Quinolone & Antifolate Antimicrobials | Chapter 40 – Brenner & Stevens’ Pharmacology (6th)

Описание: This chapter explores a diverse range of antimicrobial pharmacotherapy, focusing on agents that disrupt essential bacterial processes such as folate metabolism, DNA stability, and cell membrane integrity. It begins by examining antifolate medications, specifically sulfonamides and trimethoprim, which execute a sequential blockade of the folic acid synthesis pathway. Sulfonamides act as structural mimics of para-aminobenzoic acid to prevent the formation of dihydropteroate, while trimethoprim targets dihydrofolate reductase to stop the production of tetrahydrofolate. When combined as trimethoprim-sulfamethoxazole, these drugs provide synergistic bactericidal activity against common pathogens causing urinary tract and respiratory infections. The discussion transitions to fluoroquinolones, a potent class of bactericidal drugs that impair bacterial DNA topology by inhibiting enzymes like DNA gyrase and topoisomerase IV, effectively halting replication and transcription. While highly effective for serious infections like anthrax or community-acquired pneumonia, these agents carry significant risks, including tendon damage and peripheral neuropathy. The text also covers specialized antibiotics like nitrofurantoin for bladder infections, daptomycin for resistant gram-positive strains like MRSA, and polymyxin B for topical applications. Additionally, it highlights non-absorbed agents like rifaximin, which is used to manage travelers' diarrhea and hepatic encephalopathy, and fidaxomicin, a macrolide specifically indicated for treating gastrointestinal distress caused by Clostridioides difficile. Clinical considerations, such as the management of adverse reactions like crystalluria or hypersensitivity syndromes, and the impact of bacterial resistance through efflux pumps or enzyme mutations, are also explored to provide a comprehensive guide for therapeutic decision-making.


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