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5: Y5 - ESA 5 - Pharmacology > Antivirals (from CTFs Lecture) > Flashcards

Antivirals (from CTFs Lecture) Flashcards

1
Q

What is a virus?

A

An obligate, intracellular parasite with no cell wall or cell membrane

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2
Q

What is a virus capable of doing?

A

Causing disease in the infected host

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3
Q

How big are viruses?

A

Small - 25-400nm

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4
Q

What does the viral genome consist of?

A

RNA or DNA

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5
Q

What does viral replication use?

A

Host machinery

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6
Q

Why does the virus use the host machinery to replicate?

A

As they don’t have their own organelles (mitochondria, golgi etc)

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7
Q

What is the result of the virus using host machinery to replicate?

A

They hide inside the cell and make it hard to prevent viral replication without injury to the host

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8
Q

What are the steps in viral replication?

A
  1. Attachment
  2. Penetration
  3. Uncoating
  4. Replication/protein synthesis
  5. Assembly
  6. Release
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9
Q

What happens in the attachment stage of viral replication?

A

Virus particles (virons) must first attach to specific receptors on the surface of a host cell

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10
Q

How might penetration occur in viral replication?

A

Direct fusion wiht the cell membrane, or endocytosis and pH mediated fusion

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11
Q

What happens in the uncoating stage of viral replication?

A

The virion disassembles, freeing nucleic acid and viral proteins needed for replication

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12
Q

What happens in the replication/protein synthesis stage of viral replication?

A

Viral proteins and messages are expressed

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13
Q

What happens in the assembly stage of viral replication?

A

New virions containg viral nucleic acid are formed

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14
Q

What happens in the release stage of viral replication?

A

New virions are released from the cell via lysis of the cell, or intra- or extracellular budding

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15
Q

What antivirals are used in the treatment of influenza A and B?

A
  • Oseltamivir (Tamiflu)
  • Zanamivir
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16
Q

How is oseltamivir administered?

A

Orally

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17
Q

How is zanamivir administered?

A

Inhaled/intranasally

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18
Q

What class of antivirals are oseltamivir and zanamivir?

A

Neuroaminidase inhibitor

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19
Q

What is the mechanism of action of neuroaminidase inhibitors?

A

They block the release of newly formed virions from the host cell

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20
Q

How might the influenza virus obtain resistance to oseltamivir and zanamivir?

A

Mutation of NA (neuroanimidase enzyme), e.g. H275Y mutation so can’t bind oseltamivir

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21
Q

When can oseltamivir or zanamivir be used?

A
  • Prophylactically, to prevent infection
  • Within 48 hours of infection to reduce intensity and duration of symptoms
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22
Q

Is prophylactic use of antivirals the preferred approach in prevention of flu?

A

No, the preferred approach is yearly vaccinations for those at risk, e.g. elderly, respiratory diease, immunocompromised

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23
Q

What diseases are the herpes viruses associated with?

A
  • Cold sores
  • Encephalitis
  • Genital infections
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24
Q

What is used to treat herpes viruses?

A

Aciclovir (Zovirax)

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25
Q

How is aciclovir administered?

A
  • Orally
  • IV
  • Topical cream
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26
Q

What class of antiviral is aciclovir?

A

Purine/pyramidine (DNA base) analogue

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27
Q

What is the mechanism of action of purine/pyramidine analogues?

A

They get phosphorylated by viral thymidine kinase, which activates it and inhibits viral DNA synthesis

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28
Q

How might aciclovir resistance arise?

A

Due to thymidine kinase enzyme mutation in the virus, which prevents binding to aciclovir so it can’t act as a false substrate in DNA replication anymore

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29
Q

What is the limitation of aciclovir treatment for herpes?

A

It is only effective during the acute phase of the viral infection where the patient is symptomatic, not during the patent phase, and so won’t prevent a new outbreak, only control the time/severity of an outbrea

30
Q

What is used to treat cytomegalovirus?

A

Ganciclovir

31
Q

How is ganciclovir administered?

A

IV

32
Q

Why does ganciclovir need to be administered IV?

A

So that it crosses the blood brain barrier

33
Q

Where is gancicolovir currently used to treat CMV?

A
  • CMV retinitis in immunocompromised
  • CMV prophylaxis in transplant patients
34
Q

What is the mechanism of action of ganciclovir?

A

It is an analouge of acyclovir, which acts in the same way but is phosphorylated using a different enzyme

35
Q

How does the activity of ganciclovir against CMV differ to that of acyclovir?

A

It has 10-50 times greater activity

36
Q

What are the potential adverse reactions with ganciclovir?

A
  • Myelosuppression
  • Carciogenic/teratogenic
  • Renal failure
37
Q

What antivirals are used in the treatment of hepatitis B and C?

