Antivirals Flashcards
Amantadine MOA and Use
blocks attachment, penetration, and uncoating of Influenza A
use: prophylaxis, reduces duration of flu by 1-2 days
SE of Amantadine
atropine-like peripheral effects, livedo reticularis
Enfuvirtide MOA and use
binds gp41 and inhibits fusion of HIV1 to CD4 cells (chemokine receptor but drug is large enough to block gp120 which blocks fusion)
Maraviroc moa and use
blocks CCR5 protein on T cell membrane to prevent viral entry
use: HIV
Acyclovir moa
phosphorylation by THYMIDINE KINASE –> incorporated into DNA molecule–> chain terminator (lacks 3’OH)
*inhibits DNA polymerase
Acyclovir resistance
changes in DNA polymerase or decreased TK activity
Acyclovir uses
HSV
VZV
Why might a patient need multiple treatments with acyclovir?
it only works on dividing virus so if it is dormant, it is not killed
SE of Acyclovir
crystalluria, neurotoxicity
* NOT hematotoxic
Name the viral DNA polymerase inhbitors
acyclovir famciclovir valacyclovir ganciclovir foscarnet **pro-drugs
What are the newer versions of acyclovir? Why would you use them?
famciclovir
valacyclovir
longer t1/2 than acyclovir
may work on acyclovir resistant strains as long as they have TK
Gancyclovir use
HSV, VZV: uses Tk for phosphorylation
CMV: uses phosphotransferase
**prophylaxis and tx of CMV in AIDS and transplantation
Gancyclovir SE
dose limiting hematotoxicity (leukopenia), mucositis, fever, rash, crystalluria (nephrotox), seizures (neurotox)
Foscarnet MOA
NOT an anti-metabolite
blocks DNA and RNA polymerases
*doesn’t require TK
Foscarnet use
acyclovir-resistant HSV
CMV, VZV
Foscarnet SE
dose limiting acute tubular necrosis, hypocalcemia
Foscarnet drug interactions?
Pentamidine, will cause hypocalcemia
furosemide
Ribivarin MOA
monophosphorylase inhibits IMP dehydrogenase, triphosphorylated inhibits viral RNA polymerase
Ribivarin SE
hematotoxic, upper airway irritation, teratogenic!
Ribivarin use
adjunct to alpha interferon Hep C RSV Lassa fever hantavirus
What is an NRTI?
nucleoside reverse transcriptase inhibitor pro-drugs chain terminators activated by nonspecific kinases use with protease inhib. --> HAART
What is HAART?
highly active acute retroviral therapy
uses NRTI + protease inhibitor
What is the moa of NRTIS?
competes with natural nucleotides to inhibit reverse transcriptase and can also be incorporated into DNA to cause chain termination
*all work in the same way just with different base analogs
NRTI resistance?
mutation in gene for reverse transcriptase
there isn’t complete cross resistance between different NRTIs
Zidovudine
NRTI
SE: bone marrow suppression (SEVERE), headaches, fatigue, myalgias
Other names for Zidovudine
Azidothymidine, ZDV, AZT
Didanosine names and SE
DD1
SE: pancreatitis, peripheral neuropathy
Abacavire
NRTI
SE–> allergies
aka: ABC
zalcitabine
NRTI aka: DDC SE: peripheral neuropathy pancreatitis *don't combine with didanosine
lamivudine
NRTI
aka: 3TC
SE: least toxic, some GI sx
also used in Hep B
Emtricitabine
newer, more active version of lamivudine
aka FTC
Stavudine
NRTI
aka: D4T
dont use with AZT because they have the same base analog
Se: myelosuppression, peripheral neuropathy
NNRTI
not pro-drugs
no myelosuppression
additive/ synergistic with NRTIs
Nevirapine
NNRTI
single does at delivery decreases transmission of HIV from mom to baby (vertical transmission) by 50%
CYP450 inducer
SE: rash, increased LFT
Efavirenz
NNRTI
SE: insomnia, nightmares (dysphoric dreams)
Viral aspartate protease inhibitors moa
aspartate protease enzyme contains dipeptide structure that isn’t human form so it binds here to inhibit it
Viral aspartate protease inhibitors resistance
point mutations in pol gene, incomplete cross resistance
Common SE of Viral aspartate protease inhibitors
disordered lipids and carb metabolism with central adiposity and insulin resistance
*less with atazanavir
Indinavir
Viral aspartate protease inhibitor
used most frequently
SE: crystalluria
Ritonavir
Viral aspartate protease inhibitor
used most frequently
SE: major drug interactions from P450 induction
Saquinavir
Viral aspartate protease inhibitors
least toxic
low bioavailability
predisposes to resistance
viral neuraminidase inhibitors
influenza A and B
decreases liklihood that virus will penetrate uninfected cells
use: prophylaxis may decrease flu sx
SE: flu sx
Raltegravir
integrase inhib.
prevents integration of viral genome into host DNA
Use: HIV
Human interferons use
Hep B, C, D (alpha interferon)
Kaposi sarcoma, CML, MM, RCC (alpha)
MS (beta)
Chronic granulomatous disease (gamma)
