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CMBM E3 CB > Anti-Viral Drugs > Flashcards

Anti-Viral Drugs Flashcards

1
Q

What is the mechanism of action for Acyclovir and related drugs?

A

Acyclovir acts as a nucleotide analog.

  1. It is converted to active drug through 3 phosphorylation steps by viral thymidine kinase; next 2 by host cell enzymes.
  2. It is then added to the growing chain of herpes virus DNA, resulting in chain termination.
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2
Q

Which drugs are related to Acyclovir?

A

Valacyclovir
Famciclovir
Penciclovir

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3
Q

What are associated side effects of Acyclovir, et al?

A

Very few. N/V/D most common.

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4
Q

How are Acyclovir and related drugs administered?

A

Acyclovir: oral, IV
Valacyclovir: oral
Famciclovir: oral
Penciclovir: topical

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5
Q

What enzyme is required for the mechanism of action of Acyclovir?

A

Viral thymidine kinase

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6
Q

How would you treat cold sores?

A

Topical Penciclovir. If something stronger is needed, then Acyclovir.

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7
Q

How would you treat HSV Keratitis?

A

Trifluridine or Idoxuridine

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8
Q

What is the mechanism of action for Trifluridine and Idoxuridine?

A

Both are analogs of thymidine. Inhibit viral DNA polymerase. Same mechanism as Acyclovir.

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9
Q

How would you treat CMV?

A
  1. Ganciclovir, Valganciclovir, Cidofovir

2. Foscarnet, Fomivirsen

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10
Q

What is the mechanism of action for Ganciclovir, et al?

A

They act as nucleotide analogs. Because CMV-infected cells lack viral thymidine kinase, phosphorylation occurs by a different kinase.

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11
Q

What is a common side effect of Ganciclovir?

A

Neutropenia (20-40% of patients)

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12
Q

What are common side effects of Valganciclovir and Cidofovir?

A

Valganciclovir–similar to ganciclovir

Cidofovir–dose-dependent nephrotoxicity

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13
Q

What is the mechanism of action of Foscarnet? What is it used for?

A

A pyrophosphate that inhibits viral replication at pyrophosphate-binding site on virus-specific DNA polymerases.

Used to treat CMV.

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14
Q

What is the mechanism of action of Fomivirsen?

A

An oligonucleotide that inhibits CMV replication through anti-sense mechanism.

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15
Q

What is the mechanism of action of Interferons?

A

Upregulate MHC I expression on hepatocytes; enhance activity of CD8 cells and NK cells.

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16
Q

What is the mechanism of action of PEG Interferon?

A
  1. Attach recombinant IFN-alpha to polyethylene glycol

2. Results in slowed degradation of IFN–>reduces number of weekly doses

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17
Q

What is the role of Type 1 IFN?

A
  1. In uninfected cells: induction of enzymes that block viral replication.
  2. In infected cells: increased expression of MHC I; killing by CTLs.
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18
Q

How is Hepatitis B treated?

A

Peg IFN + NRTI

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19
Q

Drugs used for Hepatitis B and their mechanisms

A

Lamivudine and Telbivudine –> inhibit HBV reverse transcriptase

Adefovir, Tenofovir, Entecavir –> inhibit reverse transcriptase AND DNA polymerase

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20
Q

What are some side effects of Interferons?

A

Significant adverse effects due to cascading effect of overproduction of immune cells:

Flu-lke symptoms
Bone marrow suppression
Depression and other psychiatric disorders
Exacerbation of autoimmune disorders

21
Q

How is Hepatitis C treated?

A

PEG-interferon plus Ribavirin plus HCV protease inhibitor (Boceprevir or Telaprevir)

22
Q

What is the mechanism of action of Ribavirin?

A

Guanosine analog. Interferes with viral RNA-dependent RNA polymerase.

23
Q

What are some side effects of Ribavirin?

A

Dose-dependent hemolytic anemia (10-20% of patients)
Dry cough
Dyspnea
Teratogenic

24
Q

What would you use to treat Influenza?

A 
Uncoating inhibitors (A)
Neuraminidase inhibitors (A and B)
25
Q

Which drugs are uncoating inhibitors? What do they treat?

