Wk 2 - Pharmacology: Antiviral Drugs Flashcards
It is difficult to produce specific drugs that target specific viruses due to reliance on…
Host metabolism (viruses are dependent on host for replication!)
List the 5 different targets for antiviral drugs.
- Fusion
- Viral membrane fusion is the process by which enveloped viruses enter host cells.
- Uncoating
- Release of the viral genome
-
Nucleic acid replication (major target for most drugs)
- During attachment and penetration, the virus attaches itself to a host cell and injects its genetic material into it. During uncoating, replication, and assembly, the viral DNA or RNA incorporates itself into the host cell’s genetic material and induces it to replicate the viral genome.
- Proteins (that coat the replicated protein)
- Release
Give an example of an antiviral drug that targets the virus’ fusion with the membrane.
Enfuvirtide
What is enfuvirtide?
Antiviral drug used as combination salvage therapy for HIV treatment
Describe enfuvirtide’s mechanism of action.
It binds to gp41 on HIV surface, inhibits CD4 and HIV interaction – reducing viral load
List some side effects of enfuvirtide.
Side effects: injection site pain, depression (unsure why?), infections (especially bacterial pneumonia)
Give an example of an antiviral drug that targets the uncoating step of the virus replication process.
Amantadine
What is Amantadine used for?
Treatment of influenza
What is the mechanism of action of amantadine?
Inhibits a viral ion channel so acid cannot uncoat the endosome and virus remains coated. Channel is prone to mutations (over 90% resistance reported in some outbreaks)
What are some side effects of amantadine?
Side effects: CNS (dopaminergic effects) – nervousness, anxiety, insomnia.
List some antiviral drugs that inhibit nucleic acid replication.
Nucleotide analogues
- Zidovudine: HIV
- Emtricitabine: HIV
- Ribavirin: Hepatitis
- Sofosbuvir: Hepatitis
- Tenofovir: HIV and Hepatitis
Non-nucleotide analogues
- Nevirapine: HIV
- Acyclovir: Herpes
What is Zidovudine?
Antiviral drug used in HIV treatment
Describe Zidovudine’s mechanism of action.
- Targets nucleic acid replication step of viral infection - specific for viral proteins so less toxic to humans
- Incorporates into viral DNA - Thymidine analogue, slows replication via reverse transcriptase (RT)*
- *Humans do not have RT
What is Tenofovir?
HIV antiviral drug used in PrEP
Describe Tenofovir’s mechanism of action.
- Targets nucleic acid replication step of viral infection - specific for viral proteins so less toxic to humans
- Adenosine analogue – inhibits RT via competition – chain termination
What is Emtricitabine?
Antiviral HIV drug used in combination PrEP, cytosine analogue
Zidovudine, Tenofovir and Emtricitabine are nucleotide analogues used in the treatment of ____. Zidovudine is an analogue of ____, Tenofovir an analogue of _____ and Emtricitabine an analogue of ____.
Zidovudine, Tenofovir and Emtricitabine are nucleotide analogues used in the treatment of HIV. Zidovudine is an analogue of thymidine, Tenofovir an analogue of adenosine and Emtricitabine an analogue of cytosine.
What are some common side effects of antiviral nucleotide analogues used in HIV treatment?
Common Side effects: diarrhoea, headache, nausea, rash
List some less common side effects of antiviral nucleotide analogues used in HIV treatment.
Less common: anaemia, bone marrow suppression, liver toxicity, lactic acidosis
What is a common side effect of Tenofovir (antiviral nucleotide analogue used in HIV treatment)?
Tenofovir common: Abdominal distention, flatulence
_____ (bone marrow suppression/proximal renal tubulopathy) is an uncommon side effect of antiviral nucleotide analogues used in HIV treatment.
Proximal renal tubulopathy is an uncommon side effect of antiviral nucleotide analogues used in HIV treatment.
What is Ribavirin?
Adenosine/guanosine analogue used in combination with sofosbuvir in hepatitis treatment
Ribavirin is usually used in combination with ____ (sofosbuvir/tenofovir) in hepatitis treatment.
Ribavirin is usually used in combination with sofosbuvir hepatitis treatment.
What is the mechanism of action of ribavirin (hepatitis antiviral drug)?
- Increase interferon
- Depletes nucleotide pools
- Direct mutagenesis
- –> overall impacts viral replication
What are some side effects of ribavirin (hepatitis antiviral drug)?
