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Disease and Defense > Antiviral Agents > Flashcards

Antiviral Agents Flashcards

1
Q

What is the primary means to control viral spread?

A

Public health measures as well as prophylactic vaccines.

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2
Q

How does influenza enter the host cell?

A

Hemagglutinin binds to the cell and the virus is endocytosis

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3
Q

What happens when the endosome containing the influenza virus is acidified?

A

Two things: First there is a conformational change in hemagglutinin structure that mediates fusion between the influenza viral envelope and the endosomal membranes. Then, activation of viral M2 proton channel elicits the release of RNA genome.

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4
Q

What two processes occur in order for the influenza to egress from the host cell?

A
  1. Hemagglutinin interacts with cellular sialic acid moieties.
    2.Viral envelope-bound neuraminidases cleave the sequestered sialic acid moieties.
    Viral release
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5
Q

What are the three inhibitors of viral neuraminidase?

A
  1. Oseltamivir (Tamiflu)
  2. Zanamivir (Relenza)
  3. Peramivir (Rapivab)
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6
Q

What does the inhibition of the enzyme neuraminidase lead to?

A

Virus aggregates at cell surface decreasing both intracellular viral translocation and viral budding

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7
Q

Is resistance to inhibition of viral neuraminidase a particular problem?

A

Yes, but it is relatively rare 1-4%

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8
Q

Describe the pharmacokinetics of Oselamivir.

A

Oseltamivir is an oral prodrug excreted renally

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9
Q

Describe the pharmacokinetics of Zanamivir.

A

Zanamivir is inhaled and eliminated renally

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10
Q

Describe the pharmacokinetics of Peramivir.

A

Peramivir is given as a single IV dose

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11
Q

What type of influenza does neuramindase inhibitors, inhibit?

A

Both influenza A and B

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12
Q

What are two drugs that inhibit the uncoating of influenza in the host cell?

A

Amantadine (Symmetrel) and Rimantadine (Flumadine)

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13
Q

What is the target of amantadin and rimantadine?

A

Blocks the proton channel M2

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14
Q

Describe the pharmacokinetics of amantadine.

A

Orally. Excreted renally

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15
Q

Describe the pharmacokinetics of rimantadine.

A

Orally with hepatic elimination

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16
Q

What group would you not prescribe amantadine or rimantadine.

A

Breast feeding mother. It is excreted through breast milk

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17
Q

What type of influenza is used amantadine or rimantadine used for ?

A

Type A

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18
Q

Name adverse reactions of amantadine and rimantadine.

A

Amantadine- insomnia, [] difficulties,

Rimantadine- poor CNS penetration. Not for use in pregnant women

19
Q

Acyclovir, Valacyclovir, Penciclovir, and Famciclovir are all examples of what?

A

Inhibitors of viral genome replication in the treatment of herpes infection.

20
Q

What enzyme converts nucleoside analogs to the active triphosphate form?

A

VIRAL thymidine kinase

21
Q

What drug competes with dGTP to terminate viral replication? Hint: It also irreversibly binds and inactivates viral DNA polymerase

A

Acyclovir-TP

22
Q

How do herpes viruses gain resistance to inhibitors of viral genome?

A

They reduce or loose expression of viral thymidine kinase

23
Q

What are the pharmacokinetics of viral inhibition of replication drugs?

A

Acyclovir- Poor oral, IV or topical
Valacyclovir- prodrug or acyclovir oral (3-5X)

Penciclovir- Topical only
Famciclovir- Penciclovir prodrug. Increased oral bioavailability

Vidarabine-trifluidine- topical

24
Q

How are viral inhibition of replication drugs eliminated?

A

Renally but clearance in neonates is 1/3 of adults

25
Q

How would you treat genital herpes?

A

Oral acyclovir

26
Q

When would you use intravenous acyclovir?

A

To treat herpes simplex encephalitis, neonatal HSV infections, and serious HSV or VZA infections (higher doses required for zoster)

27
Q

What would you use to treat HSV keratoconjunctivitis and reccuent epithelial keratitis?

A

Topical vidarabine and trifluridine

28
Q

Name a drug that inhibits viral penetration.

A

Docosanol

29
Q

How does docosanol prevent viral penetration?

A

They prevent the fusion of viral and host membrane. Used topically for orofacial herpes.

30
Q

What drug is used for the treatment of respiratory syncitial virus?

A

Ribavirin

31
Q

What is ribavirin?

A

A purine nucleoside analog that inhibits GTP-dependent 5’ capping of viral mRNA.

32
Q

What are the pharmacokinetics of ribavirin?

A

Oral bioavailability good. Hepatic metabolism and renal excretion.

33
Q

What are the adverse reactions of Ribavirin?

A

Inhalation: fine
Oral-systemic: hemolytic anemia
TERATOGENIC = NO PREGNANT WOMEN

34
Q

How would you treat hepatitis C

A

Ribavirin with interferon

35
Q

What is the action of Ganciclovir and Valganciclovir?

A

Inhibition of viral DNA polymerase. Nucleotide analog.

36
Q

Ganciclovir and Valganciclovir must be phosphorylated in order to become activate. What enzyme phosphorylates these drugs and is it the target for resistance?

A

The enzyme is Viral protein kinase UL97 and it is the target for resistance.

37
Q

Describe the pharmacokinetics of Ganciclovir and Valganciclovir.

A

Ganciclovir- IV primarily excreted unchanged via urine

Valganciclovir- prodrug converted to ganciclovir by GI and hepatic enzymes

38
Q

What is the major side effect or concern with using ganciclovir or valganciclovir?

A

They are myelocuppressive and result in neutropenia and thrombocytopenia

39
Q

What two drugs can be used to treat cytomegalovirus?

A

Ganciclovir/Valganciclovir and Foscarnet

40
Q

Describe foscarnet.

A

Inorganic pyrophosphate analog that does not require cellular activation.

41
Q

What is the action of foscarnet?

A

It inhibits the cleavage of pyrophosphate from deoxxy-TP= block in replication

42
Q

How is foscarnet administered?

A

IV infusion and is eliminated via the urine

43
Q

What are some of the severe side effects you need to worry about when using foscarnet?

A

Nephrotoxicity and hypocalcemia can lead to death

Disease and Defense (14 decks)

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