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CLINICAL PATHOLOGY > Antivirals > Flashcards

Antivirals Flashcards

1
Q

What is the basic pathogenesis of HIV?

A

Get a primary infection where you get a burst of virus
This then comes under control of the hosts immune system to some extent and you get a clinical latency with no symptoms
The CD4 count then starts to fall and you see a loss of viral control and start to get symptoms

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2
Q

What are the 2 main types of viral infections?

A

Acute or chronic

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3
Q

Name 5 common acute viral infections?

A

1) Influenza
2) Measles
3) Mumps
4) Hepatitis A

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4
Q

What are the 2 types of chronic viral infections?

A

1) Latent with (or without) recurrences

2) Persistent

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5
Q

Give 2 examples of latent chronic viral infections?

A

1) Herpes simplex

2) Cytomegalovirus

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6
Q

Give 3 examples of persistent chronic viral infections?

A

1) HIV
2) Hepatitis B virus
3) Hepatitis C virus

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7
Q

What is meant by the term ‘viruses are obligate intracellular parasites’?

A

They need to infect host cells to cause disease

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8
Q

What is the rough structure of a virus?

A

1) Nucleic acid (either DNA or RNA)
2) Protein (coat, structural, enzymes - non-structural)
3) +/- lipid envelope

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9
Q

Viruses have a structured genome, what 3 kinds of genes can be found within it?

A

1) Those coding for core structural proteins
2) Those coding for viral enzymes
3) Those coding for envelope structural proteins

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10
Q

What is the importance of LTRs (long terminal repeats) in a viral genome?

A

Enable integration into host genome

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11
Q

What are the 8 steps in virus infection and replication?

A

1) Virus attachment to cell (via receptor)
2) Cell entry
3) Virus uncoating
4) Early proteins produced - viral enzymes
5) Replication
6) Late transcription/translation - viral structural proteins
7) Virus assembly
8) Virus release

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12
Q

How can virus replication be used in development of anti-viral therapy?

A

All viruses encode unique proteins, many of which are vital for virus replication and infectivity
These unique proteins are targets for molecular inhibition

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13
Q

What are the 4 types of polymerases and what type of organism is each found in?

A

1) DNA to DNA: found in eukaryotes and DNA viruses
2) DNA to RNA: found in eukaryotes and DNA viruses
3) RNA to RNA: found in RNA viruses
4) RNA to DNA: found in retroviruses (HIV) and Hepatitis B virus

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14
Q

Azidothymidine was originally developed as a drug to treat what?

A

Anti-cancer drug

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15
Q

What is the mode of action of Azidothymidine (AZT)?

A

Nucleoside reverse transcriptase inhibitor NRTI

It mimics the building blocks used to make DNA and blocks the enzyme

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16
Q

What do nucleoside reverse transcriptase inhibitors do?

A

Inhibit reverse transcriptase

17
Q

What are the 2 types of nucleoside reverse transcriptase inhibitors?

A

Pyrimidine analogues

Purine analogues

18
Q

Name 2 NRTIs which are pyrimidine analogues?

A

Zidovudine (thymidine analogues)

Lamivudine (cytosine analogues)

19
Q

Name 2 NRTIs which are purine analogues?

A

Abacavir and tenofovir

20
Q

Why can NRTIs be useful in therapy for duel infection of HIV and Hepatitis B?

A

Hepatitis B contains the reverse transcriptase enzyme

Some NRTIs are also active against HBV

21
Q

What are NNRTIs (non-nucleoside reverse transcriptase inhibitors)?

A

Block reverse transcriptase but don’t look like nucleotides and bind to a different part of the protein

22
Q

Name 2 NNRTIs (non nucleoside reverse transcriptase inhibitors)?

A

Efavirenz

Nevirapine

23
Q

Why can protease inhibitors be used without causing toxicity?

A

Although human cells contain proteases, viruses often contain their own unique proteases - PIs inhibit these unique proteases and you don’t get toxicity

24
Q

Why is Ritonavir, a protease inhibitor, particularly useful?

A

It boosts the levels of other protease inhibitors, allowing the use of less drugs to combat the virus thus reducing side effects

25
Q

Name a protease found in HIV which is targeted by protease inhibitors?

A

Aspartate protease of HIV

26
Q

Enfuviritide is a newer drug used to treat HIV given by IM injection, it is a fusion inhibitor, what is meant by this and why is it given as an IM injection?

A

blocks the fusion of the virus with the membrane

Has to be given by IM injection because its only a peptide

27
Q

Raltegravir is a newer drug used to treat HIV, it is an integrase inhibitor, what part of the cell cycle does it affect?

A

Affects the replication strategy of the virus - cant get its DNA integrated into cell DNA

28
Q

Maroviroc is a new drug to treat HIV which inhibits binding of the virus to CD4 cells how?

A

Chemokine receptor antagonist

HIV requires CD4 receptor but also co-receptors, Maroviroc blocks one of these co-receptors, the CCR-5 receptor

29
Q

What is HAART (Highly active antiretroviral therapy)?

A 
2NRTIs + NNRTI
2NRTIs + boosted PI
Started when CD4 falls
Aim to switch off virus replication
Taken life long
Suppression for more than 10 years
However there are starting to be problems with toxicity
30
Q

Why are viral mutations common, how can this affect HIV treatment?

A

Viruses are highly replicative
They have a mutational ability to respond when conditions change
The error rating in reverse transcriptase suggests every HIV genome will have some sort of mutations, the right mutation can result in resistance to drugs

31
Q

Give the mutation in HIV which would lead to resistance to Lamivudine?

A

M184V mutation results in resistance to Lamivudine

In the presence of Lamivudine the rare population of strains with this mutation will soon predominate

32
Q

5 years ago HIV infection was cured in one person, how?

A

A bone marrow transplant from a donor with absent CC5 co-receptor for HIV
HIV was suppressed on antivirals
Existing CD4 lymphocytes were destroyed by conditioning
Stem cells reconstituted with HLA matched by delta 32 homozygous allogeneic donor
Antiviral therapy stopped following transplantations
Remained HIV negative

33
Q

What are inteferons?

A

naturally occurring antivirals present in our own cells

34
Q

How has hepatitis C therapy changed in the last 3 years?

A

Interferons and ribavirin were used which achieved cure rates of 40-90% depending on virus genotype - they were however an IM injection and made people feel generally unwell
Last 3 years have seen an increasing number of directly acting antivirals against various virus proteins
Now have interferon free regimes with >90% cure rates for all strains

35
Q

Why can interferons be used in anti-viral therapy?

A

Administering an exogenous source of interferons can boost viral resistance - having a non specific antiviral effect

36
Q

When do antivirals work to treat acute infections?

A

In general only if given soon after symptoms develop

CLINICAL PATHOLOGY (56 decks)

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