Antiviral Agents Flashcards

1
Q

How may viruses have specific antiviral drugs?

A

Very few

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2
Q

Was this the most boring lecture in the history of ever?

A

Yep

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3
Q

How do antivirals act?

A

As virostatics, rather than virocidals i.e. they just stop them from replicating.

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4
Q

What is required to clear existing viruses?

A

The host immune response.

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5
Q

Which are the most commonly empirically used antivirals?

A

Acyclovir and oseltamivir

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6
Q

Are antivirals broad spectrum?

A

No, very few can be used on an virus that it isnt specifically designed for.

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7
Q

What are the 3 mechanisms of non-antiretroviral drugs?

A
  • Direct inactivation of viruses (virucides)
  • Inhibition of viral replication
  • Host response immunomodulation
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8
Q

What is the drawback to virucides?

A

They cannot be used systemically, only topically.

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9
Q

What are the steps of viral replication that we can target?

A
Attachment
Uncoating
DNA/RNA replication
Protein synthesis
Assembly and release
Integrase enzyme
Reverse traqnscription
Fusion/entry
Protease enzyme
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10
Q

How can we modulate the host immune response?

A

Replace deficient hot immune elements, or enhance host immunity.

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11
Q

What viral infections can we give Ig for?

A
HBV
VZV
HAV
Rabies
Vaccinia
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12
Q

What antivirals can we give for herpes?

A

Aciclovir
Valaciclovir
Penciclovir
Famciclovir

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13
Q

How do aciclovir and the other anti-herpes agents act?

A

As guanosine nucleoside analogues

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14
Q

Is aciclovir more effective againsts HSV1 & 2, or VZV?

A

HSV1&2 by about 10 times

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15
Q

Can we treat EBV with aciclovir?

A

It inhibits its replication but is not effective against latent or persistent infection.

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16
Q

Are agents such as aciclovir, valaciclovir, and penciclovir well tolerated?

A

Yes, but there is some nephrotoxicity. 1-4% experience CNS symptoms.

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17
Q

What CNS symptoms can pts on aciclovir/valaciclovir experience?

A
Lethergy
Confusion
Tremor
Myclonus
Hallucination
Delerium
Seizures
Extrapyramidal signs
ANS symptoms
Coma
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18
Q

Which anti-herpes drugs are aggressive against bone marrow?

A

Ganciclovir

Valganciclovir

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19
Q

Which agents are best for use against CMV?

A

Ganciclovir

Valganciclovir

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20
Q

How do Ganciclovir and Valganciclovir act?

A

A guanosine nucleoside analogues

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21
Q

What are the potential adverse effects of Ganciclovir and Valganciclovir?

A

Nephrotoxicity
Myelosuppression
Neurotoxicity

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22
Q

What % of pts on Ganciclovir and Valganciclovir experience CNS symptoms?

A

5-15%

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23
Q

How does cidofovir work?

A

As a cytidine nucleotide analogue

24
Q

What are the ADRs associated with cidofovir?

A

Nephrotoxicity

Neutropenia -> fever, nausea, vomiting, headache, rash

25
Q

How does foscarnet work?

A

As a pryophosphate analogue

26
Q

What is foscarnet active against?

A

Herpes viruses and HIV

27
Q

Why is foscarnet good?

A

It is active against anciclovir resistant CMV and aciclovir resistant HSV.

28
Q

What is pyrophosphate used for in viral replication?

A

Binds to viral polymerase to activate it.

29
Q

How can viral resistance occur against foscarnet?

A

Mutation in viral DNA polymerase so it cannot bind to pyrophosphate site.

30
Q

What is the problem with foscarnet?

A

Narrow therapeutic window, can be nephrotoxic, and cause adverse CNS effects.

31
Q

What are the drugs we can use against Hepatitis B?

A
Lamivudine
Adefovir
Emtricitabine
Entecavir
Telbivudine
32
Q

What kind of drug is lamivudine?

A

A cytidine nucleoside analogue

33
Q

What kind of drug is adefovir?

A

Adenosine nucleotide analogue

34
Q

What kind of drug is emtricitabine?

A

5’ fluoricil analogue

35
Q

What kind of drug is entecavir?

A

Guanasine nucleoside analogue

36
Q

What kind of drug is telbivudine?

A

Thymidine analogue

37
Q

What are nucleoside analogues?

A

Viral DNA polymerase inhibitors

38
Q

Tell me about lamivudine.

A

Terminates chain in transcription of HIV and HBV. Well tolerated. Common for liver enzymes to increase.

39
Q

Tell me about adefovir.

A

Terminates chain in transcription of HIV and HBV. Works against resistant strains of HBV. Nephrotoxic at higher doses, so not used for HIV.

40
Q

Is emtricitabine well tolerated?

A

Yes, but also can cause nausea, headaches, and hyperpigmented palms and soles.

41
Q

What drugs do we use to treat Hepatitis C?

A

Ribavirin

Interferons

42
Q

What interferons are there?

A

INF alpha
INF beta
INF gamma

43
Q

Tell me about ribavirin.

A

Guanosine analogue
Able to inhibit both RNA and DNA.
Resistance is rare.

44
Q

What are the adverse effects of ribavirin?

A

Reversible anaemia

Bone marrow suppression at higher doses

45
Q

Tell me about interferons.

A

Given IM. Mediate viral interference. Not directly antiviral but stimulate proteins to enhance cellular resistance.

46
Q

Tell me about endogenous INF alpha.

A

Produced by mast cells in response to viral infection

47
Q

Tell me about endogenous INF beta.

A

Produced by mast cells in response to viral infection

48
Q

Tell me about endogenous INF gamma.

A

Produced by T lymphocytes and NK cells in response to IL-2, antigens, and mitogens.

49
Q

What drugs do we use in the treatment of influenza?

A

Amantidine
Rimantidine
Oseltamivir
Zanamivir

50
Q

What are amantidine and rimantidine?

A

Symmetric tricyclic amines

51
Q

What are oseltamivir and zanamivir?

A

Neuraminidase inhibitors

52
Q

What do amantidine and rimantidine act on?

A

Influenza A (not B)

53
Q

How does resistance arise against amantidine and rimantidine?

A

Readily with single amino acid substitutions.

54
Q

What do oseltamivir and zanamivir work on?

A

Influenza A and B, and amantidine resistant strains

55
Q

What is the new drug under clinical trial for CMV and EBV?

A

Maribavir

56
Q

What is the new drug under clinical trial for enteroviruses and rhinoviruses?

A

Pleconaril