Anti-viral agents

Question 1

Oseltamivir - Zanamivir: MOA and resistance

Answer 1

Inhibition of neuraminidase (NA) activity in influenza A and B
-resistance via mut in N or H

Question 2

Oseltamivir - Zanamivir: PK properties

Answer 2

absorb: O= orally, Z = inhalation

- elim: O = renal, Z = 10-20% absorbed, excreted via urine

Question 3

Oseltamivir - Zanamivir: adverse drug rxns

Answer 3

O = NV and abd pain (also HA, fatigue, D); Z = cough, bronchospasm (can be severe); preg category C for both

Question 4

Oseltamivir - Zanamivir: pharmacotherapy

Answer 4

when started within 2 days of sx, decreases severity and duration
-O= >1yr and Z = > 7 yrs

Question 5

Amantadine - Rimantadine: MOA and resistance

Answer 5

Blocks virally-encoded H+ ion channel (M2 protein) -> prevents change in pH necessary for uncoating
-resistance: mutations in transmembrane domains of M2 proton channel

Question 6

Amantadine - Rimantadine: PK props

Answer 6

• oral absorb
• A = excreted unchanged in the urine
• R = hepatic elimination

Question 7

Amantadine - Rimantadine: adverse drug rxns

Answer 7

(neuro) insomnia, concentration diff, lighthead/dizz, HA

- R better tolerated due to poor CNS penetration

Question 8

Amantadine - Rimantadine: pharmacotherapy

Answer 8

Prophylaxis and tx of influenza A (lim use due to resistance!)

Question 9

acyclovir and valacyclovir: MOA and resistance

Answer 9

diffuses into cell where it is triphosphorylated by intracellular kinases which inhibit viral DNA polymerase

• also acts as DNA chain terminator w/ irreversible binding between DNA pol and terminated chain
• selectively toxic -1st phosphorylation step by Herpes-encoded thymidine kinase (only occurs in infected cells)
• resistance by reduction or loss of expression of viral TK

Question 10

acyclovir and valacyclovir: PK props

Answer 10

• A: oral (poor), topically, IV
• V: prodrug (oral?)
• crosses cell membrane -> phosphorylated -> “trapped” in cell
• renal excretion

Question 11

acyclovir and valacyclovir: adverse drug rxns

Answer 11

• HA, NV
• high levels – CNS effects
• IV can cause renal toxicity

Question 12

acyclovir and valacyclovir: pharmacotherapy

Answer 12

• Herpes I and II:
• –48-72 hrs of primary infection
• –no tx if occasional recurrence with mild sx
• –episodic tx with prodromal sx (A x5 days or V x1 day)
• –chronic suppressive tx if frequent and severe (A or V)
• VZV: VZV is inherently less sensitive to acyclovir than HSV and treatment requires doses 2-3 times higher
• –chicken pox: A= qid x5 days or IV (tid x7 days if immunosuppressed)
• –shingles (begin <72 hrs): oral A (3-d doses/day) of V (bid x7 days)