Antivirals Flashcards
what stage of herpes virus is suppressed by antivirals
lytic stage
antiviral treatments are indicated for what members of the herpesvirus family
VZV
HSV-1
HSV-2
CMV
Acyclovir MOA
requires initial phosphorylation by the viral thymidine kinase enzyme
competitive inhibitor of viral DNA polymerase
chain termination upon incorporation into the viral DNA
resistance to acyclovir
mutation of thymidine kinase gene
cross-resistance with other antivirals iwth similar mechanism
oral or IV administration of acyclovir:
- severe/disseminated mucocutaneous disease
- HSV encephalitis
- varicella zoster
- neonate infections
- VZV in immunocompromised
- genital herpes
Oral:
- genital herpes
- varicella zoster
IV:
- severe/disseminated mucocutaneous disease
- neonate infections
- HSV encephalitis
- VZV in immunocompromised patients
prodrug of acyclovir
acyclovir attached to a valine moiety. Metabolised into acyclovir in the liver and intestines
3-5x greater oral bioavailabiilty than acyclovir
Valacyclovir
therapeutic indications for valacyclovir
primary and recurrent genital herpes
varicella in older children and adults
zoster
oralabial herpes
how is foscarnet administered
IV
Analogue of pyrophosphate. Occupries site where pyrophosphate normally resides and blocks pyrophosphate release. Blocks catalytic cycle
**does not require prior phosphorylation by thymidine kinase in order to act
Foscarnet
therapeutic indications of foscarnet
HSV and VZV infections resistant to acyclovir
CMV retinitis, colitis, esophagitis
Ganciclovir requires initial phosphorylation by 1 (viral kinase enzyme). It is phosphorylated much more efficiently than acyclovir, therefore more active for 2 infections. It is also a competitive inhibitor of the viral 3. 4 termination upon incorporation into the viral DNA
- CMV UL97
- CMV
- DNA polymerase
- Chain
how is ganciclovir administered
IV
Oral
Intraocular routes
- poor bioavailability
therapeutic indications for ganciclovir
IV
- CMV retinitis (AIDs)
- CMV colitis, pneumitis, esophagitis (foscarnet does colitis, esophagitis, and retinitis)
Intraocular injection or implant
- CMV retinitis
IV followed by oral
- transplant pts.
how can you reduce the risk of CMV in transplant patients
IV followed by oral ganciclovir
prodrug of ganciclovir with higher bioavailability and serum levels approach IV ganciclovir
valganciclovir
therapeutic indications for valganciclovir
CMV retinitis (AIDs)
prevention of CMV in pts with heart, kidne, kidney-pancreas transplants
MOA of trifluridine
- phosphorylated by cellular enzymes
- competitive inhibitor of thymidine and incoorporation into newly synthesized genomes
therapuetic indication of trifluridine
- low selectivity, does not allow for systemic administration
- ocular administration to treat keratoconjunctivitis and recurrent epithelial keratitis due to HSV-1 and HSV-2
when must antivirals be administered to have any impact on influenza virus
first 48 hours
What influenzavirus antivirals inhibit neuraminidase
oseltamivir
zanamivir
peramivir
how is oseltamivir administered
oral - 80% bioavailability
therapeutic indications for oseltamivir:
for children 1 y/o. Effective for influenza 2. Given 3 for uncomplicated flu and can be given 4 for complicated influence. Can be used as 5 for influenza
- 1+
- A and B
- within first 48 hours
- chemoprophylaxis
how is zanamivir administered
administered to oropharynx and lungs by inhalation
how is therapeutic indication of zanamivir different from oseltamivir
same but approved for children 7+
how is peramivir administered
IV
therapeutic indications for peramivir
acute, uncomplicated and have not been symptomatic for more than 48 hours
what anti-influenza drugs inhibit the activity of influenza A M2 protein - ion channel forming protein required for nucleocapsid release
Amantadine
Rimantadine
*readily absorbed with high bioavailability
what is treatment of ribavirin indicated for
Respiratory syncytial virus (RSV)
indicated for severe LRT illness in:
- premature infants
- immunocompromised
- pts with lung or heart congenital heart disease
MOA of ribavirin
phosphorylated by cellular adenosine kinase
interferes with synthesis of guanasine triphosphate
inhibit viral mRNA capping
inhibits RdRp of RSV and HCV virus
how is ribavirin administered
- aerosol route for RSV
orally for combo therapy for HCV (w/ interferon+/-protease inhibitors)
contraindications for ribavirin
pregnancy
anemia
ischemic vascular disease
severe renal disease
general tx of HCV
combo therapy with direct acting antiviral - at least 2 from two different classes
oral
8-24 weeks
Tx depends on:
- HCV genotype
- +/- cirrhosis
- tx naiive vs experienced
- special populations
MOA of HCV “-previr” drugs
protease inhibitors
inhibit NS3/4A protease
MOA of HCV “-buvir” drugs
RNA polymerase inhibitor
inhibit NS5B enzyme
MOA of HCV “-asvir” drugs
NS5a inhibitors - plays role in genome replciation and virion assembly
In some patients with HCV, adding __1_ to the “previrs, buvirs, or asvirs” is indicated. This adds to the adverse effects and is contraindicated in 2
- ribavirin
2. pregnancy
HBV is a DNA virus that uses ____
reverse transcriptase
how would you treat HBV
pegylated interferon
reverse transcriptase inhibitiors
- entecavir
- tenofovir
