Antivirals

Question 1

Amantadine:

Answer 1

MOA: Blocks viral uncoating by interfering with influenza A M2 protein.

Uses: -Prophylaxis against influenza A (NOT influenza B).
-Therapeutic against influenza A if given within the first 2 days of illness.

Question 2

Tamiflu:

Answer 2

MOA: Prodrug, competitive inhibitor of influenza NA; interferes with viral release and viral penetration.

Uses: -Treatment of uncomplicated influenza A and B; must be given within 48 hrs of symptom onset.
-Influenza prophylaxis.

Question 3

Trifluridine:

Answer 3

MOA: Interferes with DNA synthesis; thymidine analog.

Uses: -Treatment of ophthalmic Herpes simplex types 1 and 2.

Question 4

Acyclovir:

Answer 4

MOA: Inhibits herpes DNA polymerase (almost exclusively); phosphorylated form is produced much more rapidly in infected cells via herpes thymidine kinase. Acts as a competitive inhibitor of dGTP and as a DNA chain terminator.

Uses:

• IV: Systemic herpes infection and severe initial genital herpes.
• Oral: Primary genital herpes, primary herpetic gingivostomatosis.
• Topical: Some effect when applied early to primary genital herpes.

Question 5

Famciclovir:

Answer 5

MOA: Similar to acyclovir, but is a prodrug that is converted to penciclovir, which is then phosphorylated intracellulary by herpes thymidine kinase, which then inhibits viral DNA polymerase.

Uses: -Shingles infections.
-Recurrent genital herpes.

Question 6

Penciclovir:

Answer 6

Similar to acyclovir, but only used topically against herpes of the lips and face.

Question 7

Ganciclovir:

Answer 7

MOA: Similar to acyclovir, but phosphorylation is carried out via CMV protein kinase.

Uses: -CMV retinitis.
-CMV prophylaxis for transplant recipients.

SEs: Bone marrow suppression.

Question 8

Foscarnet:

Answer 8

MOA: Inhibits CMV DNA polymerase by binding to its pyrophosphate-binding site. Does not require conversation to triphosphate form to be active.

Uses: -CMV retinitis.
-Acyclovir-resistant herpes simplex (thymidine kinase mutations).

SEs: Renal damage.

Question 9

3TC:

Answer 9

MOA: Nucleoside analog inhibitor of the RT domain of the hep B DNA polymerase.

Uses: -Hep B
-Synergistic with AZT in the treatment of HIV.

Question 10

Tenofovir:

Answer 10

MOA: Nucleotide inhibitor of the RT domain of the hep B DNA polymerase.
For HIV: inhibits RT by competing with dATP for incorporation into DNA, resulting in chain termination.

Uses: -Hep B.
-Given in combination therapy for HIV-infected patients.

Question 11

IFN-alpha:

Answer 11

Uses: -Condyloma cuminata

• Hep B and C
• Pegylation decreases clearance (higher and prolonged plasma concentrations).

SEs: Flu-like symptoms, bone marrow suppression.

Question 12

Ribavirin:

Answer 12

MOA: Inteferes with viral mRNA synthesis; inhibits GTP synthesis, and thus inhibits GTP-dependent capping of viral mRNA.

Uses: -Aerosol use in infants and young children with documented severe RSV infections.
-Given in combination with PEG-IFNa for Hep C.

SEs: Aerosol use: drug may precipitate in respiratory equipment.
-Pulmonary function deterioration.
IV use: bone marrow suppression.

Question 13

Simeprevir:

Answer 13

MOA: Reversibly inhibits hep C NS3/NS4A protease, thus blocking cleavage of the polyprotein and formation of infectious virus.

Uses: -hep C genotype 1
-Always in combination with other drugs.

SEs: -Rash (photosensitivity)

• GI effects
• Avoid using with inducers or inhibitors of CYP3A.

Question 14

Sofosbuvir:

Answer 14

MOA: Prodrug; triphosphate form inhibits HCV NS5B RNAP causing chain termination.

Uses: -hep C genotypes 1,2,3,4.
-Combination with other drugs.

SEs: Avoid with inducers of Pgp.

Question 15

AZT:

Answer 15

MOA: NRTI; phosphorylated by cellular kinases. Inhibits RT, and also acts as a DNA chain terminator.

Uses: Combination therapy for HIV therapy.

SEs: -Bone marrow suppression.
-Drugs which inhibit glucoronyl-transferase increase hematologic toxicity.

Question 16

FTC:

Answer 16

MOA: Fluorinated analog of 3TC that inhibits RT by competing for dCTP incorporation into DNA, resulting in chain termination.

Uses: Combination therapy for HIV.

Question 17

ABC:

Answer 17

MOA: Inhibits viral RT.

Uses: Combination therapy for HIV.

SEs: Hypersensitivity reactions associated with HLA-B*5701 antigen.

Question 18

Efavirenz:

Answer 18

MOA: Non-nucleoside inhibitor of RT; does not require phosphorylation for activity.

Uses: Combination therapy for HIV.

SEs: CNS effects, nightmares.

Question 19

Lopinavir:

Answer 19

MOA: Protease inhibitor; prevents cleavage of Gag-pol polypeptide into separate functional proteins; results in non-infectious viral particles.

Uses: Use in combination with a RT inhibitor for treatment of HIV.

SEs: Redistribution of fat, diabetes.

Question 20

Ritonavir:

Answer 20

MOA: Inhibits CYP3A and enhances the efficacy of other protease inhibitors.

Uses: Use as a protease inhibitor booster.

Question 21

Enfuvirtide:

Answer 21

MOA: Inhibits the fusion of viral and cellular membranes by binding to gp41 subunit of HIV glycoprotein.

Uses: -Effective against HIV-1 only.
-Treatment of strains resistant to other drugs.

Question 22

Maraviroc:

Answer 22

MOA: CCR5 antagonist. Blocks entry of HIV into cells.

Uses: -Treatment of CCR5-tropic HIV-1.
-CCR5-tropic strains tend to predominate early in infection.

SEs: Hepatic and cardiac effects.

Question 23

Raltegravir:

Answer 23

MOA: -Inhibits HIV-1 integrase, preventing integration of HIV-1 DNA into the genome.

Uses: -Treatment of HIV-1, works on virus strains resistant to other drugs.