Antivirals

Question 1

Zanamivir, Oseltamivir MECH

Answer 1

Inhibit influenza neuramidase, decreasing the release of progeny virus.

Question 2

Zanamivir, Oseltamivir USE

Answer 2

TX & prophy influenza A & B

Question 3

Ribavarin MECH

Answer 3

Inhibits synth of guanine nucleotides by competitively inhibiting IMP dehydrogenase - stops duplication of viral genome.

Question 4

Ribavarin USE

Answer 4

RSV, Chronic Hep C

Question 5

Ribavarin TOX

Answer 5

Hemolytic anemia, teratogen

Question 6

Acyclovir Mech

Answer 6

Monop’lated by HSV/VZV thymidine kinase. Guanosine analog. Triphosphate formed by cellular enzymes. Preferentially inhibits viral DNA pol by chain termination.

Question 7

Acyclovir USE

Answer 7

HSV & VZV. Weak act against EBV. None against CMV. Used for HSV-induced mucocutaneous & genital lesions, encephalitis. Prophy in immunocompromised patients. No effect on latent HSV & VZV. Valacyclovir has better bioavailability. For herpes zoster use a related agent, famcyclovir

Question 8

Acyclovir TOX

Answer 8

few serious

Question 9

Acyclovir RESIST

Answer 9

mutated viral thymidine kinase

Question 10

Ganciclovir MECH

Answer 10

5’-monophosphate formed by a CMV viral kinase. Guanosine analog. Triphosphate formed by cellular kinases. Preferentially inhibits viral DNA pol

Question 11

Ganciclovir USE

Answer 11

CMV, esp immunocompromised. Valganciclovir = prodrug ganciclovir w/better bioavailability.

Question 12

Ganciclovir TOX

Answer 12

leukopenia, neutropenia, thrombocytopenia, renal tox, More toxic to host enz than acyclovir.

Question 13

Ganciclovir RESIST

Answer 13

mutated CMV DNA pol or lack of viral kinase

Question 14

Foscarnet MECH

Answer 14

Viral DNA pol, RNA pol, & reverse transcriptase inhibitor that binds the pyrophosphate binding site of enz. Does not require activation by viral kinase

Foscarnet = pyroFOSphate analog

Question 15

Foscarnet USE

Answer 15

CMV retinitis in immunocompromised patients (AIDS) when ganciclovir fails; acyclovir-resistant HSV

Question 16

Foscarnet TOX

Answer 16

Nephrotox, hypOcalcemia, hypOmagnesemia, seizures

Question 17

Foscarnet RESIST

Answer 17

Mutated DNA pol

Question 18

Cidofovir MECH

Answer 18

Preferentially inhibits viral DNA pol. Does NOT require p’lation by viral kinase

Question 19

Cidofovir USE

Answer 19

CMV retinitis in immunocompromised; acyclovir-resistant HSV. Long half-life

Question 20

Cidofovir TOX

Answer 20

Nephrotox (coadminister w/probenecid & IV saline to reduce tox)

Question 21

HIV Therapy initiation

Answer 21

Highly active antiretroviral therapy HAART; initiate when patient presents w/AIDS-defining illness, low CD4 count <500, or high viral load.

Question 22

HAART regimen

Answer 22

3 drugs to prevent resistance:
[2 nucleoside reverse transcriptase inhibitors (NRTIs)] + [1 non-nucleoside reverse transcriptase inhibitor (NNRTIs OR 1 protease inhibitor]

Question 23

Protease inhibitors

Answer 23

-navir

Question 24

Protease inhibitors MECH

Answer 24

Assembly of virions depends on HIV-1 protease (pol gene), which cleaves the polypeptide products of HIV mRNA into their functional parts. Thus, protease inhibitors prevent maturation of new viruses.

**ritonavir boosts other drug [ ]s by inhibiting P450

Question 25

Protease Inhibitor TOX

Answer 25

hypERglycemia, GI intolerance (nausea, diarrhea), lipodystrophy

Question 26

Indinavir TOX

Answer 26

nephropathy, hematuria

Question 27

NRTIs

Answer 27

Tenofovir (TDF), Emtricitabine (FTC), Abacavir (ABC), Lamivudine (3TC), Zidovudine (ZDV, formerly AZT), Didanosine (ddI), Stavudine (d4T)

Question 28

NRTI MECH

Answer 28

Competitively inhibit nucleotide binding to reverse transcriptase and terminate the DNA chain (lack of 3' OH group). Tenofovir = nuc.tide analog & does not need to be activated; rest = nuc.side analogs & must be activated by p'lation. ZDV used for prophy & during pregnancy to reduce fetal transmission.

Question 29

NRTI & NNRTI TOX

Answer 29

Bone marrow suppression (can be reversed w/G-CSF & EPO), peripheral neuropathy, lactic acidosis (nuc.sides), rash (non-nuc.sides), anemia (ZDV).

Question 30

NNRTIs

Answer 30

Nevirapine, efavirenz, delavirdine

Question 31

NNRTI Mech

Answer 31

Bind to reverse transcriptase at site different from NRTIs. Do NOT require p'lation to be active

Question 32

Integrase inhibitors

Answer 32

Raltegravir

Question 33

Raltegravir (integrase inhibitor) MECH

Answer 33

Inhibits HIV genome integration into host cell chromosome by reversibly inhibitingHIV integrase.

Question 34

Raltegravir TOX

Answer 34

Hypercholesterolemia.

Question 35

IFN MECH

Answer 35

Glycoproteins synthesized by virus-infected cells; block replication of both RNA & DNA virus.

Question 36

IFN- alpha USE

Answer 36

chronic Hep B & C, Kaposi sarcoma

Question 37

IFN-Beta USE

Answer 37

MS

Question 38

IFN-gamma USE

Answer 38

NADPH oxidase deficiency

Question 39

IFN toxicity

Answer 39

Neutropenia, myopathy