Antivirals Pt. 2 Flashcards
Nucleoside Reverse Transcriptase Inhibitors for HIV
abacavir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir, zidovudine (adel sings to zebras)
Non-Nucleoside Reverse Transcriptase Inhibitors for HIV
efavirenz, etravirine, nevirapine, rilpivirine
Protease Inhibitors
atazanavir, darunavir, fosamprenavir, indinavir, nelfinavir, ritonavir, saquinavir, tipranavir (find star)
Fusion inhibitors
enfuvirtide
Entry inhibitors
maraviroc
Integrase Inhibitors
dolutegravir, elvitegravir, raltegravir (-gravir)
What percent of people do not know they are infected with AIDs?
15% –1.1 million are infected
What is the treatment for HIV (generally)?
combinations of drugs aimed at suppressing HIV replication and allowing for restoration of CD4 cells and immunocompetence, aka HAART highly active antiretroviral therapy
What are the six classes of drugs that treat HIV?
NRTIs, NNRTIs, protease inhibitors, fusion inhibitors, entry inhibitors, integrase inhibitors
What is the current recommendation for primary therapy of HIV?
2 NRTIs and either a protease inhibitor, NNRTI or integrase inhibitor
What do you need to avoid with drug combinations for HIV?
two agents of the same nucleoside analog, overlapping toxicities, impact of drug interactions etc
What is the MOA of NRTIs?
inhibit reverse transcriptase and incorporates into viral DNA resulting in DNA chain termination
What is true of NRTIs in relation to host cell and mitochondrial DNA?
affinity is much lower for host cell DNA reverse transcriptase but mitochondrial DNA is susceptible
How are NRTIs excreted?
renal excretion except abacavir!
What are the adverse effects of NRTIs?
decreased bone density, kidney disease, GI disturbance, fatty liver, abnormal distribution of body fat, anxiety/confusion/depression, lactic acidosis, pancreatitis
T/F there are many NRTI drug interactions
false (zidovudine and tenofovir have a few)
What resistance exists for NRTIs?
cross resistance between agents of the same analog class– do not combine them
How are NRTIs and ARMD related?
NRTIs block the activity of a biological inflammatory pathway
Which NRTI is associated with major hypersensitivity reactions?
abacavir 5%
Which NRTI has a long half-life (1x/day)
tenofovir
What was the first anti HIV NRTI?
zidovudine
What is the MOA of NNRTIs?
highly selective inhibitors of HIV-1 reverse transcriptase causing a conformational change to the enzyme
What are two advantages of NNRTIs?
do not require activation by cellular enzymes and do not have cross-resistance with NRTIs
What are disadvantages of NNRTIs?
there is cross resistance between NNRTIs, many drug interactions, high incidence of hypersensitivity reactions
What is the most effective NNRTI?
efavirenz, longest half life
Which NNRTI is associated with CNS side effects including vivid dreams?
efavirenz
Which NNRTI is reserved for advanced disease because of potential for severe liver toxicity?
nevirapine
What is the MOA of HIV protease inhibitors?
inhibit aspartyl protease stopping formation of essential enzymes and proteins in order to prevent maturation of the viral particles (results in production of noninfectious virions?
T/F treatment with a protease inhibitor and two NRTIs results in a decrease in viral load to undetectable levels in 60-95% of new patients
true
What is HIV treatment failure most likely due to?
lack of patient adherence
What is the pharmacokinetics of HIV protease inhibitors?
poor oral bioavailability, metabolized by CYP450, no dosage adjustments for patients with renal impairment, limited CNS penetration
What are adverse effects of HIV protease inhibitors?
paresthesias (tingling), GI disturbances, changes in glucose and lipid metabolism, fat redistribution
What are the glucose and lipid metabolism changes from HIV protease inhibitors?
diabetes, hypercholesterolemia, and hypertriglyceridemia
What is the main drug interaction dilemma with HIV protease inhibitors?
drugs that rely on metabolism for their termination of action may accumulate to toxic levels… do not use and caution lists of drugs
Which PI is used as an enhancer of other protease inhibitors?
ritonavir, increases bioavailability of second drug because CYP450 inhibitor
What are the adverse effects of ritonavir?
GI disturbance, headache, paresthesias
What is the MOA of maraviroc (entry inhibitor)?
blocks the binding of the viral membrane to the host cell by blocking host cell virus receptor
Why does the dose of an entry inhibitor (maraviroc) need to be reduced when given with protease inhibitors?
because of liver metabolism
What is the MOA of enfuvirtide (fusion inhibitor)?
binds viral transmembrane glycoprotein and prevents the conformational change that would allow viral entry into the cell
What drug is approved for therapy of patients who have already been treated and that have evidence of continued viral replication?
enfuvirtide (fusion inhibitor)
How is enfuvirtide administered?
must be given subcutaneously (peptide), adverse effects are related to the injection
What is the MOA of the integrase inhibitors?
inhibits the final step in integration of viral DNA into the host DNA
What are the pharmacokinetic considerations of raltegravir?
no CYP450 interactions because kidney metabolism, side effects: headache and GI disturbances
What drug works well in new patients AND in patients who have been treated previously?
raltegravir
What are the pharmacokinetic considerations of dolutegravir?
highly protein bound, extensive liver metabolism, once daily dosing (or twice daily if previous treatment with integrase inhibitors)
When is elvitegravir used?
only when in combination with tenofovir/emtricitabine/elvitegravir/cobicistat
What are the two new drug combinations approved as a single pill?
juluca and dovato
