A 29-year-old woman comes to the office with malaise, fever, and extremely painful genital lesions. She has never had such symptoms before. She is sexually active with a new partner. On examination, the patient has several tiny, thin-walled vesicles on an erythematous base and exquisitely tender, shallow ulcers on the labia. Tender inguinal lymphadenopathy is present. Tzanck smear of the genital lesions shows multinucleated giant cells. A drug is prescribed that can be used to manage this acute episode and prevent future episodes of this patient's condition. This drug most likely works by which of the following mechanisms?

Question

A 29-year-old woman comes to the office with malaise, fever, and extremely painful genital lesions.  She has never had such symptoms before.  She is sexually active with a new partner.  On examination, the patient has several tiny, thin-walled vesicles on an erythematous base and exquisitely tender, shallow ulcers on the labia.  Tender inguinal lymphadenopathy is present.  Tzanck smear of the genital lesions shows multinucleated giant cells.  A drug is prescribed that can be used to manage this acute episode and prevent future episodes of this patient's condition.  This drug most likely works by which of the following mechanisms?

Quizplus · Accepted Answer

11ec160b_3bee_0a6b_9249_c9de8fd2450e_MD0001_00 This patient's new genital rash and positive Tzanck smear are consistent with a primary genital herpes simplex virus (HSV) infection, likely due to HSV-2. Antiviral drugs for the treatment of primary genital herpes include acyclovir, valacyclovir (acyclovir prodrug with better oral bioavailability), and famciclovir. Acyclovir treatment during a primary episode can reduce duration of viral shedding, time to lesional healing, constitutional symptoms, and local pain. Chronic daily suppressive therapy (lower dose) can be used in patients who have recurrent episodes. In infected host cells, acyclovir (a nucleoside analog) is converted into acyclovir monophosphate principally via virus-encoded thymidine kinase. Cellular enzymes then convert the monophosphate into acyclovir triphosphate, which competes with deoxyguanosine triphosphate for viral DNA polymerase. When acyclovir triphosphate becomes incorporated into the replicating viral DNA chain, viral DNA synthesis is terminated. Acyclovir does not significantly impact uninfected cells in vitro as uptake into these cells is poor, phosphorylation in the absence of viral thymidine kinase is minimal, and cellular α-DNA polymerase has significantly less affinity for acyclovir triphosphate than does viral DNA polymerase. (Choice B) Inhibition of viral protease activity is the mechanism of action for drugs such as indinavir, an antiretroviral used in HIV treatment. (Choice C) Prevention of virion release from infected cells is the mechanism of action for drugs such as neuraminidase inhibitors (eg, oseltamivir), which are used in the early treatment of influenza. (Choice D) Drugs such as enfuvirtide and maraviroc, antiretrovirals used in HIV treatment, prevent viral entry into the target cells. Docosanol, a topical agent that prevents viral entry, is sometimes used for herpes labialis, not genital HSV. (Choice E) Upregulation of interferon synthesis in infected cells is accomplished by many interleukins. Educational objective: Antiviral drugs currently recommended for the treatment of primary genital herpes include the nucleoside analogs (eg, acyclovir). These are incorporated into newly replicating viral DNA and ultimately terminate viral DNA chain synthesis.

A 29-Year-Old Woman Comes to the Office with Malaise, Fever