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Pharmacology > Antivirals > Flashcards

Antivirals Flashcards

1
Q

What is the process of viral replication

A
  1. Attachment - Haemaglutinin on virus with host cell surface receptor
  2. Uncoating - M2 ion channel H+ influx into virus allows nucleocapsid breakdown
  3. DNA/RNA replication
  4. Protein synthesis
  5. Assembly
  6. Release - Neuraminidase prevents virus adhesion to host cell membrane on release
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2
Q

What are features of antiviral agents

A

Few types of Antiviral agents
Virostatic, not virocidal
Not broad spectrum
Not given empirically

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3
Q

What are general mechanisms of action of antiviral agents

A

Virocidal:
Organic solvents, Non-organic solvents, Cryotherapy, Radiotherapy
Not given systematically

Virostatic:
Risk of resistance, not effective in latent infection, requires host immune response to clear existing virus

Immunomodulators:
Enhance host immune (interferons), replace depleted host immune (immunoglobulin)

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4
Q

What are the main groups of antiviral agents

A

Anti-herpes virus
Anti-hepatitis virus
Anti-retroviral
Anti-influenza

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5
Q

What are types of anti-herpes drugs

A

Aciclovir
Ganiclovir
Foscarnet

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6
Q

What is mechanism of action of Aciclovir

A 
Enters virally infected cells
Activated to nucleoside triophosphate by viral Thymidylate Kinase
Incorporated into viral DNA 
Bind to and Inhibit DNA polymerase 
Act as chain terminator
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7
Q

What are indications of Aciclovir

A

Herpes simplex encephalitis
Cold sores (HSV1)
Genital ulcers (HSV2)
VZV (chicken pox, shingles >50)

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8
Q

What are types of resistance for Aciclovir

A

Viral strains that:
Lack thymidylate kinase
mutation in thymidylate kinase gene
Mutation in DNA polymerase gene that prevents binding with Aciclovir triphosphate

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9
Q

What are side effects of Aciclovir

A

Nephrotoxicity

CNS: lethargy, confusion, tremor, hallucination

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10
Q

What is mechanism of action of Ganciclovir

A

Same as Aciclovir
But phosphorylation also catalysed by host and viral enzyme (phosphotranserase)
Thus also activated in non infected host cell

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11
Q

What are indications for Ganciclovir

A 
CMV infection: 
Colitis
Retinitis 
Pneumonitis 
Pneumonia
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12
Q

What are side effects of Ganciclovir

A

Nephrotoxic

Neurotoxic: confusion, headache, behavioural change

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13
Q

What is mechanism of action of foscarnet

A

Inhibit binding of nucleoside triphosphate to viral DNA
(Thus does not need to be phosphorylated to be active)

Inhibit HIV reverse transcriptase

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14
Q

What are indications of Foscarnet

A

Aciclovir resistant HSV
Ganciclovir resistant CMV
HIV

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15
Q

What are side effects of Foscarnet

A

Narrow therapeutic index
GI: N+V, diarrhoea
Nephrotoxicity
CNS: headache, hallucination, tremor, seizure

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16
Q

What are types of anti-hepatitis drugs

A 
Lamivudine
Adefovir
Entecavir
Telbivudine
Ribavirin
IFN alpha
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17
Q

What is mechanism of action of Lamivudine

A

Nucleoside Reverse transcriptase inhibitor:
Nucleoside analogue
Gets activated by phosphorylation in cell by nucleoside kinase
Incorporated into viral DNA
Inhibits RT and acts as chain terminator

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18
Q

What are indications of Lamivudine

A

Chronic hepatitis B

HIV

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19
Q

What is resistance of Lamivudine

A

Common - 67% by 4 years

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20
Q

What are side effects of Lamivudine

A

Well tolerated

Raised liver enzymes

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21
Q

What is mechanism of action of Adefovir

A

Nucleoside Reverse Transcriptase Inhibitor

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22
Q

What are indications of Adefovir

A

Chronic hepatitis B

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23
Q

What is the resistance in Adefovir

A

Slow to develop

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24
Q

What are side effects of adefovir

A

Well tolerated
GI: nausea, diarrhoea, abdo discomfort
CNS: headache

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25
Q

What is mechanism of action of entecavir

A

Nucleoside RT inhibitor

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26
Q

What are indications of entecavir

A

Chronic hepatitis B

Lamivudine-resistant

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27
Q

What is resistance in entecavir

A

No reported resistance

28
Q

What are side effects of Entecavir

A

GI: nausea, diarrhoea
CNS: headache, dizziness, photosensitivity

29
Q

What is mechanism of action of Telbivudine

A

Potent NRTI

30
Q

When is telbivudine indicated

A

Chronic hepatitis B

When other treatments failed

31
Q

What is mechanism of action of Ribavirin

A

Inhibit RNA synthesis

32
Q

When is Ribavirin indicated

A

Hepatitis C

33
Q

What are side effects of Ribavirin

A 
Anaemia (extravascular haemolysis)
Myelosupression 
Myalgia 
Pruritus
Rash
Anxiety
34
Q

