9) Antivirals

Question 1

Give some differences between antivirals and antibiotics:

Answer 1

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

Question 2

Describe the steps in viral replication:

Answer 2

Attachment
Uncoating
RNA/DNA replication
Protein synthesis
Assembly
Release

Question 3

What are immunomodulators?

Answer 3

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

Question 4

Names some anti-herpes drugs:

Answer 4

Acyclovir
Ganciclovir
Cidofovir
Foscarnet

Question 5

What is acyclovir’s mechanism of action?

Answer 5

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

Question 6

What is acyclovir active against?

Answer 6

HSV 1/2,

Varicella-zoster virus

Question 7

What are the side effects of acyclovir?

Answer 7

Nephrotoxicity

CNS symptoms

Question 8

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

Answer 8

Cytomegalovirus

Inhibitor of DNA polymerase

Question 9

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

Answer 9

dsDNA viruses: all human herpes viruses and adenoviruses

Inhibits viral DNA polymerase

Question 10

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

Answer 10

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

Question 11

Name some anti-hepatitis drugs:

Answer 11

Lamivudine
Adefovir
Emtricitabine
Entecavir
Ribavirin (Hep C)

Question 12

What are interferons?

Answer 12

Potent cytokines that are immunomodulating and antiproliferative

Question 13

What are the major classes of interferons in clinical use?

Answer 13

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

IFN-g (produced by T and NK cells)

Question 14

When are interferons usually given?

Answer 14

Treatment of HBV and HCV

Question 15

What are the adverse effects of interferons?

Answer 15

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

Question 16

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

Answer 16

Influenza A

Inhibit the ion channel M2, preventing uncoating and disassembly

Question 17

How can resistance to amantadine arise?

Answer 17

Single AA substitutions in viral DNA

Question 18

What side effects does amantadine give?

Answer 18

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

Question 19

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

Answer 19

Influenza A and B

Reversible inhibitors of neuraminidase enzyme

Question 20

How can resistance to oseltamivir arise?

Answer 20

Mutation in NA gene

Question 21

What are the side effects of oseltamivir?

Answer 21

N&V

Abdominal discomfort

Question 22

What is an unfit virus?

Answer 22

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

Question 23

What drugs are anti-retro viral?

Answer 23

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

Question 24

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

Answer 24

HIV1, HIV2

Inhibit DNA polymerase function of HIV RT enzyme

Question 25

What are the adverse effects of NRTIs?

Answer 25

Hyperlactatemia, lactic acidosis Hepatomegaly Steatosis

Question 26

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

Answer 26

HIV-1 | Inhibit HIV RT by allosteric inhibition of enzyme function

Question 27

What are the adverse effects of NNRTIs?

Answer 27

``` Dizziness Sleep disturbance Headache Mania Psychosis Raised LFTs ```

Question 28

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

Answer 28

HIV1 and HIV2 | Block cleavage of viral polyproteins by HIV protease enzyme

Question 29

What are the adverse effects of protease inhibitors?

Answer 29

Alter hepatic metabolism of other drugs Hyperglycemia Hyperlipidemia New onset DM

Question 30

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

Answer 30

HIV1 | Interfere with attachment/fusion process between HIV and cellular receptors

Question 31

What are the adverse effects of fusion inhibitors?

Answer 31

``` Pain Induration Erythema Fever Hypotension Raised LFTs ```

Question 32

Why is antiviral drug resistance testing needed?

Answer 32

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

Question 33

Why might an antiviral therapy fail?

Answer 33

Virus becomes resistant Poor adherence Adverse effects not tolerated

Question 34

How is antiviral drug resistance testing performed?

Answer 34

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

Question 35

What are some mechanisms of viral resistance?

Answer 35

Altered/reduced enzyme Altered substrate target Point mutations