Antimicrobials for GIT 2 Infections: Antibacterials

Antimicrobials for GIT Infections: Antibacterials

• Learning Outcomes: Identify antibacterial drugs for gastrointestinal tract infections, describe mechanisms of action for fluoroquinolones (e.g., ciprofloxacin) and glycopeptides (e.g., vancomycin), understand pharmacokinetic considerations for both, and describe adverse effects and contraindications.

Fluoroquinolones: Mechanism of Action

• Fluoroquinolones inhibit type II and type IV topoisomerases, crucial enzymes in DNA replication.
• They interfere with DNA gyrase, preventing the unwinding and rejoining of DNA strands during replication.
• This disruption leads to DNA damage and ultimately cell death.

Fluoroquinolones: Pharmacokinetic Considerations

• Fluoroquinolones have high bioavailability (80-95%).
• Absorption is impaired by antacids and dairy products (e.g., Ca2+, Mg2+).
• Excretion is primarily renal, through tubular and glomerular pathways.
• Dosage adjustments are necessary in patients with renal impairment.

Fluoroquinolones: Adverse Effects & Contraindications

• Potential adverse effects include dizziness, faintness, hypersensitivity, peripheral neuropathy, and increased seizure risk.
• Avoid use in individuals with myasthenia gravis due to potential for worsened muscle weakness.
• Tendon damage, including Achilles tendon rupture, is a possible adverse effect.
• Interactions exist; ciprofloxacin inhibits CYP1A2, potentially increasing theophylline levels and narrowing its therapeutic window.

Glycopeptides: Mechanism of Action

• Glycopeptides, like vancomycin, inhibit cell wall synthesis in bacteria.
• They bind to the D-alanyl-D-alanine terminal portion of the peptide chain, blocking the formation of crosslinks crucial for cell wall integrity.
• This prevents cell wall synthesis and leads to bacterial death.

Glycopeptides: Pharmacokinetic Considerations

• Vancomycin has poor absorption.
• Absorption can be enhanced in inflammatory GI conditions.
• Renal excretion (glomerular) is the primary pathway if absorbed.
• Accumulation occurs in renal impairment.

Glycopeptides: Adverse Effects & Contraindications

• Vancomycin can cause gastrointestinal disturbances and hypersensitivity reactions.
• Nephrotoxicity and ototoxicity (dizziness, vertigo, tinnitus) are potential adverse effects, especially when combined with other nephro- or ototoxic drugs.
• Infusion reactions ("red man syndrome," histamine release) can occur.
• Dose adjustments in renal impairment are crucial.