A

Amantadine
Rimantadine

Treat influenza A.

26
Q

How does influenza virus leave a cell?

A

Hemagglutin (HA) is locked in the sialic acid until neuraminidase cleaves the bond, releasing the virus from the cells. Neuraminidase inhibitors would block the virus from leaving the cell.

27
Q

Which drugs are neuraminidase inhibitors?

A

Zanamivir

Oseltamivir

28
Q

How would you treat HPV and genital warts?

A
  1. Alpha interferon injections into wart

2. Imiquimod

29
Q

What is the mechanism of action of Imiquimod?

A

Immunomodulatory. Activates immune cells via TLR 7; stimulates IFN alpha and gamma production.

30
Q

What is Imiquimod used to treat?

A

Genital warts / HPV

31
Q

How would you treat RSV?

A
  1. Palivizumab

2. Ribavirin

32
Q

What is the mechanism of action of Palivizumab?

A

It acts as a monoclonal antibody to RSV F protein, the glycoprotein used for cell attachment.

33
Q

What is the mechanism of action of NRTIs?

A

They act as nucleotide analogs, competitively inhibiting transcription by binding to reverse transcriptase at the active site where it would normally pick up new nucleotides.

34
Q

What is the mechanism of action of NNRTIs?

A

They are NON-nucleotides. They bind directly to reverse transcriptase to shut transcription down.

35
Q

Which gene codes for protease?

A

Pol

36
Q

What is the mechanism of action of protease inhibitors?

A

They bind to the protease enzyme, preventing the splicing of polypeptide chains into functional proteins.

37
Q

What is significant about Ritonavir?

A

It inhibits protease AND cytochrome p450. This leads to a failure to metabolize other drugs and may result in toxicity.

38
Q

What is the mechanism of action of Raltegravir?

A

Integrase inhibitor. It binds to active site of Mg2+ on HIV integrase. Mg2+ is required for integrating the provirus into the host genome. If Mg2+ is blocked, integration does not occur.

39
Q

What is the mechanism of action of Integrase Inhibitors?

A

Block integration of provirus into host genome by binding to Mg2+ or Mn2+, the two required cofactors for DNA integrase.

40
Q

What is the mechanism of action of Maraviroc?

A

It is a CCR5 antagonist. It binds directly to a co-receptor (CCR5 or CXCR4), preventing the binding of gp120 on HIV cells.

41
Q

What is Maraviroc used to treat?

A

HIV-1. Not effective against HIV-2.

42
Q

What is the mechanism of action of Enfuvirtide? When is it used?

A

Enfuvirtide prevents fusion of HIV to the CD4 cell membrane by binding directly to gp41. This prevents the required folding of the gp41 molecule that brings the virus in contact with the cell membrane.

It is used after the failure of other anti-retroviral drugs.

43
Q

What are NRTIs and NNRTIs effective against?

A

NRTIs – HIV-1 and HIV-2

NNRTIs – HIV-1 only

44
Q

What is the recommended drug regimen for treatment-naive HIV patients?

A

Two NRTIs in conjunction with an NNRTI, protease inhibitor, or integrase inhibitor.

45
Q

What drugs are used as first line of treatment for HIV?

A
  1. Efavirenz / Tenofovir / Emtricitabine
  2. Ritonavir / Atazanavir / Tenofovir / Emtricitabine
  3. Ritonavir / Darunavir / Tenofovir / Emtricitabine
  4. Raltegravir / Tenofovir / Emtricitabine
46
Q

Which guidelines are used for starting ART therapy?

A
  1. Asymptomatic, CD4 count < 350 = Strongly recommended
  2. CD4 count 300 to 500 = Strongly recommended
  3. CD4 count > 500 = Moderately recommended
47
Q

What are some toxicities of ART?

A 
Lactic acidosis
Hepatotoxicity
Increased risk of MI
Bone marrow suppression
Nephrotoxicity
48
Q

What are some side effects of NNRTIs?

A

Hepatotoxicity

Rash

49
Q

What are some side effects of protease inhibitors?

A

Lipodystrophy
Hyperlipidemia
Hepatotoxicity
Increased risk of diabetes

CMBM E3 CB (12 decks)

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