antivirals Flashcards
major antiviral target
polymerases
key characteristics of antivirals targeting DNA/RNA polymerases
mimic natural nucleoside/tides and require conversion to a triphosphate derivative
Anti HSV/VZV drugs, MOA, AEs
Acyclovir and Valacyclovir
MOA: nucleoside analogs - inhibit viral DNA/RNA polymerase
AEs: nephrotoxic/seizure risk
Anti CMV drugs, MOA, AEs
Ganciclovir and Valganciclovir
MOA: nucleoside analogs, inhibit viral DNA/RNA polymerase
AEs: bone marrow suppression and bad sperm - use BC
mechanism of resistance to anti-HSV agents:
mutations in viral kinases and mutations to viral DNA polymerase
Drugs reserved for resistant CMV/HSV, MOA, AEs
Cidofovir - nucleoTIDE analog, inhibits viral DNA polymerase, patient must hydrate r/t renal AEs
Foscarnet - pyrophosphate analog, inhibits viral DNA polymerase, is a vesicant, seizure risk, and renal AEs
CMV prophylaxis for bone marrow transplant drug and MOA
Letermovir - inhibits viral DNA terminase
“I received a LETER in the mail saying I am PRE-APPROVED for a BONE MARROW TRANSPLANT so my DNA isn’t TERMINATED”
Characteristics of ALL anti-HBV drugs
ALL inhibit HBV polymerase
ALL are PO
ALL are renally excreted
ALL can cause lactic acidosis, HBV exacerbation after discontinuation, and can cause HIV resistance r/t underdosing HIV when taking for HBV - patient must be screened for both viruses
Ant-HBV drugs that are nucleoTIDE analogs and their AEs
TenoFOVIR disoproxil - nephrotoxic and decreased bone density
TenoFOVIR alafenamide - less renal/bone toxicity
Adefovir - dose dependent nephrotoxicity and NOT approved for HIV treatment
Anti-HBV nucleoSIDE drugs and AEs
Entacavir - food decreases its absorption
Lamivudine - pancreatitis
HBV - monotherapy or combo therapy?
Monotherapy. HBV can not be cured.
Does HBV have a vaccine
Yes
HCV - monotherapy or combo therapy?
combo therapy - attempt to hit 3 steps in virus life cycle
>90% of individuals treated with direct acting antiviral drugs have been cured
does HCV have a vaccine?
No
HCV direct acting antiviral targets:
NS5B - polymerase
NS5A - unknown but important
NS3/4A - protease
HCV direct acting antivirals: NS5B
NS5B DAA = polymerase inhibitors
“P” in Polymerase upside down is “B” for Buvir and for NS5B
Sofosbuvir - nucleotide polymerase inhibitor
Dasabuvir - non-nucleoside/tide polymerase inhibitor (doesn’t require phosphorylation)
HCV direct acting antivirals: NS5A
“asvir” drug endings
Asvir is 5 letters and begins with an A = NS5A inhibitor
HCV direct acting antivirals: NS3/4A
NS3/4A = protease inhibitors
“previr”
previr sounds like premiere - I am PRO going to the movie PREMIERE even at 3/4 am.
Same Pro-Drug idea:
Sofosbuvir and Tenofovir Alafenamide
Significant Key Features of HCV direct acting antivirals:
ALL have significant DDIs and are contraindicated with inducers of CYP3A4
Combo of Sofosbuvir (NS5B polymerase inhibitor) and Amiodorone can cause:
Bradycardia
Regimens with Ledipasvir (NS5A inhibitor) or Velpatasvir (NS5A inhibitor) - absorption is affected by:
decreased absorption when taken with antacids, H2R antagonists, and PPIs
Technivie and VieKira are HCV DAA that contain:
Ritonavir (a strong CYP3A4 inhibitor)
Caution when using with meds dependent on CYP3A4 metabolism
Human Immunodeficiency Virus 1 (HIV-1)
no vaccine infected for life combo therapy - sustained viral suppression is critical infects immune cells and destroys CD-4 single strand - think mRNA
Anti-HIV drug CLASSES
ENNIP
entry inhibitors nucleoside/tide RT inhibitors non-nucleoside/tide RT inhibitors integrase inhibitors (tegravir) protease inhibitors (navir)
Anti-HIV drugs (ENNIP): Entry inhibitors
MOA: Designed to
Designed to block HIV-1 entry
Fostemsavir: (PO) binds to gp120 and prevents binding to CD4
Maravoric: (PO) CCR5 antagonist that prevents gp120 CD4 complex from binding to CCR5
Ibalizumab: (IV) prevents gp120 CD4 complex binding to CCR5 or CXCR4 - used for heavily treatment experienced patients only
Enfuviritide: (SC) prevents HIV fusion with Tcell membrane - used for heavily treatment experienced patients only
Anti-HIV drugs (ENNIP): nucleoside/tide RTIs
MOA:
Key features:
MOA: COMPETITIVELY inhibits HIV RT and requires phosphorylation
Drugs:
Abacovir (side) - may cause hypersensitivity
Emtricitabine (side) - may cause hyperpigmentation
Lamivudine (side)
Zidovudine (side) - may cause bone marrow suppression and is used IV for laboring moms to prevent transfer
Tenofovir disoproxil (tide)
Tenofovir alafenamide (tide)
Key features:
NO CYP DDIs
REQUIRE renal dose adjustment
Boxed warning: lactic acidosis and hepatomegaly
Anti-HIV drugs (ENNIP): Non-nucleoside/tide RTIs
MOA:
Drugs:
Key features:
MOA: NON-competitive bind to RT causing conformational change, do NOT require phosphorylation
Drugs:
Doravirine
Efavirenz - hallucinations/insomnia/confusion
Etravirine
Nevirapine
Rilpivirine - QT prolonger
Key features:
DO have CYP DDIs
NO renal dose needed
Fast development of resistance and always used in combo
Anti-HIV drugs (ENNIP): integrase inhibitors
MOA:
Features:
HIV Integrase Inhibitors = "TEGRAVIR" MOA: prevent covalent insertion of HIV DNA into host cell genome. *KEY bc once this happens HIV is permanent* Features: NO CYP3A4 DDIs Chelation with polyvalent cations HAs/insomnia
Anti-HIV drugs (ENNIP): Protease Inhibitors
MOA:
Key features:
HIV Protease Inhibitors = “NAVIR”
MOA: competitively inhibit cleavage of non-functional viral precursor proteins into functional proteins
Key features:
*due to extensive first pass metabolism they are given with PK boosters (Ritonavir and cobicistat = CYP3A4 Pgp inhibitors)
NO renal adjustment
CYP450 DDIs
Serious AEs: GI, insulin resistance, fat accumulation, CVD risk, ECG changes, rash, bleeding, hepatotoxicity
Influenza virus surface proteins
Hemagglutinin (HA)
Neuraminidase (NA)
these surface proteins mutate seasonally and there is a vaccine for the flu developed based off mutation
Neuraminidase inhibitors
Tamiflu (PO)
Relenza (inhaled - not for COPD patients)
Rapivab (IV for ER patients)
neuropsychiatric effects
must receive within 48 hours on symptom onset
New Flu drug - Cap-dependent Endonuclease
Viral RNA polymerase binds to cap of host pre-mRNA, cuts it off, and uses it to initiate viral synthesis.
Baloxavir marboxil - inhibits endonuclease activity of RNA polymerase and prevents cap-snatching
