1.4 Antiviral Chemotherapy

Question 1

Viral life cycle and targets for intervention?

Answer 1

• bind to and enter susceptible host cell
• uncoating, release of viral genome
• after variable dormant period, synthesize early proteins (polymerases)
• synthesis of nucleic acids
• synthesis of late proteins (structural)
• assembly of viral particles, release of virus

Question 2

inhibitor of nucleic acid synthesis?

Answer 2

ribavirin

Question 3

rimantadine is used for anti-_______ chemotherapy

Answer 3

influenza

Question 4

rimantadine works by blocking _______

Answer 4

M2 proton channel

Question 5

rimantadine is administered ______ and protects against influenza type ____

Answer 5

orally, A

Question 6

anti influenza viral neuraminidase inhibitors?

Answer 6

oseltamivir and zanamivir

Question 7

• anti-influenza, effective against all common influenza virus strains
• pro drug activated in gut and liver

Answer 7

oseltamivir (tamiflu)

Question 8

• anti influenza, effective against flu A and B
• oral inhalation, causes bronchospasm in asthmatics
• renal excretion of unchanged drug

Answer 8

zanamivir

Question 9

• inhibitor of viral nucleic acid synthesis

- antimetabolite, blocks GTP formation, inhibits viral mRNA capping, inhibits viral RNA dependent polymerases

Answer 9

ribavarin

Question 10

ribavirin is activated by _________

Answer 10

host kinases

Question 11

ribavirin is used with interferon alpha to treat ________ orally, and as an aerosol for ______

Answer 11

hepatitis C, RSV

Question 12

ribavirin side effects can cause?

Answer 12

dose dependent anemia, fatigue, rash, pruritis; also a known teratogen and embryotoxin

Question 13

inhibit viral genome replication by causing chain termination

Answer 13

dideoxynucleotides

Question 14

-guanosine analog, activated by viral thymidine kinase (tk)

Answer 14

acyclovir

Question 15

acyclovir is used to manage, but not cure what disease?

Answer 15

HSV1 and 2

Question 16

initial phosphorylation requires a _____ kinase, and acyclovir triphosphate is a substrate for _______

Answer 16

viral, viral polymerase

Question 17

incorporation of acyclovir causes?

Answer 17

chain termination, inhibition of DNA polymerase

Question 18

valine ester of acyclovir, pro drug, has higher bioavailability

Answer 18

valacyclovir

Question 19

inhibitor of viral genome replication used to treat cytomegalovirus?

Answer 19

ganciclovir

Question 20

ganciclovir is a better substrate than acyclovir for _____ kinases, less selectivity leads to more toxicity

Answer 20

host

Question 21

side effects of ganciclovir in treating cytomegalovirus?

Answer 21

myelosuppression, GI effects, neuropathies, CNS toxicity, teratogenic

Question 22

• directly inhibits viral polymerases
• pyrophosphate, NOT a nucleoside analog
• synergistic with ganciclovir
• IV, crosses BBB, excreted in urine
• nephrotoxic

Answer 22

foscarnet

Question 23

• cytosine nucleotide analog
• phosphorylated by host kinases
• competitive inhibitor of viral DNA synthesis, incorporated into viral DNA
• active tubular secretion, dose dependent nephrotoxicity
• used IV for CMV retinitis

Answer 23

cidofovir

Question 24

• activated by host kinases
• competes with TTP at viral polymerase
• inhibits DNA synthesis in HSV-1, HSV-2, CMV
• incorporated into viral and host DNA
• topical use for HSV-1 and 2 conjunctivitis
• can be effective against acyclovir resistant HSV

Answer 24

trifluridine

Question 25

- cytokines given IM or subcutaneous - pegylated forms provide longer half life - glomerular filtration and proteolytic degradation - manages HBV, eradicates HCV - flu like symptom after dosing, may induce autoantibodies

Answer 25

interferon alpha

Question 26

pegylated IFN-alpha plus ________ has been standard of care for eradication of HCV

Answer 26

ribavirin

Question 27

- cytosine analog - inhibits HIV RT and HBV DNA polymerase - decrease clinical progression of HBV and reduce HCC, long term use - resistance associated with hepatitis flares, progression of liver damage

Answer 27

lamivudine

Question 28

- inhibits HCV protease (serine protease) - used in combo with peg interferon and ribavirin - oral, absorption enhanced by fatty meal - extensive hepatic clearance - rash/pruritis, fatigue - resistance can develop rapidly

Answer 28

telaprevir

Question 29

- HCV protease inhibitor - oral, take with meal - Asians show 3X higher mean exposure - sulfa moiety-hypersensitivity, Stevens Johnson

Answer 29

simeprevir

Question 30

- nucleotide analog - inhibits HCV RNA polymerase - oral administration, renal excretion - pgp substrate - combine with ribavirin and interferon for cure of HCV

Answer 30

sofosbuvir