9) Antivirals Flashcards
Give some differences between antivirals and antibiotics:
Fewer viruses have specific antivirals
Antivirals are virostatic rather virucidal
Antivirals are rarely given empirically
Much less broad-spectrum
Describe the steps in viral replication:
Attachment Uncoating RNA/DNA replication Protein synthesis Assembly Release
What are immunomodulators?
Medications used to help regulate or normalise the immune system. Replace deficiency or enhancement
Names some anti-herpes drugs:
Acyclovir
Ganciclovir
Cidofovir
Foscarnet
What is acyclovir’s mechanism of action?
Becomes phosphorylated by viral thymidine kinase, then competes as a substrate for viral DNA polymerase and acts as a chain terminator
What is acyclovir active against?
HSV 1/2,
Varicella-zoster virus
What are the side effects of acyclovir?
Nephrotoxicity
CNS symptoms
What is ganciclovir active against and what’s it mechanism of action?
Cytomegalovirus
Inhibitor of DNA polymerase
What is cidofovir active against and what’s it mechanism of action?
dsDNA viruses: all human herpes viruses and adenoviruses
Inhibits viral DNA polymerase
What is foscarnet active against and what’s it mechanism of action?
Herpes viruses and HIV
Resistant CMV and HSV
Non-competitively blocks binding site of viral polymerase or RT
Name some anti-hepatitis drugs:
Lamivudine Adefovir Emtricitabine Entecavir Ribavirin (Hep C)
What are interferons?
Potent cytokines that are immunomodulating and antiproliferative
What are the major classes of interferons in clinical use?
IFN-a and IFN-b (produced by most cells)
IFN-g (produced by T and NK cells)
When are interferons usually given?
Treatment of HBV and HCV
What are the adverse effects of interferons?
Flu like: fever, chills, headache, malaise, myalgia, arthralgia, N&V&D
What is amantadine active against and what’s it mechanism of action?
Influenza A
Inhibit the ion channel M2, preventing uncoating and disassembly
How can resistance to amantadine arise?
Single AA substitutions in viral DNA
What side effects does amantadine give?
Nervousness Difficulty concentrating Confusion Insomnia Loss of appetite Cardiac arrhythmias (overdose)
What is oseltamivir active against and what’s it mechanism of action?
Influenza A and B
Reversible inhibitors of neuraminidase enzyme
How can resistance to oseltamivir arise?
Mutation in NA gene
What are the side effects of oseltamivir?
N&V
Abdominal discomfort
What is an unfit virus?
One that has mutated to become resistant but this mutation caused viral replication to function less well
What drugs are anti-retro viral?
Nucleoside reverse transcriptase inhibitors
Non-nucleoside reverse transcriptase inhibitors
Protease inhibitors
Fusion inhibitors
Integrase inhibitors
What are NRTIs active against and what are their mechanism of action?
HIV1, HIV2
Inhibit DNA polymerase function of HIV RT enzyme
What are the adverse effects of NRTIs?
Hyperlactatemia, lactic acidosis
Hepatomegaly
Steatosis
What are NNRTIs active against and what are their mechanism of action?
HIV-1
Inhibit HIV RT by allosteric inhibition of enzyme function
What are the adverse effects of NNRTIs?
Dizziness Sleep disturbance Headache Mania Psychosis Raised LFTs
What are protease inhibitors active against and what are their mechanism of action?
HIV1 and HIV2
Block cleavage of viral polyproteins by HIV protease enzyme
What are the adverse effects of protease inhibitors?
Alter hepatic metabolism of other drugs
Hyperglycemia
Hyperlipidemia
New onset DM
What are fusion inhibitors active against and what are their mechanism of action?
HIV1
Interfere with attachment/fusion process between HIV and cellular receptors
What are the adverse effects of fusion inhibitors?
Pain Induration Erythema Fever Hypotension Raised LFTs
Why is antiviral drug resistance testing needed?
To optimise clinical outcomes
Save costs and adverse effect of ineffective therapy
Reduce pool of drug resistant viruses
Why might an antiviral therapy fail?
Virus becomes resistant
Poor adherence
Adverse effects not tolerated
How is antiviral drug resistance testing performed?
Incubate drug resistant virus with varying concentrations of drug of interest
Compare response to wild type
Sequence for drug resistant mutations
What are some mechanisms of viral resistance?
Altered/reduced enzyme
Altered substrate target
Point mutations
