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Pharmacology #1 > CMV Agents > Flashcards

CMV Agents Flashcards

1
Q

CMV can cause what?

A

Blindness

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2
Q

What agents treat CMV?

A

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

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3
Q

CMV is an…

A

opportunistic infection that infects immunocompromised

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4
Q

Anti-sense DNA is…

A

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

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5
Q

Ganciclovir is an…

A

acyclic guanosine analog

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6
Q

Ganciclovir requires what?

A

virally encoded TK UL97 for initial phosphorylation

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7
Q

Ganciclovir MOA?

A

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

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8
Q

Ganciclovir vs. Acyclovir?

A

Ganciclovir is 100x times greater on CMV!!

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9
Q

Oral bioavailability of Ganciclovir?

A

POOR 6-9%

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10
Q

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

A

foscarnet

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11
Q

How is ganciclovir administered for CMV?

A

intravitreally or by ocular implant

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12
Q

What is used to treat CMV colitis and esophagitis?

A

IV Ganciclovir

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13
Q

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

A

Ganciclovir

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14
Q

Ganciclovir treats what?

A

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

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15
Q

Ganciclovir resistance due to:

A

1) TK UL97 mutations

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

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16
Q

Ganciclovir adverse reactions:

A

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

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17
Q

ValGANciclovir is a what?

A

mono-valyl ester prodrug of ganciclovir

18
Q

ValGANciclovir MOA?

A

rapidly converted to ganciclovir by intestinal and hepatic esterases

19
Q

Oral bioavailability of ValGANciclovir?

A

60% Oral Bio

20
Q

Clinical indication for ValGANciclovir?

A

treatment of CMV retinitis in AIDS patients

21
Q

Cidofovir is a…

A

cytidilate analog

22
Q

Cidofovir MOA?

A

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

23
Q

Clinical use of cidofovir?

A

IV administration after IV probenecid is effective in CMV retinitis.

24
Q

Contraindicated in patients with renal insufficiency:

A

Cidofovir

25
Q

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

A

Cidofovir

26
Q

Adverse reactions of Cidofovir are:

A

1) Dose-dependent nephrotoxicity

27
Q

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

A 
AMPHO B, 
AMINOGLYCOSIDES, 
NSAIDS, 
PENTAMIDINE, 
FOSCARNET
28
Q

Foscarnet is a…

A

phsphanoformic acid- an inorganic pyrophosphate

29
Q

Foscarnet MOA?

A

Inhibits viral DNA Polymerase, RNA polymerase and HIV reverse transcriptase

30
Q

Foscarnet does not require what?

A

activation by phosphorylation

31
Q

Foscarnet resistance is due to what?

A

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

32
Q

Clinical use of Foscarnet?

A

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

33
Q

Dosing of foscarnet is based on what?

A

Patient’s creatinine clearance

34
Q

Foscarnet and what drug are synergistic?

A

Ganciclovir

35
Q

Foscarnet adverse reactions:

A

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

36
Q

What reduces Foscarnet nephrotoxicity?

A

Saline preloading ****

37
Q

What is the only anti-sense DNA?

A

Fomivirsen

38
Q

Fomivirsen is a…

A

anti-sense DNA oglionucleotide

39
Q

Fomivirisen MOA?

A

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

40
Q

How is fomivirisen administered and why?

A

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

41
Q

What is fomivirisen’s intravitreal half life?

A

55 hours

Pharmacology #1 (15 decks)

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