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Chapter 38: Sulfonamides, Trimethoprim-Sulfamethoxazole, Quinolones, and Agents for Urinary Tract Infections

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Sulfonamide drugs are selective for sensitive bacteria as compared to mammalian cells because

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a. mammalian cells have the ability to extrude sulfonamide drugs.

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b. mammalian cells do not take up sulfonamide drugs.

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c. mammalian cells require preformed folic acid.

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d. bacterial cells accumulate sulfonamide drugs more than mammalian cells.

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e. sulfonamide drugs interfere with the synthesis of vitamin B12 in bacterial cells but not mammalian cells.

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Answer is c. In sensitive bacteria, sulfonamide drugs inhibit the enzyme responsible for the incorporation of PABA into dihydropteroic acid, the immediate precursor of folic acid (see Figure 38-2). Mammalian cells require preformed folic acid, cannot synthesize it, and are insensitive to drugs that act by inhibiting the synthesis of folic acid.

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Figure 38-2. Steps in folate metabolism blocked by sulfonamides and trimethoprim. PABA, para-amino benzoic acid

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Mafenide is a sulfonamide drug that is used topically in burn patients. If the burn area is extensive and mafenide is sufficiently absorbed, a metabolic acidosis may occur because the mafenide

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a. inhibits carbonic anhydrase.

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b. is an acid.

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c. inhibits folic acid excretion.

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d. depresses respiration and causes the accumulation of carbon dioxide.

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e. causes an accumulation of dihydropteroic acid.

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Answer is a. Mafenide and its metabolite inhibit carbonic anhydrase, and the urine becomes alkaline. Metabolic acidosis with compensatory tachypnea and hyperventilation may ensue.

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In the combination drug trimethoprim-sulfamethoxazole, the trimethoprim moiety is selective for bacterial cells compared to mammalian cells because the trimethoprim

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a. is accumulated in bacterial cells.

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b. is a selective inhibitor of dihydrofolate reductase in lower organisms.

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c. destroys bacterial cell walls.

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d. inhibits the incorporation of PABA into dihydropteroic acid.

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e. inhibits bacterial protein synthesis.

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Answer is b. Trimethoprim is a highly selective inhibitor of dihydrolate reductase in bacteria; approximately 100,000 times more drug is required to inhibit human reductase than the bacterial enzyme. This relative selectivity is vital because this enzymatic function is essential to all species.

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A 23-year-old pregnant woman presents with the signs and symptoms ...

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