Antiviral Drugs Part 1

Question 1

Influenza A

Answer 1

Amantadine

Question 2

Amantadine reduces the duration of symptoms when administered

Answer 2

within the first 48 hours of infection

Question 3

what is the mechanism of Amantadine

Answer 3

What happens is that amantadine sits on the proton pump in the viral membrane to inhibit it. This prevents hydrogen ions in the endosome from penetrating into the viral particle. So amantadine prevents removal of the viral envelope and therefore the influenza genome cannot get released. The proton pump on the viral membrane is different from the gastric proton pump and therefore amantadine won’t interfere with our proton pump

Question 4

what is the pharmacokinetics of Amantidine

Answer 4

it is orally active

has large colume of distribution including nasal secretions

eliminated unchanged in urine

Question 5

what are some adverse effects of amantadine

Answer 5

CNS: nervousness, confusion, insomnia, high doses lead to delirium seizures and cardiac arrhythmias

GI; loss of appetite, nausea

peripheral edema

Question 6

this drug is effective against both A and B strains of influenza

Answer 6

Oseltamivir

Question 7

oseltamivir is what type of inhibitor

Answer 7

neuraminidase so it prevents the release of infectious virions

Question 8

what are the adverse effects of oseltamivir

Answer 8

GI: nausea, emesis

usually resolves

Zanamivir: related compound; must be given intranasally because of poor oral absorption

Question 9

Zanamivir is a

Answer 9

is a related compound to oseltamivir and it works the same way. Zanamivir has very poor oral absorption and so you give it intranasally. However some older people cannot tolerate that type of delivery system very well. So zanamivir is not used as much as oseltamivir since most people would prefer to take their drug orally

Question 10

what are the antiherpetic drugs

Answer 10

Acyclovir, ganciclovir, foscarnet

Question 11

what type of analog is acyclovir

Answer 11

guanine nucleoside analog

Question 12

acyclovir has the highest toxicity. describe its toxicity

Answer 12

This large Km and small relative velocity means that there’s going to be very little acyclovir phosphorylated by human thymidine kinase. So acyclovir won’t be phosphorylated very well in a human cell as long as there’s no HSV present. Therefore it’s only in HSV-infected cells that you can make acyclovir monophosphate so that host cellular enzymes can make the triphosphate which is the active form of acyclovir. This is what accounts for acyclovir’s selectivity.

Question 13

what is the mechanism of action of acyclovir

Answer 13

1. Acyclovir triphosphate binds to viral DNA polymerase and therefore competes for binding of other guanine analogs.
2. Acyclovir triphosphate can also be incorporated into the growing viral DNA genome and terminate replication because it lacks the complete ribose ring. So you wind up with chain elongation being terminated and there’s no replication of the HSV genome.

When the next nucleotide binds to any free viral DNA polymerase, the polymerase is frozen because it can’t add any further nucleotides to the growing chain

Question 14

What is the mechanism of action of acyclovir

Answer 14

The HSV thymidine kinase works on acyclovir to add one phosphate group. So the monophosphorylation step occurs in cells that are infected with herpes simplex virus.

Then host cellular enzymes add the last 2 phosphates so that you end up with acyclovir attached to 3 phosphates. So the triphosphate form of acyclovir is the active compound and it’s formed in cells that have HSV thymidine kinase