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Clinical Pharmacology > 9) Antivirals > Flashcards

9) Antivirals Flashcards

1
Q

Give some differences between antivirals and antibiotics:

A

Fewer viruses have specific antivirals
Antivirals are virostatic rather virucidal
Antivirals are rarely given empirically
Much less broad-spectrum

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2
Q

Describe the steps in viral replication:

A 
Attachment
Uncoating
RNA/DNA replication
Protein synthesis
Assembly
Release
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3
Q

What are immunomodulators?

A

Medications used to help regulate or normalise the immune system. Replace deficiency or enhancement

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4
Q

Names some anti-herpes drugs:

A

Acyclovir
Ganciclovir
Cidofovir
Foscarnet

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5
Q

What is acyclovir’s mechanism of action?

A

Becomes phosphorylated by viral thymidine kinase, then competes as a substrate for viral DNA polymerase and acts as a chain terminator

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6
Q

What is acyclovir active against?

A

HSV 1/2,

Varicella-zoster virus

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7
Q

What are the side effects of acyclovir?

A

Nephrotoxicity

CNS symptoms

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8
Q

What is ganciclovir active against and what’s it mechanism of action?

A

Cytomegalovirus

Inhibitor of DNA polymerase

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9
Q

What is cidofovir active against and what’s it mechanism of action?

A

dsDNA viruses: all human herpes viruses and adenoviruses

Inhibits viral DNA polymerase

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10
Q

What is foscarnet active against and what’s it mechanism of action?

A

Herpes viruses and HIV
Resistant CMV and HSV
Non-competitively blocks binding site of viral polymerase or RT

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11
Q

Name some anti-hepatitis drugs:

A 
Lamivudine
Adefovir
Emtricitabine
Entecavir
Ribavirin (Hep C)
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12
Q

What are interferons?

A

Potent cytokines that are immunomodulating and antiproliferative

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13
Q

What are the major classes of interferons in clinical use?

A

IFN-a and IFN-b (produced by most cells)

IFN-g (produced by T and NK cells)

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14
Q

When are interferons usually given?

A

Treatment of HBV and HCV

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15
Q

What are the adverse effects of interferons?

A

Flu like: fever, chills, headache, malaise, myalgia, arthralgia, N&V&D

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16
Q

What is amantadine active against and what’s it mechanism of action?

A

Influenza A

Inhibit the ion channel M2, preventing uncoating and disassembly

17
Q

How can resistance to amantadine arise?

A

Single AA substitutions in viral DNA

18
Q

What side effects does amantadine give?

A 
Nervousness
Difficulty concentrating 
Confusion
Insomnia
Loss of appetite
Cardiac arrhythmias (overdose)
19
Q

What is oseltamivir active against and what’s it mechanism of action?

A

Influenza A and B

Reversible inhibitors of neuraminidase enzyme

20
Q

How can resistance to oseltamivir arise?

A

Mutation in NA gene

21
Q

What are the side effects of oseltamivir?

A

N&V

Abdominal discomfort

22
Q

What is an unfit virus?

A

One that has mutated to become resistant but this mutation caused viral replication to function less well

23
Q

What drugs are anti-retro viral?

A

Nucleoside reverse transcriptase inhibitors
Non-nucleoside reverse transcriptase inhibitors
Protease inhibitors
Fusion inhibitors
Integrase inhibitors

24
Q

What are NRTIs active against and what are their mechanism of action?

A

HIV1, HIV2

Inhibit DNA polymerase function of HIV RT enzyme

25
Q

What are the adverse effects of NRTIs?

A

Hyperlactatemia, lactic acidosis
Hepatomegaly
Steatosis

26
Q

What are NNRTIs active against and what are their mechanism of action?

A

HIV-1

Inhibit HIV RT by allosteric inhibition of enzyme function

27
Q

What are the adverse effects of NNRTIs?

A 
Dizziness
Sleep disturbance
Headache
Mania
Psychosis 
Raised LFTs
28
Q

What are protease inhibitors active against and what are their mechanism of action?

A

HIV1 and HIV2

Block cleavage of viral polyproteins by HIV protease enzyme

29
Q

What are the adverse effects of protease inhibitors?

A

Alter hepatic metabolism of other drugs
Hyperglycemia
Hyperlipidemia
New onset DM

30
Q

What are fusion inhibitors active against and what are their mechanism of action?

A

HIV1

Interfere with attachment/fusion process between HIV and cellular receptors

31
Q

What are the adverse effects of fusion inhibitors?

A 
Pain
Induration 
Erythema 
Fever
Hypotension
Raised LFTs
32
Q

Why is antiviral drug resistance testing needed?

A

To optimise clinical outcomes
Save costs and adverse effect of ineffective therapy
Reduce pool of drug resistant viruses

33
Q

Why might an antiviral therapy fail?

A

Virus becomes resistant
Poor adherence
Adverse effects not tolerated

34
Q

How is antiviral drug resistance testing performed?

A

Incubate drug resistant virus with varying concentrations of drug of interest
Compare response to wild type
Sequence for drug resistant mutations

35
Q

What are some mechanisms of viral resistance?

A

Altered/reduced enzyme
Altered substrate target
Point mutations

Clinical Pharmacology (24 decks)

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