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
Valganciclovir formula and spectrum
available orally only
CMV
EBV
HSV/VZV
valganciclovir resistance
-mutation in the viral protein kinase responsible for monophosphrylation
-responsible for monophosphorylation
–confers resistance to ganciclovir alone
-mutation in the viral polymerase gene
–may show cross resistance to similar antivirals
foscarnet MOA
Inhibition of viral synthesis of DNA
does not require thymine kinase
– works on HSV strains deficient in this enzyme
selective inhibition at the pyrophosphate binding site on virus-specific DNA polymerase
noncompetitive inhibitor
does not affect cellular DNA polymerse
resistance of foscarnet
not caused by thymidine kinase alterations
Foscarnet formulation and spectrum
IV only - controlled infusions
CMV including ganciclovire strains
acyclovir resistant HSV or VZV, EBV
Foscarnet structure
phosphonomethanoic acid
Cidofovir structure
cytosine analog
Cidofovir MOA
Inhibition of viral synthesis of DNA
-acyclic nucleoside phosphonate derivative
-phosphorylation not dependent on viral kinase
-may enhance activity to TK deficient strains
Cidofovir formula
IV only
Cidofovir must be avoided in
preexisting renal impairment
Cidofovir AE
nephrotoxicity (dose-limiting), neutropenia, metabolic acidosis
cidofovir resistance
mutation in viral DNA polymerase in CMV, pox, and adenovirus
confers resistance to CMV
Foscarnet activity not affected by cidofovir resistance
what is shingles ( herpes zoster) caused by ?
reactivation of varicella zoster (VZV), initial infection causes chicken pox
effective vaccine available
Antiviral therapy for Shingles (herpees zoster)
acyclovir, famciclovir, and valaciclovir
reduces severity of shingles in Administration begins within 72hours of beginning of symptoms
Zoster Immune globin
useful for prevention of chickenpox and shingles but typically not for treatment
Human Papilloma virus
non enveloped double stranded DNA virus
associated with the development of carcinoma, cervix, anus, and penis
What can human papilloma cause
cervical, vaginal, vulvar cancers in women
penile cancer in men
anal and throat cancer, and genital warts in both men and women
papillomavirus treatment options
no specific treatment available
Imiquimod*
Podofilox
Trichloroacetic acid*
imiquimod
Immunomodulator*
- activates immune cells (monocytes, macrophages, NK cells)
produces antiviral cytokines
indirectly activates antigen presenting cells including langerhan cells and T helper cells
Podofilox
AKA podophyllotoxin
main ingredient in podophyllin
exact mechanism not known
trichloroacetic acid
keratolytic agent
given topically
crypto therapy
burning off HPV wart with liquid nitrogen
lopinavir
experimental for HPV but approved for HIV as a protease inhibitor
vaccines against HPV
Gardasil- against types 6,11,16, and 18
Cervarix- against types 16 and 18
both non living vaccines
influenza vireuses
majority respiratory virus that can cause considerable mortality and in some cases mortality
converted with 2 different type of spikes
- neuraminidase
-hemagglutinin
influenza agents
oseltamivir
zanamivir
amantadine
rimantadine
what are the two large glycoproteins on the outside of the viral particles
neuraminidase (NA)
hemagglutinin( HA)
hemagglutinin (HA)
a lectin that mediates binding of the virus to target cells and entry of the viral genome into the target cell
neuraminidase (NA)
involved in the release of progeny virus from infected cells by cleaving sugars that bind the mature viral particles
oseltamivir MOA
oral neuraminidase inhibitor *
cleaves terminal sialic acid residues on glycoconjugates and destroys receptors
newly formed virions adhere to cell surface and limit spread
Oseltamivir spectrum and AE
Influenza A and B
avian influenza
H5N1 disease
AE: HA, N/V
zanamivir MOA
Neuraminidase inhibitor
given inhalation
zanamivir spectrum and AE
Uncomplicated influenza A and B
some strains of avian influenza
possible effective fo H5N1
AE: nasal and throat discomfort, btanchospasm
Amantadine and Rimantadine MOA
prevents the release of viral nucleic acid into host cell
blocks M2 protein channel (type A only)
disrupts hydrogen transport, viral uncaring in host cell and therefore viral RNA transcription
not currently used in US
Amantadine and Rimantadine spectrum and AE
Influenza A (not influenza B) , resistance is frequent
AE: Seizures, anticholinergic , CNS, edema , blurry vision
Influenza Vaccines (best way to control flu infections)
-inactivated or recombinant (conventional)
—-IM
—-Trivalent or Quadrivalent*
-LAIV- live attenuated prep –FLUMIST
—-administered intranasally
—-not recommended due to lack of efficacy
moneypox
viral zoonosis and symptoms are similar to small pox patients
viral structure of of monkeypox
-double stranded DNA virus
-belongs to the orthopoxvirus genus of the poxvirdae family
-central african and west african cascade
Central african strain
more transmissible
more severe
west african strain
only sporadic cases
hypothesis- may be little propensity for human to human transmission
what are the natural host for monkey pox
exact natural reservoir unknown
rodents ( dormice, squirrels, and rats)
eating inadequately cooked meals from infected animals
transmission of monkeypox
human close contact with infected animal or human
person to person through lesions, bodily fluid, respiratory droplets, contaminated material (beddings)
symptoms of monkey pox
invasion period: fever, chills, HA, backache ( last 0-5 days )
skin eruption: development of rash including lesions and pustules (begin 1-3 days, most contagious)
symptoms last 2-4 weeks
diagnosis of monkey pox
Polymerase chain reaction (PCR)
-samples from skin lesions, liquid from pustules or dry crust
biopsy
treatment for monkeypox
no treatment same as small pox and cytomegalovirus
Tercovirimat ( not FDA approved)
-limited to pts who are at risk for severe disease such as immunocompromised conditions and younger than 8 yo
what is the vaccines available for monkey pox
ACAM2000
-replication competent vaccine that protects against smallpox
-contain the vaccinia virus which is live and infectious
JYNNEOS
-live virus and is replication-deficient vaccine
-18 or older and with immune deficiencies can receive the vaccine