What is mechanism of action of Interferons

A

Enhance cell-mediated immune response
Increased activation of NK cells, macrophages
IFNs are cytokines released by Th1 cells when infection by intracellular pathogen occurs

35
Q

What are indications of IFN therapy

A

Hepatitis B

Hepatitis C

36
Q

What are side effects of IFN therapy

A 
Flu-like symptoms:
Fever
Chills
Malaise 
Headache
GI
37
Q

What are types of anti-influenza drugs

A

M2 ion channel inhibitors

Neuraminidase inhibitors

38
Q

Give examples of M2 ion channel inhibitors

A

Amantadine

Ramitidine

39
Q

What is mechanism of action of M2 inhibitors

A

Inhibit proton influx into virus
Inhibit pH mediated uncoating of virus
Thus inhibit viral replication

40
Q

What are indications of M2 ion channel inhibitors

A

Influenza A

41
Q

What are side effects of M2 ion channel inhibitors

A

Low dose: nervousness, confusion, insomnia

High dose: delirium, hallucination, seizure

42
Q

Give examples of neuraminidase inhibitors

A

Oseltavir (Tamiflu)

Zanamivir

43
Q

What is mechanism of action of Neuraminidase inhibitors

A

Inhibit breaking of bond bw virus and host cell membrane

Inhibit release of virus from infected host cell

44
Q

What are indications of neuraminidase inhibitors

A

Influenza A + B
Oseltavir: treatment and prophylaxis
Zanamivir: treatment only

45
Q

What is process of HIV replication

A
  1. Attachment - to CD4+ on T cells
  2. Uncoating
  3. Reverse transcription - reverse transcriptase
  4. vDNA integration- integrase
  5. Transcription
  6. Replication
  7. Assembly + budding
  8. Maturation - proteases in new virion
46
Q

What are types of antiretroviral drugs

A

Nucleoside Reverse Transcriptase Inhibitor
Non-Nucleoside Reverse Transcriptase inhibitor
Protease inhibitor
Fusion inhibitor

47
Q

Give examples of NRTIs

A

Lamivudine

Zidovudine

48
Q

What are indications of NRTIs

A

HIV 1

HIV 2

49
Q

What is resistance in NRTIs

A

High

50
Q

What are side effects of NRTIs

A

Hyperlactataemia
Lactic acidosis
Hepatomegaly

51
Q

What are examples of NNRTIs

A

Nevirapine

Delavirdine

52
Q

What is mechanism of action of NNRTI

A

Allosteric inhibition of RT

53
Q

What are indications of NNRTI

A

HIV 1

Can be combined with NRTI (binding site on RT different )

54
Q

What are side effects of NNRTI

A

Raised LFTs
Dizziness, sleep disturbance, headache
Rash
Erythematous maculopapular rash

55
Q

Give examples of protease inhibitors

A

Saquinavir

Ritonavir

56
Q

What is mechanism of action of protease inhibitors

A

Inhibit protease activity in new virion - cleavage of polyprotein into mature proteins
Inhibit maturation

57
Q

What are indications of protease inhibitors

A

HIV 1

HIV 2

58
Q

What are side effects of protease inhibitors

A 
Inhibit CYP450
Hypercholesterolaemia
Hyperglycaemia
Increased risk of MI
Osteoporosis, osteopenia, osteonecrosis
59
Q

Give examples of fusion inhibitors

A

Enfuvirtide

60
Q

What is mechanism of action of fusion inhibitor

A

Inhibit HIV binding to CD4 receptors on T cells

61
Q

What are indications of Fusion inhibitors

A

HIV 1

When other combinations failed

62
Q

What are side effects of Fusion inhibitors

A

Injection site reaction: pain, induration, erythema, cysts
Hypersensitivity rash
Fever
Hypotension

63
Q

Why do you need to do antiviral resistance testing

A

Optimise patient outcomes
Save costs
Reduce pool of drug-resistant virus

64
Q

When is antiviral resistance testing indicated

A

Rising viral load despite good compliance
Rising viral load in Poor compliance
Newly diagnosed patients

65
Q

How is antiviral resistance testing carried out

A

Incubate suspected resistant viral strain with drug

Compare response with normal viral strain

66
Q

What does low barrier to response mean

A

Only need few mutations to develop antiviral resistance

67
Q

What does ‘unfit’ virus mean

A

Mutation that causes antiviral resistance also has negative impact on virus ability to replicate
Thus virus strain cannot survive

Pharmacology (19 decks)

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