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

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

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

b. mammalian cells do not take up sulfonamide drugs.

c. mammalian cells require preformed folic acid.

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

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

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.


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

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

a. inhibits carbonic anhydrase.

b. is an acid.

c. inhibits folic acid excretion.

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

e. causes an accumulation of dihydropteroic acid.

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

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

a. is accumulated in bacterial cells.

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

c. destroys bacterial cell walls.

d. inhibits the incorporation of PABA into dihydropteroic acid.

e. inhibits bacterial protein synthesis.

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.

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

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