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CMBM 3 > Antiviral Drugs > Flashcards

Antiviral Drugs Flashcards

1
Q

L.O. What are the key characteristics of antiviral drugs?

A
  1. able to enter the cells infected with virus
  2. interfere with viral nucleic acid synthesis and/or regulation
  3. some drugs interfere with the ability of virus to bind to cells
  4. Some drugs stimulate the body’s immune system
  5. Best targets are an essential viral protein with no homology to cellular proteins
  6. Best responses to antiviral drugs are in patients with competent immune systems
  7. Healthy immuse system works synergistically with the drug to eliminate or suppress viral activity
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2
Q

*****L.O. What are the major classes of anti-viral agents?

A
  1. Nucleoside Reverse Transcriptase (NRTIs)
  2. Non-nucleotide Reverse Transcriptase Inhibitors (NNRTIs)
  3. Protease Inhibitors (PIs)
  4. Integrase Inhibitor
  5. Fusion Inhibitors
  6. Chemokine receptor antagonists (CRAs)
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3
Q

What are the goals for initiating ART?

A

To achieve and maintain durable viral suppression

  1. Reduce HIV infection-related morbidity and prolong duration and quality of survival
  2. Restore and preserve immunologic function
  3. Maximally and durably suppress viral load
  4. Prevent vertical HIV trnasmission
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4
Q

What are the guidelines for ART-naïve patients?

A

ART is recommended for ALL HIV-infected individuals

Strength of this recommendation varies based on pretreatment CD4 cell count

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5
Q

If HIV patient is asymptomatic with CD4 count <350 cell/mm3, what is the strength of recommendation?

A

strongly recommended

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6
Q

If HIV patient has a CD4 count >500 cell/mm3, what is the strength of recommendation?

A

moderately; person must be able to complete the drug regimen no matter what

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7
Q

The strength of recommendation for ART would be strongly recommended for which populations?

A

perinatal
heterosexual
sex workers
IV drug users

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8
Q

How do you determine which drugs to choose?

A

Determine CD4+ count
Measure HIV RNA (viral load)
perform resistance testing

  • Determine viral tropism
  • HLAB*5701 testing (test hypersensitivity)
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9
Q

What are the predictors of ART success?

A

high potency of ARV regimen
excellent adherence to treatment regimen
low baseline viremia
higher baseline CD4 count (>200 cells/mm3)
rapid reduction of viremia in response to treatment

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10
Q

High CD4 count correlates with what level of viral load?

A

low viral load

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11
Q

What is a nucleoside analog?

A

artificial nucleoside

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12
Q

What is the mechanism of Nucleoside Reverse Transcriptase Inhibitors (NRTI)?

A

competitively inhibits reverse transcriptase (RT) which blocks the virus from making a provirus copy

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13
Q

What was the first NRTI drug?

A

Zidovudine (ZDV/ previously AZT)

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14
Q

How did ZDV work?

A

thymidine analogue

competitively inhibit RT

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15
Q

NRTIs are less potent than what two drug classes?

A 
NNRTIs
protease inhibitors (PIs)
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16
Q

What is the mechanism of Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI)?

A

binding directly to reverse transcriptase

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17
Q

What is an example of a NNRTI drug?

A

Efavirenz (EFV)

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18
Q

What is the mechanism of Protease Inhibitors (PI)?

A

bind to HIV protease, an enzyme essential for proteolytic processing of nascent polypeptides into individual proteins during maturation of newly formed virions

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19
Q

What is an example of a PI drug?

A

Ritonavir (RTV) - inhibits host protein cytochrome P450 3A4 - results in failure to metabolize other drugs, including other PIs - leads to higher serum levels and sometimes an increase in toxicity

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20
Q

What is the mechanism of Integrase Inhibitors (INSTIs)?

A

Proviral integration is a 2-step process

  1. 3’ processing in the host-cell cytoplasm to prepare proviral strands for attachment
  2. Strand transfer where proviral DNA is covalently linked to cellular DNA

**competitive inhibition of Mg2+ or Mn2+, both essential cofactors for integrase binding to proviral DNA

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21
Q

What are essential cofactors for integrase binding to proviral DNA?

A

Mg2+

Mn2+

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22
Q

What is an example of INSTI drug? mechanism of action?

A

Raltegravir (part of a 4 drug combo pill)

-binds to the active site of Mg2+ ions

23
Q

Describe Integrase Inhibitor Resistance?

A

mutation in the integrase gene are associated with resistance

24
Q

What is the mechanism of Fusion Inhibitors?

