Antiviral agents

Question 1

Primary means to control viral spread

Answer 1

public health measures and prophylactic vaccines

Question 2

Steps of Influenza entry

Answer 2

1. Binds cell surface of airway epithelial cell and is endocytosed
2. Acidic environment causes hemagglutin change that causes fusion w/ endosomal membrane
3. Activation of proton influx through viral M2 proton channel elicits release of RNA genome
4. Egress- hemagglutin interacts with cellular sialic acid moieties, neuroaminidases cleave the sialic acid moieties

Question 3

3 drugs that inhibit viral neuraminidase

Answer 3

1. oseltamivir
2. zanamivir
3. peramivir

Question 4

Route: oseltamivir

Answer 4

orally as prodrug

Question 5

Route: Zanamivir

Answer 5

Inhalation

Question 6

Route: Peramivir

Answer 6

Single IV dose

Question 7

Use of oseltamavir, zanamivir, peramivir in Influenza

Answer 7

• within 48 hours- decrease severity in A or B

- prophylactic in high risk

Question 8

Antivirals that clock virally-encoded H ion channel (M2 protein) (2)

Answer 8

1. Amantadine

2. Rimatadine

Question 9

Amantadine excretion

Answer 9

• unchanged in urine requiring dosage adjustment if impaired renal functino

Question 10

Rimantidine elimination

Answer 10

hepatic with t1/2 12 hours

Question 11

Amantadine and rimantidine use in influenza

Answer 11

• prophylaxis and treatment of influenza A
• 1-2 days prior and 6-7 days during infection
• if 48 hours after- only slight therapeutic

Question 12

Amantadine adverse reaction

Answer 12

insomnia, concentration difficulty, lightheadedness, headache

Question 13

Rimantadine adverse side effects

Answer 13

better tolerated due to poor CNS penetration

Question 14

Highest defgree of selective toxicity in nucleoside analogs

Answer 14

activated by viral kinases rather than host cell kinases

Question 15

Antiherpes drugs (4)

Answer 15

1. Acyclovir
2. Valacyclovir
3. Penciclovir
4. Famciclovir

Question 16

Mech of acyclovir

Answer 16

1. viral thymidine kinase phosphorylates acyclovir, other enzyme take to triphosphate form
2. acyclovir-TP terminates further DNA replication and strand elongation
3. DNA containing acyclovir_TP (competes with GTP) irreversibly binds and inactivates viral DNA polymerase

Question 17

Most common resistance to acyclovir

Answer 17

reduced or loss of expression of viral thymidine kinase

Question 18

Pharmicokinetics: acyclovir

Answer 18

Oral absorption poor (15-30%); not affected by food. Also available in topical and
intravenous formulations

Question 19

Pharmacokinetics: Calacyclovir

Answer 19

yl ester prodrug of acyclovir; given orally achieves plasma levels 3-5 times
higher than acyclovir (equivalent to IV administration)

Question 20

Pharmacokinetics: Penciclovir

Answer 20

Acyclic guanosine analog; poor oral absorption, topical only (more effective than
topical acyclovir)

Question 21

Pharmacokinetics: famciclovir

Answer 21

Penciclovir prodrug that increases oral bioavailability to 70%

Question 22

Elimination: Acyclovir

Answer 22

Acyclovir is renally excreted (adjust dosage if renal impairment). Neonatal (

Question 23

Dosing: HSV vs. VZV

Answer 23

oral acyclovir higher for VZV

Question 24

Inhibitor of viral penetration

Answer 24

Docosanol

Question 25

Drug for RSV

Answer 25

Ribavirin- purine nucleoside analog

Question 26

Adverse reactions of Ribavirin

Answer 26

• conjunctival or bronchial irritation
  2. hemolytic anemia
  3. teratogenic

ONLY use in immunocompromised patients

Question 27

RSV immunoprophylaxis

Answer 27

palivizumab

Question 28

Antivirals for CMV infections

Answer 28

1. Ganciclovir (intraocular) and valganciclovir (oral)

2. Foscarnet

Question 29

Mechanism of action: ganciclovir and valganciclovir

Answer 29

• initial phosphorylation by viral protein kinase UL97

Question 30

Resistance to ganciclovir and valganciclovir

Answer 30

mutation in UL97

mutation in viral DNA pol (UL54)

Question 31

Adverse reactions of ganciclovir and valganciclovir

Answer 31

• less selective toxicity because host kinase can perform first phosphorylation step
• GI

Question 32

Foscarnet

Answer 32

• inorganic pyrophosphate analog
• does not require cellular activation
• noncompetitively binds to pyrophosphate binding site of RNA and DNA polymerases
• used when mutation in UL97

Question 33

Adverse reaction od foscarnet

Answer 33

• nephrotoxicity and hypocalcemia

- CNS abnormalities