HIV meds viro

Question 1

Emtricitabine (FTC)
Lamivudine (3TC)
Tenofovir disoproxil fumarate (TDF)
Tenofovir alafenamide (TAF)
Abacavir
Zidovudine (AZT)
Didanosine EC (DDI-EC)
Stavudine (d4T)
Emtricitabine/Tenofovir disoproxil fumarate (FTC/TDF)
Emtricitabine/Tenofovir alafenamide (FTC/TAF)
Lamivudine/Tenofovir disoproxil fumarate (3RC/TDF)
Lamivudine/ziduvudine (3TC/AZT)

Answer 1

NRTIs (-ine except abacavir and tenofovir)
all are prodrugs
MOA:
-Competitive irriversible inhibits Reverse transcriptase in step 3 of HIV-RNA virus –> so prevent the conversion of HIV-RNA to HIV-DNA. and also causes chain termination
-They are fake nukes incorporated in the DNA growing strand –> so causing chain termination

Drug class side effects: Lactic acidosis (pt has trouble breathing and has weakness) and hepatic stenosis

Drug specific side effects:
Abacavir:
-Hypersensitive rxn–> need to screen for HLA-B 5701 and if is (+) cannot give it
-increase risk of myocardiac infaction

Tenofovir TDF and TAF:
-Decrease bone mineral density -> TDF
-Renal impairment and fanconi syndrome –> TDF
-Weight loss–> TDF
-Weight gain –> TAF
-Increase lipids –> TAF

Hepatitis B activity only: Lamivudine, emtricitabine, TNF and TAF

DO NOT COMBINE: Lamivudine and emtricitabine, TNF and TAF

PK:
-Mostly renally metabolize
Need renal dose adj if CrCl <50 and is on TDF
-Abacavir –> hepatic metabolize by alcohol dehydrogenase –> so need to avoid ethanol, retinoids, isotretinoin (accutane)

DDI:
-Nephrotoxic agents: aminoglycosides, vanco, tenofovir products, antifungals, acyclovir IV, Foscarnet IV, Cidofovir IV
-TAF is a PGP subtrate so need to avoid PGP inducers because they will decrease concentration of TAF –> so avoid: rifampin, rifabutin, rifapente, phenytoin, phenobarbital, st.john worts, oxcarbazepine

Question 2

Rilpivirine (RPV)
Doravirine (DOR)
Efavirenz (EFV)
Etravirine (ETR)
Nevirapine/nevirapine XR (NVP)
Efavirinez/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF)
Rilpivirine/emtricitabine disoproxil fumarate (DOR/3TC/TDF)
Rilpivirine/lamivudine/disoproxil fumarate (DOR/3TC/TDF)
Rilpivirine/emtricitabine/tenofovir alafenamide (RPV/FTC/TAF)
Efavirinex/Lamivudine/tenofovir disoproxil fumarate (EFV/3TV/TDF)

Answer 2

NNRTIs (-virine except Efavirinex and Nevirapine)
MOA:
-Non competitive, reversible, allosteric binding –> inhibits Reverse transcriptase –> so prevents the HIV viral single stranded RNA to ssDNA

Class side effects: Skin rxn SJS, TEN. Liver toxicity

Drug specific side effects:
Doravine:
-N/Diarrhea, abdominal pain, HA, Dizzines, abnormal dreams

Rilpivine:
-Depression, insomnia, HA

Etravirine:
CNS effects: drowsiness, dizziness, sleepyness, insomnia, abnormal vivid dreams–> need bedtime dosing

PK:
-Long half life
-Substrate of 3A4 –> so need to avoid: rifampin, carbamazepine (tegretol), phenytoin (dilantin)
-Efavirenz is a substrate to 2B6 and can decrease levels of: rifampin, voriconazole, statins, methadone
-Rilpivine –> need food when take it because need acidic pH for absorption. –>need to avoid PPI, H2 antagonist and antacids

Question 3

Rategravir (RAL)
Dolutegravir (DTG)
Cabotegravir (CAB)
Bictegravir / emtricitabine/ Tenofovir alafenamide (BIC/FTC/TAF)
Cabotegravir/rilpivirine (CAB/RPV)
Dolutegravir/lamivudine/abacavir
Elvitegravir/cobicistat / emtricitabine / tenofovir alafenamide (EGV/COB/FTC/TAF)
Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EGV/COB/FTC/TDF)

Answer 3

INSTIs (integrase inhibitors) -tegravir

MOA:
-Will inhibit integrase enzyme so prevent the viral HIV DNA from incorporating its viral DNA into the host DNA

Characteristics:
-Elvitegravir/cobicistat –> need food when taking it
-All are UGT1A1 subtrates

-3A4 substrates (BED)- Bictegravir, elvitegravir, dolutegravir

-PGP - Rategravir

-Need to avoid Antaacids (CaCO3 tums, Mg(OH)2 milk of magnesia, Al(OH)3 amphogel, Ca2+, Mg2+ –> need to separate them when taking them

-Phenytoin, carbamazepine, Stjohn worts, phenobarbital –> will decrease the concentration of all of the INSTI

-Dolutegravir –> can increase the concentration of metformin –> so need to reduce the dose to 1000mg of metformin

-Elvitegravir/cobicistat–> cannot use in pregnant pt

Drug class AE:
-Insomnia
-Increase liver enzyme
-Increase creatine kinase
-Weight gain

Drug specific AE:
Dolutegravir: Neuropsychiatric, hypersensitive rxn
Raltegravir: SJS, Hypersensitive rxn, DRESS, TEN
Boosted elvitegravir/cobicistat : Renal impairment, nausea, diarrhea, decrease bone mineral density

Question 4

Ritonavir –> is a booster
Lopinavir/ritonavir
Darunavir
Atazanavir/cobicistat
Darunavir / cobicistat
Darunavir/cobicistat/ emtricitabine/TAF

Phenylalanine proline like

Answer 4

-navir
Protease inhibitors

MOA
-Inhibit the viral protease enzyme so prevent the cleavage of the large proteins so no release of mature HIV virus

Drug class characteristics
-Need to be taken with food
-Ritonavir and cobicistat are booster
-Darunavir always needs a booster
-They increase levels of:
Warfarin, apixaban, rivoroxaban
Midazolam, triazolam
PDE5 inhibitors–> vardenafil, sildenafil, tadalafil
Quetiapine (Seroquel)
-Avoid lovastastin, simvastatin
-Ergot derivatives
HepC antivirals Elbasvir.grazoprevir, RTV-based

Drug specific characteristics:
-Atazanavir –> need to avoid PPI and antaacids and H2RA

Ritonavir and cobicistat booster:
-they booster fluticasone, salmeterol and prednisone so need to avoid them

No renal dose adj needed

Drug class AE:
-Hypercholesterolemia
-Increase cardiovascular risk
-Increase blood glucose
-Liver toxicity
-Fat redesposition

Drug specific AE:
-Darunavir–> increase cardiovascular risk and skin rxn because has sulfunamide
-Atazanavir –> inhibit UGT1A1 so inhibit metabolism of bilirubin –> so increase levels of bilirubin get hyperbiluribinemia

DDI:
-Avoid oxcarbazepine, carbamazepine, phenytoin, phenobarbital, rifampin