Anti-Herpes Agents: RNA Polymerase Inhibitors and Other Drugs – Antiviral Drugs

by Pravin Shukle, MD

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    00:00 Let's move on to RNA polymerase agents and other agents.

    00:05 Once again we're talking about nucleic acid synthesis.

    00:09 But now we're talking about RNA as oppose to DNA.

    00:13 Foscarnet that is probably the best known in this drug.

    00:18 It does not require phosphorylation for activity.

    00:21 It is not an antimetabolite.

    00:24 Now it inhibits both DNA and RNA polymerase.

    00:28 And it also inhibits HIV reverse transcriptase.

    00:32 So it's kind of a convenient drug to use for multiple situations.

    00:37 It inhibits DNA polymerase in acyclovir resistant strains that are also thymidine kinase deficient.

    00:43 So it's quite a useful drug in that regard.

    00:46 Adverse events are quite severe.

    00:48 So nephrotoxicity, up to one-third of patients can develop nephrotoxicity with this agent.

    00:55 So we tend to be very careful in monitoring renal function in people who are on this drug.

    01:00 Gastro, sorry, genitourinary ulceration can also occur in patients who are on foscarnet as well.

    01:08 So we keep an eye out for that too.

    01:10 In terms of neurological side effects patients often complain of headache.

    01:15 I see that all the time in patients that I co-manage with our HIV specialist who are hepatitis specialists.

    01:22 We also see hallucination and seizures with this agent on rare occasion.

    01:30 Let's move on to the other drugs.

    01:32 These are drugs that don't really fit in other categories.

    01:34 Vidarabine is an adenine analog.

    01:37 It has very good activity against systemic infections, HSV,VZV and cytomegalovirus.

    01:45 It doesn't have any significant effect on genital lesions.

    01:49 It's more about a systemic infection treatment.

    01:52 The next agent that I want to talk about is fomivirsen.

    01:57 So this is an interesting drug.

    01:59 It's an anti-sense oligonucleotide.

    02:02 So to give you an idea of the size of this molecule, take a look at vidarabine in top right hand corner and then take a look at fomivirsen, you can see that it's a huge molecule.

    02:15 And that suspiciously looks like a DNA molecule.

    02:18 Except it's anti-sense, it's backwards.

    02:21 Now we use this agent intravitreally.

    02:24 So we actually put it into the eye for the treatment of CMV retinitis.

    02:28 The toxicity associated with this medication includes iritis, vitreitis and increased intraocular pressures from the physical presence of this agent inside the ocular chamber or the eye.

    02:43 Other agents are also used in herpes keratitis and that is usually used as a tropical treatment.

    02:49 So in terms of these agents that we're talking about, I just wanted to put this one slide.

    02:58 So that you can see in terms of those agents that are analogs of the different components of DNA or RNA, you can see where they all fit into the armamentarium.

    03:08 Remember that analogs of the different portions of DNA do have to be phosphorylated, where the agents don't have to be phosphorylated.

    About the Lecture

    The lecture Anti-Herpes Agents: RNA Polymerase Inhibitors and Other Drugs – Antiviral Drugs by Pravin Shukle, MD is from the course Antimicrobial Pharmacology.

    Included Quiz Questions

    1. Foscarnet
    2. Vidarabine
    3. Pencyclovir
    4. Ganciclovir
    5. Fomivirsen
    1. Fomivirsen
    2. Vidarabine
    3. Ganciclovir
    4. Acyclovir
    5. Foscarnet

    Author of lecture Anti-Herpes Agents: RNA Polymerase Inhibitors and Other Drugs – Antiviral Drugs

     Pravin Shukle, MD

    Pravin Shukle, MD

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