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FM3_ EB > Antivirals > Flashcards

Antivirals Flashcards

1
Q

5-iododeoxyuridine and trifluorothymine were early antiviral agents that had poor ______ and were thus too toxic for systemic use, but are still used for topical treatment of ______

A

poor specificity- inhibited host and viral DNA

used for herpes keratitis

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2
Q

List viruses that can now be treated with antiviral therapies

A 
herpes viruses
HCV
HBV
papillomavirus
influenza 
HIV
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3
Q

All antivirals are ______; they are active only against replicating virus and do not affect latent virus

A

virustatic

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4
Q

List some drugs that inhibit viral entry or penetration

A

fusion inhibitors, soluble receptor decoys, antireceptor antibodies, interferons

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5
Q

List some drugs that inhibit release of the viral genome (uncoating)

A

ion channel blockers, capsid stabilizers

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6
Q

List some drugs that inhibit viral transcription and replication of viral genes

A

viral DNA and RNA polymerase inhibitors, reverse transcriptase inhibitors, interferons

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7
Q

List some drugs that inhibit translation of viral mRNA into protein

A

interferons, antisense oligonucleotides

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8
Q

List a drug class that inhibits post-translational modifications

A

protease inhibitors

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9
Q

List a class of drugs that inhibit assembly of virion components

A

Interferons

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10
Q

List drugs that inhibit budding and release of virus

A

Neuraminidase inhibitors, interferons, antiviral antibodies, cytotoxic lymphocytes

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11
Q

Valacyclovir is a prodrug acyclic guanosine nucleoside analogue active against:

A

HSV-1 and HSV-2
VZV
EBV

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12
Q

Describe the mechanism of action of valacyclovir

A

Viral thymidine kinase (TK) converts acyclovir into acyclovir monophosphate; the monophosphate is then converted into the triphosphate form by cellular enzymes

Acyclovir triphosphate inhibits viral DNA synthesis by competitive inhibition of viral DNA polymerase and incorporation into the growing viral DNA chain, causing chain termination

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13
Q

What are adverse reactions to valacyclovir?

A

CNS, GI, nephrotoxicity

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14
Q

What precautions should be noted for use of valacyclovir?

A

renal insufficiency- dose reduction

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15
Q

What viruses is ganciclovir active against?

A

CMV (indicated for CMV retinitis)

weak activity against HSV, VZV

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16
Q

Describe the drug ganciclovir

A

Synthetic acyclic guanosine nucleoside analogue

mainly indicated for CMV retinitis

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17
Q

Describe the mechanism of action of ganciclovir

A

CMV kinase (UL97 gene) in CMV-infected cells converts ganciclovir to the monophosphate; the monophosphate is then converted into the triphosphate form by cellular enzymes

Ganciclovir triphosphate inhibits viral DNA synthesis by competitively inhibiting viral DNA polymerase and also causing eventual chain termination

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18
Q

________ is a drug that is CMV selective and has weaker activity against HSV and VZV strains

A

Ganciclovir

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19
Q

What adverse reactions to ganciclovir can be seen>

A

GI- NVD

Heme- cytopenias

20
Q

What precautions should be noted with ganciclovir

A

bone marrow suppression

renal insufficiency

21
Q

________ is an acyclic cytosine angalog active against CMV, HSV, adenovirus, and pipillomavirus. It is 60x more potent vs CMV and is indicated for CMV retinitis

A

cidofovir

22
Q

Describe the mechanism of action of cidofovir

A

Inhibits viral DNA polymerase but does NOT require activation by viral kinase, so it is active against TK deficient or mutant strains

Works by competitively inhibiting viral DNA polymerase and causing chain termination

23
Q

What is unique about the mechanism of cidofovir compared to ganciclovir and valacyclovir?

