Pharm - Antiviral Drugs Flashcards
true or false
viruses are obligate intracellular parasites
true
they depend on the host machinery to survive
can be considered the smallest parasites
true or false
parasites are cells
FALSE
they are not
true or false
There are NO DRUGS that can kill a virus
TRUE!
can only inhibit their growth
true or false
both bacteria and fungi can live outside the host cell while viruses cannot
true
explain the structure of a virus
-has a nucleic acid core (can be DNA or RNA), surrounded by a CAPSID.
-outermost is the lipoprotein envelope that as a similar function to the cell membrane, which has SPIKE PROTEINS
there are NO ORGANELLES OR NUCLEUS
nucleic acid core + capsid/coat is called…
nucleocapsid
explain what the nucleic acid within the virus can be
ss or ds DNA or ss or ds RNA
true or false
all viruses have an envelope
FALSE - not all do
comparatively, the virion diameter of the herpes virus and the genome size are _______-
large
is herpes an RNA or DNA virus
ds linear DNA virus
only structural difference between DNA and RNA
RNA has an OH on carbon 2 and DNA does not
most RNA viruses are single or double strand?
ss
name 3 RNA viruses
retrovirus (HIV!)
coronavirus
orthomyxovirus
Aside from herpes virus, name 3 other DNA viruses
poxvirus
adenovirus
papillomavirus
what disease does poxvirus cause and is it RNA or DNA
DNA - smallpox
name 3 diseases caused by herpes virus
is it RNA or DNA
DNA
herpes
chicken pox
shingles
name 2 diseases that adenovirus causes and is it RNA or DNA
DNA
sore throat, conjunctivitis
explain the replication cycle of a DNA virus
- attachment to host cell membrane and subsequent endocytosis/fusion to get into the host cell
- uncoating and transfer of viral DNA to the host nucleus
- the viral DNA can either be used to synthesize MORE viral DNA or be transcribed into viral mRNA
- if transcribed into viral mRNA, the host cell ribosomes are used to make various viral proteins like structural proteins, enzymes, and regulatory proteins, which can be used to assemble a new virion for release to infect other cells
when a new virion is assembled and leaves the original host cell, what is this called?
budding
how can the synthesis of viral DNA be inhibited and name 4 drugs that do this
through inhibiting viral DNA polymerase
acyclovir
vidarabine
foscarnet
ganciclovir
explain the replication cycle of RNA viruses
- attachment to surface of host cell via hemagglutinin and endocytosis into the host cell - endosome is formed
- through the M2 protein channel, H ions go into the endosome
- M2 allows uncoating to open the envelope and allow the genetic material (RNA) of the virus to get into the nucleus
- within the nucleus, the viral RNA is transcribed into either mRNA or MORE viral RNA
- both the mRNA and new vRNA leave the nucleus. the mRNA uses the host ribisome to produce structural and nonstructural viral proteins where they meet with the newly formed viral RNA to form a NEW VIRION WHICH BUDS OFF AND IS RELEASED FROM THE HOST CELL TO INFECT MORE CELLS
name 2 drugs that inhibit the uncoating of the viral envelope (and thus the release of RNA into the nucleus) through inhibiting M2
amantadine and rimantadine
name a drug that inhibits RNA polymerase and thus inhibits the synthesis of viral mRNA from viral RNA
ribavirin
name 2 drugs that inhibit the RELEASE of RNA viruses
zanamavir and oseltamivir
what do NRTIs inhibit
nucleic acid synthesis
true or false
protease inhibitors inhibit late protein synthesis and processing
TRUE
inhibit proteins from breaking into smaller, functional proteins
true or false
influenza is a DNA virus
FALSE - RNA
explain the MOA of anti HERPES DRUGS
starts with a nucleoside drug
through the VIRAL ENZYME - thymidine kinase – gets a phosphate group put on it to become MONOPHOSPHATE
then, HOST kinases need to phosphorylate 2 more times to TRIPHOSPHATE
this triphosphated nucleoside has 2 different functions:
1 is to competitively inhibit viral DNA polymerase and thus inhibit viral DNA synthesis
the other is to be incorporated into VIRAL DNA (bc structurally similar to guanidine) to cause CHAIN TERMINATION OF VIRAL DNA – cannot continue to make DNA
name 3 anti herpes drugs that can skip the first step in the mechanism. how can they do this?
they already have 1 phosphate group (except trifluridine) and thus do not need the 1st step done by viral enzymes
trifluridine
cidofovir
foscarnet
nucleotides!
name 3 nucleosides used as anti herpes drugs
do they need to undergo the 1st step?
