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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
What is mechanism of action of entecavir
Nucleoside RT inhibitor
26
What are indications of entecavir
Chronic hepatitis B | Lamivudine-resistant
27
What is resistance in entecavir
No reported resistance
28
What are side effects of Entecavir
GI: nausea, diarrhoea CNS: headache, dizziness, photosensitivity
29
What is mechanism of action of Telbivudine
Potent NRTI
30
When is telbivudine indicated
Chronic hepatitis B | When other treatments failed
31
What is mechanism of action of Ribavirin
Inhibit RNA synthesis
32
When is Ribavirin indicated
Hepatitis C
33
What are side effects of Ribavirin
``` Anaemia (extravascular haemolysis) Myelosupression Myalgia Pruritus Rash Anxiety ```
34
What is mechanism of action of Interferons
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
What are indications of IFN therapy
Hepatitis B | Hepatitis C
36
What are side effects of IFN therapy
``` Flu-like symptoms: Fever Chills Malaise Headache GI ```
37
What are types of anti-influenza drugs
M2 ion channel inhibitors | Neuraminidase inhibitors
38
Give examples of M2 ion channel inhibitors
Amantadine | Ramitidine
39
What is mechanism of action of M2 inhibitors
Inhibit proton influx into virus Inhibit pH mediated uncoating of virus Thus inhibit viral replication
40
What are indications of M2 ion channel inhibitors
Influenza A
41
What are side effects of M2 ion channel inhibitors
Low dose: nervousness, confusion, insomnia | High dose: delirium, hallucination, seizure
42
Give examples of neuraminidase inhibitors
Oseltavir (Tamiflu) | Zanamivir
43
What is mechanism of action of Neuraminidase inhibitors
Inhibit breaking of bond bw virus and host cell membrane | Inhibit release of virus from infected host cell
44
What are indications of neuraminidase inhibitors
Influenza A + B Oseltavir: treatment and prophylaxis Zanamivir: treatment only
45
What is process of HIV replication
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
What are types of antiretroviral drugs
Nucleoside Reverse Transcriptase Inhibitor Non-Nucleoside Reverse Transcriptase inhibitor Protease inhibitor Fusion inhibitor
47
Give examples of NRTIs
Lamivudine | Zidovudine
48
What are indications of NRTIs
HIV 1 | HIV 2
49
What is resistance in NRTIs
High
50
What are side effects of NRTIs
Hyperlactataemia Lactic acidosis Hepatomegaly
51
What are examples of NNRTIs
Nevirapine | Delavirdine
52
What is mechanism of action of NNRTI
Allosteric inhibition of RT
53
What are indications of NNRTI
HIV 1 | Can be combined with NRTI (binding site on RT different )
54
What are side effects of NNRTI
Raised LFTs Dizziness, sleep disturbance, headache Rash Erythematous maculopapular rash
55
Give examples of protease inhibitors
Saquinavir | Ritonavir
56
What is mechanism of action of protease inhibitors
Inhibit protease activity in new virion - cleavage of polyprotein into mature proteins Inhibit maturation
57
What are indications of protease inhibitors
HIV 1 | HIV 2
58
What are side effects of protease inhibitors
``` Inhibit CYP450 Hypercholesterolaemia Hyperglycaemia Increased risk of MI Osteoporosis, osteopenia, osteonecrosis ```
59
Give examples of fusion inhibitors
Enfuvirtide
60
What is mechanism of action of fusion inhibitor
Inhibit HIV binding to CD4 receptors on T cells
61
What are indications of Fusion inhibitors
HIV 1 | When other combinations failed
62
What are side effects of Fusion inhibitors
Injection site reaction: pain, induration, erythema, cysts Hypersensitivity rash Fever Hypotension
63
Why do you need to do antiviral resistance testing
Optimise patient outcomes Save costs Reduce pool of drug-resistant virus
64
When is antiviral resistance testing indicated
Rising viral load despite good compliance Rising viral load in Poor compliance Newly diagnosed patients
65
How is antiviral resistance testing carried out
Incubate suspected resistant viral strain with drug | Compare response with normal viral strain
66
What does low barrier to response mean
Only need few mutations to develop antiviral resistance
67
What does ‘unfit’ virus mean
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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