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Year 2 - LCRS - Pharmacology > Antivirals (13.03.2020) > Flashcards

Antivirals (13.03.2020) Flashcards

1
Q

Structure of a virus (4 main components)

A
  • genetic material (RNA or DNA)
  • capsid (protein shell surrounding the genetic material of the virus)
  • lipid envelope (in more evolved viruses)
  • envelope proteins (in more developed viruses)
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2
Q

Distinguish between different types of virus and describe how they use the host cell to replicate

A
  • HIV - Retrovirus, leukocytes
  • Hepatitis - DNA & RNA viruses, hepatocytes
  • Herpes Simplex - DNA virus
  • Influenza - RNA virus
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3
Q

Summarise viral hepatitis

A
  • Tropism: Liver hepatocytes

- Hepatitis (Hep) B & C: Only chronic infection requires treatment

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4
Q

Summarise the treatment for hepatitis B

A

Tenofovir -> nucleotide analogue, given sometimes with Peginterferon alfa
- treatment not cure (as soon as you stop tenofovir the virus comes back; Hep is a chronically managed disease but it is not cured by tenofovir)

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5
Q

Summarise the treatment for hepatitis C

A
  • Ribavirin & Peginterferon alfa
    Ribavirin -> nucleoside analogue prevents viral RNA synthesis
  • Boceprevir -> protease inhibitor
    Most effective against Hep C genotype 1
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6
Q

Describe the pharmacological treatment of different types of hepatitis:

A

A:

B: Tenofovir -> nucleotide analogue, given sometimes with Peginterferon alfa

C:

  • Ribavirin & Peginterferon alfa
  • Ribavirin -> nucleoside analogue prevents viral RNA synthesis
  • Boceprevir -> protease inhibitor (Most effective against Hep C genotype )
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7
Q

Tenofovir

A
  • nucleotide analogue
  • given sometimes with peg interferon alpha to treat hepatitis B
  • also used in HIV
  • as soon as you stop tenofovir the virus comes back
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8
Q

What is the goal of hep C treatment today?

A

The goal of HCV treatment TODAY is to cure the virus

-> combination of drugs

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9
Q

The specific drugs and the duration of HCV treatment depend on….. (6)

A
  • HCV genotype (genetic structure of the virus)
  • viral load
  • past treatment experience
  • degree of liver damage
  • ability to tolerate the prescribed treatment
  • need for liver transplant
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10
Q

Summarise the HIV life cycle

A
  1. Attachment & Entry
    - Viral membrane proteins interact with leukocyte membrane receptors
    - Viral capsid endocytosis
  2. Replication & Integration
    - Within cytoplasm - reverse transciptase enzyme converts viral RNA -> DNA
    - DNA transported into nucleus & integrated into host DNA
  3. Assembly & Release
    - Host cell’s ‘machinery’ utilised to produce viral RNA & essential proteins
    - Virus is assembled within cell -> mature virion is released
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11
Q

HIV attachment and entry

A
  • HIV Glycoprotein (GP)120 attaches to CD4 receptor
  • GP120 also binds to either CCR5 or CXCR4
  • GP41 penetrates host cell membrane & viral capsid enters
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12
Q

Drugs that target HIV attachment and entry

A
  • Enfuvirtide: Binds to HIV GP41 transmembrane glycoprotein

- Maraviroc: Blocks CCR5 chemokine receptor

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13
Q

Enfuviritide

A
  • used to treat HIV

- binds to GP41 transmembrane glycoprotein

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14
Q

Maraviroc

A
  • used to treat HIV

- blocks CCR5 chemokine receptor

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15
Q

HIV replication

A

a) Reverse transcription: Viral single-stranded RNA -> double stranded DNA by reverse transcriptase
b) Integration: DNA integration
Viral integrase inserts viral DNA into host DNA

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16
Q

Name HIV replication inhibitor types and how they work

A
  • Nucleoside RT inhibitors
    Activated by 3 step phosphorylation process
    E.g. Zidovudine
  • Nucleotide RT inhibitors
    Fewer phosphorylation steps required
    E.g. Tenofovir
  • Non-nucleoside RT inhibitors
    No phosphorylation required
    Not incorporated into viral DNA
    E.g. Efavirenz
17
Q

Zidovudine

A
  • nucleoside RT inhibitors
  • activated by 3 step phosphorylation process
  • also known az AZT
  • when given for HIV the virus becomes resistant soon so it only works for a while and should be given as part of triple therapy
18
Q

How does Tenofovir work? Which conditions is it used for?

