Anti-Virals Flashcards
What are the targets for anti-viral drugs?
Viral glycoprotein envelope uncoating, DNA/RNA polymer synthesis, viral release.
What are the challenges in developing effective anti-viral agents?
Viruses are intercellular parasites so they are hard to target whilst avoiding host toxicity. It is also hard to design culture systems for viruses as they require host cells. Viruses are often host-specific so animal tests don’t yield much information.
What drugs target viral glycoprotein envelope uncoating?
Amantadine, rimantadine.
What was amantadine used for before it was used as an anti-viral drug?
An anti-parkinsonian medication.
Chemically, what type of drugs are amantadine and rimantadine?
Tricyclic amines.
What type of virus are amantadine and rimantadine only effective against?
Influenza A.
Apart from its narrow spectrum of activity, what other problem might there be with using amantadine/rimantadine?
It may be difficult to build up high enough concentrations of the drug.
What serious side effect can amantadine and rimantadine have? Which drug has a greater risk of causing this?
Neurotoxicity. Amantadine has a greater risk of causing neurotoxicity than rimantadine.
What drugs prevent the release of viruses from the host cell?
Oseltamivir (tamiflu) and zanamivir (relenza).
What have large-scale trials shown about the efficacy of oseltamivir and zanamivir?
That they may be no more effective than placebos.
What are oseltamivir and zanamivir indicated for?
They are indicated for the treatment of influenza A and B within 24-48 hours of symptom onset. They are also indicated for prophylaxis of these infections.
How do oseltamivir and zanamivir act to prevent the viral release from the host cell?
They block the action of the enzyme neuraminidase, which cleaves the terminal sialic acid residues attached to glycoproteins and glycolipids, a process necessary for the release of the virus from host cells.
How is oseltamivir administered?
Orally.
How is zanamivir administered?
Orally or by inhalation.
How is oseltamivir excreted?
Renally.
What are the side effects of zanamivir?
Reactive airway disease.
What are the side effects of oseltamivir?
Nausea and vomiting.
What drugs inhibit viral DNA/RNA synthesis?
Anti-herpesvirus drugs such as famciclovir, ganciclovir, idoxuridine, trifluridine.
How do anti-herpesvirus agents work?
They are either analogues of pyrimidine or purine nucleotides, they competatively inhibit the enzymes used for DNA/RNA synthesis.
Describe the structure of famciclovir and ganciclovir.
They are purines with incorrect sugar groups attached to them.
Describe the structure of idoxuridine and trifluridine.
They are molecules in which the sugar part of the molecule is correct but the pyrimidine is incorrect.
Why must one part of the nucleotide analogue anti-herpesvirus agents be the same as the molecule they resemble?
So they can be recognised by the enzyme which they are designed to inhibit the action of. If they were too different from the molecules they resemble, the enzyme wouldn’t recognise them and they wouldn’t be able to inhibit the enzyme.
What is one of the most commonly used anti-viral drugs?
Acyclovir.
Which anti-viral drug is an acyclic guanosine analogue?
Acyclovir.
How does acyclovir work to prevent viral DNA/RNA replication?
It is preferentially taken up by virally infected cells, is it phosphorylated by viral kinases and then di- and tri-phosphorylated by cellular kinases. It then acts as a competitive inhibitor of viral DNA polymerase. This leads to viral DNA chain termination.
What are the side effects associated with acyclovir use?
Headache, nausea, renal toxicity, neurotoxicity.
What drug is used as an antiviral agent primarily in the eye?
Trifluridine.
Where is the anti-herpesvirus drug trifluridine primarily used?
The eye.