A
  • Lamivudine
  • Sofosbuvir
  • Interferon alpha
  • Ribavirin
38
Q

How is lamivudine administered?

A

Orally

39
Q

Where is lamivudine used?

A

In HIV and Hep B

40
Q

What class of antiviral is lamivudine?

A

Reverse transcriptase inhibitor

41
Q

What is the mechanism of action of reverse transcriptase inhibitors?

A

Act as false substrate and chain terminator of reverse transcriptase enzyme in viral replication

42
Q

What is the mechanism of action of sofosbuvir?

A

Blocks action of HCV viral polymerase to prevent production of new virus

43
Q

How is interferon alpha administered?

A

Intramuscular injection

44
Q

Where is interferon alpha used?

A

Mainily in the treatment of HepB/C

45
Q

What is the mechanism of action of interferon alpha?

A

Immunomodulatory effect - not directly antiviral, but stimulates proteins to enhance cellular resistance to viral infection

46
Q

What are the adverse effects of interferon alpha?

A
  • Flu-like illness
  • Fever
  • Chills
  • Headache
  • Malaise
  • Myalgia
  • Athralgia
  • Nausea
  • Vomiting
  • Diarrhoea
47
Q

Where is ribavirin used?

A
  • Chronic hepatitis C
  • Infants with severe RSV infection
48
Q

What is ribavirin used in combination with in chronic hepatitis C?

A

Interferon alpha

49
Q

How is ribavirin administered?

A

Oral or IV

50
Q

What class of antiviral is ribavirin?

A

Guanosine analogue

51
Q

What is the mechanism of action of guanine analogue antivirals?

A

They inhibit guanine triphosphate formation, preventing viral messenger RNA cappping, and essentially preventing the assembly of viral genome/DNA

52
Q

What are the ADRs of ribavirin?

A
  • Transient anaemia
  • Teratogenic
53
Q

What drugs are used in the treatment of HIV?

A
  • Nucleoside reverse transcriptase inhibitiors
  • Non-nucleoside reverse transcriptase inhibitors
  • Protease inhibitors
  • Fusion inhibitors
  • Integrase inhibitors
  • Receptor inhibitors
54
Q

Give an example of a nucleoside reverse transcriptase inhibitor

A

Zidovudine

55
Q

What is the mechanism of action of nucleoside reverse transcriptase inhibitors?

A

Inhibit DNA polymerase, so DNA can’t be replicated

56
Q

What are the adverse drug reactions of nucleoside reverse transcriptase inhibitors?

A
  • Hyperlactataemia
  • Lactic acidosis
  • Hepatomegaly
  • Steatosis
57
Q

Give an example of a non-nucleoside reverse transcriptase inhibitor

A

Nevirapine

58
Q

What is the mechanism of action of non-nucleoside reverse transcriptase inhibitors?

A

They are non-competitive inhibitors of HIV reverse transcriptase. They bind at different sites to the nucleoside reverse transcriptase inhibitors, but have the same effect

59
Q

Are non-nucleoside reverse transcriptase without further phosphylation?

A

Yes

60
Q

What is the result of non-nucleoside reverse trancriptase inhibitors binding at a different site but having the same effect as nucleoside reverse transcriptase inhibitors?

A

They can be used as combination therapy

61
Q

What form of HIV do non-nucleoside reverse transcriptase inhibitors work for?

A

HIV-1, not HIV-2

62
Q

Give an example of a protease inhibitor

A

Ritonavir

63
Q

What is the mechansim of action of protease inhibitors?

A

They block the cleavage of viral polyproteins by HIV protease enzyme, preventing the production of viral proteins for the formation of final mature virions

64
Q

Give an example of a fusion inhibitor

A

Enfuvirtide

65
Q

Where are fusion inhibitors used?

A

Salvage therapy if other treatments havent worked

66
Q

Give an example of an integrase inhibitor

A

Raltegravir

67
Q

What is the mechanism of action of raltegravir?

A

Prevents the integration of HIV DNA provirus into the host cell genome

68
Q

Why is antiviral drug resistance testing needed?

A
  • Optimise clinical outcomes
  • Save costs and adverse effects of ineffective therapy
  • Reduce pool of drug resistant viruses in the population that may transmit between individuals, reducing the effectiveness of standard therapy
69
Q

When is antiviral drug resistance testing performed?

A
  • When there is evidence of therapeutic failure
  • As a baseline prior to starting new therapy
70
Q

oWhat could cause therapeutic failure?

A
  • Resistance
  • Compliance
71
Q

How is antiviral drug resistance testing done?

A

Phenotypic characterisation linked to genetic mutations;

  1. Incubate suspected drug resistant virus with varying concentrationsof drug of interest in culture
  2. Look for graded response compared to wild-type virusm
  3. Can then look at specific sequencing/genotype of the mutation
72
Q
A

5: Y5 - ESA 5 - Pharmacology (28 decks)

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