Viral Pharmacology Flashcards
Ho do Oseltamivir and Zanamivir work?
They inhbiit influenza neuraminidiase to prevent release of progenzy in the tx and prevention of influenza A and B
What are acyclovir, famciclovir, and valacyclovir?
These are GUANOSINE analogs which are monophosphorylated by HSV/VZV thymidine kinase and not phosphorylated in uninfected cells (few AEs). Triphosphohate foremed by cellular enzymes
Preferentially inhibit viral DNA polymerase by chain termination
Uses of acyclovir, famciclovir, and valacyclovir (better bioavailability)?
HSV and VZV and some weak activity against EBV. No activity against CMV. Used for HSV- induced mucocutanoeus and genital lesions as well as for encephalitis.
Prophylaxis in immunocompromised pts.
No effects on the latent forms of HSV and VZV.
For herpes zoster, used famiclovir
AEs of acyclovir, famciclovir, and valacyclovir?
Obstructive cystralline nephropathy and acute renal failure if not hydrated well
How does ganciclovir work?
5’-monophosphate formed by a CMV viral kinase (resistance: muatted viral kinase). Guanosine analog. Triphosphate formed by cellular kinases. Preferentially inhibits viral DNA polymerase by chain termination
Uses of ganciclovir?
CMV, esp. in immunocompromised. Valganciclovir has better bioavailability
AEs of ganciclovir?
pancytopenia, renal toxicity
How does Foscarnet work?
Viral DNA/RNA polymerase inhbiitor and HIV reverse transcriptase inhibitor. Bnds to pyrophosphate-binding site of enzyme. Does NOT require virl kinase activation (resistance: mutated DNA polymerase)
Uses of Foscarnet?
CMV retinitis when ganciclovir failures, acyclovir-resistant HSV
AEs of Foscarnet?
nephrototocitiy, electrolyte abnormalities can lead to seizures
How does Cidofovir work?
Inhibits viral DNA polymerase. Does NOT require phosphorylation by viral kinase
Used in tx of CMV retinitis (long half-life)
Note on HIV therapy
HAART therapy initiated at the time of HIV diagnosis. Strongest indication for pts presenting ith AIDs-defining illnes, low CD4 counts, or high viral load.
Regimen needs to consst of 3+ drugs to prevent resistance: 2 NRTIs and 1 of: NNRTI, protease inhbiitor, or integrase inhbitior
What are the HIV protease inhibitors?
-NAVIRs (e.g. atazanavir, darunavir, idinavir, ritonavir, lopinavir)
How do HIV protease inhibitors work?
Assembly of virions depends of HIV-1 protease (pol gene) which cleaves the polypeptide prodcuts of HIV mRNA into functional parts.
What are the NRTIs?
Abacavir
Didanosine
Emtricitabine
Lamivudine
Stavudine
Tenofovir
Zidovudine
How do the NRTIs work?
Competitively inhbiit nucleoide abinding to reverse transcriptase and terminate the DNA chains (lack a 3’OH group). tenofovir is a nucleotide and the others are nucleosides and need to be phosphorylated to be active
What is the prophylaxis for HIV and the drug used to decrease fetal transmission risk?
Zidovudine
What are the NNRTIs?
Delaviridne, Efavirenza, Nevirapine (bind to reverse transcriptase at sites different from NRTIs and do NOT require phosphorylation to be active)
AEs of NNRTIs?
Rash and hepatotoxicity are common to all
vivid dreams and CNS symtposm with Efavirenza
Delaviridine and Efavirenza contraindicated in pregnancy
What is Raltegravir?
Integrase inhbiitor, which inhbiits HIV genome integration into host cell chromosomes (elevated creatine as an AE)
What are the HIV fusion inhbitiors?
Enfuvirtide- Binds gp41, inhibiting viral entry
Maraviroc- Binds CCr-5 on surface of T cells/monocytes, inhibiting interaction with gp120
What are Interferons?
Glycoproteins norally synthesized by virus-infected cells, exhibiting antiviral and antitumoral properties
What are the clinical uses of IFN-a?
chronic HBV and HCV, Kaposi sarcoma, hairy cell leukemia, condyloma acuminatum, renal cell carcinoma, malignant melanoma
What are the clinical uses of IFN-B?
MS
What are the clinical uses of IFN-y?
CGD
What are the mainstays of HCV therapy?
- Ribavirin- inhbiits synthesis of guanine nucleotides by inhibiting inosine monophosphate dehydrogenase
- Simeprevir- HCV proetase inhibitor; prevents viral replication (dont use as monotherapy)
- Sofosbuvir- Inhibits HCV RNA-dependent RNA polymerase acting as a chain terminator (Dont use as monotherapy)
Infection control techniques:
Autoclave- pressurized steam at 120C. May be sporicidal
Alcohols and Chlorhexidine- denature proteins and disrupts cell membranes and not sporicidal
Hydorgen Peroxide- Free Radical Oxidation. Sporicidal
Iodine- halogenation of DNA, RNA, proteins. May be sporicidal