A

Cidofovir does not need to be activated by a viral kinase

24
Q

List some of the adverse reactions to cidofovir

A 
renal
hemeatolgic
opt
derm
GI
fever, chills
25
Q

What special precaution exists for cidofovir

A

Must prehydrate with a liter of normal saline with probenecid

26
Q

______ is a synthetic thymidine nucleoside analogue with specific activity against HBV

A

telbivudine

27
Q

Describe the mechanism of action of telbivudine

A

Phosphorylated by cellular kinase to a triphosphate
competitively inhibits HBV DNA polymerase by competing with D-thymidine
Incorporation into viral DNA leads to chain termination

28
Q

What adverse reactions can be seen with telbivudine

A

fatigue, lactic acidosis, hepatomegaly with steatosis, peripheral neuropathy

29
Q

-2, HIVWhat viral infections can be treated with interferons?

A

HBV, HCV, HSV-1 and HSV, HIV

30
Q

What is the mechanism of action of interferons against viral infection

A

induce signal cascades that result in inhibition of viral penetration, translation, transcription, protein processing, maturation, and release, and they induce enzymes that cleave viral RNA

Also activate and enhance killing ability of NK cells and macrophages and have antiproliferative effects on tumor cells

31
Q

What are precautions for interferon use?

A

hepatic dz
thyroid dz
autoimmune dz

32
Q

________ is a purine analogue active vs many RNA and DNA viruses including HSV, VZV, and RSV

A

Ribavirin

33
Q

Ribavirin is formulated with ____________ to treat HCV infections

A

interferon a-2b (Rebetron)

34
Q

What is the mechanism of action of ribavirin?

A

Phosphorylated by cellular enzymes to the triphosphate; interferes with the synthesis of GTP by inhibiting IMPDH, inhibits viral RNA-dependent polymerase; increases the mutation rate of viral RNA to the point at which viable virions are not produced

Inhibits the replication of a wide range of DNA and RNA viruses, including influenza A and B, parainfluenza, RSV, paramyxoviruses, HCV, and HIV-1

35
Q

What precautions exist for ribavirin?

A

Pregnancy risk X
monitor hematocrit
renal insufficiency

36
Q

_______ is used for HCV genotype 1 infection in combination with peginterferon alpha and ribavirin

A

beceprevir

37
Q

Describe the mechanism of action of beoceprevir

A

HCV NS3/4A serine protease inhibitor; binds to the NS3/4A active site serine (S139) through an α-ketoamide functional group; NS3/4A is necessary for the proteolytic cleavage of the HCV encoded polyprotein into mature forms of NS4A, NS4B, NS5A and NS5B proteins

38
Q

How can resistance to boceprevir arise?

A

Resistance can arise from one or more amino acid substitutions in the NS3 protease domain

39
Q

What precautions exist for boceprevir?

A

Not for monotherapy

Strong CYP inhibitor

40
Q

________ is used for phrophylactic or symptomatic treatment of influenza esp in high risk patients, must be initiated within 48 hours of symptom onset, and potentiates DA transmission so can be used in Parkinson’s tx

A

amantadine

41
Q

Describe the mechanism of action of amantadine

A

blocks the M2 proton channel within the viral membrane, preventing acid-dependent uncoating of viral capsid and release of viral RNA; inhibits influenza A virus replication by preventing release of viral RNA into host cell

42
Q

Amantadine is specific for influenza ___

A

A

43
Q

What precautions exist for amantatine

A

renal insufficiency
psychosis
narrow angle glaucoma

44
Q

_______ is a sialic acid mimic that inhibits spread of influenza A and B and is used for tx and prophylaxis

A

oseltamivir

45
Q

Describe the mechanism of action of oseltamivir

A

prodrug, hydrolyzed by hepatic esterases to the active form which competes with sialic acid for binding to the viral neuraminidase

Blocks the ability of neuraminidase to cleave sialic acid-containing receptors on the surface of the cell to which hemagglutinin binds

Result is an inability to release progeny virions from infected cells, thus halting the spread of infection

46
Q

How can resistance to oseltamivir arise?

A

mutations in viral neuraminidase or hemagglutinin proteins

47
Q

Oseltamivir prevents ______ of virus from cells

A

release

FM3_ EB (25 decks)

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