Anti-Virals Flashcards

1
Q

What are Amantadine and Rimantadine? How do they work, and what are they used for now?

A
  • Anti-influenza agents against Influenza A only
  • Block the M2 channel, preventing lysosomal acidification and viral uncoating.
  • NOTHING, there is too much resistance.
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2
Q

What is the “nomenclature” for the 2009 swine flu pandemic?

A

Influenza A (H1N1)pdm09

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3
Q

What is the one way to prevent the flu?

A

Vaccination

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4
Q

What is the use and mechanism of action of Zanamivir (Relenza) and Oseltamivir (Tamiflu)? How are they administered and what are the relevant side effects?

A
  • Anti-influenza A and B agents that work by inhibiting neuraminidase, preventing viral spread.
  • Zanamivir: Inhaled powder, causes bronchospasm (do not use is asthmatics)
  • Oseltamivir: PO, causes nausea and vomiting
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5
Q

What are the benefits to Oseltamivir and Zanamivir compared to older agents? What are the drawbacks?

A

Pros: Less resistance, almost all flu is resistant to older anti-flu agents. Less toxicity
Cons: Different toxicities. More costly

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6
Q

What is the spectrum and mechanism of action of Acyclovir (Zovirax)?

A

Spectrum: Herpesviruses, HSV1 > HSV2 > VZV > EBV&raquo_space; CMV
Mechanism: Phosphorylated by HSV thymidine kinase to monophosphate, phosphorylated to triphosphate by host proteins, which inhibits viral DNA polymerase and acts as a CHAIN TERMINATOR.

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7
Q

Mutations in what viral genes lead to Acyclovir Resistance?

A

Thymidine Kinase is the main one, but also POL

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8
Q

What is the route, excretion, and toxicities associated with Acyclovir

A

Route: IV is best, PO also available (20% bioavailability), topical
Excretion: Renal (may need to adjust dose)
Toxicity: Renal crystallization in dehydrated patients, encephalopathy.

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9
Q

What are the clinical indications for Acyclovir use?

A

HSV

  • Genital (primary, recurrent, suppressive)
  • Orolabial (suppressive, minimal benefit)
  • Mucucutaneous disease in immunocompromised
  • Drug of choice for HSV encephalitis, prevents death

VZV

  • Used in immunocompromised patients
  • Some efficacy but questionable use for Chickenpox (reduces lesion number) and Shingles (but definitely use in V1 shingles)

EBV: Oral hairy leukoplakia in AIDS
CMV: Protective in transplantation.

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10
Q

What are the new Oral Anti-Herpes Drugs and how do they work?

A
  • Valacyclovir (Valtrex): Prodrug of acyclovir
  • Famciclovir (Famvir): Prodrug of penciclovir
  • Converted to active agents by passing through intestine/liver, reaches higher levels than PO acyclovir.
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11
Q

What are the indications for new Oral Herpes Agents? Are there any bad toxicities?

A
  • Initial episode of genital herpes, recurrent genital herpes, genital herpes suppression, and shingles.
  • Herpes labialis - use before lesions appear
  • Any of these agents (including acyclovir) can be used for post-herpetic neuralgia

Toxicity: Valacyclovir can cause TTP in immunocompromised persons.

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12
Q

What is the benefit of valganciclovir?

A

This oral prodrug of ganciclovir produces blood levels identical to IV ganciclovir - now the drug of choice.

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13
Q

What is the main use of Ganciclovir, and what is its mechanism of action? How is it administered and excreted? What is the main associated toxicity?

A

Uses: 1) CMV retinitis. 2) CMV esophagitis, colitis, pneumonitis. 3) Also covers HSV, VZV
Mechanism: Chain terminator - triphosphate inhibits viral DNA Polymerase
Route: IV (PO bioavailability = 5%, not useful except for prophylaxis, maitenance)
Excretion: Renal
Toxicity: Neutropenia, a big deal (limiting)

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14
Q

What is Foscarnet (Foscavir) and how does it work? How is it given and excreted? What is the main toxicity?

A

-A pyrophosphate analogue that is used as a second line drug for CMV retinitis, acyclovir-resistant HSV or VZV (2nd line for all acyclovir and ganciclovir uses)
Mechanism: Inhibits viral DNA polymerase
Route: IV only
Excretion: Renal
Toxicity: VERY nephrotoxic, renal function must be measured daily

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15
Q

Describe the pharmacology and mechanism of action of Zidovudine(Azidothymidine, AZT, ZDV, Retrovir).

