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Infectious Disease > 1.4 Antiviral Chemotherapy > Flashcards

1.4 Antiviral Chemotherapy Flashcards

1
Q

Viral life cycle and targets for intervention?

A
  • 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
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2
Q

inhibitor of nucleic acid synthesis?

A

ribavirin

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3
Q

rimantadine is used for anti-_______ chemotherapy

A

influenza

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4
Q

rimantadine works by blocking _______

A

M2 proton channel

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5
Q

rimantadine is administered ______ and protects against influenza type ____

A

orally, A

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6
Q

anti influenza viral neuraminidase inhibitors?

A

oseltamivir and zanamivir

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7
Q
  • anti-influenza, effective against all common influenza virus strains
  • pro drug activated in gut and liver
A

oseltamivir (tamiflu)

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8
Q
  • anti influenza, effective against flu A and B
  • oral inhalation, causes bronchospasm in asthmatics
  • renal excretion of unchanged drug
A

zanamivir

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9
Q
  • inhibitor of viral nucleic acid synthesis

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

A

ribavarin

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10
Q

ribavirin is activated by _________

A

host kinases

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11
Q

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

A

hepatitis C, RSV

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12
Q

ribavirin side effects can cause?

A

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

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13
Q

inhibit viral genome replication by causing chain termination

A

dideoxynucleotides

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14
Q

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

A

acyclovir

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15
Q

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

A

HSV1 and 2

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16
Q

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

A

viral, viral polymerase

17
Q

incorporation of acyclovir causes?

A

chain termination, inhibition of DNA polymerase

18
Q

valine ester of acyclovir, pro drug, has higher bioavailability

A

valacyclovir

19
Q

inhibitor of viral genome replication used to treat cytomegalovirus?

A

ganciclovir

20
Q

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

A

host

21
Q

side effects of ganciclovir in treating cytomegalovirus?

A

myelosuppression, GI effects, neuropathies, CNS toxicity, teratogenic

22
Q
  • directly inhibits viral polymerases
  • pyrophosphate, NOT a nucleoside analog
  • synergistic with ganciclovir
  • IV, crosses BBB, excreted in urine
  • nephrotoxic
A

foscarnet

23
Q
  • 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
A

cidofovir

24
Q
  • 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
A

trifluridine

25
Q
  • 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
A

interferon alpha

26
Q

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

A

ribavirin

27
Q
  • 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
A

lamivudine

28
Q
  • 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
A

telaprevir

29
Q
  • HCV protease inhibitor
  • oral, take with meal
  • Asians show 3X higher mean exposure
  • sulfa moiety-hypersensitivity, Stevens Johnson
A

simeprevir

30
Q
  • nucleotide analog
  • inhibits HCV RNA polymerase
  • oral administration, renal excretion
  • pgp substrate
  • combine with ribavirin and interferon for cure of HCV
A

sofosbuvir

Infectious Disease (22 decks)

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