C5 Flashcards
Agents to treat HSV and VZV?
Acyclovir
Valacyclovir (prodrug)
Acyclovir MOA
- HSV-1, HSV-2, VZV
- Activated by the viral thymidine kinase TK—> inhibit viral DNA polymerase
- Resistance: changes in viral DNA polymerase
Acyclovir PharmacoKinetix?
- administeration: topical, oral, I.V.
- 1/2 life: short (oral requires multiple daily doses)
- Elimination: Renal excretion
(dosage reduced in renal impairment)
Acyclovir clinical uses?
VZV, HSV treatment + prophylaxis
- Oral:
1. mucocutaneous
2. genital herpes
3. prophylaxis in immunocompromised patients - I.V. administration:
severe herpes disease (including encephalitis) - neonatal HSV infection
topical
Acyclovir Toxicity?
- oral: well tolerated but may cause:
GI distress. nausea, diarhhea , headache - the I.V. drug:
CNS toxicity
Nephrotoxicity
Hypotension
Valacyclovir MOA?
- Activated by the viral thymidine kinase TK—> inhibit viral DNA polymerase
- prodrug converted to acyclovir by hepatic metabolism after oral administration
- longer duration of action than acyclovir
Ganci.cyclovir MOA?
Inhibits DNA polymerases of CMV & HSV –> chain termination
Gancicyclovir PharmacoKinetix?
- administration: I.V , oral, intra-ocular forms
- distribution : penetrates well into tissues
- Elimination: renal elimination
- Oral bioavailability: is less than 10%
- intraocular implant: used in CMV retinitis
what about Valganciclovir?
- prodrug of Ganciclovir
- high oral bioavailability: given orally!!!!
- Alternative to I.V. Ganciclovir, Cidofovir (in end-organ CMV)
Gancicyclovir Clinical uses?
- prophylaxis and treatment of CMV retinitis
- other CMV infections in immunocompromised and organ transplantation
Gancicyclovir Toxicity?
- Systemic toxic effects:
1. Bone marrow supression (Leuko, Thrombo, Neutropenia)
2. Neurologic dysfunction
3. Hepatic dysfunction
Cidofovir MOA?
activated by host cell kinases
inhibits DNA polymerases of HSV, CMV, and HPV
Cidofovir Pharmacokinetix?
- given I.V
- elimination: kidney
- Dosage is adjusted in proportion to creatinine clearance
- full hydration must be maintained
Cidofovir clinical uses?
- in CMV retinitis
- in mucocutaneous HSV
- in genital warts.
Cidofovir Toxicity?
Nephrotoxicity
major dose-limiting toxicity
Phosphonoformate drug used for CMV?
Foscarnet
Foscarnet MOA?
- does NOT require viral bioactivation (phosphorylation) for antiviral activity!
- inhibits:
1. viral RNA polymerase
2. DNA polymerase
3. HIV reverse transcriptase.
Foscarnet Pharmacokinetix?
- bioavailability: given I.V.
- distribution: penetrates well into tissues (also CNS).
- Elimination: kidney
Foscarnet clinical uses?
an alternative OR adjunct for prophylaxis and treatment of CMV, HSV, VZV infections
Foscarnet Toxicity?
- severe
- nephrotoxicity
- electrolyte imbalance (especially hypocalcemia)
- genitourinary ulceration
- CNS effects (headache, hallucinations, seizures)
drugs RSV?
palivizumab
also Ribavirin
what about palivizumab ?
- Ab’s to surface protein of RSV
- for prophylaxis & treatment of RSV
Anti-influenza agents?
Oseltamivir
Oseltamivir MOA?
- inhibitors of neuraminidases produced by influenza A and B
- inhibit virion release and prevent clumping of newly released virions –> impede viral spread
Oseltamivir Clinical uses?
- bioavailability: prodrug orally, activated in the gut & the liver
- decrease the duration of influenza sym’s
- more effective if used within 24h after onset of sym’s
- taken prophylactically to decrease the incidence of influenza & shorten sym’s
Oseltamivir Toxicity?
GI symptoms
Ribavirin MOA?
Prevents capping of viral mRNA
Block RNA-dep RNA polymerase
influenza A and B, parainfluenza, respiratory syncytial virus (RSV), paramyxoviruses, HCV, and HIV
Ribavirin administration
Parenteral
oral
ribavirin SE
anemia
teratogen
