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25 Cards in this Set
- Front
- Back
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Nucleic Acid Synthesis Inhibitors
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Sulfonamides, Trimethoprim, Quinolones, Fluoroquinolones
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Sulfonamides
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Rarely used as single agents, but combo of SMZ/TMP is often used (Bactrim)
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General Mechanism of Sulfonamides
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This class disrupts Folic Acid synthesis pathway in bacteria >> shows selective toxicity b/c bacteria must synthesize it but mammals can get from their diet.
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FA anatomy
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Pteridine moiety + PABA + glutamate
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sulfonamide structure
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structural analog and competitive antagonist of PABA
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Where Sulfonamide acts
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Compete w/ PABA to bind pteridine, thus Inhibiting pteroate synthase
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Trimethoprim
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structural analog of dihydrofolate; used in combo but never alone.
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TMP specific mechanism
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Inhibits DHFR, much more active in bact than mammal.
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Uses of SMZ/TMP
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Broad spectrum (+/-), uncomplicated UTIs, Pneumonia due to Pneumocystis jirivecii in AIDS pt, Shigella, respiratory infections like Haemophilus, Strep pneumo.
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pharmacokinetics of SMZ/TMP
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2 drugs have similar pharmacokinetic profiles; can be oral or topical
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Sulfonamide major toxicities
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hematopoetic disorders, hypersensitivity - skin rashes, Kernicterus
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Kernicterus
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displaced protein-bound bilirubin is deposited in basal ganglia of newborns >> irreversible neurological damage
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SMZ/TMP other toxicities
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Megaloblastosis, leukopenia, and thrombocytopenia in patients with folic acid deficiency; Rash, fever, hepatitis in AIDS pts
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Sulfonamide drug interactions
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potentiates effects of warfarin by interfering w/ P450 metabolism
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Sulfonamide mechanisms of resistance
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Changes to Dihydropteroate Synthase, with less affinity for drug (#1). Increased uptake of PABA, decreased drug uptake
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SMZ/TMP resistance
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overproduction of DHFR, altered DHFR w/ less affinity for TMP
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Quinolones/Fluoroquinolones mechanism
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inhibit DNA gyrase, which relieves positive supercoiling >> leads to cell death. Inhibit bacterial enzyme at lower level than mammalian, so show selective toxicities. Also inhibit Topoisomerase IV
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Quinolones
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rarely used
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Fluoroquinolones
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Include Ciprofoxacin, Ofloxacin, Levofloxacin. Oral, broad-spectrum AB
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FQ uses
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UTI, enteritis, Vibrio cholera, Respiratory/bone/soft tissue infections
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FQ major toxicities
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nausea, GI distress, CNS effects, damages growing cartilage (not for pt <18 or pregnant women)
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Drug interactions
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inhibits degradation of theophylline (asthma) and caffeine (heavy coffee drinkers) >> seizures
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Resistance mechanisms
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changes in DNA gyrase and Topo IV that decrease affinity for drug
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Nalidixic Acid
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older quinolone that can treat UTI
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Nitrofurantoin
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older UTI drug; prodrug that is reduced by bacterial enzymes and can destroy DNA. Should not be combined w/ Nalidixic Acid - antagonists
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