EXAM 4 antivirals 1 HSV, VZV, CMV, FLU

Question 1

Herpes simplex viruses 1 (HSV1)

Answer 1

oral herpes
diagnosis via swab and PCR testing

Question 2

Herpes simplex viruses 2 (HSV2)

Answer 2

Genital mucosa
Commonly causes genital herpes
Infection within sacral ganglia

Question 3

HSV1 + HSV2

Answer 3

central nervous system

HSV encephalitis is mostly caused by HSV1

Can see changes on imaging

Question 4

anti-herpes agents

Answer 4

Acyclovir
Valacyclovir
Famciclovir (not used in practice)
Penciclovir

Question 5

acyclovir MOA

Answer 5

Prodrug that gets requires 3 step phosphorylation

Virus produces enzyme that causes selective phosphorylation

competitive inhibitor of viral DNA polymerase and competes with dGTP (guanine).

Acts as a chain terminator and inhibits DNA synthesis

Question 6

acyclovir spectrum

Answer 6

active against HSV-1, HSV-2, and VZV

Question 7

acyclovir resistance

Answer 7

Two mechanisms: mutations in thymidine kinase and DNA polymerase

More likely to occur in immunocompromised people

Question 8

acyclovir adverse effects

Answer 8

Nephrotoxicity: more likely to occur with IV admin

Give w/ IV fluids to prevent

but generally well tolerated

Question 9

valacyclovir

Answer 9

L-valyl ester of acyclovir and is converted to acyclovir by esterase in intestine and liver

improved efficacy compared to acyclovir (increased oral bioavailability)

SAME ADRs, MOA, and spectrum as acyclovir

Question 10

famciclovir and penciclovir MOA

Answer 10

competitive inhibitor of viral DNA polymerase

Does not cause immediate chain termination

Obligate DNA chain terminator (incorporate into DNA)

Question 11

famciclovir and penciclovir resistance

Answer 11

Viral kinase mutants: confer cross-resistance to penciclovir and acyclovir

Question 12

famciclovir vs penciclovir

Answer 12

famiclovir is a prodrug of penciclovir

famciclovir is converted by first pass metabolism in intestine and liver

Question 13

penciclovir vs acyclovir

Answer 13

higher affinity for HSV TK than acyclovir because it is more stable

HSV DNA polymerase have higher affinity for acyclovir triphosphate than penciclovir triphosphate

Question 14

Varicella Zoster virus

Answer 14

DNA virus that cases infections referred to chickenpox or shingles

Varicella (chicken pox)

Zoster (shingles)

Question 15

Varicella Zoster virus treatment

Answer 15

acyclovir

valacyclovir
oral for varicella or zoster
IV for disseminated zoster

famciclovir
used to treat zoster

Question 16

Cytomegalovirus

Answer 16

Severe infection can occur if during fetal development or in immunocompromised patients

Question 17

Cytomegalovirus drug therapy

Answer 17

ganciclovir
valganciclovir

Question 18

ganciclovir and valganciclovir MOA

Answer 18

same as penciclovir

competitive inhibitor of viral DNA polymerase

Does not cause immediate chain termination

Obligate DNA chain terminator (incorporate into DNA)

Question 19

ganciclovir vs acyclovir

Answer 19

better substrate for CMV than acyclovir

Question 20

ganciclovir ADRS

Answer 20

bone marrow suppression
main side effect –> dose limiting

Question 21

ganciclovir resistance

Answer 21

due to mutations in CMV kinase (UL97) or CMV DNA pol (UL54)

mutations in kinase are not cross-resistant to cidofovir or foscarnet

mutations in DNA pol may be cross-resistant to cidofovir or foscarnet

Question 22

valganciclovir

Answer 22

Monovalyl ester of ganciclovir (increases oral bioavailability 60%)

Rapidly hydrolyzed to ganciclovir

Uses: treat CMV retinitis

Question 23

foscarnet MOA

Answer 23

inhibits viral DNA polymerase

Does not require phosphorylation for activity

Carboxyl overlaps with binding site of phosphonates and traps polymerase in closed formation

Question 24

foscarnet spectrum

Answer 24

CMV retinitis

Question 25

foscarnet resistance

Answer 25

mutations in DNA pol or HIV RT Resistant CMV isolates are cross resistant to ganciclovir Foscarnet is usually still effective against cidofovir resistant CMV

Question 26

Cidofovir MOA

Answer 26

competitive inhibitor and chain terminator Does not require activation by viral kinases

Question 27

Cidofovir spectrum

Answer 27

CMV HSV1/2 VZV adenovirus poxvirus polymavirus HPV

Question 28

Letermovir MOA

Answer 28

inhibits terminase complex (responsible for cutting out genomes during DNA replication process): pUL56/89/51 Result: inhibition of CMV replication and prevention of CMV infection

Question 29

letermovir drug interactions

Answer 29

CYP3A4 inhibitor, substrate/inhibitor of OATP1B1/3

Question 30

life cycle of influenza virus

Answer 30

Virus is sysnthesized within the cell which undergoes mRNA synthesis and RNA replication The mature cell is connected to the outside of the host cell Neuraminidase cleaves this connection (glycolytic bonds) and frees the virus cell This facilitates virus dissemination: hemataglutin binds to terminal sialic acid residues

Question 31

target for influenza virus

Answer 31

Neuraminidase: is the main target Neuraminidase inhibitors block this cleavage Essential for virus replication

Question 32

drugs to treat influenza virus

Answer 32

oseltamivir zanamivir permivir baloxavir marboxil

Question 33

oseltamivir and zanamivir MOA

Answer 33

Prodrug converted to active form by liver Metabolite is an effective inhibitor of NA

Question 34

oseltamivir and zanamivir spectrum

Answer 34

active against influenza A and B

Question 35

oseltamivir and zanamivir resistance

Answer 35

mutations in active site of neuraminidase There is flu A virus with reduced susceptibility to oseltamivir Drug resistant virus occurs in 3% of patients receiving oseltamivir More resistance against oseltamivir compared to zanamivir

Question 36

peramivir MOA

Answer 36

Parental NA inhibitor

Question 37

peramivir spectrum

Answer 37

effective against influenza A and B

Question 38

peramivir resistance

Answer 38

mutation in active site of neuraminidase

Question 39

Baloxavir marboxil MOA

Answer 39

inhibits viral “cap-snatching” --> blocks transcription Binds to PB2 subunit of RNA pol and inhibits cap-dependent endonuclease

Question 40

Baloxavir marboxil spectrum

Answer 40

flu within first 48 hrs of symptoms