antivirals

Question 1

major antiviral target

Answer 1

polymerases

Question 2

key characteristics of antivirals targeting DNA/RNA polymerases

Answer 2

mimic natural nucleoside/tides and require conversion to a triphosphate derivative

Question 3

Anti HSV/VZV drugs, MOA, AEs

Answer 3

Acyclovir and Valacyclovir
MOA: nucleoside analogs - inhibit viral DNA/RNA polymerase
AEs: nephrotoxic/seizure risk

Question 4

Anti CMV drugs, MOA, AEs

Answer 4

Ganciclovir and Valganciclovir
MOA: nucleoside analogs, inhibit viral DNA/RNA polymerase
AEs: bone marrow suppression and bad sperm - use BC

Question 5

mechanism of resistance to anti-HSV agents:

Answer 5

mutations in viral kinases and mutations to viral DNA polymerase

Question 6

Drugs reserved for resistant CMV/HSV, MOA, AEs

Answer 6

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

Question 7

CMV prophylaxis for bone marrow transplant drug and MOA

Answer 7

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”

Question 8

Characteristics of ALL anti-HBV drugs

Answer 8

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

Question 9

Ant-HBV drugs that are nucleoTIDE analogs and their AEs

Answer 9

TenoFOVIR disoproxil - nephrotoxic and decreased bone density
TenoFOVIR alafenamide - less renal/bone toxicity
Adefovir - dose dependent nephrotoxicity and NOT approved for HIV treatment

Question 10

Anti-HBV nucleoSIDE drugs and AEs

Answer 10

Entacavir - food decreases its absorption

Lamivudine - pancreatitis

Question 11

HBV - monotherapy or combo therapy?

Answer 11

Monotherapy. HBV can not be cured.

Question 12

Does HBV have a vaccine

Answer 12

Yes

Question 13

HCV - monotherapy or combo therapy?

Answer 13

combo therapy - attempt to hit 3 steps in virus life cycle

>90% of individuals treated with direct acting antiviral drugs have been cured

Question 14

does HCV have a vaccine?

Answer 14

No

Question 15

HCV direct acting antiviral targets:

Answer 15

NS5B - polymerase
NS5A - unknown but important
NS3/4A - protease

Question 16

HCV direct acting antivirals: NS5B

Answer 16

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)

Question 17

HCV direct acting antivirals: NS5A

Answer 17

“asvir” drug endings

Asvir is 5 letters and begins with an A = NS5A inhibitor

Question 18

HCV direct acting antivirals: NS3/4A

Answer 18

NS3/4A = protease inhibitors
“previr”
previr sounds like premiere - I am PRO going to the movie PREMIERE even at 3/4 am.

Question 19

Same Pro-Drug idea:

Answer 19

Sofosbuvir and Tenofovir Alafenamide

Question 20

Significant Key Features of HCV direct acting antivirals:

Answer 20

ALL have significant DDIs and are contraindicated with inducers of CYP3A4

Question 21

Combo of Sofosbuvir (NS5B polymerase inhibitor) and Amiodorone can cause:

Answer 21

Bradycardia

Question 22

Regimens with Ledipasvir (NS5A inhibitor) or Velpatasvir (NS5A inhibitor) - absorption is affected by:

Answer 22

decreased absorption when taken with antacids, H2R antagonists, and PPIs

Question 23

Technivie and VieKira are HCV DAA that contain:

Answer 23

Ritonavir (a strong CYP3A4 inhibitor)

Caution when using with meds dependent on CYP3A4 metabolism

Question 24

Human Immunodeficiency Virus 1 (HIV-1)

Answer 24

no vaccine
infected for life
combo therapy - sustained viral suppression is critical
infects immune cells and destroys CD-4
single strand - think mRNA

Question 25

Anti-HIV drug CLASSES

Answer 25

ENNIP ``` entry inhibitors nucleoside/tide RT inhibitors non-nucleoside/tide RT inhibitors integrase inhibitors (tegravir) protease inhibitors (navir) ```

Question 26

Anti-HIV drugs (ENNIP): Entry inhibitors | MOA: Designed to

Answer 26

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

Question 27

Anti-HIV drugs (ENNIP): nucleoside/tide RTIs MOA: Key features:

Answer 27

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

Question 28

Anti-HIV drugs (ENNIP): Non-nucleoside/tide RTIs MOA: Drugs: Key features:

Answer 28

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

Question 29

Anti-HIV drugs (ENNIP): integrase inhibitors MOA: Features:

Answer 29

``` 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 ```

Question 30

Anti-HIV drugs (ENNIP): Protease Inhibitors MOA: Key features:

Answer 30

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

Question 31

Influenza virus surface proteins

Answer 31

Hemagglutinin (HA) Neuraminidase (NA) these surface proteins mutate seasonally and there is a vaccine for the flu developed based off mutation

Question 32

Neuraminidase inhibitors

Answer 32

Tamiflu (PO) Relenza (inhaled - not for COPD patients) Rapivab (IV for ER patients) neuropsychiatric effects must receive within 48 hours on symptom onset

Question 33

New Flu drug - Cap-dependent Endonuclease

Answer 33

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