Antimicrobial Drugs

• Antimicrobial drugs treat infections caused by microorganisms like bacteria, fungi, viruses, and parasites.
• These drugs either kill microorganisms (bactericidal, fungicidal, virucidal, parasiticidal) or inhibit their growth (bacteriostatic, fungistatic).

Antibacterial Drugs

• Antibacterial drugs target bacteria to treat bacterial infections.
• Broad-spectrum antibacterial drugs are effective against a wide range of bacteria.
• Narrow-spectrum antibacterial drugs are effective against specific types of bacteria.
• Common mechanisms of action include inhibition of:
  • Cell wall synthesis
  • Protein synthesis
  • Nucleic acid synthesis
  • Disruption of cell membrane function
  • Metabolic pathways

Antifungal Drugs

• Antifungal drugs target fungi and treat fungal infections.
• Fungal infections can be localized, such as athlete's foot, or systemic, such as aspergillosis.
• Common mechanisms of action include:
  • Disruption of cell membrane synthesis via azoles and polyenes
  • Inhibition of cell wall synthesis via echinocandins
  • Inhibition of nucleic acid synthesis via flucytosine

Antiviral Drugs

• Antiviral drugs target viruses to treat viral infections.
• Viruses replicate inside host cells, making them difficult to target without harming the host.
• Common mechanisms of action include:
  • Inhibition of viral entry into host cells
  • Inhibition of viral replication
  • Inhibition of viral assembly and release

Antiparasitic Drugs

• Antiparasitic drugs target parasites to treat parasitic infections.
• Parasitic infections can be caused by protozoa (e.g., malaria, giardiasis) or helminths (e.g., roundworms, tapeworms).
• Common mechanisms of action include:
  • Interference with parasite metabolism
  • Inhibition of parasite neuromuscular function
  • Disruption of parasite cell structure

Antibacterial Drugs: Mechanism of Action

• Inhibition of Cell Wall Synthesis:

  • Beta-Lactams (e.g., Penicillins, Cephalosporins, Carbapenems, Monobactams) inhibit peptidoglycan synthesis by binding to penicillin-binding proteins (PBPs), leading to cell wall weakening and lysis.
  • Glycopeptides (e.g., Vancomycin) bind to the D-alanyl-D-alanine terminus of peptidoglycan precursors, preventing incorporation into the cell wall.
  • Cycloserine inhibits enzymes involved in the synthesis of D-alanine, a component of peptidoglycan.

• Inhibition of Protein Synthesis:

  • Aminoglycosides (e.g., Gentamicin, Tobramycin) bind to the 30S ribosomal subunit, causing misreading of mRNA and premature termination of protein synthesis.
  • Tetracyclines bind to the 30S ribosomal subunit, preventing the binding of aminoacyl-tRNA to the A site.
  • Macrolides (e.g., Erythromycin, Azithromycin) bind to the 23S rRNA of the 50S ribosomal subunit, blocking the translocation step of protein synthesis.
  • Lincosamides (e.g., Clindamycin) bind to the 23S rRNA of the 50S ribosomal subunit, inhibiting peptide bond formation.
  • Oxazolidinones (e.g., Linezolid) bind to the 23S rRNA of the 50S ribosomal subunit, preventing the formation of the initiation complex.
  • Streptogramins (e.g., Quinupristin/Dalfopristin) bind to the 23S rRNA of the 50S ribosomal subunit, synergistically inhibiting protein synthesis.

• Inhibition of Nucleic Acid Synthesis:

  • Quinolones (e.g., Ciprofloxacin, Levofloxacin) inhibit bacterial DNA gyrase and topoisomerase IV, preventing DNA replication and repair.
  • Rifamycins (e.g., Rifampin) inhibit bacterial RNA polymerase, blocking RNA synthesis.
  • Metronidazole forms cytotoxic products that disrupt bacterial DNA.

• Disruption of Cell Membrane Function:

  • Polymyxins (e.g., Polymyxin B, Colistin) interact with bacterial lipopolysaccharide (LPS) and phospholipids, disrupting cell membrane integrity.

