Antiretroviral Agents MT2 Flashcards
this is a retrovirus of the lentivirus group; it uses host machinery to replicate, therefore it can’t survive outside the host cell for very long. Replication of this virus is constant in the host cell
human immunodeficiency virus (HIV)
is HIV a DNA or RNA virus
RNA
what cells do HIV target
CD4 lymphocytes
Abacavir, Emtricitabine, Lamivudine and Zidovudine all belong to this first-line class for HIV treatment
nucleoSIDE RT inhibitors (NRTI)
Tenofovir disoproxil fumarate and Tenofovir alafenamide belong to this first-line class for HIV treatment
nucleoTIDE RT inhibitors (NtRTI)
Doravirine, Efavirenz, Nevirapine, Etravirine and Rilpivirine all belong to this first-line class for HIV treatment
non-nucleoside RT inhibitors (nnRTI)
Bictegravir, Cabotegravir, Dolutegravir, Elvitegravir/cobi and Raltegravir all belong to this first-line class for HIV treatment
Integrase inhibitors (INSTI)
Atazanavir, Darunavir, Lopinavir/ritovanir and Ritovanir all belong to this first-line class for HIV treatment
Protease Inhibitors (PI)
Most PI’s and elvitegravir (INSTI) are used clinically in their “boosted” form; that is in combination with a CYP inhibitor (PK booster). this results in elevated drug concentrations of the PI or INSTI, which results in enhanced efficacy, reduced dosing frequency or both. which are the two PK boosters used?
Ritovanir and Cobistat (cobi)
does resistance occur within or between antiretroviral drug classes?
within not between
what are the two main drug interactions with antiretroviral agents
- antacids, H2 receptor antagonists and PPIs can reduce acidic environment needs for absorption of some ARVs (e.g. rilprivirine - nnRTI and atazanavir - PI)
- cytochrome P450 interactions are common, as well as interactions affecting other drug transport systems (e.g. P-glycoprotein, OAT and OCT systems)
true or false: ARVs may be inhibitors of CYP enzymes
false - may be substrates, inhibitors or inducers of CYP enzymes
Fostemasavir is in this second-line class for HIV treatment
attachments inhibitor (gp120 inhibitor)
Lenacapavir is in this second line class for HIV treatment
Capsid inhibitor
Maravrioc is in this second line class for HIV treatment
entry inhibitors (CCR5 co-receptor antagonist)
Enfuviritide is in this second line class for HIV treatment
Fusion inhibitors
what is the timeframe for the onset of CYP induction drug reactions?
enzymes are being produced thus days to weeks
what is the timeframe for the onset of CYP inhibition drug interactions
inactivating an enzyme that is already there thus a day or two
what is the mechanism of action of nucleoside/nucleotide RT inhibitors?
NRTI or NtRTI’s bind competitively to viral RT in place of natural nucleotide and act as chain terminators
NRTI or NtRTI?
these are synthetic nucleoside analogue prodrugs, therefore they must undergo triphosphorylation by intracellular enzymes to active form
NRTI
NRTI or NtRTI?
these are essentially a nucleotide monophosphate
NtRTI
Tenofovir disoproxil fumarate (TDF - old version) or Tenofovir alafenamide (TAF - new version)?
attachment of lipophilic groups allow passive drug diffusion across cell membranes - not stable in plasma and bloodstream, therefore most of TFV gets taken up into renal cells instead of CD4 target cells which can cause renal toxicity
TDF
Tenofovir disoproxil fumarate (TDF - old version) or Tenofovir alafenamide (TAF - new version)?
phosphonoamidate prodrug designed to be more stable in plasma vs other drug, therefore less plasma exposure to tenofovir, resulting in less uptake in renal tubular cells and less Renal and bone toxicity
TAF
these NRTI/NtRTI agents need dosing adjustment in renal impairment
- emtricitabine
- lamivudine
- tenofovir
- zidovudine
true or false: NRTI/NtRTI have no metabolism or effect on cytochrome P450 system
true
intracellular concentrations and half-life are of _________ (less/greater) clinical significance than plasma levels
greater