2-25 Antiviral Drugs Flashcards Preview

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Flashcards in 2-25 Antiviral Drugs Deck (19):
1

What are some viruses that are treatable with antiviral drugs?

  • Hepatitis C
  • HIV
  • Flu
  • Croup
  • Warts
  • Systemic adenovirus
  • Hepatitis B
  • Some herpesvirus
  • Smallpox

2

What are some types of antivirals?

  • Nucleoside analogs (“Nucs”)
  • Non-nucleosides (“Non nucs”)
  • Protease inhibitors
  • Entry inhibitors

3

How do antiviral drugs work?

  • Target essential virus functions: entry, uncoating, genome replication, assembly, release from cell
  • Target host cell defenses (intrinsic immunity): interferon pathway
  • Activate immune response

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4

How can antiviral drugs be involved in the nucleotide synthesis pathways?

  • Many antivirals are nucleoside analogs that compete for the enzymes in the purine and pyrimidine synthesis pathways
  • Viral enzymes are also involved

5

What are some important problems with antivirals?

  • Specificity: most drugs target functions of only one virus; broad-spectrum drugs are rare (high viral mutation rate)
  • Cytotoxicity: “off-target” effects can harm cells; “on-target” drugs directed at viral enzymes can be defeated by resistance mutations
  • Duration of antiviral effects: most drugs are reversible (competitive inhibitors); virus replication can resume when drug is cleared (rebound); treatment might need to be life long!

6

How is resistance a problem for antivirals?

  • Resistance mutations often exist in a patient BEFORE drug treatment
  • Drug treatment selects for resistant virus strains

Factors that increase resistant variants:

  • High rate of virus replication
  • High mutation rate (RNA viruses >> DNA viruses)
  • High selective drug pressure (long-term or multiple treatments)
  • Immunosuppressed host that cannot clear virus-infected cells

7

How do we counter resistance to antivirals?

  • Alleviate immunosuppression: reduce doses of anti-T cell drugs (steroids, cyclosporin, etc.)
  • Combine drugs with different targets (standard of care for HIV and HCV infections): drugs with different mechanisms of action synergize; lower probability that multiple resistance mutations will be present
  • Target host functions: infected cells may have unique profile that can be a drug target; virus mutations do not impact cellular genes (some cancer drugs target dividing cells and also inhibit viruses)

BUT beware of toxicity!

8

Who should be treated for HSV-1, HSV-2, and VZV?

(With acyclovir.)

  • Neonates infected w/ HSV at birth
  • People with freq. recurrences (Type 1 or 2)
  • Complicated HSV infections: encephalitis, dissemination throughout body, eye infxns
  • People w/ zoster (w/in 3 days of appearance of rash)

9

What is acyclovir?

An antiviral treatment for HSV-1, HSV-2, and VZV.

  • Nucleoside analog of guanosine
  • Effective against: HSV-1 = HSV-2 >> VZV
  • Trade name: Zovirax
  • Derivatives: Valaciclovir (Valtrex), Penciclovir (Denavir), Famciclovir (Famvir)

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10

What is the mechanism of acyclovir?

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11

What is ganciclovir?

An antiviral treatment for CMV.

  • Nucleoside analog of guanosine
  • Ganciclovir = Cytovene; derivative: Valganciclovir = Valcyte
  • Similar mechanism of action to acyclovir
  • Highly toxic: suppresses bone marrow, mutagenic and teratogenic, severe side effects

Who should be treated?

  • Bone marrow and organ transplant patients
  • Immunosuppressed people w/ active CMV
  • Patients w/ CMV retinitis

12

What are some “broad-spectrum” treatments
for DNA viruses?

Foscarnet (Foscavir):

  • Trisodium phosphonoformate
  • Inhibits viral DNA polymerase
  • Effective against all herpesviruses
  • I.V. route only
  • Toxic to kidneys

Cidofovir (Vistide):

  • Nucleoside analog of cytosine
  • Effective against DNA viruses: herpesvirus, adenovirus, papillomavirus, poxvirus
  • I.V. route only
  • Toxic to kidneys

13

What are antiviral treatments for HBV, and who should receive them?

HBV is treated with drugs designed for HCV and HIV. Current drug options:

  • Pegylated interferon alpha (PEG-IFN-α) = Pegasys
  • Entecavir = Baraclude
  • Tenofovir disoproxil fumarate = Viread

Who should be treated?

  • People w/ chronic active HBV disease
  • People co-infected w/ HCV and/or HIV
  • People who are progressing to cirrhosis, liver failure, or hepatocellular carcinoma

14

Who should be treated for influenza virus?

  • The severely ill (hospitalized)
  • Children < 2yo
  • Adults > 65yo
  • Pregnant women
  • Immunosuppressed people
  • ANYONE suspected of having influenza

15

What are the treatments for influenza virus?

Zanamivir (Relenza) and Oseltamivir (Tamiflu).

  • Both are sialic acid analogs that inhibit viral neuraminidase (sialidase)
  • Virions remain attached to cell

16

What is Ribavirin?

 An inexpensive, OTC, “broad-spectrum” medication for RNA viruses.

  • Nucleoside analog of guanosine
  • Oral, I.V., and aerosol formulations
  • Approved for use against HCV and RSV
  • Off-label use: HSV, influenza, SARS, and MANY others

17

What is AZT?

Zidovudine, the first drug for HIV. Now an “antique.”

  • Nucleoside analog of thymidine
  • “NRTI” class (Nucleoside Reverse Transcriptase Inhibitor)

18

What are the classes of anti-HIV drugs, and how are they typically used?

  1. Entry inhibitor: Maraviroc (Selzentry)
  2. NRTI (Nucleoside/tide RT inhibitor): Tenofovir (Viread), Emtricitabine (Emtriva)
  3. NNRTI (Non-nucleoside RT inhibitor): Efavirenz (Sustiva)
  4. IN (Integrase inhibitor): Raltegravir (Isentress)
  5. PI (Protease inhibitor): Darunavir (Prezista)

They are typically used in combination.

19

What is Stribild?

A four-drug combination for HIV that can be given in one daily pill.

  1. Elvitegravir: integrase
  2. Cobicistat (boosts potency of elvitegravir): liver enzyme
  3. Emtricitabine: reverse transcriptase
  4. Tenofovir disoproxil fumarate: reverse transcriptase