YES - need to undergo 1st step
acyclovir
penciclovir
ganiciclovir
acyclovir structurally mimics…..
guanosine
HHV3
varicella-zoster virus
it is in the herpes virus family
HHV5
cytomegalovirus
it is in the herpes virus family
HHV1 vs HHV2
both are herpes viruses
HHV1 is oral HHV2 is genital
how many human herpes viruses (HHV) are there
8
what type of virus is the herpes virus
dsDNA virus
differentiate between lytic vs latent phase of the herpes virus
lytic - primary infection - you have symptoms
latent - persistent infection but no symptoms - can have intermittent reactivation
how are herpes viruses spread to others?
through secretions - oral or genital secretion
true or false
HSV2 is oral herpes
FALSE
HSV2 is genital and HSV1 is oral
true or false
there is a vaccination that can prevent HSV1/2 infection
FALSE - NONE
HSV1 (oral herpes) occurs most often in who??
what are some symptoms?
young children
causes lesions near the mouth, fever, sore throat
COMPLICATIONS of HSV2 (genital herpes)
lesions other than in genital area, aseptic meningitis
explain components of varicells zoster virus (HHV3)
Varicella = chickenpox
zoster = shingles
symptoms of varicella and how long for immune system to take control
fever, rash
1-3 weeks
the latent phase of the varicella-zoster virus is present where?
name some symptoms of when it’s reactivated
latent in the ganglion of CNS
pain, burning, red rash, itching
7 drugs for HSV/VZV
acyclovir
valacyclovir
penciclovir
famiciclovir
docosanol
trifluridine
idoxuridine
true or false
foscarnet is a nucleotide
FALSE
has phosphate group (so can skip 1st step) but no nucleic acid base
MOA of acyclovir and how can you tell by looking at the structure
Terminates DNA elongation. BECAUSE MISSING 3’ OH GROUP!!!
Phosphate on DNA will only link to this 3’ OH group but there isn’t one present
also competitively inhibits viral DNA polymerase
acyclovir is an _____ ____ ___ analog
ACYCLIC GUANINE NUCLEOSIDE
as an acyclic sugar instead of 5 membered ribose
acyclovir lacks _______ on its side chain
3’ hydroxyl
acyclovir is most potent for which herpes virus
mainly HSV1 then HSV2
less active vs VZV and CMV
what does acyclovir compete with
GTP
2 major resistance mechanisms against acyclovir
- MAIN = decreased production of viral thymidine kinase (1st step of phosphorylation!!)
- mutations in viral DNA polymerase.
if there is resistance to acyclovir bc the virus is decreasing production of its viral thymidine kinase, are there any alternative agents we can use?
YES - use drugs that don’t need that 1st step:
-foscarnet
-cidofovir
-trifluridine
aside from being used for HSV1/HSV2 treatment, what else can acyclovir be used for
prophylaxis in organ transplant patients
can also be helpful in HIV-HSV dual infections
3 routes of administration for acyclovir
oral
IV
topical
2 main AE’s of IV acyclovir formulation**
nephrotoxic and neurotoxic
can also cause headache
generally well tolerated
what other drugs is acyclovir contraindicated with
other drugs that cause nephrotoxicity
valacyclovir is a _______ of acyclovir
prodrug
technically all are considered prodrugs tho bc they all need to be phosphorylated
is valacylovir given IV
NO - only oral
has very high oral bioavailability
3 main AE’s of valacyclovir
headache
rash
nephrotoxicity
both peniciclovir and famiciclovir are _____ analogs
guanine
_____- is a diacetyl ester PRODRUG of 6-deoxypenciclovir
famicilovir
true or false
famciclovir and penciclovir are nucleosides
TRUE
is there any advantage to famciclovir/penciclovir over acyclovir?
YES - only advanatage is that they have longer tissue half life
mechanism of famciclovir/penciclovir
JUST 1 MOA - inhibits viral DNA polymerase
DOES NOT DO DNA CHAIN TERMINATION
differentiate between the routes of administration for famciclovir vs penciclovir
penciclovir is ONLY GIVEN TOPICALLY FOR HERPES LABIALIS AS A 1% CREAM
famciclovir however has good oral bioavailbility and is excreted in the urine
AE famciclovir and penciclovir
famciclovir - same as acyclovir – headache, nephrotoxic, neurotoxic
penciclovir - only given orally so just application site reactions
what is the only antiviral that is NOT a prodrug??
what is MOA
docosanol
has totally different MOA
it prevents ENTRY of the virus by inhibiting fusion of the viral envelope to the host cell membrane
how is docosanol administered
only as a cream for orolabial herpes (around mouth) – available OTC
true or flase
docosonal needs to be used in the early stages of viral infection or it will have no benefit
TRUE
TRUE OR FALSE
trifluridine can be used for acyclovir-resistant HSV infection
true!!!
it doesnt need the1st step by viral thymidine kinase
it’s phosphorylated by HOST ENZYMES to triphosphate
trifluridine MOA
inhibits viral DNA synthesis by incorporating into the DNA strand through viral DNA polymerase
prevents base pairing
ALSO the monophosphate form inhibits thymidylate synthase, thus inhibiting thymine production
true or false
trifluridine cannot be used if there is mutation in the viral enzyme for thymidine kinase
FALSE - it can