A
  • used in Hep B and HIV
  • RT inhibitor
  • nucleotide analogue
  • fewer phosphorylation steps are needed than for activation
19
Q

Efavirenz

A
  • non nucleoside RT inhibitor
  • no phosphorylation required
  • not incorporated into viral DNA
  • has many SE including nightmares, night sweats, insomnia, anxiety, depression.
20
Q

Which drugs are part of the triple therapy in HIV?

A

?

21
Q

How is HIV treated now?

A

Triple therapy

22
Q

HIV integrale inhibitor example

A

Raltegravir

23
Q

Raltegravir

A
  • first of three licensed integrates inhibitors
24
Q

Assembly and release in HIV

A
  • Gag precursor -> encodes all viral structural proteins
  • HIV protease cleaves Gag precursor protein

Drugs: Protease inhibitors

25
Q

Name some protease inhibitors used for HIV

A

Saquinavir

Ritonavir

26
Q

Saquinavir

A
  • 1st generation protease inhibitor

stops HIV protease from claeaving Gag chains (Gag precursor encodes all viral structural proteins

27
Q

Ritonavir

A
  • low dose reduces PI metabolism
  • co-administered booster
  • now rarely used for its own antiviral activity, but remains widely used as a booster of other protease inhibitors.
28
Q

Herpes simplex virus (Virology, tropism and treatment)

A

Virology

  • Double-stranded DNA
  • Surrounded by tegument & enclosed in a lipid bilayer

Tropism

  • Herpes Simplex Virus (HSV)-1 -> cold-sores
  • HSV-2 -> genital herpes

Treatment
Nucleoside analogues -> Aciclovir

29
Q

Influenza

A

Virology

  • Multipartite single stranded RNA virus
  • Envelope protein neuraminidase -> release

Tropism
- Nose, throat & bronchi

Treatment
- Neuraminidase inhibitor -> Oseltamivir

30
Q

Acyclovir

A

Nucleoside analogue used to treat Herpes simplex

31
Q

Oseltamivir

A

= Neuraminidase inhibitor

used to treat influenza

32
Q

Name some viral capsid proteins and drugs targeting them (3)

A
  • HIV GP41
    Enfuvirtide prevents HV fusion & entry
  • Macrophage CCR5 receptor
    Maraviroc inhibits CCR5 receptor
  • Influenza neuraminidase
    Oseltamivir inhibits influenza virus neuraminidase
33
Q

Name some nucleoside analogues that are used as antiviral treatment (3 diseases, 5 drugs)

A

HIV

  • Nucleoside (e.g. zidovudine) & nucleotide RT inhibitors bind to active site of enzyme
  • Efavirenz -> non-nucleoside binds to allosteric site on RT enzyme

Hepatitis
Hep B -> Tenofovir (RT inhibitor)
Hep C -> Ribavirin (purine analogue)

Herpes Simplex: Aciclovir -> nucleoside analogue

34
Q

Drugs targeting viral integrase

A
  • raltegravir
  • used in HIV
  • inhibits the viral integrate enzyme
35
Q

Drugs targeting proteases

A

HIV

  • Saquinavir -> protease inhibitor
  • Ritonavir -> booster

Hepatitis C
- Boceprevir

36
Q

LO1: Distinguish between different types of virus and describe how they use the host cell to replicate (4)

A
  • HIV - Retrovirus, leukocytes
  • Hepatitis - DNA & RNA viruses, hepatocytes
  • Herpes Simplex - DNA virus
  • Influenza - RNA virus
37
Q

LO2: Summarise the MoA of antiretroviral drugs

A
  • Entry inhibitors - Enfuvirtide & Maraviroc
  • RT inhibitors - Nucleoside analogues (Zidovudine), Non-nucleoside analogues (Efavirenz)
  • Integrase inhibitors - Raltegravir
  • Protease inhibitors - Saquinavir
38
Q

LO3: Describe the actions of other antiviral drugs (not anti-retroviral?)

A
  • Nucleotide analogues - Ribavirin, Aciclovir
  • Protease inhibitors - Boceprevir
  • Neuraminidase inhibitors - Oseltamivir

Year 2 - LCRS - Pharmacology (34 decks)

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