Non HIV Drugs Med chem Flashcards
viral entry, replication and possible site for anti viral
viral attachment
cell entry
transcription
translation
viral assembly
what is a dominant factor for infectious disease
aging
what kind of analogs are antivirals
purines or pyrimidine
what kind of drugs are antivirals and how do they become active?
prodrugs
must be phosphorylated by viral or cellular enzymes
what do antivirals inhibit?
active replication so the viral growth resumes after drug removal
anti-viral agents do not eliminate
non replicating or latent virus
what is important for the prevention of and recovery from a number of viral infections
effective host immune response
what are herpes virial infection and disease structure
a linear double stranded virus, all similar and known to cause latent infections
herpes simplex virus 1
infections above the waist, gingivostamatitis, herpes labialis, encephalitis
herpes simple virus 2
infection below the waist, herpes genitals
varicella zoster virus
causes varicella (chickenpox) or zoster (shingles)
epstein barr virus
infectious mononucleosis and development of nasopharyngeal carcinoma
cytomegalovirus
congenital infections, mononucleosis
human herpes virus type 8
kasposi sarcoma
oral agents for herpes virus
acyclovir
valacyclovir
famciclovir
MOA: inhibition of viral synthesis of DNA
topical agents for herpes
acyclovir
dococanol
peniciclovir
ophthalmic agents for herpes
trifluridine
Acyclovir MOA
uptake of infected cell
-thymidine kinase phosphorylates to acyclovir monophosphate
-converted to acyclovir triphosphate
completes with deoxygusnosine triphosphate for viral DNA polymerase
-lacks 3 hydroxyl group –> chain termination
-inactivates the viral DNA polymerase-guanosine analog
acyclovir fomulations and spectrums
-oral, topical, IV formulas
-spectrum: Herpes simplex 1 and 2, varicella , possibly the epstein barr virus
valacyclovir
-L-valyl ester prodrug
-rapidly and almost converted to acyclovir
-spectrum: Herpes simplex 1 and 2, varicella , possibly the epstein barr virus
- oral only
what are three basic resistance mechanisms of acyclovir resistance
reduced or absent thymidine kinase
altered TK substrate specificity
alterations in DNA polymerase
cross resistance to famciclovir& valacyclovir
famciclovir
-cyclic adenine analog
-converted to penciclovir in the liver and intestine
-oral only
-spectrum: Herpes simplex 1 and 2, varicella ,epstein barr virus (less)
-AE: HA, GI
famciclovir resistance
-mutations in viral TK or DNA polymerase
-cross resistance w acyclovir in TK negative strain
-may still have activity in TK altered strains
topical agents for orolabial herpes
Penciclovir
-inhibit DNA synthesis
-topical guanine analog similar to acyclovir*
-apply every 2 hrs
Docosanol
-active against a broad range of lipid envelop virus **
-MOA: interferes with viral fusion to host *
HSV ocular keratoconjuctivitis
Trifluridine
inhibits dna synthesis
anti-cmv agents
ganciclovir
valganciclovir
foscarnet
cidofovir
ganciclovir MOA
inhibits DNA polymerase
-complets with deoxyguanosin triphosphate
-viral encoded phosphotransferase converts to ganciclovir
-more effective than acyclovir
ganciclovir formulation and spectrum
oral, IV, Intraocular
CMV
EBV
HSV/VZV
very effective in treating CMV retinitis in AIDS patients
Valganciclovir MOA
Inhibition of viral synthesis of DNA
L-valyl prodrug of ganciclovir