22. Anti-Viral Agents Flashcards
attachment > entry > mRNA > protein and genome synthesis > virion assembly > egress
viral life cycle
DNA virus encoding it’s own polymerase, lytic and latent stages, treatment goal is to speed time to healing and increase time between outbreaks, antiviral treatments only indicated for VZV, HSV-1. HSV-2, and CMV
herpesvirus
herpetic lesions/cold sores, genital herpes, neonatal herpes, disseminated herpes infections, herpes encephalitis, ocular herpes infections
herpes simplex virus 1 and 2
varicella, zoster/shingles
varicella zoster virus
pneumonitis, gastroenteritis, retinitis
cytomegalovirus
nucleoside analogue, needs to be phophorylated to be activated by viral thymidine kinase, competitive inhibitor of viral DNA polymerase, chain termination upon incorporation into the viral DNA, low bioavailability, resistance is developing by mutations of the thymidine kinase gene or cross resistance with other antivirals of a similar mechanism, given orally for genital herpes, varicella zoster, IV for severe or disseminated mucocutaneous disease, neonate infections, HSV encephalitis, VZV in immunocompromised patients, causes nausea, headache, diarrhea, crystalline nephrotoxicity and neurological effecst which increase with dehydration, caution with renal patients, keep hydrated
acyclovir
prodrug of acyclovir, is attached to valine moeity, metabolized to acyclovir, 3-5 greater oral bioavailability than acylcovir, used for primary and recurrent genital herpes, varicella in older children and adults, zoster, and orolabial herpes
valacyclovir
used in viruses resistant to acyclovir, phophonoformic acid, analogue of pyrophosphate, inhibits DNA polymerase where pyrophosphate normally resides and blocks release preventing catalytic cycle, doesn’t require prior phosphorylation by thymidine kinase in order to act, only given intravenously, rarely mutations in DNA pol cause resistance, used in HSV and VZV infections resistant to acyclcovir, CMV retinitis, CMV colitis, CMV esophagitis, can cause renal impairment, changes in Ca++, phosphate, K+, Mg++ levels, avoid concurrent administration of drugs with nephrotoxic potential
foscarnet
acyclic guanosine analogue, requires phosphorylation by viral kinase enzyme, phosphorylated by CMV UL97 much more efficiently vs acyclovir, competitive inhibitor of the viral DNA polymerase, chain termination upon incorporation into the viral DNA, poor oral bioavailability, approved for administration through IV, oral, or intraocularly, resistance by mutation of UL97 gene and cross resistance possible with anti-virals with the same mechanism, IV for CMV retinitis/colitis/pneumonitis/esophagitis, IV is followed by oral administration for reduce risk of CMV disease in transplant recipients, intraocular injection or implant is used in CMV retinitis, causes bone marrow and CNS toxicity, IV ganciclovir can cause phlebitis, anemia, rash, fever, liver enzyme abnormalities, nausea, vomiting, esophagitis
ganciclovir
prodrug of ganciclovir to increase bioavailability, metabolized to ganciclovir in liver and intestines, higher oral bioavailability than ganciclovir, serum levels approach IV ganciclovir, used in CMV rentinitis in AIDS patients, prevention of CMV disease in patients with heart, kidney, and kidney-pancreas transplants
valganciclovir
flourinated nucleoside, competitive inhibitor of thymidine for incorporation into newly synthesized genomes, competitive inhbitor of thymidine, cannot be given systemically since low selectivity, ocular adminstration to treat keratoconjunctivities and recurrent epithelial keratitis due to HSV-1 and HSV-2
trifluridine
segmented RNA genome, orthomyxovirus family, A/B/C serotypes, injectables, inactivated, inhaled, and attenuated formulations are powerful tools for combatting disease, high propensity for mutation and therefore acquiring resistance to antivirals, antivirals must be given within the 48 hours to have an impact on disease progression in otherwise healthy individuals, uncomplictated seasonal presentation with fever, mylagia, headache, shaking, chills, cough, fatigue, cough/fatigue/generalized weakness may last 2-6 weeks, increased risk of complications with the very young, elderly, pregnant women, and those in the postpartum period, and in patients with certain pre-existing medical conditions, most common complication is pneumonia
influenza
neuroaminidase inhibitors, endonuclease inhibitors, M2 inhibitors/adamantanes, if uncomplicated disease, give within the first 48 hours, do not give with attenuated influenza vaccine
influenza antivirals
sialic acid analogue, adminstered as a prodrug, metabolized to active compound by hepatic esterases, binds to active site of neuraminidase and inhibits spread of progeny virions through the respiratory tract, 80% bioavailability, some resistance due to point mutations in hemagglutinin or neuraminidase genes, resistance is common in seasonal H1N1 strains, however since 2009, most of the H1N1 circulating in the US is derived from the 2009 pandemic which is sensitive to this drug, approved for children 2 weeks and older, effective for influenza A and B viruses, given within the first 48 hours of symptoms for uncomplicated seasonal influenza, complicated illness can be given later than 48 hour window, chemoprophylaxis for influenza, can cause nausea, vomiting, abdominal pain, headache, fatigue, diarrhea, rarely rash or neuropsychiatric events
oseltamavir (tamiflu)
sialic acid analogue, same mechanism oseltamavir, administered to oropharynx and lungs by inhalation, rare resistance, apoproved for children of at least 7 years or older, can cause cough, bronchospasm which is occasionally severe, temporary decrease in pulmonary function, nasal and throat discomfort, contraindicated in patients with pre-existing pulmonary disease
zanamivir
neuraminidase inhibitor, adminstered IV, similar to oseltamvir, except approved for children 2 years and older, adverse effects are GI effects, rash, steven johnson syndrome, hyperglycemia, hypertension, delirium, hallucinations, psychosis (rarely associated with neuraminidase inhibitors)
peramivir
inhibits endonuclease of influenza viruses, inhibiting cap dependent endonuclease of influenza A and B viruses, adminstered orally with a single dose, approved for use in individuals 12 years of age and older, experiencing acute, uncomplicated influenza, given within the first 48 hours of symptoms, not many adverse effects different from placebo
baloxavir marboxil
symmetric tricyclic amines, inhibit influenza A M2 protein, ion channel forming protein required for nucleocapsid release, readily absorbed due to high bioavailability, amino acid substitutions in M2 confer resistance to both drugs, use is not recommended by the CDC
amandatine and rimantadine
