Question
A 48-year-old man with HIV infection comes to the physician because of a 1-week history of severe retrosternal pain while swallowing. He has not been compliant with his antiretroviral drug regimen. His CD4+ T-lymphocyte count is 98/mm3. Endoscopy shows white plaques in the esophagus. The most appropriate immediate treatment is a drug that inhibits which of the following enzymes?
| A. |
DNA polymerase
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| B. |
Hydrogen-potassium ATPase
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| C. |
Phospholipase A2
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| D. |
Cytochrome p450 enzymes
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Show Answer
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Correct Answer � D
Explanation
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|
Ans-D-Cytochrome p450 enzymes
DNA polymerase
Inhibition of DNA polymerase is the mechanism of action of certain antiviral medications (e.g., ganciclovir and acyclovir) and antifungal medications (e.g., flucytosine). Ganciclovir and acyclovir are used to treat infections caused by herpes simplex virus (HSV) and cytomegalovirus (CMV). Although immunocompromised patients with decreased CD4+ counts are at increased risk of viral infection, viral esophagitis caused by CMV manifests with linear ulcers and esophagitis caused by HSV with circumscribed ulcers in the distal esophagus, in contrast to this patient’s white plaques. Flucytosine can be used to treat systemic fungal infections (e.g., disseminated candidiasis) when combined with amphotericin B and is particularly useful for the treatment of cryptococcal meningitis. It would not effectively treat esophageal candidiasis.
Hydrogen-potassium ATPase
Inhibition of H+/K+ ATPase, which decreases gastric acid production, is the mechanism of action of PPIs. PPIs are the first-line treatment for gastroesophageal reflux disease (GERD), which manifests with retrosternal pain, odynophagia, and dysphagia, which are seen in this patient. However, GERD would not explain his white plaques, and PPIs play no role in the treatment of esophageal candidiasis.
Phospholipase A2
Inhibition of phospholipase A2, an enzyme in the arachidonic acid synthesis pathway that leads to the formation of eicosanoids, is the mechanism of action of glucocorticoids. Glucocorticoids are prescribed for a variety of conditions, including hypersensitivity reactions, autoimmune conditions, and adrenal insufficiency. Because of their immunosuppressive effects, glucocorticoids are contraindicated in this patient; they would exacerbate his esophageal candidiasis and predispose him to further infections.
Cytochrome p450 enzymes
Fluconazole is one of the first-line treatments for candida esophagitis. Fluconazole inhibits the yeast cytochrome p450 enzyme 14a-demethylase, which prevents ergosterol synthesis and therefore decreases cell membrane integrity, leading to cell destruction. It is also indicated for the treatment of systemic candidiasis, cryptococcal meningitis, and antifungal prophylaxis.