- lots of common: alopecia; anaemia; anxiety; appetite decreased; arrhythmias; arthralgia; arthritis and so much more (see BNF)
- uncommon things like diabetes
What is Sofosbuvir?
Antiviral drug - nucleotide analogue - used in hepatitis treatment
What is sofosbuvir’s mechanism of action?
- Defective substrate for RNA-dependent RNA polymerase –uridine analogue, probable chain termination.
- Sofosbuvir is an inhibitor of the HCV NS5B RNA-dependent RNA polymerase, which is essential for viral replication.
Tenofovir is an antiviral _____ (non-nucleotide/nucleotide) analogue used in the treatment of both _____ and _____ (HIV/Hepatitis/Herpes/Influenza).
Tenofovir is an antiviral nucleotide analogue used in the treatment of both HIV and Hepatitis.
What is nevirapine?
Non-nucleotide analogue antiviral drug used in HIV treatment
What is nevirapine’s mechanism of action?
Inhibits reverse transcriptase by binding at a non active site so cannot produce viral DNA from the start
What is nevirapine used for?
- Used in ART and cART in low CD4 count patients
- Also to prevent vertical (mother to fetus) transmission (+ continue to treat during breastfeeding to prevent infection from that)
List some side effects of nevirapine.
Side effects: anaemia, bone marrow suppression, liver toxicity
What is acyclovir?
Non-nucleotide analogue antiviral drug used in management of herpes infection
How does acyclovir work?
- Inhibits viral DNA polymerase; guanosine analogue 100x affinity for viral polymerase (so fewer SE on human DNA polymerase) - leads to chain termination
- Requires activation by viral enzymes (thymidine kinase phosphorylates acyclovir to active drug for action) –increases specificity
What are some side effects of acyclovir?
Side effects: nausea, vomiting, headache
How is acyclovir activated?
Requires activation by viral enzymes (thymidine kinase phosphorylates drug to its active form) – increases specificity.
List some drugs that target the proteins that coat the replicated virus.
- Indinavir: HIV
- Ledipasvir: Hepatitis
What is indinavir?
A protease inhibitor used as a component of highly active antiretroviral therapy to treat HIV/AIDS
Describe indinavir’s (HIV antiviral targets protein) mechanism of action.
- Binds to active site of HIV protease (protease inhibitor)
- What do proteases do? cleave new proteins required for the formation and assembly of virus coat – if virus uncoated –> does not go into bloodstream
List some side effects of indinavir.
Side effects: Kidney stones, hyperlipidaemia
What is Ledipasvir?
Antiviral drug used for hepatitis - targets proteins that make up active virus
How does Ledipasvir work?
- Interferes in replication complex formation
- Viral repackaging is slowed or blocked via NS5A inhibition
- Virus cannot be released in bloodstream
Inhibitor of the hepatitis C virus (HCV) non-structural protein 5A (NS5A) replication complex, with potential activity against HCV. Upon oral administration and after intracellular uptake, ledipasvir binds to and blocks the activity of the NS5A protein.
Ledipasvir is used in combination with _____ to treat hepatitis.
Ledipasvir is used in combination with Sofosbuvir to treat hepatitis.
What are some side effects of Ledipasvir?
Side effects: Fatigue, headache common, angioedema arrhythmia less so
When is Ledipasvir (hepatitis antiviral drug) contraindicated?
Contraindications: PPI and H2 antagonist – reduce the dose (not sure why)
List some antiviral drugs that target virus release.
Oseltamivir
What is Oseltamivir?
Antiviral drug used in influenza treatment - targets virus release
What is the mechanism of action of Oseltamivir?
Blocks viral release by inhibiting Influenza neuraminidase activity – doesn’t block the formation of a new virus in the individual but blocks its release –> so prevent INFECTING other people.
What are some side effects of Oseltamivir?
Side effects: Nausea, vomiting, diarrhoea, headache, possible neurological (self harm)
Why are antivirals generally used in combination - ie combination therapy?
To reduce the likelihood of resistance!
What is acyclovir mechanism of action?
viral dna polymerase inhibitor
A drug that blocks virus entry?
enfurvitide
A drug that blocks flu virus release?
oseltamivir
Treatment strategy for resistance?
multiple drugs