A

This can be taken orally or by IV. It gets into the CSSF and has a short half life. The nucleoside is phosphorylated by host enzymes. Tri-P then inhibits viral DNA polymerase thus acting as a chain terminator. The virus cannot replicate.

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16
Q

What is a downfall to Zidovudine(Azidothymidine, AZT, ZDV, Retrovir)?

A

With continued use, resistance is common. In addition, AZT causes neutropenia, anemia, myopathy. It, and actually all Nucleoside Analogue RT Inhibitors, can also cause fatal lactic acidosis, steatosis.

17
Q

What is tenofovir?

A

It is a nucelotide (comes with the phosphate group attached) reverse transcriptase inhibitor.

18
Q

What are the two main categories for Reverse Transcriptase Inhibitors?

A

Nucleoside (or tide) and Non-nucleoside RT Inhibitors. Non-nucleoside RT Inhibitors, block at a different site on the enzyme from that of the NRTIs. Resistane is an issue with both drug categories.

19
Q

Clinically, what must a physician be concerned about and check before prescribing Abacavir?

A

Abacavir can cause a fatal hypersensitivity rxn. The patient must first be tested to see if they have the partilular leukocyte antigen that causes the hypersensitivity. If they don’t have this, then they are NOT at risk for this reaction and it is ok to prescribe the drug. (Great example of pharmacogenetics - these reactions were shown to be limited to the 5% of people who have the human leukocyte antigen - B*5701 - and genetic screening before use is recommended.

20
Q

What were the results and importance of the placebo controlled trial discussed in class in relation to AZT.

A

This was the first and only drug ever to show a benefit from mortality when compared to palcebo as a single agent – One patient in the treatment group died, 19 in placebo died – there are no studies that show such dramatic results — within a year, though many were already resistant to it

21
Q

What is the benefit of taking AZT during pregnancy.

A

It helps reduce rate of transmission to fetus. Can diminish perinatal transmission (the 26% risk drops to 8%) when given in the latter part of pregnancy, intrapartum, and to the infant for 6 wks

22
Q

There are 5 FDA approved non-nucleoside RT Inhibitors, but why was Nevirapine (Viramune) singled out?

A

It is shown to prevent perinatal transmission but there is controversy around the drug because 10 days after delivery, the mothers show resistance to the drug.

23
Q

What are protesase inhibitors?

A

These agents competitively inhibit the HIV protease that is necessary for processing the viral polyprotein precursor and thus interfere with virion maturation. They are more potent than RT inhibitors but resistance occurs rapidly if used alone and there are several drug interactions via hepatic enzymes. (Entire viral population in the patient turns over so rapidly that the patient can become resistant to protease inhibitors in days) They can cause redistribution of fat and diabetes. There are 10 approved by the FDA.

24
Q

What is the mechanism of action of Integrase Inhibitors?

A

They are strand transfer inhibitors. Integrase nicks the ends of viral DNA to prepare them for integration, then inserts the ends into cellular DNA (this 2nd step is called strand transfer). (Integration of a DNA copy of the viral genome into cellular DNA makes infection permanent, and makes retroviruses unique among animal viruses. Integrase inhibitors prevent this from happening. )

25
Q

What are the two types of entry inhibitors?

A

Fusion Inhibitors and Coreceptor antagonists (must have only CCR5-tropic strains of HIV-1, otherwise if using alternative CXCR4, this drug won’t work)

26
Q

What is the goal of HIV therapy?

A

Goal of therapy is maximum virus suppression.

27
Q

What is the standard of care for HIV patients?

A

Highly active anti-retroviral therapy (HAART) with 3 or 4 drugs is the standard of care. To use fewer than 3 is not appropriate. The latest evidence-based recommendation for initial therapy lits 5 preferred regimens, all with tenofovir ( a nuceleoTide RT inhibitor) plus a nucleoSide RT inhibitor plus a NNRTI or Integrase Inhibitor.

28
Q

What is the set point in HIV?

A

Steady state level (“set point”) of circulating virus (HIV RNA) becomes fixed in first year after infection and predicts disease progression - virus finds the set point within the first year and this helps predict progression

29
Q

What is viral load?

A

Viral load in plasma determines progression, and risk of transmission to fetus and sexual partners - The viral load tells us how much risk/chance there is to that individual transmitting the disease. The viral load in plasma predicts the risk of progression and the risk of transmission to the fetus and sexual partners.

30
Q

Explain the train analogy in regards to HIV patients and assessing their status?

A

Their CD4 count tells us the distance to the end of the tracks. The viral load, however, tells the speed to which we are approaching the end of the tracks.