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Module 7: Multisystem > Antiviral Drugs > Flashcards

Antiviral Drugs Flashcards

1
Q

What are the major sites of antiviral Drug action?

A

1. Viral attachment and entry
Blocked by:
Enfuvirtide (HIV)
Maraviroc (HIV)
Docosanol (HSV)
Palivizumab (RSV)

2. Viral Penetration
Blocked by:
Interferon-a (HBV, HCV)

3. Uncoating of viral proteins
Blocked by:
Amantadine, Rimantadine (Influenza)

4. Nucleic acid synthesis
Blocked by:
NRTIs (HIV, HBV)
NNRTIs (HIV)
Acyclovir (HSV)
Foscarnet (CMV)

5. Late Protein synthesis and processing
Blocked by:
Protease Inhibitors (HIV)

6. Viral release
Blocked by:
Neuraminidase inhibitors (Influenza)

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2
Q

Amantadine

A

Used for prophylaxis of Influenza A

  • *Inhibits M2 proton channel** (unique to viruses)
  • -> prevents acidification necessary for uncoating
  • Toxicities are those expected from a dopamine agonist
    (originally deeloped as an anti-parkinson drug)

Rimantidine is an alpha-mehtyl derivative of Amantadine with similar mode of action

  • May shorten duration of illness if taken after symptoms present
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3
Q

Maraviroc

A

Inhibits HIV attachment

Inhibits bindign of gp120 to CCR5

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4
Q

Enfuvirtide

A

Inhibits HIV attachment
Synthetic peptide

  • Locks gp41 in extended conformation

–> No fusion of viral envelop and cell membrane

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5
Q

Docosanol

A

Topical treatment against HSV
(abreva)

–> prevents attachment and penetration of virus

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6
Q

Palivizumab

A

Humanized mAb against coat protein of RSV for high-risk patients

  • Prevents attachment and penetration
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7
Q

Triflundine

A

Treatment for herpes keratitis treatment

Inhibits thymidylate synthase

(very toxic)

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8
Q

Ribavirin

A

Inhibits purine biosynthesis

Interferes with RNA metabolism needed for viral replication; widely active with DNA and RNA viruses

Aerosolized delivery for RSV (especially infants)

Hepatitis C (in combination with IFN-alpha)

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9
Q

Acyclovir

A

Acyclovir is a pro-drug that is phosphorylated by viral Thymidine Kinase

Then cellular kinases convert it to acycloguanosine triphosphate (acyclo GTP) which is incorporated into infected DNA

–> acyclo GTP doesn’t have the hydroxyl group required to make phosphodiester bonds

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10
Q

Ganciclovir

A

Another nucleoside analog (like acyclovir) that is most useful against CMV

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11
Q

What are the types of Nucleoside Reverse Transcriptase Inhibitors (NRTIs) for HIV?

A

Azidothymidine/Zidovudine

Stavudine

Lamivudine - used with IFN-a to treat HBV and pregnant women (lower side effects)

Zalcitabine

Didanosine

Abacavir

Emtricitabine - fluorinated analog of lamivudine

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12
Q

Azidothymidine (AZT, zidovudine)

A

Prodrug converted by cellular kinases into AZT-TP in which Reverse Transcriptase has and increased affinity for, making it more specific to infected cells

  • -> many Side Effects:
    i. e. Anemia, granulocytopenia

Short 1/2 life

–> frequent dosing required

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13
Q

Didanosine

A

Nucleoside RT inhibitor

Side effect: pancreatitis

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14
Q

Abacavir side effects

A

Nucleoside RT inhibitor for HIV

Hypersensitivty rxns

hepatosplenomegaly

–> especially in HLA-B*5701 patients

–> used only after genotyping

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15
Q

What are the nucleoside RT inhibitors for HBV only?

A

Entecavir (guanosine analog)

Telbivudine (thymidine analog)

–> not effective against HIV

–> effective against HBV RT/DNA polymerase

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16
Q

What are the available Nucleotide Reverse Transcriptase Inhibitors?

