Antiviral Drugs Flashcards
1
Q
Viruses treatable with drugs
A
- DNA- Herpesvirus (Acyclovirs), Hep B
- RNA- Influenza, Hep C (Ribavirin). HIV
2
Q
Types of antiviral treatment
A
- virucidal- detergents, cryotherapy
- immunomodulatory- alpha-interferon
- antiviral
3
Q
Types of antivirals
A
- Nucleoside analogs (“Nucs”)
- Non-nucleosides (“Non nucs”)
- Protease inhibitors
- entry inhibitors
- > 50 antiviral drugs are in use, more in the pipeline
4
Q
How do antiviral drugs work?
A
- target essential virus functions- entry, genome replication, assembly, release from cell
- target host cell defenses (intrinisic immunity)-interferon pathway
- activate immune response (closer to vaccines)
5
Q
Antiviral drugs and places of attack
A
- viral entry- (against HIV) enfuvirtide
- viral uncoating- (against influenza A)- Amantadine- Resistance
- Nucleic acid synthesis (against herpesviruses ad HIV)- nucleoside analogs, non-nucleoside polymerase inhibitors
- Assembly and release of viral particles (against HIV)- protease inhibitors, (against influenza)- neuraminidase inhibitors
6
Q
Nucleotide synthesis pathways
A
- many antivirals are nucleoside analogs that compete for the enzymes in the purine and pyrimidine synthesis pathways
- viral enzymes are also involved
- herpesvirus thymidine kinase is used to increase the pool of dTTP in infected cells
- acyclovir is a substrate of viral TK and takes place of thymidine
- acylcovir-triphosphate is incorporated into viral DNA in place of dTTP
7
Q
Important Issues about Antivirals
A
- Specificity- most drugs target functions of only one virus, broad spectrum drugs are rare
- Cytotoxicity- off target effects can harm cells, on target drugs directed at viral enzymes can be defeated by resistance mutations
- Duration of antiviral effects- 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
- resistance mutations often exist in patient before drug treatment
- drug treatment selects for resistant virus strains
- factors favoring the emergence of resistant variants- high rate of virus replication, high mutation rate (RNA» DNA), high selective drug pressure, immunosuppressed host that cannot clear virus infected cells
9
Q
How do we counter resistance to antivirals
A
- alleviate immunosuppression in the treated person- lower doses of anti-T cell drugs (steriods, cyclosporin, etc)
- combine drugs with different targets- standard of care for HIV and HCV infections, drugs with different mechanisms of action synergize, lower probability that multiple resistance mutantions will be present
- target host functions- infected cells may have unique profile that can be a drug target, virus mutations do not impact cellular genes, some cancer drugs target dividing cells and also inhibit viruses, beware of toxicity
10
Q
Treatments for HSV-1, HSV-2, and VZV
A
- who should be treated- acyclovir
- neonates infected with HSV at birth
- people with frequent recurrences (type 1 and 2)
- complicated HSV infections: encephalitis, dissemination throughout body, eye infections
- people with zoster (within 3 days of appearance of rash)
11
Q
Acyclovir
A
- nucleoside analog of guanosine
- effective against- HSV-1= HSV-2»_space; VZV
- trade name: Zovirax
- derivatives- Valaciclovir=Valtrex, Penciclovir=Denavir, Famciclovir=Famvir
- there is a viral thymidine kinase that phosphorylates, then there are host kinases, then there are viral DNA polymerase
12
Q
Ganciclovir for CMV
A
- ganciclovir is nucleoside analog for guanosine
- ganciclovir= cytovene, derivative: valganciclovir- Valcyte
- similar mechanism of action to acyclovir
- highly toxic- suppresses bone marrow mutagenic and teratogenic, severe side effects
- who should be treated?
- bone marrow and organ transplant patients
- immunosuppressed people with active CMV
- CMV retinitis
13
Q
Broad Spectrum Treatments for DNA viruses
A
- Foscarnet=Foscavir
- trisodium phosphonoformate
- inhibits viral DNA polymerase
- effective against all herpesviruses
- IV route only, toxic to kidneys
- Cidofovir=Vistide
- nucleoside analog of cytosine
- effective against DNA viruses: herpesvirus, adenovirus, papillomavirus, poxvirus, IV route only, toxic to kidneys
14
Q
Treatments for Hep B
A
- HBV is treated with drugs designed for HCV and HIV
- current drug options:
- pegylated interferon alpha= Pegasys
- entecavir= baraclude
- tenofovir disoproxil fumarate= Viread
- who should be treated?
- people with chronic active HBV disease
- people co-infected with HCV and/or HIV
- people who are progressing to cirrhosis, liver failure, or hepatocellular carcinoma
15
Q
Treatments for Influenza
A
- Zanamivir= Relenza, Oseltamivir= Tamiflu
- both are sialic acid analogs that inhibit viral neuraminidase (sialidase)
- virions remain attached to cell
- who should be treated?
- the severely ill (hospitalized)
- children younger than 2
- adults over 65
- pregnant women
- immunosuppressed people
- anyone suspected of having influenza
