Anti-Herpes Agents: Thymidine Kinase Agents – Antiviral Drugs

Let's move on in our discussion on antiviral agents. Let's focus now on those agents that are active against herpes. Specially let's focus on what we call "Thymidine Kinase Agents." Now these agents are important in the nucleic acid synthesis, portion of antiviral therapy. These thymidine kinase dependent agents include a acyclcovir and ganciclovir. They are active against HSV-1 and HSV-2 as well as varicella zoster. They have a very short half life and they are often administered three to five times a day. Now they are renally excreted as well. So we do adjust the dose in renal failure. Let's have a look where they work on our slide here. Now as we're going through the production of DNA, we have several steps. Now the host kinases are acted upon acyclcovir, and ganciclovir to prevent the diphosphate form of these agents from being produced. There are competitive substrates for DNA polymerase. And they lead to chain termination after incorporation into the DNA. Because they are defective agents, because they cause a defect in the actual DNA, you are unable to continue production of the DNA chain itself. That's why we call it chain termination. Now valacyclovir or Valtrex is a prodrug of acyclovir. So you can see here that I've pasted it in a little pink box above acyclcovir and ganciclovir. Now valacyclovir is able to achieve three to five times greater concentration levels and it also lasts lot longer. So for the most part it's replaced acyclovir as a means of therapy for certain types of disease. Pencyclovir actually works at the level of the DNA polymerase. So it doesn't cause chain termination. But what it does is it inhibits the production of DNA. Now famciclovir is converted to pencicyclovir by the liver. So once again I've put...