Acyclovir, Ganciclovir

[seminoma]

Couldn't find the thread, but I remember a huge discussion about mutations in viral thymidine kinase vs lack of viral thymidine kinase. I was happy to just go with what's in FA14 (acyclovir==mutation, ganciclovir==either), but Lange Pharmcards says acyclovir resistance due to lack of thymidine kinase. I didn't think this was a big deal until reading that thread sometime last year.. Was there ever any resolution? I remember @Phloston having a pretty good explanation.

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[Transposony]

http://forums.studentdoctor.net/threads/mircro-question.951610/

http://forums.studentdoctor.net/threads/acyclovir-and-ganciclovir.1072533/

 

[Transposony]

Couldn't find the thread, but I remember a huge discussion about mutations in viral thymidine kinase vs lack of viral thymidine kinase. I was happy to just go with what's in FA14 (acyclovir==mutation, ganciclovir==either), but Lange Pharmcards says acyclovir resistance due to lack of thymidine kinase. I didn't think this was a big deal until reading that thread sometime last year.. Was there ever any resolution? I remember @Phloston having a pretty good explanation.

Be careful.
FA 2014 says "Mutated CMV DNA polymerase or lack of viral kinase" for Ganciclovir MOR.
For Acyclovir, famciclovir & valacyclovir MOR FA 2014 says "Mutated viral thymidine kinase"

I may be wrong but think this issue was addressed by Phloston himself (being the author of Micro section in FA 2014).
Maybe Phloston can chime in himself.

 

[Transposony]

According to Goodman Gilman's:

Acyclovir resistance in HSV has been linked to one of three mechanisms: impaired production of viral thymidine kinase, altered thymidine kinase substrate specificity (e.g., phosphorylation of thymidine but not acyclovir), or altered viral DNA polymerase.
The most common resistance mechanism in clinical HSV isolates is absent or deficient viral thymidine kinase activity; viral DNA polymerase mutants are rare.
Acyclovir resistance in VZV isolates is caused by mutations in VZV thymidine kinase and less often by mutations in viral DNA polymerase.

CMV can become resistant to ganciclovir by one of two mechanisms: reduced intracellular ganciclovir phosphorylation owing to mutations in the viral phosphotransferase encoded by the UL97 gene and mutations in viral DNA polymerase.
Resistance has been associated primarily with impaired phosphorylation but sometimes only with DNA polymerase mutations.

 

[Phloston]

From UpToDate:

"MECHANISM OF RESISTANCE — The mechanisms of resistance to valacyclovir are identical to those described for acyclovir. Three mechanisms have been shown to endow herpes simplex viruses with resistance to acyclovir, a phenomenon rare in the immunocompetent host [5]:

●Reduced or absent thymidine kinase

●Altered thymidine kinase activity resulting in decreased acyclovir phosphorylation

●Altered viral DNA polymerase with decreased affinity for acyclovir triphosphate"

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I've just started as an editor for USMLE Rx QBank. Any preexisting question that specifies one mechanism over the other can't necessarily be justified because in reality there are multiple mechanisms, and it doesn't make a difference in terms of alternative therapy which one had occurred.

When I had said in my slides that I had seen both mechanisms as answers to the same question and "lack of" was correct over "altered," as I just said above now, this can no longer be justified. In terms of the real deal, they would not require you to make this distinction, however "lack of" is most certainly an answer they would assess for. That doesn't make "altered" wrong, but the USMLE still assesses "lack of."

 

[seminoma]

Did not know Phloston was the writer of FA14 Micro