Antivirals

Question 1

Name 4 antiviral agents for Herpesvirus:

Answer 1

Acyclovir, Ganciclovir, Foscarnet, Cidofovir

Question 2

Name 4 antiviral agents for influenza:

Answer 2

Oseltamivir, Zanamavir, Amantadine, Rimantadine

Question 3

Antiviral agents for Hep B and C:

Answer 3

Hep C protease inhibitors

Question 4

Acyclovir is an analogue of ________, with a(n) ______ side chain that lacks a ________

Answer 4

Acyclovir is an analogue of DEOXYGUANOSINE, with a(n) ACYCLIC side chain that lacks a 3’ HYDROXYL

Question 5

Acyclovir is specific for _______

Answer 5

HSV-infected cells / viral DNA

Question 6

ACV requires ______ to become active (explain)

Answer 6

phosphorylation; initial step is accomplished by HSV viral thymidine kinase (TK)

• cellular enzymes activate ACV inefficiently
• phosphorylated mainly in virus infected cells (selective)

Question 7

What is acyclovir (zovirax) considered one of the safest antivirals?

Answer 7

It is very specific for virally-infected cells and not healthy cells.

The drug must be phosphorylated inside the cell by VIRAL thymidine kinase (not phosphorylated if no virus).

Drug also targets VIRAL DNA polymerase more than hose cell.

Question 8

Describe the drug activity of Acyclovir (Zovirax):

Answer 8

• Very effective against HSV-1 and HSV-2
• Less active (but usually effective) against VZV
• Considered drug of choice for HSV and VZV
• Little to no in vivo activity against other herpesviruses (e.g. EBV)

Question 9

What are the methods of administration of Acyclovir? Explain.

Answer 9

• Oral acyclovir is used, but has low bioavailability so generally will prescribe Valacyclovir or Famciclovir because these are pro-drugs which yield higher active drug levels.
• For serious infections (e.g. if patient has encephalitis), NEED IV acyclovir

Question 10

Ganciclovir (GCV):

Answer 10

Used to treat severe CMV infections.

• Similar to Acyclovir, because it needs to be phosphorylated by a CMV kinase. BUT can also be phosphorylated by cellular kinases (less specific).
• Greater adverse effects (bone marrow toxicity) than acyclovir

Question 11

What is ganciclovir effective against and used to treat?

Answer 11

Effective against HHV-6, HSV, and VZV (but never use to treat for HSV or VZV because of toxicity vs. acyclovir efficacy)

Question 12

Valganciclovir

Answer 12

A pro-drug variant of ganciclovir

Used for oral prophylaxis and preemptive therapy (when you think you’ll be at risk you take it)

Question 13

Describe the adverse/toxic effects of Ganciclovir (GCV):

Answer 13

Bone marrow toxicity will cause clinical findings of lowered neutrophil and platelet counts because the bone marrow cells aren’t replicating as actively

Question 14

Foscarnet:

Answer 14

DNA polymerase inhibitor for herpesvirus

Causes nephrotoxicity

Question 15

Cidofovir:

Answer 15

DNA polymerase inhibitor for herpesvirus

Causes nephrotoxicity

Question 16

Where do mutations arise in antiviral therapies for herpesvirus?

Answer 16

Generally due to mutations in the viral tyrosine kinase or viral polymerase

[generally only see in immunocompromised people]

Question 17

Oseltamivir:

Answer 17

Tamiflu

Neuraminidase inhibitor, effective for influenza A and B

Basically, before influenza can leave the cell while budding, the host cell is attached to the virus. Have to have viral enzyme neuraminidase cleave this connection to release viral particles. This drug stops this action, so the virus particles can’t leave.

Question 18

How effective is Oseltamivir?

Answer 18

If you start taking the first day you’re sick you might have a day less of symptoms, and a day or so less without fever. But you have to start within the first 24-36 hours to have an effect.

