Antivirals

Question 1

Zanamivir/oseltamivir

Answer 1

Block neuraminidase. Decreases release of progeny. Used to treat influenza A and B

Question 2

Ribavirin

Answer 2

Inhibits synthesis of guanine nucleotides by inhibiting inosine monophosphate dehydrogenase.

Used for RSV, hepatitis C (chronic)

Question 3

Ribavirin toxicity

Answer 3

Severe teratogen, hemolytic anemia.

Question 4

Acyclovir, famciclovir, valacyclovir

Answer 4

Must be phosphorylated to be active. Phosphorylated in HSV/VZV by thymidine kinase. Guanosine analog. Preferentially inhibits DNA polymerase via chain termination.
Few adverse effects.

Resistance if thymidine kinase mutated.

Used in HSV and VZV. Weak activity against EBV.

Valacyclovir is a prodrug and has better oral bioavailability

Question 5

Toxicity of acyclovir, famciclovir, valacyclovir?

Answer 5

Obstructive crystalline nephropathy and acute renal failure if not hydrated.

Question 6

Ganciclovir

Answer 6

5’monophosphate formed by CMV viral kinase. Guanosine analog. Triphosphate formed by cellular kinases. Inhibits DNA polymerase.

Use in CMV.

Question 7

Ganciclovir toxicity

Answer 7

Leukopenia, neutropenia, thrombocytopenia, renal toxicity. Much more toxic to host enzymes than acyclovir.

Question 8

Foscarnet

Answer 8

Pyrophosphate analog
Viral DNA polymerase inhibitor that binds to the pyrophosphate binding site of the enzyme. Does not require activation by viral kinase.

Used in CMV retinitis or when CMV has UL97 mutation.

Question 9

Foscarnet toxicity

Answer 9

Nephrotoxicity

Question 10

Cidofovir

Answer 10

Preferentially inhibits viral DNA polymerase. Does not require phosphorylation by viral kinases.

Used in CMV retinitis in immunocompromised or in acyclovir resistant HSV.

Question 11

Cidofovir toxicity

Answer 11

Severely nephrotoxic so administer with saline and probenecid.

Question 12

HAART

Answer 12

Initiated when patients present with AIDS defining illness or low CD4

Question 13

Protease inhibitors

Answer 13

End in -navir (atazanavir, darunavir, indinavir, etc).

Assembly of virions depends on HIV protease (pol), which cleaves polypeptide into functional parts).

Question 14

Ritonavir advantage

Answer 14

Inhibits CYP450 so can boost drug concentrations

Question 15

NRTIs

Answer 15

Abacavir, didanosine, emtracitabine, lamivudine, stavudine, zidovudine, tenofovir.

(-vudine mostly)

Mostly nucleosides and must be phosphorylated to be active

Question 16

Which NRTI is a nucleotide and doesn’t need to be phosphorylated to be active?

Answer 16

Tenofovir.

Question 17

NRTIs side effects

Answer 17

Bone marrow suppression, peripheral neuropathy, pancreatitis

Question 18

NNRTIs

Answer 18

Efavirinz, nevirapine, delavirdine

Bind to reverse transcriptase at different site than NRTIs, do not require phosphorylation.

Rash/hepatotoxicity/VIVID dreams

Question 19

Raltegravir

Answer 19

Integrase inhibitor, prevents integration of HIV genome into host cell chromosomes. Can cause hypercholesterolemia.

Question 20

Fusion inhibitors

Answer 20

Maraviroc, enfuviratide.

Enfuviritide blocks GP41, inhibiting entry

Maraviroc binds CCR-5 on t-cell/monocytes and inhibits interaction with GP120.

Question 21

Interferons

Answer 21

Glycoproteins normally synthesized by virus infected cells.

Question 22

IFN a use

Answer 22

used in chronic hepatitis B and C, KS, hairy cell leukemia, condyloma accuminatum, renal cell carcinoma, malignant melanoma

Question 23

IFN b use

Answer 23

MS

Question 24

IFN gamma use

Answer 24

Chronic granulomatous disease