Antivirals

Question 1

What are the four main mechanisms of antivirals?

Answer 1

Prevent replication of viral nucleic acid

Inhibit viral entry (unique binding)

Inhibit viral uncoating (releasing of viral DNA)

Inhibit viral release (virus exiting)

Question 2

What type of drug is used to treat herpes viruses?

Answer 2

Nucleoside analogues = time dependent virstatin

Naturally occurring purine or pyrimidine base combined with carbohydrate moiety

Question 3

Name the guanine analogue antiviral drugs

Answer 3

Aciclovir, valaciclovir, famciclovir

ganciclovir

All VIRUSTATIC

Question 4

What is the MOA of antiviral guanine analogues?

Answer 4

Following phosphorylation by viral and cellular enzymes (thymidine kinase), guanine analogies inhibit viral DNA polymerase and DNA synthesis

Question 5

Compare the guanine analogues used in antiviral treatment

Answer 5

Aciclovir = low oral F (0.22), T1/2 =3 hr

Valaciclovir = prodrug, better oral F (0.55) –> converted to aciclovir by liver/intestinal enzymres

Famciclovir = best oral bioavailability (F= 0.8), converted to penciclovir after absorption

Question 6

Outline the indications for aciclovir

Answer 6

Treatment/prevention of herpes simplex infection

Shingles

Acute chickenpox = immunocompromised patients

herpetic eye infections

prophylaxis of CMV infections

not sufficiently active against CMV

Question 7

How does the MOA of ganciclovir differ from aciclovir?

Answer 7

Ganciclovir = woken up by host thymidine kinase

Question 8

What is the indication of ganciclovir?

Answer 8

Treatment and prevention of CMV disease (ganciclovir, valganciclovir)

Question 9

What is valganciclovir?

Answer 9

Is a prodrug with improved F compared to ganciclovir

Converted to ganciclovir in intestinal wall and liver

Question 10

What are the ADRs of viral guanin analogues?

Answer 10

Encephalopathy

Agitation, vertigo, confusion, dizziness, renal impairment

Coma, seizures (w/ renal problems), cyrstalluria, neutropenia, leucopenia

Question 11

What is the class and MOA of foscarnet

Answer 11

Class = pyrophosphate derivative

MOA = block pyrophosphate-binding site on viral DNA polymerase –> preventing attachment of nucleotide precursors to DNA

Virustatic

Question 12

Does forcarnet need to be activation by enz/other mechanisms to work?

Answer 12

no, already phosphorylated =)

Question 13

List the notable neuraminidase inhibitor antiviral drugs

Answer 13

Oseltamavir (tamiflu tablets)

Zanamivir

Question 14

Generally, what is the MOA of neuraminidase inhibitors?

Answer 14

MOA = Inactivates resp tract mucus that would spread virions through the resp tract

neuraminidase usually cleaves sialic acid residues attached to mucus proteins

Question 15

What is oseltamavir? (spectrum of activity, indication)

Answer 15

Pro-drug –> hydrolysed to oseltamivir carboxylate

Active against = influenza A and B

Indication = sx tx of flu A,B in adults who present with sx w/in 48 hrs, flu prophylaxis in patient >13 yrs old

Question 16

What are some ADRs of oseltamivir?

Answer 16

N/V

Rare = psychiatric sx

Question 17

What is Zanamivir used for?

Answer 17

Treatment of Flu A/B

Prevention of infection due to flu A/B virus

Question 18

What are the C/I for Zanamivir?

Answer 18

Airways disease (e.g. asthma) = bronchoconstriction or worsening resp function may occur