nephrotoxic if administered systematically.

• Amphotericin B: Broad-spectrum antifungal; binds to ergosterol and causes cell membrane permeability; significant nephrotoxicity is a major concern.

Cell Wall Synthesis Inhibitor

• Chitin Inhibitors:

  • Caspofungin: Inhibits the enzyme involved in chitin synthesis, providing treatment against fungal infections like candidiasis.

Nucleic Acid Synthesis Inhibitor

• Flucytosine: Converted to 5-FU; inhibits fungal nucleic acid synthesis.

Spindle Fiber (Mitotic) Inhibitor

• Grisofulvin: Inhibits fungal mitosis; used in dermatophyte infections; side effects include hepatotoxicity.

Antiprotozoal Drugs

• Interfere with Nucleic Acid Synthesis:

  • Quinine derivatives (Chloroquine): Antimalarial, inhibits heme polymerase in malaria parasites.

  • Metronidazole: Effective against Giardia and anaerobic bacteria; disrupts DNA synthesis.

Antihelminthic Drugs

• Nicosamide: Inhibits ATP formation in anaerobic environments; effective against tapeworms; has some antibacterial, antiviral, and antitumor effects.

Antiviral Drugs

• Nucleoside Analogs:

  • Acyclovir, Ribavirin: Inhibit nucleic acid biosynthesis, often used in viral infections.

• Inhibit Viral Escape:

  • Neuraminidase inhibitors: Prevents release of virus from infected cells; examples include Tamiflu (Oseltamivir) and Relenza (Zanamivir).

• HIV Drugs:

  • Reverse Transcriptase Inhibitors (AZT - Azidothymidine): Inhibit HIV reverse transcriptase, preventing viral replication.

  • Protease Inhibitors: Interfere with the protease enzyme required for viral maturation.

  • Integrase Inhibitors: Inhibit the integration of viral DNA into the host genome.

  • Fusion Inhibitors and Entry Inhibitors: Block the entry of HIV into host cells, preventing infection.