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NBME 20 Answers

nbme20/Block 1/Question#7 (reveal difficulty score)
A 5-year-old girl with AIDS develops a ...
Thymidine kinase ๐Ÿ” / ๐Ÿ“บ / ๐ŸŒณ / ๐Ÿ“–
tags: pharm repeat

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 +19  upvote downvote
submitted by โˆ—hayayah(1212)
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Acyclovir, famciclovir, valacyclovir are guanosine analogs. They undergo conversion to acyclovir monophosphate via virus encoded thymidine-kinase. Ultimately, they inhibit viral DNA polymerase by chain termination.

Mutated viral thymidine kinase can cause resistance.

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len49  Foscarnet and Cidofovir on the other hand do not require phosphorylation by viral kinase, therefore should be used in strains that are shown to be resistant. +6
l0ud_minority  This also depends on the source lecturio has a lecture on Anti-Herpes Agents: Thymidine Kinase Agents โ€“ Antiviral Drugs by Pravin Shukle, MD and it states that resistant mutations can occur in Thymidine Kinase or DNA polymerase. AMBOSS states Mechanism of antiviral resistance is mutation in viral Thymidine Kinase I hate when sources contradict each other. +
abhishek021196  I think it is a mutation in HOST thymidine kinase acc. to Sketchy - that's why she is not susceptible to antivirals that require phosphorylation in host cell in order to be activated. +1



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submitted by andremosq(9)
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this question is asking about mechanism of resistance of Acyclovir, famciclovir, valacyclovir. They are Monophosphorylated by HSV/VZV thymidine kinase. Clinical use: HSV and VZV. Mechanism of resistance: Mutated viral thymidine kinase

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 -2  upvote downvote
submitted by nafilnaf(1)
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What does she have? My assumption was that she was getting NRTIs for HIV/AIDS which get phosphorylated by HOST thymidine kinases and the mechanism for viral resistance is mutations in reverse transcriptase

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azibird  I think she has chickenpox, caused by varicella-zoster virus. From FA 2020 p 183: "Vesicular rash begins on trunk; spreads to face D and extremities with lesions of different stages" +4



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