pharma of antiviral agents Flashcards
what type of inhibitors are these medications? what do they treat?
amantadine, rimantidine
M2 inhibitors used for influenza
what type of inhibitors are these medications? what do they treat?
oseltamivir, zanamivir, peramavir
Neuraminidase inhibitors used for influenza
Given viruses use host cell machinery, antiviral drugs must act against viral targets that ______ virus from host
distinguish
Antivirals may inhibit one or more of the following:
3
- Viral nucleic acid synthesis
- Viral uncoating
- Binding of viral particle to host cell
Treatment with antiviral agents:
- Greatest effect when rx begun w/in _____
- Indication for prompt treatment include ________ patients and patients at risk for complications of influenza due to high risk condition
- Greatest effect when rx begun w/in 24 hrs
- Indication for prompt treatment include hospitalized patients and patients at risk for complications of influenza due to high risk condition
M2 Inhibitors (influenza A only) is infrequently used… why?
high rates of resistance
**Resistance conferred by a single amino acid mutation in the M2 protein
M2 inhibitors MOA
M2 protein is a protein channel which enhances viral uncoating and thus inhibition of M2 protein inhibits viral replication
side effects of amantadine
***Mutation confers cross resistance between amantadine and rimantadine
CNS side effects
rimantadine has lower rate of CNS effects
NA inhibitors used for
and MOA
influenza both A and B
Blocks neuraminidase preventing release of viral particles
NA prophylaxis
reduces odds of developing influenza by 70-90%
most common side effect of oseltamivir
GI symptoms/upset
zanamivir differences to other NA inhibitors and SE
it is inhaled and may precipitate bronchospasm (avoid pt. with COPD/asthma)
it is given via IV and only a one time dose is needed. rash and diarrhea as SE
peramivir
has a long half life thus only one dose is needed and it has the greatest reduction in viral load. reduced susceptibility after treatment
Baloxavir
Baloxavir MOA
Inhibits influenza cap dependent endonuclease (inhibits initiation of mRNA synthesis)
Acyclovir requires ______ to work
phosphorylation
what is up with valacyclovir and famciclovir?
prodrugs with increased biovailability than oral acyclovir
Acyclovir require phosphorylation to monophosphate form by virus-encoded_________. Drug concentrates in herpes virus-infected cells as little phosphorylation occurs in uninfected cells
Monophosphate form is converted to a ______ form by host cell kinases
___________ form inhibits viral DNA polymerase
Acyclovir require phosphorylation to monophosphate form by virus-encoded thymidine kinase. Drug concentrates in herpes virus-infected cells as little phosphorylation occurs in uninfected cells
Monophosphate form is converted to a triphosphate form by host cell kinases
Triphosphate form inhibits viral DNA polymerase
Acyclovir toxicity (2)
- nephrotoxicity
2. neurotoxicity
which antiviral agent do we use against CMV
ganciclovir
***Not commonly used to rx HSV given that it is more toxic than acyclovir
Ganciclovir triphosphate selectively inhibits CMV ___________
DNA polymerase
**Resistance may develop due to mutations in CMV UL97 gene
ganciclovir toxicity
2
- bone marrow suppression
2. nephrotoxicity
Orally bioavailable prodrug that is rapidly metabolized to ganciclovir in the intestine and liver
valganciclovir
Inhibits DNA polymerase – does not require UL97 phosphorylation and is Effective against resistant CMV and HSV
Less well tolerated than ganciclovir and associated with considerable toxicity
Nephrotoxicity
Hypomagnesemia, hypokalemia, hypocalcaemia
foscarnet
CMV:
- first line therapy
- reserved for patients with evidence of resistance
- not indicated for treatment of
- first line therapy- ganciclovir
- reserved for patients with evidence of resistance- foscarnet
- not indicated for treatment of mono-like illness in immunocompetent patients
