Anti-Virals - Herpes and CMV

Question 1

Acyclovir

Answer 1

Herpes Virus (1, 2) 
Oral and IV- excreted in kidney, short half life (5x/day admin) 
Safe for use in pregnancy 

MOA: guanosine analog
enters cell –> phosphorylated by viral thymidine kinase (locks in cell) –> host cell enzymes phosphorylate three more times –> similar structure to guanine (GTP) –> incorporated into DNA but no 3’ OH –> inhibts DNA polyermase elongation
*inhibits DNA replication

Uses:

• Reduce viral shedding
• increases the speed of healing of existing ulcers
• dec. the pain and formation of new ulcers
• used topically to tx herpes keritis
• IV in herpes encephalitis or neonatal herpes
• prophylactically in transplant pts or immunocompromised
• milde to moderate VZV
• AIDs pts to tx hairy leukoplakia

SE:
minimal-
- somnolence and lethargy when combined with zidovudine
- can cause renal tubular obstruction esp with cyclosporine - (avoid with hydration adn slow infusion)

Question 2

Valacyclorvir

Answer 2

Same as acyclovir- better oral bioavailability

Question 3

Famciclovir

Answer 3

HSV-1, HSV-2, EBV, VZV, HBV
Longer half like than acyclorvir - admin 2x/day, kidney elimination

Uses:

• initial tx and prevention of genital herpes and herpes zoster
• converted invivo to penciclovir - topical agent for herpes labalis

MOA: gaunosine analog- enters cell- phosphorylated by the viral thymidine kinase –> competitive inhibition of the DNA polymerase

SE

• N/V/HA/DIA
• Testicular toxicity in animals

Question 4

Trifluridine

Answer 4

Herpes Drug
MOA:
- fluorinated thymidine analogue that inhibits viral DNA synthesis

Use;
Topical tx for herpes type 1 and 2 for infections that are resistant to acyclovir

SE:
visual haze

Question 5

Docosanol (Abreva)

Answer 5

Herpes drug
MOA: inhibits fusion between the plasma membrane and the herpes simplex virus envelope 
Uses:
- Topically for tx of cold sores 
SE:
- may irritate skin or cause a HA

Question 6

Gangciclovir Sodium

Answer 6

CMV and herpes drug
IV admin, more toxic and less selective than acyc.
MOA: enters cell -> phosphorylated by thymidine kinase in herpes cells and viral protein kinase phosphotransferase in CMV infected cells > inhibits DNA polymerase, suppresses DNA elongations and inhibits CMV replication
* resistance can develop due to dec. cellular phosphotransferase kinase
Uses:
- IV to tx life threatening CMV, initial tx for chronic CMV in immunocompromised pts, transplant pts to reduce risk of CMV, for ocular implant pts
SE:
- neutopenia, and thrombocytopenia when combined with ziduvudine
- N/V/HA/ rash, fever, phelbitis, confusion
- Tertatogenic and carcinogenic in animals- safe in humans

Question 7

Valgangciclovir

Answer 7

CMV and herpes drug
Oral admin
Same as gangciclovir
Used mostly for prophylaxis and therapy of CMV infections

Question 8

Cidofovir

Answer 8

CMV and Herpes Drug
MOA: cytosine analogue–> inhibits viral DNA polymerase
*no activation necessary– useful against resistant strains
Uses:
- CMV retinitis
- resistant herpes infections
SE
- renal tubular necrosis may occur (prevent with hydration and probenecid)
- Ocular hypotonia
- uveitis
-

Question 9

Foscarnet

Answer 9

CMV and Herpes drug
IV admin, kidney elimination
MOA: phophonoformic acid (analogue or inorganic pyrophosphate) –> directly inhibits DNA polymerase, RNA polymerase and reverse transcriptase

Uses:

• acyclovir resistant herpes simplex
• CMV retinitis

SE

• nephrotoxicity and, renal insufficiency
• hypocalcemia when combined with pentamidine
• N/V/HALLUNICATIONS
• genital ulcers due to high levels in urine
• teratogenic

Question 10

Fomivirsen

Answer 10

CMV and herpes drug
Intravitreal injection
MOA: antisense compound with complementary to RNA sequence in CMV –> inhibits protein synthesis, and CMV replication
Uses:
- CMV retinitis in AIDs pt’s who fail therapy with other drugs
SE
- ocular inflammation and visual impairment