Antiviral Agents Flashcards
Antiviral therapy for HIV patients
Recommended for ALL patients ragrdless of CD4 counts
General HIV therapy for tx naive patient
2 RT inhibitors with either ingrase inhibitor, non-nucleside RT inhibitor or protease inhibitor
Abacavir mechanism of action
Nucleoside RT inhibitor…specific to retroviruses because of RT
Incorporated into the viral DNA and terminate growing polypeptide
Human enzyme similar to RT
Telomerase
RTI selectivity
Higher affinity for RT than normal nucleotides and prefernetiall bind RT compared ot host DNA polymerases
Limitation of RTIs
Do not inhibit the virus from binding, only the replication inside of the cell
Kinetics/dynamis of abacavir
Phosphorylated by host adenosine kinase, then guanylate kinase, then multiple kinases…products can feedback and inhibit original host enzyme
Can be taken orally
Prodrug
Side effects of abacavir
Hypersensitivity (increased with HLA-B5701), nausea, headache, fatigue
HLA marker will bind to abacavir and present as foreign antigen
Other important nucleoside transcriptase inhibitor
lamivudine
Tenofovir mechanism
Nucleotide RTI inhibitor
Monophosphate that requires phosphorylation to work
Inhibit RT directly and incorporate into DNA
Phosphorylated by cellular kinases
Typical combination of nucleoside/nucleotide inhibitors
Abacavir/lamivudine
or tenofovir/emtrcitabine
NNRTIs
Bind to different site of RT than the nucleoside RTIs…lots of resistance
PI mechanism of action
Target protease that cleaves pol and gag proteins
Virions still produced but inactive
Typically used with RTIs
PI side effects
Hyperglycemia and abnormal fat distribtuion
Darunavir metabolism
CYP3A4 metabolilzed
Potent CYP450 inhibitor
Given with another CYP450 inhibitor in order (ritnoavir) in order to keep it around longer
Darunavir drug interactions
Statins, pain meds, antifungals , reflux meds, antibiotics
Statins in HIV patients
Probably a bad idea
Integrase inhibitor mech
Prevent integration of viral DNA
Elvitegravir mech and how used
Integrase inhibitor - binds metal ions essential for integrase…not only targeting infected cells
Used in genvoya with tenofovir and cobicistat (used as P450 inhibitor)
Elvitegravir side effects
Modest, but increase with combination
Combination regimen side effects
Abnormal fat, high LDL/low HDL and coronary artery dz
Patients with diabetes should avoid
Regimen with PIs
For patients at high risk of resistane
Can use genetic profiling to determine best drug
Enfuvirtide
Fusion inhibitor that interacts with Gp41 and blocks entry
Enfuvritide side effects and issues
Pain and hardening at injecton site…GI upset and weight loss
Expensive
____ elevated in patients who have long been on retroviral therapy
CXCR-4
Maraviroc use and mech
Inhibitor of CCR5…only used in R5-trophic patients
Maraviroc side effects
Liver, skin, and allergic…more than others because targeting host cell protein
Maravoric metab and kinetics
Taken as a pill with other HIV drugs
It is a P450 and P glycoprotein substrate and some other HIV drugs are P450 inhibitors
ganciclovir use
Preferred tx. for CMV in immunocompromised patients
Other drugs like ganciclovir
Acyclovir and valacyclovir
Acyclovir vs ganciclovir
Acyclovir HSV1/2>VSV>EBV, CMV
Ganciclovir is more active against CMV
Mech of acyclovir family
Inhibt viral DNA polymerase preferentially compared to host DNA polymerase…makes inactive enzyme complex
Also incorporated into viral DNA to cause chain termination
Resistance rates of herpesvirsues
Lower than HIV because the viral DNA polymerase has a exonuclease function so fewer mutations
Acyclovir kinetics
Phosphorylated first by viral, then by cellular…product feeds back onto itself
Means this is more specific because targeting infected cells more than healthy cells
Distributes throughout body except for CSF
Administration of acyclovir fam
Acy - IV and poor oral
Ganc - Poor oral
Val - better oral because of valine side group
Side effects of ganciclovir
Neutropenia (also caused by CMV), local irritation, CNS effects, and fever
HSV treatment
Acyclovir…no effect on latency
Must be taken systemically
If frequent recurrence, then take daily
Pregnancy and acyclovir family
Acy - safe after 36 weeks but little is known
Can give acyclovir to the child once born
How to tx cancer patient positive for HSvV
Prophylactically with acyclovir
What is used in cases of acyclovir infection
Foscarnet
Hep B first tx
Lamivudine…tenofovir is alternative
Hep B weird sturctutre
Hep B produces RNA which is RT’d into single stranded DNA and then partially dsDNA by HBV polymerase
DNA virus that uses RNA intermediate and RT
Resistant hep B
Mutations in HBV polymerase
use tenofovir
Measure efficacy with ALT
EBV tx
Normally none
VZV tx
Can be treated with acyclovir
RNA virus challenge
Use RNA replicase that is very mutagenic
Influenza tx that is not recommended
Amantidine inhibits viral ion channel M2
Better prophylactically
Causes neuro side effects
Better influenza txs and side effects
Oseltamavir and zanamivir
Neuraminidase inhibitors that prevent detachment
Should be used within 2 days of symptoms…used more for prophylaxis
Nausea, vomiting, mood changes
Hep C tx 1
Ribavirin
Tx 2 for Hep C
Pegylated IFN
Tx 3 for Hep C and mechs
Sofosbuvir and ledipasvir
Sofosbuvir is inhibitor of the RNA dependent RNA polymerase of the virus…does NOT inhibit host DNA or RNA polymerases
Ledipasvir - inhibits a large phosphoprotein required for replication…may genotype to use this
Side effects of sofosbuvir
Fatigue and headaches
Hep C tx 4 and mech and side effects
Paritaprevir inhibits viral protease and arrests course of infection
Does NOT cure
Side effects include sleep loss, rash, and itching
Part of Viekra pak
