Antiviral Agents Flashcards
How may viruses have specific antiviral drugs?
Very few
Was this the most boring lecture in the history of ever?
Yep
How do antivirals act?
As virostatics, rather than virocidals i.e. they just stop them from replicating.
What is required to clear existing viruses?
The host immune response.
Which are the most commonly empirically used antivirals?
Acyclovir and oseltamivir
Are antivirals broad spectrum?
No, very few can be used on an virus that it isnt specifically designed for.
What are the 3 mechanisms of non-antiretroviral drugs?
- Direct inactivation of viruses (virucides)
- Inhibition of viral replication
- Host response immunomodulation
What is the drawback to virucides?
They cannot be used systemically, only topically.
What are the steps of viral replication that we can target?
Attachment Uncoating DNA/RNA replication Protein synthesis Assembly and release Integrase enzyme Reverse traqnscription Fusion/entry Protease enzyme
How can we modulate the host immune response?
Replace deficient hot immune elements, or enhance host immunity.
What viral infections can we give Ig for?
HBV VZV HAV Rabies Vaccinia
What antivirals can we give for herpes?
Aciclovir
Valaciclovir
Penciclovir
Famciclovir
How do aciclovir and the other anti-herpes agents act?
As guanosine nucleoside analogues
Is aciclovir more effective againsts HSV1 & 2, or VZV?
HSV1&2 by about 10 times
Can we treat EBV with aciclovir?
It inhibits its replication but is not effective against latent or persistent infection.
Are agents such as aciclovir, valaciclovir, and penciclovir well tolerated?
Yes, but there is some nephrotoxicity. 1-4% experience CNS symptoms.
What CNS symptoms can pts on aciclovir/valaciclovir experience?
Lethergy Confusion Tremor Myclonus Hallucination Delerium Seizures Extrapyramidal signs ANS symptoms Coma
Which anti-herpes drugs are aggressive against bone marrow?
Ganciclovir
Valganciclovir
Which agents are best for use against CMV?
Ganciclovir
Valganciclovir
How do Ganciclovir and Valganciclovir act?
A guanosine nucleoside analogues
What are the potential adverse effects of Ganciclovir and Valganciclovir?
Nephrotoxicity
Myelosuppression
Neurotoxicity
What % of pts on Ganciclovir and Valganciclovir experience CNS symptoms?
5-15%
How does cidofovir work?
As a cytidine nucleotide analogue
What are the ADRs associated with cidofovir?
Nephrotoxicity
Neutropenia -> fever, nausea, vomiting, headache, rash
How does foscarnet work?
As a pryophosphate analogue
What is foscarnet active against?
Herpes viruses and HIV
Why is foscarnet good?
It is active against anciclovir resistant CMV and aciclovir resistant HSV.
What is pyrophosphate used for in viral replication?
Binds to viral polymerase to activate it.
How can viral resistance occur against foscarnet?
Mutation in viral DNA polymerase so it cannot bind to pyrophosphate site.
What is the problem with foscarnet?
Narrow therapeutic window, can be nephrotoxic, and cause adverse CNS effects.
What are the drugs we can use against Hepatitis B?
Lamivudine Adefovir Emtricitabine Entecavir Telbivudine
What kind of drug is lamivudine?
A cytidine nucleoside analogue
What kind of drug is adefovir?
Adenosine nucleotide analogue
What kind of drug is emtricitabine?
5’ fluoricil analogue
What kind of drug is entecavir?
Guanasine nucleoside analogue
What kind of drug is telbivudine?
Thymidine analogue
What are nucleoside analogues?
Viral DNA polymerase inhibitors
Tell me about lamivudine.
Terminates chain in transcription of HIV and HBV. Well tolerated. Common for liver enzymes to increase.
Tell me about adefovir.
Terminates chain in transcription of HIV and HBV. Works against resistant strains of HBV. Nephrotoxic at higher doses, so not used for HIV.
Is emtricitabine well tolerated?
Yes, but also can cause nausea, headaches, and hyperpigmented palms and soles.
What drugs do we use to treat Hepatitis C?
Ribavirin
Interferons
What interferons are there?
INF alpha
INF beta
INF gamma
Tell me about ribavirin.
Guanosine analogue
Able to inhibit both RNA and DNA.
Resistance is rare.
What are the adverse effects of ribavirin?
Reversible anaemia
Bone marrow suppression at higher doses
Tell me about interferons.
Given IM. Mediate viral interference. Not directly antiviral but stimulate proteins to enhance cellular resistance.
Tell me about endogenous INF alpha.
Produced by mast cells in response to viral infection
Tell me about endogenous INF beta.
Produced by mast cells in response to viral infection
Tell me about endogenous INF gamma.
Produced by T lymphocytes and NK cells in response to IL-2, antigens, and mitogens.
What drugs do we use in the treatment of influenza?
Amantidine
Rimantidine
Oseltamivir
Zanamivir
What are amantidine and rimantidine?
Symmetric tricyclic amines
What are oseltamivir and zanamivir?
Neuraminidase inhibitors
What do amantidine and rimantidine act on?
Influenza A (not B)
How does resistance arise against amantidine and rimantidine?
Readily with single amino acid substitutions.
What do oseltamivir and zanamivir work on?
Influenza A and B, and amantidine resistant strains
What is the new drug under clinical trial for CMV and EBV?
Maribavir
What is the new drug under clinical trial for enteroviruses and rhinoviruses?
Pleconaril
