Antivirals Flashcards
1
Q
viruses that can be treated by antivirals
A
- hep c
- HIV
- flu
- croup
- warts
- systemic
- hep b
- some herpes
- smallpox
2
Q
types of antivirals
A
-virucidal-detergents and cryotherapy
-immunomodulatory
^indirect
-antiviral-direct
3
Q
types of antivirals
A
- nucleoside analogs
- non-nucleosides
- protease inhibitors
- entry inhibitors
- > 50 antiviral drugs in use, more in the pipeline
4
Q
how do antiviral drugs work?
A
- target essential functions:
- entry
- genome replication
- assembly
- release from cell
- target host cell defenses (intrinsic immunity)-interferon pathway
- activate immune response
5
Q
specificity
A
- most drugs target functions of only 1 virus
- broad spectrum are rare
- all viruses are different
6
Q
cytotoxicity
A
- off target can harm cells
- on target can be defeated by resistance
7
Q
duration of antiviral effects
A
- most drugs are reversible competitive inhibitors
- virus replication can resume when drug is cleared (rebound)
- treatment might need to be lifelong
8
Q
resistance to antivirals
A
- mutations often exist before drug treatment
- drug treatment selects for resistant virus strains
- factors favoring this:
- high rate of replication
- high mutation rate
- high selective drug pressure
- immunosuppressed host that cannot clear virus infected cells
9
Q
how do we counter resistance?
A
- alleviate immunosuppression in the treated person-lower doses of anti T cell drugs
- combine drugs with different targets:
- standard for HIV and HCV
- drugs with different mechanisms synergize
- lower prob of multiple resistance
- target host functions
- infected cells have unique profile
- virus mutations do not impact our genes
- some cancer drugs target dividing cells and also inhibit viruses
- beware of toxicity!
10
Q
who should be treated for HSV 1, 2 and VZV?
A
- neonates with HSV at birth
- people with frequent recurrences of 1 or 2
- complicated HSV infections-encephalitis, dissemination, eye infections
- people with zoster-within 3 days
11
Q
acyclovir
A
- nucleoside analog of guanosine
- effective against HSV1=HSV2»VZV
- zovirax
- derivates like valtrex make it more bioavailable
12
Q
acyclovir mechanism of actoin
A
- gets into cells
- viral thymidine kinase phosphorylates molecule
- cell kinases add two more phosphates
- viral DNA polymerase inserts molecule into DNA
- chain terminator
- can have mutations of TK or viral Pol
13
Q
ganciclovir for CMV
A
- nucleoside analog of guanosine
- cytovene or valcyte (more bioavailable)
- similar mech to acyclovir
- highly toxic
- suppresses bone marrow
- mutagenic and teratogenic
- severe side effects
- for bone marrow transplant patients or immunosuppressed people with active CMV or CMV retinitis
14
Q
“broad spectrum” treatments for DNA viruses
A
- foscarnet-foscavir- trisodium phospohonoformate
- inhibits viral DNA polymerase
- effective against all herpesvirus
- IV route only, toxic to kidneys
cidofovir-vistide
- nucleoside analog of cytosine
- effective against herpes, adeno, papillo, pox
- IV only, toxic to kidneys
15
Q
treatments for Hep B
A
- treated with drugs designed for HCV and HIV
- peg IFN
- entecavir
- viread
- chronic HBV
- co infected with HCV and/or HIV
- people who are progressing to cirrhosis, liver failure, hepatocellular carcinoma
16
Q
treatments for flu
A
- zanamivir-relenza
- oseltamivir-tamiflu
- sialic acid analogs that inhibit neuraminidase
- virions remained attached to cells
- severely ill
- children younger than 2
- adults over 65
- immunosuppressed
- anyone suspected of having the flu
17
Q
ribavirin
A
- nucleoside analog of guanosine
- oral, IV, and aerosol formulations
- approved for use against HCV and RSV
- but used for HSV, flu, SARS and many others
18
Q
ribavirin mechanism of action
A
- not well known
- helps TH1 repsonse
- lowers GTP pool
- stops RDRP
- mutagen of RNA
19
Q
treatments for hep c
A
- peg IFN and ribavirin
- not all genotypes respons
- difficult and complicated regimen
- flu like symptoms
- anemia
- neutropenia
- rashes
- hair loss
- thyroid dysfunction
- depression and fatigue
20
Q
sofosbuvir
A
- new drug
- nucleoside analog of uridine
- inhibits RDRP
21
Q
ledipasvir
A
- inhibits hep C protein
- complex
22
Q
treatments for HIV
A
- AZT
- nucleoside analog of thymidin
- nucleoside RT inhibitor
- entry inhibition, RT inhibition, protease inhibition
23
Q
classes of antiHIV drugs
A
- entry inhibitor
- nucleoside RT inhibitor
- nonnucleoside RT inhibitor
- integrase inhibitor
- protease inhibitor
24
Q
sttibild
A
- 4 drug combo-integrase, liver enzyme, 2 RT
- liver enzyme inhibits breakdown in liver
- boots potency
- allows for fewer pills or doses
- one pill daily
25
Q
final thoughts
A
- new drugs always needed
- infectious disease specilists are helpful
- translational research is hot
