Antiviral Drugs Flashcards
What are 2 “virucidal” virus treatments?
Detergents and Cryotherapy
What are three types of virus treatments?
Virucidal, Immunomodulary, antivirals
What is an example of immunomodulary virus treatments? What is the goal of the treatment?
Example: Pegylated Interferon
Goal: Stimulate the intrinsic immune system
What are 4 classes of antivirals?
1- nucleoside analogs
2- non- nucleosides
3- protease inhibitors
4- entry inhibitors
Which antivirials are the most effective?
“Nucs” and “Non nucs”
Which type of antivirals are no longer used?
Antivirals inhibiting uncoating of the virus
What are the key viral function targets of antivirals?
1- Entry
2- Genome replication
3- Assembly
4- Release from the Cell
Why is there a general lack of “broad spectrum” antivirals?
Specificity of antivirals is a problem. Typically antivirals tend to target one function of one virus. Not universal.
What can happen when a drug is cleared from an individual’s system? What is done to prevent this?
Viral rebounding. Leads to need for life-long therapy in some cases.
Can resistance mutations exist in a patient before drug treatment?
Yes
How does antivirals lead to increased drug resistance?
Drug treatment selects for resistant virus strains
What are 4 factors leading to emergence of resistant variants?
1- High rate of virus replication
2- High Mutation rate (RNA»DNA)
3- High selective drug pressure
4- Immunosuppression of the host
Which of these counters resistnace to antivirals?
1- alleviating immunosuppression in the treated person
2- HAART
3- Targeting host functions
All of them!
Why is targeting host functions with antivirals dangerous?
Need to be careful of toxicity. Can be helpful is infected cells have a unique profile that can be a drug target and if virus mutations do not impact cellular genes.
What antiviral is used to treat HSV-1, HSV-2, and CZV?
Acyclovir
Who should be treated for a HSV-1, HSV-2, or CZV infection?
1- Neonates infected at birth
2- Immunodeficient
3- People with complicated HSV infections
4- People with frequent reoccurences
What is the structure of Acyclovir?
Nucleoside analog of guanosine
Explain the mechanism of Acyclovir
Phosphorylated once by a viral kinase. Phosphorylated twice more by host kinases. The triphosphate ACV inhibits viral DNA polymerase by competing with G for incorporation into DNA. It is a chain terminator
What is the structure of ganciclovir?
nucleoside analog of guanosine
What is the problem with ganciclovir treatment?
High toxicity, suppresses the bone marrow, mutagenic and teratogenic
What virus is ganciclovir effective in treating?
CMV
What are the two “broad spectrum” antivirals for DNA viruses?
Foscarnet and Cidovir
How are Foscarsnet and Cidofovir administered?
IV only
What viruses is foscarnet effective against?
all the Herpesviruses
What viruses is cidofovir effective against?
Herpesviruses, adenoviruses, papillomavirues, poxvirus
Where does the most toxicity occur with Foscarnet and Cidofovir?
Kidneys
Drugs designed for what, are used to treat HBV?
HCV and HIV
For people with HBV, who should be treated?
People with chronic or active HBV disease, people co-infected with HCV and or HIV, people whoare progressing to cirrhosis, liver failure, or hepatocellular carcinoma.
What are the antivirals used to treat influenza?
Zanamivir and Oseltamivir
What is the main treatment option for people who need treatment for HBV?
PEG-IFN-alpha
What is the structure and function of Zanamivir and Oseltamivir?
Sialic acid analogs that inhibit viral neuraminidase. Virions remain attached to the cell.
What is the “broad spectrum” RNA antiviral?
Ribavirin
What is the structure of ribavirin?
nuceoside analogu of guanosine
How is ribavirin formulated?
oral, IV and aerosole
What is Ribavirin approved for used against?
HCV and RSV
Which antiviral has a lot of off label use?
Ribavirin
How is HCV treated?
combined therapy of Peg-interferon-alpha with Ribavirin
Problem with HCV therapy?
Not all HCV genotypes respond to drugs
Which hepatitis virus has awful treatment side effects?
HCV
What are two alternative treatments for HCV? Are they approved yet?
Sofosbuvir and Ledipasvir. They are not approved yet!
What are the classes of anti-HIV drugs?
1- Entry inhibitors 2- Nucleoside/tide RT inhibitor 3- Non-nucleoside RT inhibitor 4- Integrase inhibitor 5- Protease inhibitor
What is critical in HIV treatment?
HAART (using multiple drugs in treatment that target different stages of viral replication) and compliance.
What is cobicistat? What are its benefits?
a drug enhancer that inhibits CYP3A4 that breaks down drugs in the liver. Benefit is that it allows for fewer pills or doses.
