CMV Agents

Question 1

CMV can cause what?

Answer 1

Blindness

Question 2

What agents treat CMV?

Answer 2

1) Ganciclovir
2) ValGANciclovir
3) Cidofovir
4) Foscarnet
5) Fomivirsen

Question 3

CMV is an…

Answer 3

opportunistic infection that infects immunocompromised

Question 4

Anti-sense DNA is…

Answer 4

a short oligopeptide that matches the complimentary mRNA and blocks translation and degrades mRNA so it can’t replicate

Question 5

Ganciclovir is an…

Answer 5

acyclic guanosine analog

Question 6

Ganciclovir requires what?

Answer 6

virally encoded TK UL97 for initial phosphorylation

Question 7

Ganciclovir MOA?

Answer 7

1) TK UL97 phosphorylates initially
2) then is converted into a triphosphate for activity
3) competitively inhibits VIRAL DNA polymerase and causes chain termination

Question 8

Ganciclovir vs. Acyclovir?

Answer 8

Ganciclovir is 100x times greater on CMV!!

Question 9

Oral bioavailability of Ganciclovir?

Answer 9

POOR 6-9%

Question 10

Ganciclovir has synergy with what drug in delaying progression of retinitis?

Answer 10

foscarnet

Question 11

How is ganciclovir administered for CMV?

Answer 11

intravitreally or by ocular implant

Question 12

What is used to treat CMV colitis and esophagitis?

Answer 12

IV Ganciclovir

Question 13

What reduces the risk of CMV infection (prophylaxis) in transplant patients?

Answer 13

Ganciclovir

Question 14

Ganciclovir treats what?

Answer 14

1) Delays progression of CMV retinitis synergistically with foscarnet
2) CMV cololitis
3) CMV esophagitis
4) prophylaxis for CMV infxn in transplant patients

Question 15

Ganciclovir resistance due to:

Answer 15

1) TK UL97 mutations

2) Viral DNA polymerase (UL 54) mutations (rare)

Question 16

Ganciclovir adverse reactions:

Answer 16

1) myelosuppression (mostly neutropenia)
(esp when given with: mycophenolate mofetil, zidovudine, and azathioprine)
2) Increases concentration of didanosine- and probenacid may slow down renal elimination

Question 17

ValGANciclovir is a what?

Answer 17

mono-valyl ester prodrug of ganciclovir

Question 18

ValGANciclovir MOA?

Answer 18

rapidly converted to ganciclovir by intestinal and hepatic esterases

Question 19

Oral bioavailability of ValGANciclovir?

Answer 19

60% Oral Bio

Question 20

Clinical indication for ValGANciclovir?

Answer 20

treatment of CMV retinitis in AIDS patients

Question 21

Cidofovir is a…

Answer 21

cytidilate analog

Question 22

Cidofovir MOA?

Answer 22

phosphorylation to di and tri-phosphate by cellular enzymes. (so no cross resistance due to viral TK mutations with nucleoside analogs)

Question 23

Clinical use of cidofovir?

Answer 23

IV administration after IV probenecid is effective in CMV retinitis.

Question 24

Contraindicated in patients with renal insufficiency:

Answer 24

Cidofovir

Question 25

Direct intra-ocular administration is not recommended in what drug due to ocular toxicity?

Answer 25

Cidofovir

Question 26

Adverse reactions of Cidofovir are:

Answer 26

1) Dose-dependent nephrotoxicity

Question 27

Cidofovir should not be admin'd with what nephrotoxic drugs?

Answer 27

``` AMPHO B, AMINOGLYCOSIDES, NSAIDS, PENTAMIDINE, FOSCARNET ```

Question 28

Foscarnet is a...

Answer 28

phsphanoformic acid- an inorganic pyrophosphate

Question 29

Foscarnet MOA?

Answer 29

Inhibits viral DNA Polymerase, RNA polymerase and HIV reverse transcriptase

Question 30

Foscarnet does not require what?

Answer 30

activation by phosphorylation

Question 31

Foscarnet resistance is due to what?

Answer 31

Point mutations in the DNA polymerase gene- which be cross resistant to ganciclovir.

Question 32

Clinical use of Foscarnet?

Answer 32

1) CMV retinitis 2) CMV colitis and esophagitis 3) Acyclovir-resistant HSV and VZV infections

Question 33

Dosing of foscarnet is based on what?

Answer 33

Patient's creatinine clearance

Question 34

Foscarnet and what drug are synergistic?

Answer 34

Ganciclovir

Question 35

Foscarnet adverse reactions:

Answer 35

1) Nephrotoxic 2) renal insufficiency 3) hypo- or hyper-calcemia 4) hypo- or hyper-phosphotemia 5) C/I'd with other nephrotoxic drugs

Question 36

What reduces Foscarnet nephrotoxicity?

Answer 36

Saline preloading ******

Question 37

What is the only anti-sense DNA?

Answer 37

Fomivirsen

Question 38

Fomivirsen is a...

Answer 38

anti-sense DNA oglionucleotide

Question 39

Fomivirisen MOA?

Answer 39

hybridizes with CMV mRNA to inhibit immediate early region 2 protein synthesis (translation) to prevent viral replication

Question 40

How is fomivirisen administered and why?

Answer 40

Delivered by direct intravitreal administration to treat CMV retinitis in AIDS patients

Question 41

What is fomivirisen's intravitreal half life?

Answer 41

55 hours