Antivirals Flashcards
Name 4 antiviral agents for Herpesvirus:
Acyclovir, Ganciclovir, Foscarnet, Cidofovir
Name 4 antiviral agents for influenza:
Oseltamivir, Zanamavir, Amantadine, Rimantadine
Antiviral agents for Hep B and C:
Hep C protease inhibitors
Acyclovir is an analogue of ________, with a(n) ______ side chain that lacks a ________
Acyclovir is an analogue of DEOXYGUANOSINE, with a(n) ACYCLIC side chain that lacks a 3’ HYDROXYL
Acyclovir is specific for _______
HSV-infected cells / viral DNA
ACV requires ______ to become active (explain)
phosphorylation; initial step is accomplished by HSV viral thymidine kinase (TK)
- cellular enzymes activate ACV inefficiently
- phosphorylated mainly in virus infected cells (selective)
What is acyclovir (zovirax) considered one of the safest antivirals?
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.
Describe the drug activity of Acyclovir (Zovirax):
- 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)
What are the methods of administration of Acyclovir? Explain.
- 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
Ganciclovir (GCV):
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
What is ganciclovir effective against and used to treat?
Effective against HHV-6, HSV, and VZV (but never use to treat for HSV or VZV because of toxicity vs. acyclovir efficacy)
Valganciclovir
A pro-drug variant of ganciclovir
Used for oral prophylaxis and preemptive therapy (when you think you’ll be at risk you take it)
Describe the adverse/toxic effects of Ganciclovir (GCV):
Bone marrow toxicity will cause clinical findings of lowered neutrophil and platelet counts because the bone marrow cells aren’t replicating as actively
Foscarnet:
DNA polymerase inhibitor for herpesvirus
Causes nephrotoxicity
Cidofovir:
DNA polymerase inhibitor for herpesvirus
Causes nephrotoxicity
Where do mutations arise in antiviral therapies for herpesvirus?
Generally due to mutations in the viral tyrosine kinase or viral polymerase
[generally only see in immunocompromised people]
Oseltamivir:
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.
How effective is Oseltamivir?
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.
Describe when tamiflu might be prescribed as a prophylactic therapy?
Might prescribe to e.g. an immunocompromised HIV infected patient whose roommate was just diagnosed with the flu
Small Particle Aerosol Generator (SPAG nebulizers):
For administration of ribavirin to infants
Ribavirin:
Nucleoside analogue with some antiviral activity against many viruses. Historically administed as aerosol for treatment of patients with severe RSV
What is Ribavirin used for?
Historically, aerosolized for RSV.
Currently, used in combination therapy for Hep C (oral) or Lassa Fever (IV)
The predominant adverse effect of Ribavirin is _____
anemia
Describe the classes of antiretroviral agents of HIV:
- Nucleoside reverse transcriptase inhibitors (NRTI)
- Nucleotide RT inhibitors (NtRTI)
- Non-nucleoside reverse transcriptase inhibitors (NNRTI)
- Protease inhibitors (PI)
- Fusion/entry inhibitors
- integrase inhibitors
Zidovudine (Retrovir, or “AZT”):
-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.
Which antiretroviral treatments for HIV are available IV?
Only Zidovudine (AZT)
What toxicities are associated with Zidovudine?
Neutropenia, severe anemia, myopathy
[Has a black box warning]
Abacavir (Ziagen):
–Currently greater use than zidovudine
–Risk of serious hypersensivity reaction
•Must screen for presence of HLA-B*5701
–Increased risk of cardiac disease
Lamivudine (Epivir):
Commonly used with Zidovudine or Tenofovir
Also effective for Hep B
Emtricitabine (Emtriva):
HIV antiretroviral:
Commonly used with Zidovudine or Tenofovir
Also effective for Hep B
Tenofovir Disoproxil Fumarate (Viread, TDF) & Tenofovir Alafenamide (TAF):
-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
Lopinavir/Ritonavir (Kaletra)
–PI: Protease inhibitor
–Ritonavir used to boost levels of primary drug
–Potent drugs; like all beware of drug interactions
Raltegravir
HIV Integrase inhibitor
Integrase inhibitors in general are well-tolerated, fewer side effects, less resistance
Maraviroc:
Unique in mechanism (inhibits co-receptor, may not be active in all stages of disease)
Describe immediate, life-threatening side effects of antiretroviral therapies:
Abacavir hypersensitivity, Stevens Johnson Syndrome, lactic acidosis, hepatitis
Describe acute or short-term adverse effects of antiretroviral therapy:
E.g. hematologic, HI (diarrhea), CNS (HA, fatigue), renal (nephrolithiasis), etc.
Describe long-term adverse effects of antiretroviral therapy:
Morphologic (fat redistribution)
Metabolic (lipid, glucose, neuropathy, myopathy, cardiac disease)
