Anti-Virals Flashcards
What are Amantadine and Rimantadine? How do they work, and what are they used for now?
- Anti-influenza agents against Influenza A only
- Block the M2 channel, preventing lysosomal acidification and viral uncoating.
- NOTHING, there is too much resistance.
What is the “nomenclature” for the 2009 swine flu pandemic?
Influenza A (H1N1)pdm09
What is the one way to prevent the flu?
Vaccination
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?
- 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
What are the benefits to Oseltamivir and Zanamivir compared to older agents? What are the drawbacks?
Pros: Less resistance, almost all flu is resistant to older anti-flu agents. Less toxicity
Cons: Different toxicities. More costly
What is the spectrum and mechanism of action of Acyclovir (Zovirax)?
Spectrum: Herpesviruses, HSV1 > HSV2 > VZV > EBV»_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.
Mutations in what viral genes lead to Acyclovir Resistance?
Thymidine Kinase is the main one, but also POL
What is the route, excretion, and toxicities associated with Acyclovir
Route: IV is best, PO also available (20% bioavailability), topical
Excretion: Renal (may need to adjust dose)
Toxicity: Renal crystallization in dehydrated patients, encephalopathy.
What are the clinical indications for Acyclovir use?
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.
What are the new Oral Anti-Herpes Drugs and how do they work?
- 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.
What are the indications for new Oral Herpes Agents? Are there any bad toxicities?
- 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.
What is the benefit of valganciclovir?
This oral prodrug of ganciclovir produces blood levels identical to IV ganciclovir - now the drug of choice.
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?
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)
What is Foscarnet (Foscavir) and how does it work? How is it given and excreted? What is the main toxicity?
-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
Describe the pharmacology and mechanism of action of Zidovudine(Azidothymidine, AZT, ZDV, Retrovir).
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.