Anti-viral agents II

Question 1

Doconasol: MOA

Answer 1

long chain saturated alcohol that inhibits rep of many lipid-enveloped viruses by preventing fusion between cellular and viran envelop membranes -> block entry into cell

Question 2

Doconasol: PK props

Answer 2

topical (w/in 12 hours)

Question 3

Doconasol: adverse drug rxns

Answer 3

well tolerated

Question 4

Doconasol: pharmacotherapy

Answer 4

Abreva – reduces healing time to about 1 day

Question 5

Ganciclovir - Valganciclovir: MOA and resistance

Answer 5

phosphorylated to Gan-MP by viral kinase -> active Gan-TP (10-fold higher in infected cells)

• incorporaes into replicating viral DNA strands -> slowing -> ceasing DNA elongation
• resistance via mut in activating kinase (UL97) or DNA polymerase target (UL54)

Question 6

Ganciclovir - Valganciclovir: PK props

Answer 6

• G: poor oral; IV or intraocularly; renal elim
• V: prodrug
• Foscarnet: IV only; renal clearance
• Cidofovir: nucleotide analog; IV only; active metabolite (+ provenecid to dec nephrotoxicity)

Question 7

Ganciclovir - Valganciclovir: adverse drug rxns

Answer 7

myelosuppression

• can be NV, fever, rash, HA, insomnia
• F: renal impairment (also hypocalcemia and CAN abnormalities)
• C: dose-dependent proximal tubular nephrotoxicity (need to prehydrate!)

Question 8

Ganciclovir - Valganciclovir: pharmacotherapy

Answer 8

• G: CMV retinitis and prevention of CMV in transplant patients (IV or ocular implant)
• V: tx of CMV retinitis (oral)
• F: CMV retinitis in AIDs pts (IV)
• C: CMV retinitis if no other response (IV)

Question 9

Ribavirin: MOA

Answer 9

inhibits wide variety of DNA and RNA, but MOA not completely understood

• converted to ribavirin-TP by cellular kinases which interferes with GTP and nuc acid synthesis and inhibits GTP-dep 5’ capping of viral mRNA -> dec stability and translatability
• also inc viral mut rates -> apoptosis

Question 10

Ribavirin: PK properties

Answer 10

oral, better with fatty meals

• emil via hepatic met and renal excretion
• T1/2 dep on route (inc with oral)

Question 11

Ribavirin: adverse drug rxns

Answer 11

• inhal: generally well tol
• –can cause conjunctival or bronchial irritation
• –dec resp fn in pts with lung disease
• –HA and conjunctivitis in healthcare workers
• –DO NOT USE IN PREGNCNY
• Hep C
• –hemolytic anemia

Question 12

Ribavirin: pharmacotherapy

Answer 12

• RSV bronchiolitis and PNE in hospitalized children (aerosol)
• RSV in BM transplant and immunocompromised pts (w/IVIG)
• Hep C (oral)

Question 13

Palivixumab (Synagis®): what is it? what is it used for? How is it administered? Adverse effects?

Answer 13

• humanized monoclonal AB to RSV F glycoprotein
• RSV immunoprophylaxis in young children w/ CHD
• IM
• well tolerated