Anti-HIV Agents: Reverse Transcriptase Inhibitors (NNRTI) – Antiviral Drugs

by Pravin Shukle, MD

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    00:00 Let's move on to the Non-Nucleoside Reverse Transcriptase Inhibitors.

    00:06 So these are a little bit different from the NRTIs.

    00:10 They bind on a different site.

    00:12 They do no require phosphorylation to be activated.

    00:17 And there is no cross resistance with the nucleoside reverse transcriptase inhibitors.

    00:22 We have use these agents as monotherapy.

    00:25 But if we do use as monotherapy, resistance develops quite quickly.

    00:29 So we try not to if possible used it as monotherapy.

    00:33 Now monotherapy occurs through a mutation in the pol gene.

    00:38 So this is something that does show up on the exams.

    00:41 It's worthwhile remembering that the pol gene codes for a mutation that can cause a resistance to the non-nucleoside reverse transcriptase inhibitors.

    00:52 Now one of the first agents that I'm going to talk about more for alphabetical reasons than usage reasons is delavirdine.

    01:04 It's got a lot of drug interactions because it's metabolised through cytochrome, sorry cytochrome P450.

    01:12 The 3A4 and the 2D6 isoenzymes.

    01:16 So there's a lot of drug interactions that we have be concerned about.

    01:20 These include the azoles and macrolides which can increase their blood levels.

    01:25 And they can also be decreased by things like antacids, by ddI, by phenytonin, rifampin.

    01:31 So there's all kinds of agents that will reduce their dosages as low as well.

    01:36 The other thing that is concerning with this patient on this medication is that if they are also on warfarin, it will effect the INR values.

    01:44 Toxicity with this agent, you can get a skin rash and up to one-fifth of all patients.

    01:50 So it is a significant level of skin rash.

    01:53 And of course we can't use this agent in pregnancy.

    01:59 EFV can be given once a day.

    02:02 It's metabolized by cytochrome as well.

    02:04 So there are going to be some drug interactions too.

    02:08 In terms of toxicity and adverse events, neurologically, we'll see CNS dysfunction.

    02:13 So remember, headache, insomnia, fatigue.

    02:15 In terms of skin there is skin rash that can occur.

    02:19 Pregnancy it's teratogenic in the first trimester.

    02:22 But it has been used in second and third trimester patients on occasion.

    02:26 And in terms of the lipids, it increases the LDL cholesterol which is something that we need to be aware of.

    02:34 But from a practical point of view hasn't stopped us from using the medication.

    02:40 ETR is now the newest non-nucleoside reverse transcriptase inhibitors.

    02:45 It is a substrate and an inducer of cytochrome 3A4.

    02:50 It inhibits 2C9 and 2C19.

    02:53 The toxicity and adverse events include diarrhea, skin rash.

    02:58 And remember that it can be teratogenic in the first trimester.

    03:04 It will also increase the blood triglycerol and triglycerides.

    03:07 Sorry, it will increase the blood cholesterol and triglycerides.

    03:11 And it can increase serum transaminases.

    03:13 So we monitor these values on an on going basis.

    03:18 NVP is very commonly used in 3 drug regimens.

    03:22 Note that I've underlined this agent.

    03:24 I do want you to know this particular agent as well.

    03:27 It's effective in preventing vertical transmission.

    03:30 So this is important because we worry about mothers with HIV transmitting it to their children.

    03:36 So NVP can be used in this situation.

    03:40 That's one of the reasons why I want you to remember this drug.

    03:43 Because remembering this drug as part of a three drug regimen and part of vertical transmission prevention, we want to remember the toxicity and adverse events.

    03:53 So, in terms of skin and it can cause a skin rash in 15 to 20 percent of our patients.

    03:59 You can get a Stevens- Johnson syndrome which is a very severe necrolysis of the skin.

    04:05 And toxic epidermal necrolysis can occur as well on top of that.

    04:10 So be very aware that there is some serious skin disorders that can occur as a reaction to this medication.

    04:16 And remember that this is an effective agent in preventing vertical transmission.

    04:23 So there you have the list of the medications.

    04:26 And please not which ones I've underlined so that you can perhaps focus, you are studying onto those ones that are more likely to be for you to be tested on.

    04:36 And remember which of these agents, and just ask yourself right now, which of these agents is responsible or effective in vertical transmission reduction.

    About the Lecture

    The lecture Anti-HIV Agents: Reverse Transcriptase Inhibitors (NNRTI) – Antiviral Drugs by Pravin Shukle, MD is from the course Antimicrobial Pharmacology.

    Included Quiz Questions

    1. Nevirapine
    2. Etravirine
    3. Emtricitabine
    4. Delaviridine
    5. Efavirenz
    1. Skin
    2. Cardiovascular
    3. Lipids
    4. CNS
    5. Kidney
    1. Azoles.
    2. Antacids.
    3. Nelfinavir.
    4. Rifampin.
    5. Phenytoin.

    Author of lecture Anti-HIV Agents: Reverse Transcriptase Inhibitors (NNRTI) – Antiviral Drugs

     Pravin Shukle, MD

    Pravin Shukle, MD

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