54: Antiviral Drugs

Question 1

productive =

clinically silent =

Answer 1

lytic
latent

only the lytic stage is suppressed by antivirals, so treatment goals are to speed time to healing and increase time between outbreaks

Question 2

the herpesvirus diseases are…

Answer 2

herpes simplex 1 and 2
varicella zoster virus
cytomegalovirus

Question 3

MOA acyclovir

Answer 3

nucleoside analogue that requires initial phosphorylation by the viral thymidine kinase enzyme

competitive inhibitor of viral DNA pol –> chain termination upon incorporation into viral DNA

Question 4

acyclovir resistance

Answer 4

mutation of thymidine kinase gene required for activation

Question 5

indications for acyclovir

Answer 5

oral = genital herpes, varicella zoster

IV = severe or disseminated mucocutaneous disease, neonate infections, HSV encephalitis, VZV in immunocompromised pts

Question 6

adverse effects acyclovir

Answer 6

nausea, headache, diarrhea

reversible crystalline nephrotoxicity with neurological effects –> caution when administered concurrently with nephrotoxic agents

Question 7

prodrug of acyclovir

Answer 7

metabolizes to acyclovir in liver and intestines –> greater oral bioavailability

Question 8

therapeutic indications for valacyclovir

Answer 8

primary and recurrent genital herpes
varicella in older children and adults
zoster
orolabial herpes

Question 9

MOA foscarnet

Answer 9

occupies the site when pyrophosphate normally resides and blocks pyrophosphate release –> blocks catalytic cycle

Question 10

foscarnet _______ prior phosphorlyation by thymidine kinase in order to act

Answer 10

does not require *

Question 11

indications for foscarnet

Answer 11

*only IV

HSV and VZV infections that are resistant to acyclovir

CMV retinitis, CMV colitis, CMZ esophagitis

Question 12

adverse effect foscarnet

Answer 12

renal impairment –> avoid concurrent admin of drugs with nephrotoxicity

also changes in Ca, Ph, K, or Mg levels

Question 13

MOA ganciclovir

Answer 13

acyclic guanosine analogue that requires initial phosphorylation by viral kinase enzyme

competitive inhibitor of viral DNA pol –> chain termination upon incorporation into viral DNA

Question 14

which is more active against CMV- ganciclovir or acyclovir?

Answer 14

ganciclovir

Question 15

therapeutic indications ganciclovir

Answer 15

IV - CMV retinitis and CMV colitis, pneumonitis, and esophagitis

IV followed by oral - reduce risk of CMV disease in transplant recipients

intraocular injection or implant - CMV retinitis

Question 16

adverse effect ganciclovir

Answer 16

myelosuppression

Question 17

prodrug of ganciclovir

Answer 17

valganciclovir

metabolized into ganciclovir in liver and intestines –> higher oral bioavailability

Question 18

therapeutiv indications valganciclovir

Answer 18

CMV retinitis

prevention of CMV disease in pts with heart, kidney and kidney-pancreas transplants

Question 19

MOA trifluridine

Answer 19

phosphorylated by cellular enzymes

competitive inhibitor of thymidine for incorporation into newly synthesized genomes

Question 20

therapeutic indications for trifluridine

Answer 20

not systemic

ocular admin to treat keratoconjunctivitis and recurrent epithelial keratitis due to HSV-1 and HSV-2

Question 21

MOA tamiflu

Answer 21

sialic acid analogue that is metabolized to active compound by hepatic esterases

binds to active site of neuraminidse to inhibit its function. inhibits spread of progeny virion sthrough respiratory tract

Question 22

indications for oseltamivir

Answer 22

flu A and B virus within 48 hrs

Question 23

MOA zanamivir

Answer 23

sialic acid analogue with same MOA as oseltamivi r

Question 24

administration zanmivir

Answer 24

oropharynx and lungs by inhalation

Question 25

contraindications for zanmivir

Answer 25

pre-existing pulmonary disease only approved 7yo and up

Question 26

MOA peramvir

Answer 26

neuraminidase inhibitor administered IV

Question 27

MOA amantadine and rimantadine

Answer 27

symmetric tricyclic amines that inhibit the activity of FLU A M2 PRTN (ion channels forming prtn requried for nucleocapsid release)

Question 28

most common cause bronchiolitis and pneumonia in children under 1 yr

Answer 28

RSV common cold in adults and older children

Question 29

treatment for severe LRT illness in premees, immunocompromised, chronic lung or heart disease

Answer 29

ribavirin

Question 30

MOA ribavirin

Answer 30

guanosine analogue that is phosphorylated by cellular adenosine kinase. interferes with synthesis of guanosine triphosphate, inhibit viral mRNA cappin, inhibits RdRp of RSV and hep C virus aerosol route for RSV treatment, orally as part of combo for hep C

Question 31

therapeutic indications for ribavirin

Answer 31

aerosolized for severe respiratory illness due to RSV in certain populations oral with pegylated interferon and other hcv inhibitors for chronic hep C infections

Question 32

adverse effects and contraindications ribavirin

Answer 32

hemolytic anemia pregnancy and anemia contra

Question 33

which hep C genotype is less responsive to treatment?

Answer 33

genotype 1 hep C is transmitted through percutaneous exposure, contaminated blood exposure and sexual transmission

Question 34

hep C -->

Answer 34

chronic hepatitis

Question 35

MOA paritaprevir

Answer 35

HCV protease inhibitor (HCV NS3/4A - necessary for cleavage of immature viral polypeptides into mature)

Question 36

MOA simeprevir

Answer 36

HCV protease inhibitor (NS3/4A)

Question 37

what do you need to check before simeprevir use?

Answer 37

screen pts for presence of NS3 Q80K polymorphism (reduces response)

Question 38

MOA ledipasvir

Answer 38

nucleoside analogue HCV Ns5VA inhibitor - necessary for viral RNA replication and virion assembly used orally in combo with sofosbuvir

Question 39

MOA ombitasvir

Answer 39

HCV Ns5A inhibitor used in combo orally with paritaprevir and ritonavir

Question 40

MOA sofosbuvir

Answer 40

nucleotide analogue prodrug that is incorporated into newly synthesized RNA by RNA pol --> premature chain termination

Question 41

bad drug mixes with sofosbuvir

Answer 41

rifampin, st. johns wort lead to significantly reduced plasma concentration of drug

Question 42

MOA dasbuvir

Answer 42

non-nucleoside inhibitor of RNA dependent RNA pol -- causes viral life cycle to halt before synthesis of RNA genome orally used with ombitasvir, paritaprevir, and ritonavir