A

Tenofovir

Cidofovir

Adefovir

17
Q

Tenofovir

A

Nuceotide analog

Nucleoside phosphonate that is converted to the di- and tri-phosphate in resting cells

–> this gets around the problem of initial phosphorylation

Competitively inhibits HIV RT, causes chain termination
(approved for HBV as well)

reduced renal function over time

18
Q

Cidofovir

A

Nucleotide RTI

** Inhibitory effect on viral DNA polymerase**

used for ganciclovir/foscarnet-resistant CMV and acyclovir-resistant HSV

Doesn’t require virally coded enzymes for phosphorylation

19
Q

Adefovir

A

Nucleotide RTI

Used against HBV

Potential for lactic acidosis

20
Q

What are the available Non-nucleoside RT inhibitors?

A

Nevirapine - recommended against pregnant patients, Stevens Johnson syndrome possible, risk fo hepatotoxicity

Rilpivirine

Etravirine

Delavirdine

Efavirenz

21
Q

Efavirenz

A

NNRTI for HIV

Once a day dosing

Fewer serious toxic side effects (nightmares)

NOT to be used during pregnancy

22
Q

Foscarnet

A

Inorganic pyrophosphate analog

Inhibits HSV and CMV DNA polymerase

Used for treatment of ganciclovir-resistant CMV retinitis

IV only

Side effects:
Nephrotoxicity
Hypocalcemia

23
Q

What are the available integrase inhibitors?

A

Raltegravir

Elvitagravir - newer inhibitor; only used in combination therapy

24
Q

What are the available protease inhibitors?

A

Fosamprenavir
atanazavir
darunavir
indinavir
Lopinavir*
Nelfinavir
Ritonavir*
Saquinavir
Tipranavir
Telaprevir** (inhibits HCV serine protease)
Boceprevir** (inhibits HCV serine protease)

*Recommended for pregnant patients
**Beware drug interactions!

25
Q

Does resistance to one protease inhibitor mean resistance to all?

A

Not necessarily

protease inhibitors each have different sites of action, thus making them variable in resistance

–> sequencing of viral protease can help predict resistance to various inhibitors

26
Q

Side effects of protease inhibitors

A

Increased LDL

Decreased HDL

Increased Triglycerides
–> Lipodystrophies

Hyperglycemia (insulin resistance)

*Atanazavir has lower incidence of lipodystrophies

27
Q

Why are Interferons used for antiviral treatment?

A

IFN-alfa has antiviral activity (hepatitis B and C)
Transcription inhibition
Translation Inhibition
Protein Processing Inhibition
Virus Maturation Inhibition

–> most effective against C when used in combination with:
Ribavirin (Nucleoside RTI) and Protease Inhibitors

–> pegylated forms have improved pharmacokinetics

28
Q

What are available neuraminidase inhibitors?

A
29
Q

How is use of Anti-Retroviral Therapy determined for HIV patients?

A

CD4 Count is the major indicator (
–> best predictor of disease progression

Regardless of CD4 Count:
History of AIDS-defining illness
Pregnant women
HIV-associated nephropathy
Hepatitis B coinfection, when HBV treatment is indicated
Acute opportunistic infections
Age >50yrs

HIV Viral load is not a determinant in ART

30
Q

When would deferral of ART be considered for HIV?

A

Clinical or personal factors may support deferral

  • When there are significant barriers to adherence
  • if co-morbidities complicate or prohibit ART
  • “Elite controllers” and long-term nonprogressors
31
Q

What are potential risks of early ART for HIV?

A

ARV-related side effects and toxicities

Drug resistance (attributable to ART failure)

Inadequate time to learn about HIV, treatment, and adherence

Increase in total time on ART; greater chance of treatment fatigue

Current ART may be less effective or more toxic than future therapies

Transmission of ARV-resistant virus, if incomplete virologic suppression

Pill Fatigue –> increases risk of developing resistance

32
Q

What are the benefits of early ART for HIV?

A

Maintain higher CD4 count; prevent irreversible immune system damage

Decrease risk of HIV-associated complications

Decrease risk of nonopportunistic conditions and non-AIDS associated conditions

Decrease risk of HIV transmission

33
Q

What are the ART options for HIV?

A

2 NRTIs + a Protease Inhibitor*

2 NRTIs and a NNRTI* (PI sparing regimen)

2 NRTIs + and Integrase Strand Inhibitor*

*Denotes backbone agent of regimen; most powerful

Module 7: Multisystem (15 decks)

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