This drug is way over-prescribed because it’s usually not given until the patient has been sick for a few days.

Still good to give to someone who is immunocompromised (e.g. HIV patient) because they will be having replication periods that are longer than otherwise healthy people.

Question 19

Describe when tamiflu might be prescribed as a prophylactic therapy?

Answer 19

Might prescribe to e.g. an immunocompromised HIV infected patient whose roommate was just diagnosed with the flu

Question 20

Small Particle Aerosol Generator (SPAG nebulizers):

Answer 20

For administration of ribavirin to infants

Question 21

Ribavirin:

Answer 21

Nucleoside analogue with some antiviral activity against many viruses. Historically administed as aerosol for treatment of patients with severe RSV

Question 22

What is Ribavirin used for?

Answer 22

Historically, aerosolized for RSV.

Currently, used in combination therapy for Hep C (oral) or Lassa Fever (IV)

Question 23

The predominant adverse effect of Ribavirin is _____

Answer 23

anemia

Question 24

Describe the classes of antiretroviral agents of HIV:

Answer 24

• Nucleoside reverse transcriptase inhibitors (NRTI)
• Nucleotide RT inhibitors (NtRTI)
• Non-nucleoside reverse transcriptase inhibitors (NNRTI)
• Protease inhibitors (PI)
• Fusion/entry inhibitors
• integrase inhibitors

Question 25

Zidovudine (Retrovir, or “AZT”):

Answer 25

-First ARV drug developed/used to treat HIV

–Synthetic analogue of thymidine; active drug phosphorylated

–NRTI: Competitive binding of reverse transcriptase

–DNA chain elongation terminator

–Only ARV also available in intravenous formulation

–Black box warnings for neutropenia, severe anemia, myopathy etc.

Question 26

Which antiretroviral treatments for HIV are available IV?

Answer 26

Only Zidovudine (AZT)

Question 27

What toxicities are associated with Zidovudine?

Answer 27

Neutropenia, severe anemia, myopathy

[Has a black box warning]

Question 28

Abacavir (Ziagen):

Answer 28

–Currently greater use than zidovudine

–Risk of serious hypersensivity reaction

•Must screen for presence of HLA-B*5701

–Increased risk of cardiac disease

Question 29

Lamivudine (Epivir):

Answer 29

Commonly used with Zidovudine or Tenofovir

Also effective for Hep B

Question 30

Emtricitabine (Emtriva):

Answer 30

HIV antiretroviral:

Commonly used with Zidovudine or Tenofovir

Also effective for Hep B

Question 31

Tenofovir Disoproxil Fumarate (Viread, TDF) & Tenofovir Alafenamide (TAF):

Answer 31

-NRTI (For HIV)

–Currently one of most common drugs in combination pills

–TAF less renal and bone toxicity than TDF

–Also effective against Hepatitis B

Question 32

Lopinavir/Ritonavir (Kaletra)

Answer 32

–PI: Protease inhibitor

–Ritonavir used to boost levels of primary drug

–Potent drugs; like all beware of drug interactions

Question 33

Raltegravir

Answer 33

HIV Integrase inhibitor

Integrase inhibitors in general are well-tolerated, fewer side effects, less resistance

Question 34

Maraviroc:

Answer 34

Unique in mechanism (inhibits co-receptor, may not be active in all stages of disease)

Question 35

Describe immediate, life-threatening side effects of antiretroviral therapies:

Answer 35

Abacavir hypersensitivity, Stevens Johnson Syndrome, lactic acidosis, hepatitis

Question 36

Describe acute or short-term adverse effects of antiretroviral therapy:

Answer 36

E.g. hematologic, HI (diarrhea), CNS (HA, fatigue), renal (nephrolithiasis), etc.

Question 37

Describe long-term adverse effects of antiretroviral therapy:

Answer 37

Morphologic (fat redistribution)

Metabolic (lipid, glucose, neuropathy, myopathy, cardiac disease)