• Inhibition of Metabolic Pathways:

  • Sulfonamides inhibit dihydropteroate synthetase, an enzyme involved in folic acid synthesis.
  • Trimethoprim inhibits dihydrofolate reductase, another enzyme involved in folic acid synthesis.

Antifungal Drugs: Mechanism of Action

• Disruption of Cell Membrane Synthesis:

  • Azoles (e.g., Fluconazole, Itraconazole, Voriconazole) inhibit fungal cytochrome P450 enzymes, blocking the synthesis of ergosterol, a crucial component of the fungal cell membrane.
  • Polyenes (e.g., Amphotericin B, Nystatin) bind to ergosterol in the fungal cell membrane, forming pores that disrupt membrane integrity.

• Inhibition of Cell Wall Synthesis:

  • Echinocandins (e.g., Caspofungin, Micafungin) inhibit the synthesis of beta-1,3-glucan, a major component of the fungal cell wall.

• Inhibition of Nucleic Acid Synthesis:

  • Flucytosine is converted to 5-fluorouracil in fungal cells, inhibiting DNA and RNA synthesis.

Antiviral Drugs: Mechanism of Action

• Inhibition of Viral Entry:

  • Fusion Inhibitors (e.g., Enfuvirtide) bind to the viral envelope protein gp41, preventing fusion of the viral membrane with the host cell membrane.
  • CCR5 Antagonists (e.g., Maraviroc) block the CCR5 receptor on host cells, preventing HIV from entering cells.

• Inhibition of Viral Replication:

  • Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs/NtRTIs) (e.g., Zidovudine, Tenofovir) inhibit reverse transcriptase. This enzyme is essential for HIV replication; NRTIs/NtRTIs act as chain terminators.
  • Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) (e.g., Efavirenz, Nevirapine) bind directly to reverse transcriptase, inhibiting its activity.
  • Protease Inhibitors (PIs) (e.g., Ritonavir, Lopinavir) inhibit viral protease, needed for cleavage of viral proteins into their functional forms.
  • Integrase Inhibitors (e.g., Raltegravir, Dolutegravir) inhibit viral integrase, the enzyme that integrates viral DNA into the host cell genome.

• Inhibition of Viral Assembly and Release:

  • Neuraminidase Inhibitors (e.g., Oseltamivir, Zanamivir) inhibit neuraminidase, which facilitates the release of new viral particles from infected cells.

Antiparasitic Drugs: Mechanism of Action

• Interference with Parasite Metabolism:

  • Antimalarials (e.g., Chloroquine, Quinine, Artemisinins) interfere with various stages of the malaria parasite's life cycle, such as heme detoxification (chloroquine, quinine) or targeting parasite proteins (artemisinins).
  • Benzimidazoles (e.g., Mebendazole, Albendazole) inhibit microtubule polymerization, disrupting parasite cell structure and function.

• Inhibition of Parasite Neuromuscular Function:

  • Pyrantel Pamoate acts as a depolarizing neuromuscular blocking agent, causing paralysis of worms.
  • Ivermectin binds to glutamate-gated chloride channels in invertebrate nerve and muscle cells, causing hyperpolarization and paralysis.

• Disruption of Parasite Cell Structure:

  • Metronidazole is effective against protozoa and forms cytotoxic products that disrupt parasite DNA.

Antibiotic Resistance

• Antibiotic resistance is a major global health threat, arising when bacteria evolve mechanisms to survive exposure to antibiotics.

• Mechanisms of resistance include:

  • Enzymatic inactivation of the antibiotic (e.g., beta-lactamases)
  • Modification of the antibiotic target (e.g., mutations in PBPs)
  • Decreased uptake of the antibiotic (e.g., altered porins)
  • Increased efflux of the antibiotic (e.g., efflux pumps)
  • Development of alternative metabolic pathways

• Strategies to combat antibiotic resistance include:

  • Prudent use of antibiotics
  • Development of new antibiotics
  • Use of combination therapy
  • Improved infection control practices
  • Development of vaccines