8. Antiviral Agents Flashcards
What is a virus?
An obligate intracellular parasite with no cell wall/membrane that is capable of causing disease in the infected host.
What is the range of size for viruses?
25-400 nanometres.
What do viral genomes consist of?
DNA or RNA.
How do viruses replicate?
Using host metabolic machinery, hide within host cell.
Why are there not many successful antivirals?
Because the virus is in the host cell so can’t prevent replication unless the host is injured too.
What are the 6 stages of viral replication?
Attachment, penetration, uncoating, replication/protein synthesis, assembly, release.
Name two antivirals used to treat influenza A and B.
Oseltamivir (tamiflu), zanamivir.
What is the route of administration for flu drugs oseltamivir and zanamivir?
Oseltamivir - oral, zanamivir - inhaled/intranasal.
What is the mechanism of action of flu drugs oseltamivir and zanamivir?
Neuraminidase inhibitors, blocks release of newly assembled influenza virions from the host cell.
How can resistance to flu drugs oseltamivir and zanamivir develop?
Mutation of neuraminidase so it doesn’t allow the drugs to bind well.
Why are flu drugs oseltamivir and zanamivir still used despite resistance?
The mutations causing resistance form less fit viruses whereby the virus is ineffective in its job of infecting so less severe disease state.
When are flu drugs oseltamivir and zanamivir administered to exert therapeutic effects?
Prophylactically to prevent infection or within 48 hours of infection to reduce intensity and duration of symptoms.
Which diseases are herpes viruses associated with?
Cold sores, encephalitis, genital infections.
Which antiviral is directed at herpes viruses?
Aciclovir (‘zovirax’).
What are the routes of administration for the herpes antiviral drug aciclovir?
IV, oral, or topical cream.
What is the mechanism of action for herpes antiviral drug aciclovir?
Purine/pyramidine analogues which are phosphorylated by viral thymidine kinase (activates) to inhibit viral DNA synthesis.
How does resistance develop against herpes antiviral drug aciclovir?
Thymidine kinase enzyme mutation in virus which prevents binding to acyclovir so it can’t act as a false substrate in DNA replication.
When is herpes antiviral drug aciclovir active?
In acute phase of viral infection where patient is symptomatic, not in latent phase as prevention of outbreak.
Which antiviral treats cytomegalovirus?
Ganciclovir.
What is the route of administration for CMV antiviral drug ganciclovir?
IV to cross BBB.
When is CMV antiviral drug ganciclovir used?
For CMV retinitis in immunocompromised patient and CMV prophylaxis in transplant patients.
What is the mechanism of action of CMV antiviral drug ganciclovir?
Analogue of acyclovir with greater affinity for CMV, phosphorylates using a different enzyme, inhibits viral DNA synthesis.
What are the ADRs of CMV antiviral drug ganciclovir?
Myelosuppressive, carcinogenic/teratogenic.
Why is renal failure a contraindication for ganciclovir antiviral therapy in CMV?
It’s renal cleared so accumulates in renal failure.
Name three antivirals used to treat HBV/HCV.
Lamivudine, sofosbuvir, interferon alpha.
What is lamivudine used for and what is its route of administration?
For HIV and hepatitis B, oral route.
What is the mechanism of action of HIV/HBV antiviral drug lamivudine?
Reverse transcriptase inhibitor - acts as false substrate and chain terminator of reverse transcriptase enzyme in viral replication.
What is the mechanism of action of HCV antiviral drug sofosbuvir?
Blocks action of HCV viral polymerase to prevent production of new virus.
What is interferon alpha used for and what is its route of administration?
Treatment of hepatitis B/C, IM injection.
What is the mechanism of action of HBV/HCV drug interferon alpha?
Immunomodulatory effect, stimulates proteins to enhance cellular resistance to viral infection.
What are the ADRs of interferon alpha treatment for HBV/HCV?
Flu-like illness, fever, chills, headaches, malaise, myalgia, arthralgia, nausea, vomiting, diarrhoea in first few hours-days.
What is ribavirin use to treat?
Chronic hepatitis C and infants with severe respiratory syncytial virus.
What is the route of administration for chronic HCV and infant RSV drug ribavirin?
Oral or IV.
What is the mechanism of action of chronic HCV and infant RSV drug ribavirin?
Guanosine analogue - inhibits guanosine triphosphate formation to prevent viral messenger RNA capping. Presents assembly of viral genome/DNA.
What are the ADRs of chronic HCV and infant RSV drug ribavirin?
Transient anaemia, teratogenic.
What is the prevalence of resistance to chronic HCV and infant RSV drug ribavirin?
Rare, hardly any reports.
What are the groups of antivirals used to treat HIV?
Nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, fusion inhibitors. New therapies - integrase inhibitors, and receptor inhibitors.
What is the mechanism of action for HIV nucleoside reverse transcriptase inhibitor drugs?
Inhibit DNA polymerase so CNA can’t replicate.
Name one nucleoside reverse transcriptase inhibitor.
Zidovudine.
What are some ADRs of HIV nucleoside reverse transcriptase inhibitor drugs?
Hyperlactataemia, lactic acidosis, hepatomegaly and steatosis.
Name on non-nucleoside reverse transcriptase inhibitor for HIV treatment.
Nevirapine.
What is the mechanism of action of non-nucleoside reverse transcriptase inhibitors used for HIV treatment?
Active without future phosphorylation, non-competitive inhibitors of HIV reverse transcriptase so it binds at different site to the NRTI but same effect.
Which HIV strand do non-nucleoside reverse transcriptase inhibitors work on?
HIV-1, not HIV-2.
Name on protease inhibitor used in HIV therapy.
Ritonavir.
What is the mechanism of action of protease inhibitors used in HIV treatment?
Blocks cleavage of viral polyproteins by HIV protease enzymes, preventing the production of viral proteins for the formation of final mature virions.
Name one fusion inhibitor used in HIV therapy.
Enfuviritide.
When are fusion inhibitors used in HIV therapy?
As salvage drug if all else haven’t worked.
What is the route of administration of fusion inhibitors in HIV therapy?
Subcutaneous (only HIV therapy).
Name one integrase inhibitor used in HIV therapy.
Raltegravir.
What is the mechanism of action of integrase inhibitors used in HIV therapy?
Prevent integration of HIV DNA provirus into host cell genome.
Why should antiviral drug resistance be tested for?
To optimise clinical outcomes, quality of life, longevity of the patient; save costs and adverse effects of ineffective therapy; reduce pool of drug resistant viruses in population that may transmit between individuals, reducing effectiveness of standard therapy.
When is antiviral drug resistance tested?
With evidence of therapeutic failure, due to resistance, poor compliance.
How is antiviral drug resistance tested?
Phenotypic characterisation linked to genetic mutations: incubate suspected drug resistant virus with varying concentrations of drug of interest in culture, look for graded response compared to a wild-type virus, look at specific sequencing/genotype of the mutation.
