Antiretroviral Drugs Flashcards
What are the Nucleoside/tide Reverse Transcriptase Inhibitors (NRTIs) and MOA?
MOA: lack of 3’OH terminates DNA elongation, competitive inhibitors of RT with activity against HIV-2/1
- Abacavir
- Didanosine
- Emtricitabine
- Lamivudine
- Stavudine
- Tenofovir (only nucleotide)
- Zidovudine
Abacavir AE and DI
NRTI
AE: hypersensitivity reactions with fever, rash malaise, respiratory, and/or GI
DI: avoid alcohol
Didanosine AE, DI
NRTI
AE: pancreatitis, peripheral neuropathy, GI disturbances, insulin resistance, retinal changes, optic neuritis
DI: Tenofovir, avoid concurrent neuropathic drugs
Emtricitabine AE
NRTI
AE: well tolerated but can cause hyperpigmentation of the palms and soles (especially in dark skinned pts)
Lamivudine AE
NRTI
AE: well tolerated compared to other NRTIs
Stavudine AE, DI
NRTI
AE: hyperlipidemia, peripheral neuropathy, increased serum aminotransferase levels, diabetes, pancreatitis, fatal lactic acidosis
DI: avoid concurrent neuropathic drugs
Tenofovir AE, DI
NRTI
AE: generally well tolerated; renal toxicity, decreased bone density and osteomalacia can occur
DI: Tenofovir lowers serum concentrations of Atazanavir; combined use with didanosine has been associated with CD4+ decline
Zidovudine AE, DI
NRTI
AE: bone marrow suppression, nausea, vomiting, headache, fatigue, confusion, malaise, hepatitis, diabetes
DI: myelosuppression may increase with coadministration of Ganciclovir, interferon alpha, Ribavirin, and other bone marrow suppressive agents; Coadministration with Doxorubicin or Stavudine should be avoided
What are the Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs) and MOA?
MOA: highly selective, noncompetitive inhibitors of HIV-1 RT and do not require phosphorylation
- Efavirenz
- Nevirapine
- Rilpivirine
Efavirenz AE, DI
NNRTI
AE: difficulty concentrating, vivid dreams, nightmares, teratogenic in 1st trimester, rash diziness, HA, insomnia, reduction in vitamin D levels, and hyperlipidemia
DI: substrate of CYP3A4 and inducer of CYP3A4 and 2B6
Nevirapine AE, DI
NNRTI
AE: rash, fever, nausea, HA, severe, hepatotoxicity, hepative failure and death
DI: inducer of CYP3A4 and 2B6
Rilpivirine AE
NNRTI
AE: rash, insomnia, depression, increased liver enzymes
What are the Protease Inhibitors and MOA?
MOA: reversible inhibitors of HIV aspartyl protease (which cleaves viral polyprotein into RT, protease, integrase)
- Atazanavir
- Darunavir
- Indinavir
- Lopinavir
- Nelfinavir
Atazanavir AE, DI
PI
AE: benign hyperbilirubinemia, rash, PR interval prolongation, nephrolithiasis
DI: concurrent use of drugs that increase gastric pH, such as PPIs, H2 blockers, and antacids may decrease absoprtion of Atazanavir
Darunavir AE, DI
PI
AE: rash
DI: inhibits CYP3A4; avoid in pts with sulfur allergy
Indinavir AE, DI
PI
AE: asymptomatic elevation of indirect bilirubin, nephrolithiasis, cholelithiasis, rash, blurred vision
DI: inhibits CYP3A4
Lopinavir AE, DI
PI
AE: generally well tolereated, HA, asthenia, pancreatitis
DI: inhibits CYP3A4
Nelfinavir AE, DI
PI
AE: generally well tolerated, diarrhea, nausea, and flatulence are common
DI: metabolized by severeal CYP enzymes (3A4 and 2C19)
What are the Integrase Strand Transfer Inhibitors (INSTI) and MOA?
MOA: bind integrase causing inhibition of the final step in integration of viral DNA into host cell DNA
- Bicetegravir
- Dolutegravir
- Elevitegravir
- Raltegravir
Bicetegravir PK, AE, DI
INSTI
PK: UGT1A1 and CYP3A4 substrate
AE: diarrhea, nausea, HA
DI: some CYP interactions
Dolutegravir PK, AE, DI
INSTI
PK: UGT1A1 and CYP3A4 substrate
AE: diarrhea, headache, nausea
DI: some CYP interactions and contraindicated in pregnancy due to neural tube defects
Elvitegravir PK, AE, DI
INSTI
PK: primarily CYP3A4 so requies PK enchancing with Cobicistat
AE: diarrhea, nausea, headache
DI: CYP interaction likely
Raltegravir PK, AE, DI
INSTI
PK: primarily UGT1A1 substrate
AE: diarrhea, headache, nausea, and slight increase in creatine phosphokinases
DI: Rifampin, Tipranavir, and Efavirenz may decrease concentrations; PPIs may increase concentration
What is the Fusion Inhibitor MOA and AE?
Enfuvirtide
MOA: structurally similar to gp41 preventing ability of virion to fuse cell membrane
AE: injection related hypersensitivity reactions and eosinophilia rarely
Entry Inhibitor MOA and DI
Maraviroc
MOA: binds specifically and selectivity to CCR5 to block HIV entry
AE: well tolerated, risk of hepatotoxicity
What are the Pharmacokinetic Enhancers and MOA
MOA: potent inhibitors of CYP 3A4, increase plasma concentrations of ARV allowing less frequent dosing with better tolerability
- Ritonavir (protease inhibitor)
- Cobicistat (usually combined with INSTI Elvitegravir and combination with Darunavir and Atazanavir)
What are the 4 current preffered recommendations for Treatment-Naive pts?
- Bictegravir + Tenofovir + Emtricitabine
- Dolutegravir + Abacavir + Lamivudine (HLA-B*5701 negative)
- Dolutefravir + Tenofovir + Emtricitabine
- Raltegravir + Tenofovir + Emtricitiabine
What is the recommendations for infant borne to HIV infected mother?
- Nevirapine + Zidovudine
What is the HIV prophylaxis following a needle stick?
- Raltegravir + Tenofovir + Emtricitabine
- Dolutegravir + Tenofovir + Emtricitabine
