2010-10-04_ Matthews_3[1] - Inhibitors of DNA and RNA...

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Inhibitors of DNA and RNA Synthesis Direct and Indirect Inhibition Antifungals and Antimicrobials
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Nucleic acid replication Uncoiling of the helix Strand separation by breaking the hydrogen bonds between the complementary strands Unwinding enzymes called DNA helicases Parent DNA strands unwind and separate from one another Topoisomerases produce breaks in the DNA and then rejoin them in order to relieve the stress in the helical molecule during replication ( topoisomerase II = DNA gyrase) Topoisomerase IV – responsible for decatenation of linked daughter DNA molecules DNA and RNA polymerases
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Nucleic acid replication
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Anti-Fungals Griseolfulvin Inhibits mitosis Systemic treatment of dermatophyte infections from Micosporum, Trichophyton unresponsive to topical treatment 5-Fluorocytosine (5-FC) Interferes with DNA synthesis via 5-Fluro derivative that inhibits thymidylate synthetase Cutaneous and mucocutaneous candidiasis and Candida UTI combine with amphotericin B for cryptococcal meningitis Total daily dose of 50-150mg/kg given over 4 doses Absorbed well orally and 90% excreted unchanged in urine, remaining in feces High incidence of adverse reactions: thrombocytopenia, agranulocytosis and aplastic anemia, nausea, vomiting
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