Antivirals

Question 1

what stage of herpes virus is suppressed by antivirals

Answer 1

lytic stage

Question 2

antiviral treatments are indicated for what members of the herpesvirus family

Answer 2

VZV
HSV-1
HSV-2
CMV

Question 3

Acyclovir MOA

Answer 3

requires initial phosphorylation by the viral thymidine kinase enzyme

competitive inhibitor of viral DNA polymerase

chain termination upon incorporation into the viral DNA

Question 4

resistance to acyclovir

Answer 4

mutation of thymidine kinase gene

cross-resistance with other antivirals iwth similar mechanism

Question 5

oral or IV administration of acyclovir:

• severe/disseminated mucocutaneous disease
• HSV encephalitis
• varicella zoster
• neonate infections
• VZV in immunocompromised
• genital herpes

Answer 5

Oral:

• genital herpes
• varicella zoster

IV:

• severe/disseminated mucocutaneous disease
• neonate infections
• HSV encephalitis
• VZV in immunocompromised patients

Question 6

prodrug of acyclovir

acyclovir attached to a valine moiety. Metabolised into acyclovir in the liver and intestines

3-5x greater oral bioavailabiilty than acyclovir

Answer 6

Valacyclovir

Question 7

therapeutic indications for valacyclovir

Answer 7

primary and recurrent genital herpes

varicella in older children and adults

zoster

oralabial herpes

Question 8

how is foscarnet administered

Answer 8

IV

Question 9

Analogue of pyrophosphate. Occupries site where pyrophosphate normally resides and blocks pyrophosphate release. Blocks catalytic cycle

**does not require prior phosphorylation by thymidine kinase in order to act

Answer 9

Foscarnet

Question 10

therapeutic indications of foscarnet

Answer 10

HSV and VZV infections resistant to acyclovir

CMV retinitis, colitis, esophagitis

Question 11

Ganciclovir requires initial phosphorylation by 1 (viral kinase enzyme). It is phosphorylated much more efficiently than acyclovir, therefore more active for 2 infections. It is also a competitive inhibitor of the viral 3. 4 termination upon incorporation into the viral DNA

Answer 11

1. CMV UL97
2. CMV
3. DNA polymerase
4. Chain

Question 12

how is ganciclovir administered

Answer 12

IV
Oral
Intraocular routes

• poor bioavailability

Question 13

therapeutic indications for ganciclovir

Answer 13

IV

• CMV retinitis (AIDs)
• CMV colitis, pneumitis, esophagitis (foscarnet does colitis, esophagitis, and retinitis)

Intraocular injection or implant
- CMV retinitis

IV followed by oral
- transplant pts.

Question 14

how can you reduce the risk of CMV in transplant patients

Answer 14

IV followed by oral ganciclovir

Question 15

prodrug of ganciclovir with higher bioavailability and serum levels approach IV ganciclovir

Answer 15

valganciclovir

Question 16

therapeutic indications for valganciclovir

Answer 16

CMV retinitis (AIDs)

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

Question 17

MOA of trifluridine

Answer 17

• phosphorylated by cellular enzymes

- competitive inhibitor of thymidine and incoorporation into newly synthesized genomes

Question 18

therapuetic indication of trifluridine

Answer 18

• low selectivity, does not allow for systemic administration
• ocular administration to treat keratoconjunctivitis and recurrent epithelial keratitis due to HSV-1 and HSV-2

Question 19

when must antivirals be administered to have any impact on influenza virus

Answer 19

first 48 hours

Question 20

What influenzavirus antivirals inhibit neuraminidase

Answer 20

oseltamivir
zanamivir
peramivir

Question 21

how is oseltamivir administered

Answer 21

oral - 80% bioavailability

Question 22

therapeutic indications for oseltamivir:

for children 1 y/o. Effective for influenza 2. Given 3 for uncomplicated flu and can be given 4 for complicated influence. Can be used as 5 for influenza

Answer 22

1. 1+
2. A and B
3. within first 48 hours
4. chemoprophylaxis

Question 23

how is zanamivir administered

Answer 23

administered to oropharynx and lungs by inhalation

Question 24

how is therapeutic indication of zanamivir different from oseltamivir

Answer 24

same but approved for children 7+

Question 25

how is peramivir administered

Answer 25

IV

Question 26

therapeutic indications for peramivir

Answer 26

acute, uncomplicated and have not been symptomatic for more than 48 hours

Question 27

what anti-influenza drugs inhibit the activity of influenza A M2 protein - ion channel forming protein required for nucleocapsid release

Answer 27

Amantadine Rimantadine *readily absorbed with high bioavailability

Question 28

what is treatment of ribavirin indicated for

Answer 28

Respiratory syncytial virus (RSV) indicated for severe LRT illness in: - premature infants - immunocompromised - pts with lung or heart congenital heart disease

Question 29

MOA of ribavirin

Answer 29

phosphorylated by cellular adenosine kinase interferes with synthesis of guanasine triphosphate inhibit viral mRNA capping inhibits RdRp of RSV and HCV virus

Question 30

how is ribavirin administered

Answer 30

- aerosol route for RSV orally for combo therapy for HCV (w/ interferon+/-protease inhibitors)

Question 31

contraindications for ribavirin

Answer 31

pregnancy anemia ischemic vascular disease severe renal disease

Question 32

general tx of HCV

Answer 32

combo therapy with direct acting antiviral - at least 2 from two different classes oral 8-24 weeks Tx depends on: - HCV genotype - +/- cirrhosis - tx naiive vs experienced - special populations

Question 33

MOA of HCV "-previr" drugs

Answer 33

protease inhibitors inhibit NS3/4A protease

Question 34

MOA of HCV "-buvir" drugs

Answer 34

RNA polymerase inhibitor inhibit NS5B enzyme

Question 35

MOA of HCV "-asvir" drugs

Answer 35

NS5a inhibitors - plays role in genome replciation and virion assembly

Question 36

In some patients with HCV, adding __1_ to the "previrs, buvirs, or asvirs" is indicated. This adds to the adverse effects and is contraindicated in _2_

Answer 36

1. ribavirin | 2. pregnancy

Question 37

HBV is a DNA virus that uses ____

Answer 37

reverse transcriptase

Question 38

how would you treat HBV

Answer 38

pegylated interferon reverse transcriptase inhibitiors - entecavir - tenofovir