Antivirals - HIV Flashcards
HIV attacks which human cells?
CD4, macrophages, microglial
goal of antiviral HIV therapy
reduce viral load
which 2 classes of HIV antivirals BLOCK VIRAL ENTRY INTO CELLS
- CCR5 antagonists
2. fusion inhibitors
which 3 classes of HIV antivirals INHIBIT ENZYMES REQUIRED FOR HIV REPLICATION
- reverse transcriptase inhibitors
- integrase inhibitors
- protease inhibitors
what are the 2 subclasses of reverse transcriptase inhibitors?
nucleoside + non-nucleoside
what is the receptor on CD4 cells that HIV virus likes to bind with for entry into cell?
CCR5
mechanism of action for CCR5 antagonists?
blocks CCR5 receptor from binding with gp 120 on HIV virion
which receptor on the CD4 cell is present much more often at the START of infection?
CCR5
main thing to know / test for before administering CCR5 antagonists for HIV treatment?
test client to determine if their HIV strain is CCR5 tropic
using this receptor ro gain entry into CD4 cell
what is the prototype for CCR5 antagonists?
maraviroc (SelzENTRY)
AE/risk of maraviroc
hepatotoxicity risk
mechanism of action for fusion inhibitors
blocks fusion of HIV cells with CD4 cell (drug binds to gp41 on HIV cell to prevent fusion)
prototype of fusion inhibitor
enFUvirtide (FUZEon)
when are fusion inhibitors used?
when there is resistance to other HIV antivirals
2 downsides to fusion inhibitors (r/t patient access)
- costly!!
- Subcut injections BID
=not an easy drug
most common AE of enFUvirtide (FUZEon) + how to avoid
injection site rxns (98%)
erythema, tenderness, pain, ecchymosis
prevention: rotate sites + avoid deep injections
mechanism of action for: nucleotide/nucleoside reverse transcriptase inhibitors (NRTI) aka NUKES
subs a dummy base pair –> inhibits creation of viral DNA
what class of drug is used mostly for initial regimen?
nukes (NRTIs)
what are the 2 prototype for NRTI/nukes
- zidovudine (AZT)
2. abacavir (Ziagen, ABC)
side effects of AZT (long term use)
anemia + neutropenia (affects bone marrow) = low H+H/low WBCs
re: pharmacogenomics, what do we need to look for with abacavir? if they have this, what are they at risk for if they take the drug?
test for genetic variant HLA-B*5701 –> @ risk for severe hypersensitivity rxn (anaphylaxis)
what is the mechanism of action for non-nukes/non-nucleotide reverse transcriptase inhibitors (NNRTIs)
a cog in a wheel - binds to center of enzyme and causes direct inhibition –> STOPS it!
AE of non-nukes
rash
hypersensitivity rxns
–> SJS (STOP if they have a severe rxn!!!)
a lot of drug-drug interactions
what is the prototype for non-nukes
efaVIRenz (Sustiva)
reVERse Nukes = VIR enZ
3 main points to know for effects of non-nukes
NO TO THE 3 B’s!!!!!! (BBB, babies, BC)
- crosses BBB (can be good OR bad thing)
- teratogenic
- can interfere with oral contraceptives - need new method
adverse effects of protease inhibitors (5)
- dyslipidemia
- hyperglycemia/DM (secondary)
- lipodystrophy (central obesity)
- increased liver enzymes
- decreased cardiac conduction
how can you recognize integrase inhibitors by their name?
“___tegr___”
are INTEGRASE inhibitors tolerated well? Y or N?
YES! well tolerated and rarely cause hypersensitivity reactions
what is the mechanism of action for integrase inhibitors?
prevents HIV genetic material from being INTEGRATED into DNA of CD4 cell
name one side effect of integrase inhibitors (patient teaching/prepare them)
weight gain
which type of HIV antiviral has recently risen to the top of the list for tx b/c they’re tolerated so well?
integrase inhibitors
what type of HIV antiviral is the most effective antiviral available and can reduce viral load to undetectable levels?
protease inhibitors
what is the mechanism of action of protease inhibitors?
prevents cutting of the HIV polyprotein, so it can’t be made into smaller virions
re: the adverse effects of protease inhibitors, what kind of condition can this cause in the body? and could lead to what type of problems?
metabolic syndrome –> cardiovascular problems
what is lipodystrophy r/t protease inhibitors?
redistribution of fat (back, trunk, face)
re: increased liver enzymes as an AE of protease inhibitors, what is your concern for the patient?
if they’re co-infected with hep B or C
re: decreased cardiac conduction as an AE of protease inhibitors, what other class of drug would you be concerned about the patient might be taking?
beta blockers
pharmacokinetic enhancers are also known as what?
boosters!!
ritonavir (Norvir) and Cobicistat (Tybost) are known as what? and act in what kind of fashion re: pharmacokinetics?
boosters ; synergistic = one drug increases the level of the other drug
what is the point of a booster?
to be able to use lower levels of HIV drugs and have better effects :)
mechanism of action for cobicistat (tybost)
blocks CYP450 3A4 enzyme
mneumonic for NNRTIs (non-nukes) to recognize them by their name
___vir___ = “THROW A WRENCH IN THE MIDDLE”
mneumonic for protease inhibitors
____navir = “NAVIR/NEVER tease a PRO”
mneumonic for CCR5 and fusion inhibitors
“Preventing the ROC and the TIDE from coming to together”
MaraviROC + EnfuvirTIDE
when does tx happen during L+D of positive pregnant person?
before delivery, during delivery, tx baby after delivery
if a pregnant person had a viral load >1000 copies, what would you expect re: delivery?
C/S @ 38 weeks
what is the pre-exposure prophylaxis drug for HIV?
Trevada
when is post-exposure prophylaxis tx most effective?
1-2 hours after exposure –> up to 72 hours
what is the best test to predict clinical outcomes and response to meds (HIV)
HIV viral load
you should see a dramatic change in HIV viral load within _______ (time frame) of starting medication
6 weeks
