Write the general mechanism of action of antimicrobial drugs. Discuss the mechanism of action and adverse reactions of penicillins.

General Mechanisms of Action of Antimicrobial Drugs

Antimicrobial drugs exert their effects by targeting essential processes within microbial cells. These targets can be broadly categorized as follows:

• Inhibition of Cell Wall Synthesis: Drugs like penicillins, cephalosporins, and vancomycin interfere with the synthesis of peptidoglycan, a crucial component of bacterial cell walls. This leads to cell lysis due to osmotic pressure.
• Inhibition of Protein Synthesis: Antibiotics such as tetracyclines, aminoglycosides, macrolides, and chloramphenicol bind to bacterial ribosomes (30S or 50S subunits), disrupting protein synthesis.
• Inhibition of Nucleic Acid Synthesis: Drugs like quinolones (e.g., ciprofloxacin) inhibit DNA gyrase, an enzyme essential for DNA replication. Rifampicin inhibits RNA polymerase, blocking RNA synthesis.
• Inhibition of Metabolic Pathways: Sulfonamides and trimethoprim interfere with folic acid synthesis, a vital pathway for nucleotide production.
• Disruption of Cell Membrane: Polymyxins interact with the bacterial cell membrane, increasing its permeability and causing leakage of cellular contents.

Penicillins: Mechanism of Action

Penicillins belong to the beta-lactam antibiotic family. Their mechanism of action revolves around inhibiting bacterial cell wall synthesis.

Detailed Mechanism

Penicillins contain a beta-lactam ring, which is structurally similar to D-alanyl-D-alanine, a component of peptidoglycan precursors. Penicillins bind to penicillin-binding proteins (PBPs) located on the bacterial cell membrane. PBPs are enzymes responsible for cross-linking peptidoglycan chains, providing structural integrity to the cell wall. By binding to PBPs, penicillins prevent cross-linking, weakening the cell wall. This leads to cell lysis, particularly in actively growing bacteria.

Different penicillins exhibit varying affinities for different PBPs, influencing their spectrum of activity. For example, methicillin has a high affinity for PBP2a in Staphylococcus aureus, conferring resistance to beta-lactamase enzymes.

Adverse Reactions of Penicillins

Penicillin adverse reactions can range from mild to severe. They are broadly categorized as follows:

• Hypersensitivity Reactions: These are the most common adverse reactions.
  • Mild: Skin rashes, urticaria (hives), pruritus (itching).
  • Moderate: Angioedema (swelling of the face, lips, tongue), fever.
  • Severe: Anaphylaxis – a life-threatening allergic reaction characterized by bronchospasm, hypotension, and shock.
• Gastrointestinal Disturbances: Nausea, vomiting, diarrhea, and abdominal pain are common, often due to alterations in gut microbiota.
• Hematologic Effects: Rarely, penicillins can cause leukopenia (low white blood cell count), thrombocytopenia (low platelet count), or hemolytic anemia.
• Nephrotoxicity: High doses of some penicillins can cause interstitial nephritis, leading to kidney damage.
• Neurotoxicity: In patients with renal failure, penicillin accumulation can lead to seizures.
• Superinfection: Prolonged penicillin use can disrupt the normal flora, leading to overgrowth of opportunistic pathogens like Clostridium difficile, causing pseudomembranous colitis.

Penicillin Type	Spectrum of Activity	Key Adverse Effects
Penicillin G	Streptococci, pneumococci, syphilis	Hypersensitivity, GI upset
Ampicillin	Gram-positive & some Gram-negative bacteria	Hypersensitivity, GI upset, C. difficile infection
Methicillin	Staphylococcus aureus (methicillin-sensitive strains)	Hypersensitivity, interstitial nephritis