C5

Question 1

Agents to treat HSV and VZV?

Answer 1

Acyclovir

Valacyclovir

Question 2

Acyclovir MOA

Answer 2

• guanosine analog active against
  herpes simplex virus (HSV-1, HSV-2)
• The drug is activated initially by the viral kinase —> acyclovir triphosphate –> interferes with viral synthesis:
  1. Competitive substrate for DNA polymerase
  2. chain termination after its incorporation into viral DNA
• Resistance: changes in viral DNA polymerase

Question 3

Acyclovir PharmacoKinetix?

Answer 3

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

Question 4

Acyclovir clinical uses?

Answer 4

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

Question 5

Acyclovir Toxicity?

Answer 5

• The oral drug: is well tolerated but may cause GI distress and headache
• the I.V. drug:
  delirium, tremor, seizures, hypotension, and nephrotoxicity

Question 6

Valacyclovir MOA?

Answer 6

• same as Acyclovir
• prodrug converted to acyclovir by hepatic metabolism after oral administration
• reaches plasma levels 3–5x greater than those achieved by acyclovir
• longer duration of action than acyclovir

Question 7

Ganci.cyclovir MOA?

Answer 7

it is guanine derivative –> triphosphorylated –> inhibits DNA polymerases of CMV and HSV –> chain termination

Question 8

Gancicyclovir PharmacoKinetix?

Answer 8

• Bioavailability: given intravenously and 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
• alternative to I.V. ganciclovir, cidofovir and foscarnet (in end-organ CMV)

Question 10

Gancicyclovir Clinical uses?

Answer 10

• prophylaxis and treatment of CMV retinitis

- other CMV infections in immunocompromised

Question 11

Gancicyclovir Toxicity?

Answer 11

• Systemic toxic effects:
  1. leukopenia
  2. thrombocytopenia
  3. mucositis
  4. hepatic dysfunction
  5. severe neutropenia (if used with zidovudine or other myelosuppressive agents)

Question 12

Cidofovir MOA?

Answer 12

activated by host cell kinases –> active diphosphate –> inhibits DNA polymerases of HSV, CMV, Adenovirus, and HPV.

Question 13

Cidofovir Pharmacokinetix?

Answer 13

• given intravenously a
• 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 phosphorylation for antiviral activity!

- inhibits viral RNA polymerase, DNA polymerase, and HIV reverse transcriptase.

Question 18

Foscarnet Pharmacokinetix?

Answer 18

• bioavailability: given I.V.
• distribution: penetrates well into tissues (also CNS).
• Elimination: kidney (in direct proportion to creatinine clearance)

Question 19

Foscarnet clinical uses?

Answer 19

an alternative for prophylaxis and treatment of CMV infections

Question 20

Foscarnet Toxicity?

Answer 20

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

Question 21

drugs RSV?

Answer 21

palivizumab

Question 22

what about palivizumab ?

Answer 22

• Antibody to surface protein of RSV

- used for prophylaxis and treatment of RSV infection

Question 23

Anti-influenza agents?

Answer 23

Oseltamivir

Question 24

Oseltamivir MOA?

Answer 24

• inhibitors of neuraminidases produced by influenza A and B a
• cleave sialic acid residues from viral proteins and surface proteins of infected cells –> inhibit virion release and prevent clumping of newly released virions –> impede viral spread

Question 25

Oseltamivir Clinical uses?

Answer 25

• bioavailability: prodrug used orally, activated in the gut and the liver
• decrease the duration of influenza symptoms
• more effective if used within 24h after onset of symptoms
• taken prophylactically to decrease the incidence of influenza

Question 26

Oseltamivir Toxicity?

Answer 26

GI symptoms