CMV Agents Flashcards
CMV can cause what?
Blindness
What agents treat CMV?
1) Ganciclovir
2) ValGANciclovir
3) Cidofovir
4) Foscarnet
5) Fomivirsen
CMV is an…
opportunistic infection that infects immunocompromised
Anti-sense DNA is…
a short oligopeptide that matches the complimentary mRNA and blocks translation and degrades mRNA so it can’t replicate
Ganciclovir is an…
acyclic guanosine analog
Ganciclovir requires what?
virally encoded TK UL97 for initial phosphorylation
Ganciclovir MOA?
1) TK UL97 phosphorylates initially
2) then is converted into a triphosphate for activity
3) competitively inhibits VIRAL DNA polymerase and causes chain termination
Ganciclovir vs. Acyclovir?
Ganciclovir is 100x times greater on CMV!!
Oral bioavailability of Ganciclovir?
POOR 6-9%
Ganciclovir has synergy with what drug in delaying progression of retinitis?
foscarnet
How is ganciclovir administered for CMV?
intravitreally or by ocular implant
What is used to treat CMV colitis and esophagitis?
IV Ganciclovir
What reduces the risk of CMV infection (prophylaxis) in transplant patients?
Ganciclovir
Ganciclovir treats what?
1) Delays progression of CMV retinitis synergistically with foscarnet
2) CMV cololitis
3) CMV esophagitis
4) prophylaxis for CMV infxn in transplant patients
Ganciclovir resistance due to:
1) TK UL97 mutations
2) Viral DNA polymerase (UL 54) mutations (rare)
Ganciclovir adverse reactions:
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
ValGANciclovir is a what?
mono-valyl ester prodrug of ganciclovir
ValGANciclovir MOA?
rapidly converted to ganciclovir by intestinal and hepatic esterases
Oral bioavailability of ValGANciclovir?
60% Oral Bio
Clinical indication for ValGANciclovir?
treatment of CMV retinitis in AIDS patients
Cidofovir is a…
cytidilate analog
Cidofovir MOA?
phosphorylation to di and tri-phosphate by cellular enzymes. (so no cross resistance due to viral TK mutations with nucleoside analogs)
Clinical use of cidofovir?
IV administration after IV probenecid is effective in CMV retinitis.
Contraindicated in patients with renal insufficiency:
Cidofovir
Direct intra-ocular administration is not recommended in what drug due to ocular toxicity?
Cidofovir
Adverse reactions of Cidofovir are:
1) Dose-dependent nephrotoxicity
Cidofovir should not be admin’d with what nephrotoxic drugs?
AMPHO B, AMINOGLYCOSIDES, NSAIDS, PENTAMIDINE, FOSCARNET
Foscarnet is a…
phsphanoformic acid- an inorganic pyrophosphate
Foscarnet MOA?
Inhibits viral DNA Polymerase, RNA polymerase and HIV reverse transcriptase
Foscarnet does not require what?
activation by phosphorylation
Foscarnet resistance is due to what?
Point mutations in the DNA polymerase gene- which be cross resistant to ganciclovir.
Clinical use of Foscarnet?
1) CMV retinitis
2) CMV colitis and esophagitis
3) Acyclovir-resistant HSV and VZV infections
Dosing of foscarnet is based on what?
Patient’s creatinine clearance
Foscarnet and what drug are synergistic?
Ganciclovir
Foscarnet adverse reactions:
1) Nephrotoxic
2) renal insufficiency
3) hypo- or hyper-calcemia
4) hypo- or hyper-phosphotemia
5) C/I’d with other nephrotoxic drugs
What reduces Foscarnet nephrotoxicity?
Saline preloading ****
What is the only anti-sense DNA?
Fomivirsen
Fomivirsen is a…
anti-sense DNA oglionucleotide
Fomivirisen MOA?
hybridizes with CMV mRNA to inhibit immediate early region 2 protein synthesis (translation) to prevent viral replication
How is fomivirisen administered and why?
Delivered by direct intravitreal administration to treat CMV retinitis in AIDS patients
What is fomivirisen’s intravitreal half life?
55 hours
