9.1 Anti-virals Flashcards
Label 1-6 of a virus lifecycle
Antiviral drugs shows the best response in which type of patients?
In patients with competent immune systems ➞ a healthy immune system works synergistically with drug to eliminate or suppress viral activity
Give 4 DNA viruses treated with anti-viral agents
- Herpes simplex I & II
- Varicella-zoster virus
- Cytomegalovirus
- Hepatitis B
- Epstein Barr Virus
- Human Herpes-virus 8
Give 4 RNA viruses treated with anti-viral agents
- Influenza
- Human Immunodeficiency Virus (HIV)
- Hepatitis C
- Respiratory Syncitial Virus (RSV)
Give 2 drugs used to treat Influenza
- Oseltamivir
- Zanamivir
- Amantadine
- Rimantadine
Give 4 Influenza-related complications
- bronchitis
- pneumonia
- sinusitis
- exacerbation of underlying disease
Give the 3 types of Influenza virus and give a feature of each
1) Influenza A: has multiple host species and does antigenic drift and shift
2) Influenza B: has no animal reservoir and lower mortality
3) Influenza C: common cold like flu
Give the 3 main surface antigens of Influenza and explain how each causes damage
1) Neuraminidase: glycoprotein that hydrolyses mucus on respiratory epithelia, then digests sialic acid on cell surface. Allows entry and exit of influenz into host cell
2) Hemagglutinin: attachment + membrane fusion with endosome.
3) Matrix 2: viral uncoating which releases viral RNA and proteins
Which part of the influenza lifecycle do vaccines target?
Attachement and entering of host cell
Give the MoA of M2 ion channel blockers
Blocks the ion channel function of the M2 protein of influenza A virus which Inhibits viral uncoating ➞ interferes with corresponding steps in viral life cycle
Give an example of an M2 ion channel blocker and which type of influenza these target
Which drug family do these belong too?
Amantadine and Rimantadine ➞ active against influenza A
Belong to the Tricyclic primary amines class
Give an example of a neuraminidase inhibitor
Zanamavir and Oseltamivir
Zanamavir is a ________. It has a ______ bioavailability and is detectable in ______ up to 24 hours post dosing. Following metabolism it is excreted ______.
Neuraminidase inhibitors, low, sputum, renally
How is Zanamivir administered and what types of influenza does it treat?
Give 2 adverse effects
Given via inhalation
Spectrum: Uncomplicated influenza A and B, some strains of avian influenza, H5N1
Adverse effects: nasal and throat discomfort, bronchospasm
What is Oseltamivir and which type of influenza does this treat
Give 2 adverse effects
Oseltamivir is a neuraminidase inhibitor which is a pro-drug and has 80% bioavailability
Spectrum: Infuenza A and B in children and adults, avian influenza and H5N1
Adverse effects: Nausea and vomitting, headache
Give the MoA of Oseltamivir
Cleaves terminal sialic acid residues on glycoconjugates and destroys receptors
Newly formed virions adhere to cell surface because they cannot digest sialic acid which limits spread
Resistance is emerging against what neuraminidase inhibitor and why?
Which drug are viruses still sensitive too?
Oseltamivir H1N1 resistance due to H274Y mutation around active site
Viruses generally remain zanamivir sensitive
Give 2 oral agents again Herpes simplex and Varicella zoster
- Aciclovir
- Valaciclovir
- Famciclovir
Give 2 topical agents again Herpes simplex and Varicella zoster
Aciclovir and Penciclovir
Aciclovir is uptaken by infected cell where ________ phosphorylates it to acyclovir ________
Cellular enzymes then convert it to acyclovir triphosphate which competes with ________ for viral DNA polymerases
When acyclovir triphosphate incorperates into DNA it results in _________ due to the absence of a ________ group
This prevents attachment of additional nucleosides and Inactivates the viral DNA polymerase
VSTK (virus-specific thymidine kinase), monophosphate, dGTP, chain termination, 3’ hydroxyl
What are the 2 types of Herpes virus?
HSV-1: Oral Herpes
HSV-2: Genital Herpes
Give 2 consequences of HSV
Herpes encephalitis and Herpes Meningitis
What is Mollaret’s meningitis?
