pharma of antiviral agents

Question 1

what type of inhibitors are these medications? what do they treat?

amantadine, rimantidine

Answer 1

M2 inhibitors used for influenza

Question 2

what type of inhibitors are these medications? what do they treat?

oseltamivir, zanamivir, peramavir

Answer 2

Neuraminidase inhibitors used for influenza

Question 3

Given viruses use host cell machinery, antiviral drugs must act against viral targets that ______ virus from host

Answer 3

distinguish

Question 4

Antivirals may inhibit one or more of the following:

3

Answer 4

1. Viral nucleic acid synthesis
2. Viral uncoating
3. Binding of viral particle to host cell

Question 5

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

Answer 5

• 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

Question 6

M2 Inhibitors (influenza A only) is infrequently used… why?

Answer 6

high rates of resistance

**Resistance conferred by a single amino acid mutation in the M2 protein

Question 7

M2 inhibitors MOA

Answer 7

M2 protein is a protein channel which enhances viral uncoating and thus inhibition of M2 protein inhibits viral replication

Question 8

side effects of amantadine

***Mutation confers cross resistance between amantadine and rimantadine

Answer 8

CNS side effects

rimantadine has lower rate of CNS effects

Question 9

NA inhibitors used for

and MOA

Answer 9

influenza both A and B

Blocks neuraminidase preventing release of viral particles

Question 10

NA prophylaxis

Answer 10

reduces odds of developing influenza by 70-90%

Question 11

most common side effect of oseltamivir

Answer 11

GI symptoms/upset

Question 12

zanamivir differences to other NA inhibitors and SE

Answer 12

it is inhaled and may precipitate bronchospasm (avoid pt. with COPD/asthma)

Question 13

it is given via IV and only a one time dose is needed. rash and diarrhea as SE

Answer 13

peramivir

Question 14

has a long half life thus only one dose is needed and it has the greatest reduction in viral load. reduced susceptibility after treatment

Answer 14

Baloxavir

Question 15

Baloxavir MOA

Answer 15

Inhibits influenza cap dependent endonuclease (inhibits initiation of mRNA synthesis)

Question 16

Acyclovir requires ______ to work

Answer 16

phosphorylation

Question 17

what is up with valacyclovir and famciclovir?

Answer 17

prodrugs with increased biovailability than oral acyclovir

Question 18

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

Answer 18

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

Question 19

Acyclovir toxicity (2)

Answer 19

1. nephrotoxicity

2. neurotoxicity

Question 20

which antiviral agent do we use against CMV

Answer 20

ganciclovir

***Not commonly used to rx HSV given that it is more toxic than acyclovir

Question 21

Ganciclovir triphosphate selectively inhibits CMV ___________

Answer 21

DNA polymerase

**Resistance may develop due to mutations in CMV UL97 gene

Question 22

ganciclovir toxicity

2

Answer 22

1. bone marrow suppression

2. nephrotoxicity

Question 23

Orally bioavailable prodrug that is rapidly metabolized to ganciclovir in the intestine and liver

Answer 23

valganciclovir

Question 24

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

Answer 24

foscarnet

Question 25

CMV:

1. first line therapy
2. reserved for patients with evidence of resistance
3. not indicated for treatment of

Answer 25

1. first line therapy- ganciclovir
2. reserved for patients with evidence of resistance- foscarnet
3. not indicated for treatment of mono-like illness in immunocompetent patients