Antiretrovirals Flashcards
what are the six classes of antiretrovirals
- nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)
- non nucleoside/nucleotide reverse transcriptase inhibitors (NNRTIs)
- Protease Inhibitors (PIs)
- Fusion Inhibitors (FIs)
- CCR5 antagonists
- Integrase Strand Transfer Inhibitors (INSTIs)
what drugs are used to improve the pharmacokinetic profiles of some antiretrovirals
pharmacokinetic enhancers
-ex: PIs and the INSTIs, elvitegravir
what does a typical antiretroviral regimen consist of
- two NRTIs
- usually abacavir + lamivudine
- or tenofivir + emtricitabine
- with a third antiretroviral from the classes NNRTIs, INSTIs, or PIs
- with a pharmacokinetic enhancer
what are the NRTIs (nucleoside/nucleotide reverse transcriptase inhibitors)
TADELSZ
Tenofovir Abacavir Didanosine Emtricitabine Lamivudine Stavudine Zidovudine
mechanism of NRTIs
TADELSZ - tenofovir, abacavir, didanosine, emtricitabine, lamivudine, stavudine, zidovudine
- enters the cells and undergoes phosphorylation to generate synthetic substrates for the HIV RNA dependent DNA polymerase enzyme aka reverse transcriptase
- phosphorylated analogue competitively inhibits incorporation of native nucleotides and prevents elongation of nascent provirus because they lack a 3’ OH
- essentially prevents formation of provirus from HIV RNA
what are most of the adverse effects of NRTIs associated with (name them)
TADELSZ - tenofovir, abacavir, didanosine, emtricitabine, lamivudine, stavudine, zidovudine
-some NRTIs have an affinity for human DNA polymerase-gamma, a mitochondrial enzyme –> anemia, granulocytopenia, myopathy, peripheral neuropathy, lipatrophy, lactic acidosis, and pancreatitis
adverse effects of abacavir and what drug should be avoided
hypersensitivity rash with fever, rash, malaise, respiratory and or GI symptoms
avoid alcohol
adverse effects of didanosine and what drug should be avoided
PANCREATITIS (insulin disturbance)
Peripheral Neuropahty
Retinal Changes
avoid Tenofovir because it increases the concentration of didanosine –> more likely cause side effects
of all the NRTIs which are nucleoside and which are nucleotide
Tenofovir is a nucleotide while the rest are nucleosides and hence need to be phosphorylated to be active
adverse effect of emtricitabine
hyperpigmentation of palms and soles especially in darker skinned people
adverse of Staduvine and what drug to avoid
FATAL LACTIC ACIDOSIS
Peripheral Neuropathy
Diabetes
Pancreatitis
avoid concurrent neuropathic drugs
drug interactions of Tenofovir
- lowers serum conc of atazanavir
- increases conc of didanosine
- together with didanosine –> decreased CD4 T cells
adverse effects of Tenofovir
Renal Toxicity
Decreased bone density
Osteomalacia
adverse effects of Zidovudine and what drugs should be avoided
Myelosuppression (bone marrow suppression)
avoid co-administration with doxorubicin and stavudine; also avoid other myelosuppressive drugs
what are the NNRTIs (non nucleoside/nucleotide reverse transcriptase inhibitors)
REN
Rilpivirine
Efavirenz
Nevirapine
mechanism of NNRTIs (name them)
REN - Rilpivirine, Efavirenz, Nevirapine
they non-competitively bind to reverse transcriptase distant from the active site and cause conformational changes hence reducing its activity without the need for phosphorylation
adverse effect of Efavirenz
DVN’T (DON’T
Difficulty concentrating
Vivid Dreams
Nightmares
Teratogenic (avoid in 1st trimester)
adverse effects of Rilpivirine
Insomnia
Depression
adverse effects of Nevirapine
Severe Hepatotoxicity
Hepatic Failure
what are inducers of both CYP3A4 and CYP2B6
Nevirapine and Efavirenz
what are the protease inhibitors
NAVIR tease a Protease LIDAN
Lopinavir Indinavir Darunavir Atazanavir Nelfinavir
which protease inhibitor is not a substrate for CYP3A4
Nelfinavir
mechanism of protease inhibitors (name them)
NAVIR tease a protease LIDAN - lopinavir, indinavir, darunavir, atazanavir, nelfinavir
competitively inhibits virus aspartyl protease hence inhibiting proteolytic cleavage of HIV gag and pol that includes enzymatic and structural component of HIV
adverse effects of Lopinavir, Indinavir, and Darunavir
Lopinavir - Asthenia (lack of energy) and Pancreatitis
Indinavir - increased indirect bilirubin, nephrolithiasis, cholelithiasis, rash, blurred vision
Darunavir - Rash
