Anti-viral Flashcards
Anti-viral for CMV
Ganciclovir
Valganciclovir
Anti-viral for HSV, VZV
Acyclovir
Valacyclovir
Mechanism of Action for
acyclovir and valacyclovir
Acyclovir is an acyclic guanosine analog.
it is approximately 10 times more potent against HSV-1 and HSV-2 than against VZV.
Acyclovir requires three phosphorylation steps for activation. It is converted first to the monophosphate derivative by the virus specified thymidine kinase and then to the di- and triphosphate compounds by host cell enzymes.
Acyclovir triphosphate inhibits viral DNA synthesis by two mechanisms: competition with deoxyGTP for the viral DNA polymerase, resulting in binding to the DNA template as an irreversible complex;
and
chain termination following incorporation into the viral DNA
Mechanism of action for Ganciclovir and valganciclovir
Ganciclovir is an acyclic guanosine analog that requires activation by triphosphorylation before inhibiting the viral DNA polymerase. (to become drug triphosphate)
Thus interfering with Viral DNA synthesis.
Acts as a competitive substrate for DNA polymerase leading to chain termination following its incorporation into viral DNA.
Mode of administration of Anti-HSV
acyclovir ——– Oral, IV, topical
valacyclovir = oral
Mode of administration of Anti-CMV
ganciclovir ———-IV , intravitreal
Valganciclovir——– Oral
Absorption for acyclovir
low (15-20%)
absorption for valacyclovir
54-70%
absorption ganciclovir
0%
absorption valganciclovir
60% recommended to take with food
Distribution of acyclovir
diffuse readily to all tissue
CSF 20-30%
Distribution of valacyclovir
CSF ~50%
Distribution of ganciclovir
CSF ~50%
Acyclovir metabolism
hepatic
thru oxidation and hydroxylation
valacyclovir metabolism
hepatic and intestinal hydrolysis
to acyclovir
ganciclovir metabolism
0
valganciclovir metabolism
rapidly hydrolyzed in the intestinal wall and liver to ganciclovir
Elimination of acyclovir , valacyclovir , ganciclovir and valganciclovir
Renal:
glomerular filtration and active secretion.
half life acyclovir
2.5-3.3h
half life valacyclovir
serum x5 more than acyclovir
2.5-3.3h
half life ganciclovir
4h
can be removed by hemodialysis
half life valganciclovir
4h
can be removed by hemodialysis
Clinical application of acycovir and valacyclovir
Genital herpes, varicella and zooster treatment, herpes encephalitis.
Prophylactic use of acyclovir in patients on immunosuppressants undergoing transplant or radiation therapy, who are all at risk of infection from reactivation of the virus frequent recurrence of HSV infection of genitalia
Clinical application of Ganciclovir and valganciclovir
Ganciclovir:
- for systemic CMV infection in HIV and immunocompromised patients.
- As maintenance therapy for Cytomegalovirus (CMV) retinitis in immunocompetent patients
Valganciclovir
1. Valganciclovir has recently been shown to reduce transmission of genital HSV
Side effect of acyclovir and valacyclovir
- GIT-related symptoms
- Renal dysfunction from IV administration (due to deposition of drug in renal tubules) (Caution: give drug slowly (over 1 hr or more), and ensure adequate hydration).
- CNS-related:
i. headache
ii. encephalopathy – tremors, with IV doses - Hematologic
i. thrombotic thrombocytopenic purpura (TTP);
ii. hemolytic uremic syndrome (in immunocompromised patients given valacyclovir).
Non-teratogenic compared to ganciclovir
Side effect of ganciclovir and alganciclovir
- Bone marrow suppression, particularly neutropenia (less with the oral route)
- GIT-related: diarrhoea, nausea, vomiting
- irreversible aspermatogenesis at high doses
- potential mutagenicity and carcinogenesis;
- teratogenicity and possible embryotoxicity.
Women are to avoid pregnancy until at least 90 days
after the end of treatment. - CNS-related: headache
More toxic than acyclovir
DDI for acyclovir and valacyclovir
nephrotoxic agents
Probenecid and cimetidine decrease acyclovir clearance and increase exposure.
DDI for gancicloir and valgancicloir
Imipenem
- enhance the ADR effect of imipenem and increase risk of seizure
NNRTI
- enhance the ADR effect of reverse transcriptase inhibitors (nucleoside)
- hematologic toxicity is of specific concern.
High fat meal
- increase AUC by 30%