A

prevents HIV from entering immune cells

  • *binds gp41
  • only treatment for HIV-1 patients for whom other drug treatments have failed.
25
Q

What is an example of Fusion Inhibitor drug?

A

Enfuvirtide (T-20)

26
Q

What is the mechanism of Chemokine receptor antagonists (CRAs)?

A
  • leads to a confirmation change to prevent entry
  • outcompetes gp120
  • patient must have tropism for CCR5
27
Q

What is an example of CRA drug?

A

Maraviroc

28
Q

Antiviral drugs can inhibit:

A

attachment
entry
nucleic acid synthesis
release

29
Q

What are the two major classes of antivirals for influenza?

A 
Adamantes (Amantadine, Rimantadine)
Neuraminidase (NA) Inhibitors:
Permavir
Oseltamivir (Tamiflu)
Zanamivir (Relenza)
30
Q

What populations are immediately treated with antivirals for influenza?

A

hospitalized, severely ill, high risk patients (diabetics..)

31
Q

When must NA inhibitors be administered?

A

must be started within 48 hours of symptoms

32
Q

Describe peramivir

A

(new drug, 12/19/14)
single does IV
adult >18

33
Q

When can Oseltamivir be used?

A

all ages
prophylactically in ages>1 years old
2x/day for 5 days oral

34
Q

Describe Zanamivir?

A

ages> 7 years old
Prophylactically in ages >5 years old
2x for 5 days (inhalation)

35
Q

Which class of antivirals do we currently not use?

A

H+ ion channel inhibitors for influenza A

Adamantes

36
Q

What are the mechanism for the drug families for herpes virus (antiherpatics)?

A

Block nucleic acid synthesis

Inhibition of translation of viral mRNA

37
Q

What is the mechanism for nucleoside analogues for HSV, VZV?

A

Converted to active drug by 3 phosphorylation steps in viral-infected cells

  1. 1st phosphorylation step by viral thymidine kinase
  2. next 2 phosphorylation steps by host cell enzymes
  3. Acyclovir tri-phosphate added to growing chain of herpes virus DNA (results in chain termination)
38
Q

What are three acyclovir related compounds?

A

Valacyclovir (oral) Valtrax
Famciclovir
Penciclovir

39
Q

What population is resistant to Acyclovir?

A

HIV+ patients

40
Q

What are some CMV (cytomegalovirus) diseases in immuno compromised patients?

A 
retinitis
esophagitis
colitis
encephalitis
pneumonia
41
Q

What kinase does CMV not encode?

A

thymidine kinase (used in Acyclovir)

42
Q

Which enzyme is responsible for the the 1st phosphorylation step for CMV drug?

A

Viral phosphotransferase UL97

43
Q

What are some drug examples for the treatment of CMV?

A

Ganciclovir
Valganiciclovir
Cidofovir

Others: Foscarnet (IV)
Fomiversen

44
Q

What is the primary symptom for RSV?

A

bronchitis

45
Q

What drug is used for RSV?

A

Palivizumab - monoclonal antibody to RSV F protein; stops fusion
Ribavirin

46
Q

What is the mechanism of Ribavirin

A

acts as a GTP analog

- interferes with viral RNA-dependent RNA polymerase

47
Q

When is Ribavirin prescribed?

A

RSV
Hepatitis C
Vaccinia, Monkeypox

48
Q

Does Ribavirin decrease mortality or length of hospitalization?

A

no

49
Q

What is the mechanism of the nucleoside analogues for HBV?

A

RT inhibitor

RT and DNA polymerase inhibitor

50
Q

What are the drugs for HBV drugs?

A

RT inhibitor: laminudine, telbivudine

RT/DNA: adefovis, tenofovir, entecavir

51
Q

What is the mechanism of Hep C antivirals?

A

increase immune response by upregulating macrophages, MHC-1 expression, CD8 toxicity

52
Q

What are some drug classes for Hep C?

A

Antivirals:
Ribavirin
IFN-a
Protease inhibitors (Boceprevir, telaprevir)

53
Q

What are the drugs for papillomaviruses?

A

Immunse response modifiers (imiquimod, interferon alpha)

Cytotoxic agents:
-Antiproliferative drugs
 (podofilox, podophyllin, 5-FU)
-chemodestructive or keratolytic agents
(Salicylic acid, trichloroacetic acid (TCA) & bichloracetic acid (BCA)
54
Q

What injections might be given for genital warts?

A

IFN- alpha

CMBM 3 (28 decks)

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