Antivirals

Question 1

zanamivir, oseltamivir

Answer 1

inhibit influenza neuraminidase –> decrease the release of progeny virus
- used for treatment and prevention of influenza A and B

Question 2

ribavirin mech, use and tox

Answer 2

• inhibits synthesis of guanine nucleotides by competitively inhibiting inosine monophosphate dehydrogenase
• used for RSV, chronic Hep C
• tox: hemolytic anemia, severe teratogen

Question 3

acyclovir, famciclovir, valacyclovir mech and clinical use

Answer 3

• monophosphorylated by HSV/VZV thymidine kinase and not uninfected cells. guanosine analog, triphosphate formed by cellular enzymes
• preferentially inhibits viral DNA polymerase by chain termination
• used for HSV, VZV, weak activity against EBV
• use famciclovir for herpes zoster

Question 4

ganciclovir mech and clinical use

Answer 4

• 5’ monophosphate formed by a CMV viral kinase
• guanosine analog
• triphosphate formed by cellular kinases, preferentially inhibits viral DNA polymerase
• used for CMV, esp immunocompromised pts
• valgancyclovir has better oral availability

Question 5

acyclovir, famciclovir, valacyclovir tox and mech of resistance

Answer 5

• tox: obstructive crystalline nephropathy and acute renal failure if not hydrated
• resist: mutated viral thymidine kinase

Question 6

ganciclovir tox and mech of resistance

Answer 6

• tox: leukopenia, neutropenia, thrombocytopenia, renal tox

- resist: mutated CMV DNA polymerase or lack of viral kinase

Question 7

foscarnet mech and clinical use

Answer 7

• viral DNA polymerase inhibitor that binds to pyrophosphate binding site of the enzyme. does not require activation by viral kinase
• used in CMV retinitis when ganciclovir fails, or in acyclovir-resistant HSV

Question 8

foscarnet tox and mech of resistance

Answer 8

• tox: nephrotoxic (can lead to hypocalcemia and hypomag –> seizures)
• resist: mutated DNA polymerase

Question 9

cidofovir

Answer 9

• preferentially inhibits viral DNA polymerase, does not require phosphorylation
• used in CMV retinitis and acyclovir resistant HSV
• long half life
• tox: nephrotoxic (give probenecid and IV saline)

Question 10

protease inhibitors

Answer 10

• prevent cleavage of polypeptide products of HIV (will see increased pol mutations with treatment)
• ritonavir is a P450 inhibitor
• all end in navir
• tox: hyperglycemia, GI intolerance, lipodystrophy
• idinavir causes nephropathy and hematuria

Question 11

NRTIs

Answer 11

• no 3’OH, DNA chain terminators
• zidovudine (formerly AZT) given during pregnancy to decrease fetal transmission
• tox: bone marrow suppression, peripheral neuropathy, lactic acidosis, rash, anemia, pancreatitis (didanosine)

Question 12

NRTI names

Answer 12

abacavir, didanosine, emtriitabine, lamuvidine, stavudine, tenofovir, zidovudine (formerly AZT)

Question 13

NNRTIs

Answer 13

• bind to reverse trascriptase, but not at nucleoside binding site
• do not require phosphorylation
• rash and hepatotoxicity
• names: efavirenz, necirapine, delaviridine

Question 14

integrase inhibitors

Answer 14

• raltegravir
• inhibits HIV genome integration into host cell by reversibly inhibiting HIV integrase
• tox: hypercholesterolemia

Question 15

fusion inhibitors

Answer 15

• enfuvirtide binds gp41, inhibiting viral entry
• maraviroc binds CCR5, inhibiting interaction with gp120
• tox: skin reaction at injection site

Question 16

interferons mech, use and tox

Answer 16

• glycoproteins usually synthesized by virus-infected cells, wide range of antiviral properties
• alpha used in Hep B/C, Kaposi sarcoma, hairy cell leukemia, condyloma acuminatum, RCC and malignant melanoma
• beta used in MS
• gamma used in chronic granulomatous disease
• tox: neutropenia, myopathy