C5

Question 1

Agents to treat HSV and VZV?

Answer 1

Acyclovir

Valacyclovir (prodrug)

Question 2

Acyclovir MOA

Answer 2

• HSV-1, HSV-2, VZV
• Activated by the viral thymidine kinase TK—> inhibit viral DNA polymerase
• Resistance: changes in viral DNA polymerase

Question 3

Acyclovir PharmacoKinetix?

Answer 3

• administeration: topical, oral, I.V.
• 1/2 life: short (oral requires multiple daily doses)
• Elimination: Renal excretion
  (dosage reduced in renal impairment)

Question 4

Acyclovir clinical uses?

Answer 4

VZV, HSV treatment + prophylaxis

• Oral:
  1. mucocutaneous
  2. genital herpes
  3. prophylaxis in immunocompromised patients
• I.V. administration:
  severe herpes disease (including encephalitis)
• neonatal HSV infection

topical

Question 5

Acyclovir Toxicity?

Answer 5

• oral: well tolerated but may cause:
  GI distress. nausea, diarhhea , headache
• the I.V. drug:
  CNS toxicity
  Nephrotoxicity
  Hypotension

Question 6

Valacyclovir MOA?

Answer 6

• Activated by the viral thymidine kinase TK—> inhibit viral DNA polymerase
• prodrug converted to acyclovir by hepatic metabolism after oral administration
• longer duration of action than acyclovir

Question 7

Ganci.cyclovir MOA?

Answer 7

Inhibits DNA polymerases of CMV & HSV –> chain termination

Question 8

Gancicyclovir PharmacoKinetix?

Answer 8

• administration: I.V , oral, intra-ocular forms
• distribution : penetrates well into tissues
• Elimination: renal elimination
• Oral bioavailability: is less than 10%
• intraocular implant: used in CMV retinitis

Question 9

what about Valganciclovir?

Answer 9

• prodrug of Ganciclovir
• high oral bioavailability: given orally!!!!
• Alternative to I.V. Ganciclovir, Cidofovir (in end-organ CMV)

Question 10

Gancicyclovir Clinical uses?

Answer 10

• prophylaxis and treatment of CMV retinitis

- other CMV infections in immunocompromised and organ transplantation

Question 11

Gancicyclovir Toxicity?

Answer 11

• Systemic toxic effects:
  1. Bone marrow supression (Leuko, Thrombo, Neutropenia)
  2. Neurologic dysfunction
  3. Hepatic dysfunction

Question 12

Cidofovir MOA?

Answer 12

activated by host cell kinases

inhibits DNA polymerases of HSV, CMV, and HPV

Question 13

Cidofovir Pharmacokinetix?

Answer 13

• given I.V
• elimination: kidney
• Dosage is adjusted in proportion to creatinine clearance
• full hydration must be maintained

Question 14

Cidofovir clinical uses?

Answer 14

• in CMV retinitis
• in mucocutaneous HSV
• in genital warts.

Question 15

Cidofovir Toxicity?

Answer 15

Nephrotoxicity

major dose-limiting toxicity

Question 16

Phosphonoformate drug used for CMV?

Answer 16

Foscarnet

Question 17

Foscarnet MOA?

Answer 17

• does NOT require viral bioactivation (phosphorylation) for antiviral activity!
• inhibits:
  1. viral RNA polymerase
  2. DNA polymerase
  3. HIV reverse transcriptase.

Question 18

Foscarnet Pharmacokinetix?

Answer 18

• bioavailability: given I.V.
• distribution: penetrates well into tissues (also CNS).
• Elimination: kidney

Question 19

Foscarnet clinical uses?

Answer 19

an alternative OR adjunct for prophylaxis and treatment of CMV, HSV, VZV infections

Question 20

Foscarnet Toxicity?

Answer 20

• severe
• nephrotoxicity
• electrolyte imbalance (especially hypocalcemia)
• genitourinary ulceration
• CNS effects (headache, hallucinations, seizures)

Question 21

drugs RSV?

Answer 21

palivizumab

also Ribavirin

Question 22

what about palivizumab ?

Answer 22

• Ab’s to surface protein of RSV

- for prophylaxis & treatment of RSV

Question 23

Anti-influenza agents?

Answer 23

Oseltamivir

Question 24

Oseltamivir MOA?

Answer 24

• inhibitors of neuraminidases produced by influenza A and B
• inhibit virion release and prevent clumping of newly released virions –> impede viral spread

Question 25

Oseltamivir Clinical uses?

Answer 25

- bioavailability: prodrug orally, activated in the gut & the liver - decrease the duration of influenza sym's - more effective if used within 24h after onset of sym's - taken prophylactically to decrease the incidence of influenza & shorten sym's

Question 26

Oseltamivir Toxicity?

Answer 26

GI symptoms

Question 27

Ribavirin MOA?

Answer 27

Prevents capping of viral mRNA Block RNA-dep RNA polymerase ``` influenza A and B, parainfluenza, respiratory syncytial virus (RSV), paramyxoviruses, HCV, and HIV ```

Question 28

Ribavirin administration

Answer 28

Parenteral | oral

Question 29

ribavirin SE

Answer 29

anemia | teratogen