Antiviral Agents Flashcards
What is acyclovir effective against?
herpes simplex 1,2 and herpes zoster virus
What does acyclovir convert?
To monophosphate acyclo-GMP by viral thymidine kinase, then to triphosphate by a cellular enzyme
How does acyclovir work?
The triphosphate formed inhibits DNA polymerase through chain terminations
How is acyclovir administered?
Topically
Orally
IV
How are some adverse effects of acyclovir?
psychiatric = Cotards
Toxicity if overdose = lethargy, confusion, myoclonus
What is the difference between valacyclovir and acyclovir?
Vala is acyclovir esterified to valine
greater oral bioavilability
How does resistance to acyclovir and valaciclovir occur?
Mutation of viral thymidine kinase and/or DNA polymerase
What is idoxuridine used for?
Topically only = herpes keratitis
- too toxic for systemic use
What are ganciclovir and valganciclovir against?
Active CMV
What is acyclovir an analogue of?
Guanosine
What is ganciclovir an analogue of?
Deoxyguanosine
What does ganciclovir do?
Phosphorylated to monophosphate by CMB thymidine kinase then to triphosphate by cellular kinases
How does ganciclovir work?
Inhibits viral DNA polymerase by acting as a chain terminator
What is the difference between valganciclovir and ganciclovir?
Valine ester of it
Greater oral bioavailability
What are the adverse effects of valganciclovir and ganciclovir?
Adverse effects such as bone marrow suppression
Which drugs are effective against herpes?
foscarnet acyclovir valacyclovir ganciclovir valgancyclovir
Which drugs are reverse transcriptase inhibitors?
Nuceloside and nucleotide analgoues (NRTIs)
- nuceloside analogues = zidovudine, lamivudine
- nucleotide analogues = tenofovir
What do NRTIs do?
inhibit reverse transcriptase by incorporating into growing DNA chain and not linking subsequent base
Adverse effects of zidovudine?
GI, haem, headache, hepatotoxic, cardiomyopathy
Adverse effects of lamivudine?
nausea, fatigue, headache, diarrhoeaa, cough, pro-inflamm response, autoimmunity
Adverse effects of tenofovir?
renal insufficiency
Fanconi syndrome
What do NNRTIs do?
Non-nucleoside/tide reverse transcriptase inhib
- bind to reverse transcriptase enzyme not at active site and distort it
Examples of NNRTIs?
- nevirapine
What are some adverse effects of nevirapine?
hepatitis
Stevens-Johnson
What do protease inhibitors do?
Bind to viral protease which cuts viral precursor proteins into virion structure parts
Examples of protease inhibitors?
Saquinavir
Indinavir
Ritonavir
What are some adverse effects of Saquinavir?
GI, rash, neuro, metabolic, QT prolonged
What do integrase inhibitors do?
Inhibit integrase which is a viral enzyme for HIV DNA integration into host genome
What do fusion inhibitors do?
Block gp41 on surface of HIV virion which mediates fusion between HIV envelope and cell membrane
What do entry inhibitors do?
Block CCR5 (chemokine) receptor on cell surface which with CD4 enables gp120 on HIV surface to bind and enter
What is ribvarin an analogue of?
Guanosine
Ribo-nucleoside
How does ribvarin work?
Inhibits viral RNA dependent RNA polymerase so terminates chain
What does ribvarin do?
Against hep C, viral haemorrhagic fevers, resp syncytial virus
Influenza
What are adverse effects of ribvarin?
Haemolytic anaemia
Bone Marrow suppression
Depression
Cough
Which drugs are effective against retroviruses?
NRTIs NNRTIs Protease inhibitors Integrase inhibitors fusion inhibitors entry inhibitors ribvarin
How does neurominidase inhibitors work?
viral neurominidase cleaves siliac acid release virion from host cell,
- aggregation of virions,
- viral inactivation by host mucus
Examples of neurominidase inhibitors?
Oseltamivir
Zanamivir
How do M2 inhibitors work?
Inhibit M2 protein of virus to decrease hydrogen ion influx
Inhibits upcoating and recoating
Examples of M2 inhibitors?
Amantidine
Rimantadine
Which drugs are used in influenza treatment
Ribvarin
Neurominidase inhibtiors
M2 inhibtiors
Which drugs treat Hep C?
Protease Inhibitors (DAA) NSSA Inhib NSSB Inhib Ribvarin Pegylated interferon
What do DAA do?
Direct acting agents
Inhibit viral NS3/4A serine protease
Examples of DAAs?
Telaprevir
What is NSSA?
Viral protein enabling assembly
Example of NSSA inhib?
Ledipasvir
What does NSSB inhib do?
Inhibits Viral RNA polymerase
Examples of NSSB inhib?
Sofosbuvir
Dasabuvir
What does PEGylated interferon do?
Interferon alpha or beta
Human cytokines enhancing immune response
What does PEGylated mean?
Linked to poly-ethylene glycol to prolong half life
Which drugs are used in hep B treatment?
Reverse transcriptase inhibitors
Iamivudine
Tenfovir
Interferon pegylated
What drugs are used for resp syncytial virus?
Monoclonal antibody against RSV fusion glycoprotein (palvizumab)
Ribvirine (inhaled)
What are the stages of the viral replication cycle from entry to release?
- docking on
- escape from the vacuole
- replication of DNA/RNA
- integration of DNA into genome
- assembly of virions
- escape from host cell
