Sheehy Flashcards
What kind of virus is HIV?
Retrovirus
SsRNA is reverse transcribed into DNA and inserted into the host cell genome
MOA of Maraviroc
Binds specifically and selectively to CCR5 to prevent viral entry into the host cell (entry inhibitor)
AE of Maraviroc
Generally well tolerated
Systemic allergic reaction followed by hepatoxicity
MOA of Enfuvirtide
Binds to gp41 preventing the conformational and structural changes needed to allow fusion of the viral envelope with the host cell membrane
(Fusion inhibitor)
How must enfuvirtide be administered?
SubQ
What drug class is included in treatment for all patients beginning antiretroviral therapy?
NRTIs (nucleoside/nucleotide reverse transcriptase inhibitors)
MOA of NRTIs
Competitive inhibition of HIV reverse transcriptase
Leads to premature chain termination due to inhibition of binding with the incoming nucleotide
What is the one nucleotide RTI?
Tenofovir
What are the 6 nucleoside reverse transcriptase inhibitors?
Abacavir, didanosine, lamivudine, emtricatibine, stavudine, zidovudine
What drug is also metabolized by alcohol dehydrogenase?
Abacavir
What analog is abacavir
Guanosine
AEs of abacavir
Skin rash in 50% (do not reintroduce abacavir if hypersensitivity is observed)
Constitutional sx, abdominal, and respiratory (dyspnea, pharyngitis, cough)
What analog is didanosine?
Deoxyadenosine
AEs of didanosine
Dose dependent pancreatitis
Retinal changes with optic neuritis
Increased risk of lactic acidosis and hepatic steatosis when combine with stavudine
What analog is lamivudine
Cytosine
[active against HIV and HBV]
Which two drugs select for the same point mutation in HIV reverse transcriptase?
Lamivudine and emtricitabine
What analog is emtricitabine
Fluorinated analog of lamivudine (which is a cytosine analog) with a long intracellular half-life allowing for once daily dosing
Also active against HIV and HBV
AEs of emtricitabine
Hyperpigmentation of the palms or soles (especially in AA’s)
What analog is stavudine
Thymidine
AEs of stavudine
Dose dependent peripheral sensory neuropathy
Dyslipidemia (more common with stavudine than other NRTIs)
Increased risk of lactic acidosis and hepatic steatosis when combined with didanosine
What analog is zidovudine
Deoxythymidine
AEs of zidovudine
Macrocytic anemia, neutropenia, GI intolerance, HA, insomnia
What was the first antiretroviral drug to be approved
Zidovudine
What analog is tenofovir
Acyclic nucleotide analog of adenosine
Active against both HIV and HBV
What 2 drugs enhance oral absorption of tenofovir
Disoproxil and alafenamide
AEs of tenofovir
Generally well tolerated
Flatulence
MOA of NN (non-nucleoside)RTIs
Binds directly to HIV reverse transcriptase in site distant from active site
Binding causes conformational change in enzyme and leads to reduced activity
(Noncompetitive inhibitors)
Why is monotherapy with NNRTIs not preferred?
Resistance can rapidly develop
How are NNRTIs metabolized
By CYP450, so lots of drug interactions
What are the 3 first generation NNRTIs
Delavirdine
Efavirenz
Nevirapine
What are the 2 second generation NNRTIs
Etravirine
Rilpivirine
AEs of delaviridine
Skin rash
Increased aminotransferase levels
How is delavirdine metabolized
Extensively by CYP3A & CYP2D6
What are the benefits of efavirenz
Can be given once daily due to increased half life
Typically given in a combo pill of tenofovir and emtricitabine for a once daily pill
What is efavirenz metabolized by
CYP3A4 & CYP2B6
AEs of efavirenz
CNS: dizziness, drowsiness, insomnia, NIGHTMARES, HA
Also skin rash
What drug is used to prevent transmission of HIV from mother to child
Nevirapine
What is nevirapine metabolized by
CYP3A
AEs of nevirapine
Rash which can be dose limiting
Liver toxicity
What drug was designed to overcome HIV resistance to first generation NNRTIs
Etravirine
Etravirine is an inducer and inhibitor of which enzymes
Inducer: CYP3A4
Inhibitor: CYP2C9 & CYP2C19
AEs of rilpivirine
Rash, DEPRESSION, headache, insomnia, increased serum aminotransferases
High doses associated with QT prolongation **
MOA of INSTIs
Integrase strand transfer inhibitors
Binds HIV integrase and inhibits the strand transfer and prevents ligation of reverse-transcribed HIV DNA into the chromosomes of the host cell
What are the most common AEs in INSTIs
HA and GI effects
What are the 3 INSTIs
Dolutegravir
Elvitegravir
Raltegravir
What are preferred drug combos for treatment naive patients
Tenofovir/emtricitabine/dolutegravir
Abacavir/lamivudine/dolutegravir
What is the only available form of elvitegravir
A combo pill of elvitegravir, cobicistat, emtricitabine, tenofovir
What is the half life for raltegravir
9 hours
What is the MOA of protease inhibitors
Block HIV protease and prevent maturation of the final structural proteins that make up the mature virion core
AEs of protease inhibitors
GI intolerance
Lipodystrophy (hyperglycemia, hyperlipidemia, lipoatrophy, fat deposition)
Redistribution and accumulation of body fat
What are protease inhibitors metabolized by
CYP3A4
Which drug has the most pronounced inhibitory effect on CYP3A4?
The least?
Most: Ritonavir
Least: Saquinavir
Which drug inhibits CYP3A4, CYP2C9, UGT1A1?
Atazanavir
What drug has to be co-administered with ritonavir or cobicistat
Darunavir
Which drugs can lead to a potential hypersensitivity reaction in someone who has a sulfa allergy?
Darunavir, fosamprenavir, tipranavir
AEs of indinavir
Unconjugated hyperbilirubinemia and nephrolithiasis
Which protease inhibitor is a very potent CYP450 inhibitor
Ritonavir
Which protease inhibitor is indicated in patients resistant to other protease inhibitors
Tipranavir
Which is normally combined with ritonavir
AEs of tipranavir
Abd sx
Urticarial or maculopapular rash
What combo of drugs make up a highly active antiretroviral therapy (HAART)
2 NRTIS +
1 protease inhibitor OR 1 NNRTI OR 1 INSTI
