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What antiviral drugs inhibit viral replication at "penetration and uncoating"?
Please take my COAT off D-E-A-R!

Docosanol- HSV1
Enfuvirtide- HIV (gp41)
Amantadine- blocks M2 proton pump (prophy FluA not FluB)
Rimantidine- similar to amant.
What antiviral drugs inhibit viral replication at "assembly and release"?
Dorothy ASSEMBLED munchkins in OZ

Zanamavir & Oseltamivir

tx of Flu A & B. works at end/viral budding step by inhibiting viral NEURAMINIDASE.
reduces severity and duration os sxs, not curative.
What is special about Oseltamivir?
It is effective against H5N1 strain of flu. Oral prodrug
(zanamivir is inhaled)
What antiviral drug is a Humanized monoclonal antibody?
directed against the F prot of RSV and is used in prophy tx of RSV in high risk infants
What antiviral drugs inhibit viral replication at "Nucleic Acid Synthesis"?
V-GRAFT is the new target for NA synthesis
Whats great about Acyclovir?
The most perfect drug ever: guanosine analog w acyclic side chain.
HSV 1 & 2, VZV
DOC for herpes encephalitis, chickenpox in adolescents and adults
Extremely potent inhibitor of VIRAL DNA POL
What other drugs do we think of with Acyclovir?
Valacyclovir- a prodrug for higher theraputic levels 3-5X greater serum conc HSV2

Penciclovir- acyclovir analogue HSV1. well tolerated

Famciclovir- prodrug form of Penciclovir
What do we use Vidarabine for?
It is an adenosine analogue
Used for tx of OCULAR herpes simplex infections.
What do we use Ganciclovir for?
CMV retinitis

another acyclic guanine analog closely related to acyclovir

bc it can be phosphorylated to a limited extent by cellular kinase its use is limited to severe CMV infections in immunocomprimised pts
What do we use Ribavarin for?
For RSV in kids
In comb w IFN-alpha for Hep C!!!
What is trifluridine?
Athymidine analogue, 3 H's in 5-methyl group of thymidines have been replaced by flourines.

MOA: Inhibits thyidylate synthetase and feedback inhibits other steps in pyrimidine biosynthesis.
What is trifluridine used for?
DOC for herpetic conjunctival keratitis (about the same effect as vidarabine)
BC this drug is rapidly metabolized by nucleotidases, it is only useful in metabolically inactive sites (ie: the eye)
What is unique about foscarnet?
It is a inhibitor of viral DNA synthesis but in tow ways.
1) it inhibits HSV and CMV-encoded DNA POL
2) in inhibits HIV-encoded reverse transcriptase
What are the uses for foscarnet?
Effective against ganciclovir-resistant CMV retinitis in AIDS pts
DOC for acyclovir-resistant HSV in AIDS pts
What are the dose limiting toxicities of foscarnet?
Nephrotoxicity and symptomatic hypocalcemia
What is the prototypic NUCLEOSIDE Reverse Transcriptase inhibitor?
Zidovudine (AZT)
sunthetic thymidine analogue
HIV RT is 100 times more likely to use AZT instead of thymidine.
What is a big prob with the NRTIs?
All NRTIs have the potential to induce LACTIC ACIDOSIS as a result of their MITOCHONDRIAL toxicity
What are the other NRTIs?
ddI- Didanosine (peripheral neuropathy, fatal pancreatitis)
3TC- lamivudine (in comb w IFN-alpha--->tx HepB)
d4T- Stavudine & ddC-Zalcitabine (peripheral neuropathy)
abacavir (severe hypersensitivity and hepatomegaly)
When do we use a nucleoTIDE reverse transcriptase inhibitor?
Antiviral activity in RESTING cells
What are the nucleoTIDE RTIs?
tenofovir disoproxil (in comb w ddI inc risk of pancreatitis)
cidofovir (ganc and fosc resistant CMV retinitis)
adefovir (hepB, nephrotox)
What are the non-NRTIs?
Efavirenz- 1x daily dose, fewest side effects. SUPERIOR
Delaviridine (rash, fatigue, nausea)
Nevirapine (hepatotoxicity, Stevens Johnson syndrome, toxic epidermal necrolysis)
What are the protease inhibitors?
all the -AVIRs
MOA: bind to the catalytic site of the HIV encoded protease, blocking the cleavage of the multiprotein gag-pol precursor into mature proteins

Should ONLY be used in comb therapy w 1 or more nucleoside ANALOG
What can significantly decrease serum conc of PIs?
Inducers of CYP34A (RIFAMPIN)
If we want to tx Hep C??
Ribavarin and IFN alfa-2B
IFN alfa2B alone ---> Hep B
What are the more serious side effects of PIs?

atazanavir has the lowest incidence of lipodystrophies

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