Anti-viral drugs
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- When is anti-viral therapy most important? 3 things
- severe disease, immunocompromised patient, latent disease
- What are the two uncoating inhibitors?
- Amantadine and rimantadine
- What is the mechanism of action for Amantadine?
- Its a cyclic compount that binds to the M2 channel of influenza A. With M2 inhibited the endosome cannot be acidified and viral RNA transcriptase can't be activated.
- How are amantadine and rimantadine metabolized?
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Amantadine by renal excretion.
Rimatadine by hepatic metabolism - What are the adverse effects of amantadine?
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CNS aniexty, insomnia, dizziness
GI nausea/vomiting
Teratogen - Which anti influenza drugs are also effective against type B influenza?
- Zanamivir and osteltamivir
- How do Zanamivir and osteltamivir work?
- They inhibit neuroaminidase cleave sialic acid from viral proteins and surface proteins of infected cells. they prevent release and spread of mature virus particles.
- How does acyclovir (ACV) work?
- Gets activated to ACV TP - a competitive inhibitor of DNA pol. It lead s to chain termination. A viral thymidine kinase (TK) is needed for phosporylation.
- What is ACV used for?
- HSV or VZV infections. HSV-1, HSV-2, VZV are most sensitive. EBV is less sensitive and CMV is least sensitive. § Oral – mucucutaneous and genital herpes lesions. Prophylaxis in AIDS and other immunocompromised patients
- ACV toxicity?
- usually well tolerated, GI disturbances or headache can occur. Rapid IV infusion can produce renal dysfunction.
- How is ACV selectively toxic?
- acyclovir requires activation by a viral enzyme (Thymidine Kinase). Phosphorylated drug (ACV TP) actively inhibits viral DNA polymerase. Acylovir binds more strongly to viral DNA polymerase than the host polymerase.
- Mechanism of viral resistance to ACV?
- mutations in TK or DNAP genes, mutants are resistant to other drugs of the ACV class
- How is ganciclovir different from ACV?
- Ganciclovir is 100x more active than AC against CMV. · A viral specific TK phosphorylates GCV and cellular enzymes convert it to triphosphate which inhibits viral DNAP. Chain termination is minimal
- Uses of GCV?
- CMV prophylaxis, and retininitis in immunocompromised or transplant recipients
- Adverse effects of GCV?
- bone marrow suppression (leukopenia, thrombocytopenia) mucositis, hepatic dysfunction, seizures. If used with zidovudine or other myelosuppressive agents, it may causes severe neutropenia.