Recurrent Herpes Meningitis
Giveve 3 ways resistance against Aciclovir may occur
1) reduced or absent thymidine kinase
2) altered thymidine kinase activity resulting in decreased acyclovir phosphorylation
3) altered viral DNA polymerase with decreased affinity for acyclovir triphosphate
Give 2 drugs used to treat Cytomegalovirus
- Ganciclovir
- Valganciclovir
- Foscarnet
- Cidofovir
Does CMV always require treatment? Explain your answer
Primary CMV infection rarely requires treatment in immunocompetent host
However, in immunocompromised hosts re-activation of CMV can be dangerous hence requires treatment
Compare presentation of primary vs reactivated CMV
Primary: usually asymptomatic or flu-like symptoms (usually goes undiagnosed)
reactivation: CMV retinitis, CMV colitis, etc…
What is ART and explain simply what it does
What is HART?
Antiretroviral Treatment- aims to suppress the virus and may help to reverse some damage to the immune system. Acts by halting viral replication at various places throughout the HIV life cycle
HART: Highly active antiretroviral therapy
What are the 3 main drugs used in ART and what is the “basic recipe”?
1) nucleoside reverse transcriptase inhibitors (NRTI)
2) protease inhibitors
3) Integrase inhibitors
Basic recipe = two NRTIs + one drug from a different class
Genotypic testing is done when a new diagnosis of viral infection is made, why?
To test for resistance through mutations
Give a drug used to treat Hepatitis B
- Lamivudine
- Entecavir
- Interferons
Compare the need for treatment of acute Hep B vs chronic Hep B
Acute Hepatitis B rarely requires treatment
Chronic Hepatitis B may require treatment
Give the MoA of Interferons
Not directly virucidal or virustatic
Induces changes in the infected or exposed cell to promote resistance to the virus and Induces several enzyme activities that promote an antiviral state
What is SVR in terms of Hep C treatment and how is it defined?
SVR = Sustained virologic response
Defined as an undetectable RNA level 12 weeks following the completion of therapy
Give 4 targets to promote an anti-viral state
- Proteins that inhibit synthesis of RNA
- Proteins that cleave viral DNA
- Proteins that inhibit mRNA
- Alterations of the cell membrane that inhibit the release of replicated virions
Give a drug used to treat Hepatitis C + a new drug class used in treatment
- Drug = Ribavirin
- Pegylated interferon
New drug class ➞ Novel DAA’s
What is Ribavirin?
A purine nucleoside analog used in the treatment of Hep C
The MoA of Ribavirin is unclear but it is though to do what 4 things?
- causes alterations to cellular nucleotide pools
- inhibits viral RNA synthesis
- lethal mutagenesis of certain RNA viral genomes
- possibly acts as an analog of guanosine or xanthosine
Explain the targets of new DDAs in treatment of Hep C
When inside the cell, viral polyproteins are synthesised on ER and then processed by protease such as NS3-4A which cleaves proteins (target for DDAs)
2 of these proteins are also impt targets of DDAs
- NS5A which regulates Hep C viral RNA
- NS5B which serves as the RNA dependant RNA polymerase
Give the 4 classes of DDA’s
- NS3-4A protease inhibitors
- NS5B nucleoside polymerase inhibitors
- NS5B non-nucleoside polymerase inhibitors
- NS5A inhibitors
Give 2 advantages of NS3-4A protease inhibitors + an example
low barrier to resistance and high potency varies c genotype
Example ➞ Simeprevir
Give an example of NS5A inhibitor
Daclatasvir
Give an example of NS5B nucleoside polymerase inhibitor + 2 advantages of this
Sofosbuvir
Advantages: moderate to high efficacy across all six genotypes and high barrier to resistance
Give an example of NS5B nucleoside polymerase inhibitor
Give one advantage and one disadvantage of this
Dasabuvir
Advantages: low barrier to resistance
Disadvantage: potency varies among c genotype
Give 2 examples of fixed dose combinations
- Elbasvir-grazoprevir
- Glecaprevir-pibrentasvir
