key note: Antiviral therapy for herpesvirus infections--> Pyrimidine nucleosides (do what? what are the 3 main drugs in this category, and the subtypes of the one?)
inhibition of viral DNA polymerase. (1) idoxuridine (2) trifluridine (3) Sorivudine (phosphorylation by viral enzymes: thymidine and thymidylate kinases) (pyramids-- I do sorely tri. Tri with my thighs as kisses)
Key note: Antiviral therapy for herpesvirus infections--> Purine nucleosides (do what? what are the 5 drugs in this category?)
inhibit viral DNA polymerase. (1) Vidarabine (2) Acyclovir - Valacyclovir (pro-drug): small spectrum (3) Penciclovir - Famciclovir (pro-drug): small spectrum (4)Ganciclovir: small spectrum (5) Ribavirin (the pure stuff is what we care about)
all the herpes fighters (pyrimidine and purine) both do what?
NRTIS undergo phosphorylation by host cell enzymes and becomes a triphosphate form. This form competes with host cell triphosphates that viruses use to syn DNA. The NRTIS triphosphate form is incorporated into the growing viral DNA chain resulting in termination. (retros are IN the DNA, so this has to wedge in the DNA to stop it)
ZIDOVULDINE (AZT) what is the admin with the best bioavailability?
MOA of viral DNA polymerase inhibitors? explain how this doesnt hurt the host?
Converted into monophosphate (MP) by viral thymidine kinase (only in infected cells!!).--> The host cell converts MP to triphosphate (active form) that inhibits viral DNA polymerase. 30x more potent against herpes virus enzyme than host enzymes so not as toxic to host!!
what are viral DNA polymerase inhibitors good against?
Effective against EHV & FHV
ACYCLOVIR--> what is the PK like of this drug, compared to others in the group?
Analogues & Prodrugs have better PK (Valacyclovir, Peciclovir, Famciclovir) (ace isnt the ace.....go figure.)
what is the oral bioavailabiltiy like for acyclovir?
Variable oral bioavailability (Dogs > 80%, Horses < 5%) (ace would rather put his hand in the mouth of a dog rather than a horse)
what is the half life like for acyclovir?
Half live variable (Dogs=2.3 hr, Horses=5-9 hr, Cats=2.5 hr) (Ace's life depends on the adventure)
uses for acyclovir?
EHV-1, FHV, CHV and Neonatal herpes virus in horses (~26% oral bioavailability) (higher bioavail in neonates b/c not full gut closure--> more drug into system) (herpes is a vicious CYCLE of being spread around)
what to know about VALACYCLOVIR?
toxic to cats (Valarie doesnt like cats because theyre PECky)
PENCLOVIR is used for what?
Only use topically in cats (little kid drawing on cat with a pen)
what to know about FAMCICLOVIR?
questionable efficacy (that family is questionable)
what are the drugs listed in the DNA polymerase inhibitors category?
INFLUENZA (the flu makes you feel like youre breathing acid)
Viral Hemagglutinin attaches to host neuraminic acid and enters through endocytosis. The endosome is acidified after the influx of H+ through the M2 ion channel. This allows disassembly of the viral structure and RNA release.
note about resistance in M2-ion channel inhibitors?
Use in poultry responsible for resistant strains in China? (harmful acid chicken from china)
what are the two drugs in this category?
AMANTADINE, RIMANTADINE (WE DINE ON ACID...so amanda started rimming)
amantadine--> admin? Use? which animal is this best in? side effects?
NOT good oral admin (amanda needs to keep her mouth shut), Used to treat influenza A (amantadine, a) and PAIN (watching the AMANDA show is painful) pain via NMDA receptor antagonist (ketamine) (AMANda is on ketamine, so she doesnt feel pain from her flu)-->Relief of pain symptoms-->Combined with NSAIDS. Well tolerated in dogs. This drug is TOXIC (AMANda is a toxic person with her drug use and influenza)
RIMANTADINE--> admin? uses?
Better oral admin than amantadine (rim and mouths. hur.) and used for EQUINE influenza (M2ions are all influenza, but ANAL RIM on a horse is....apparently better, since the oral avail is better)