HIV drugs Flashcards
Briefly describe the lifecycle of HIV
Attachment: gp120 binds to CD4/CCR5 or CXCR4
Fusion and release of capsid with viral components
Uncoating and reverse transcription of viral rna to dna
Integration of viral dna into host genome via integrase
Synthesis of new viral RNA and viral proteins
Assembly via protease (cleaves long polypeptide products to functional units)
Viral release and maturation
Describe the mechanisms of action of the following drug:
Enfuvirtide
Enfuvirtide: fusion inhibitor: works at the level of viral fusion with the host cell membrane following GP120 binding to CD4/CCR5
Which drug is a CCR5 anatgonist, thereby blocking HIV docking to the host cell membrane?
Maraviroc
CCR5 antagonist: maraviroc – inhibits docking of virus to cell by blocking CCR5
(maraviroc won’t let HIV dock)
What are the primary side effects of enfuvirtide?
Skin reaction at injection site (drug is an injectable)
What is an X4 HIV-1 virus and why doesn’t Maraviroc work against it?
X4 strain binds to CXCR4, instead of CCR5, which renders Maraviroc ineffective against such strains because Maraviroc is a CCR5 antagonist so it only works against R5 strains
Which class of drugs block the transcription of viral dna from viral rna?
Reverse transcriptase inhibitors
**
2 classes: Nucleoside Reverse Transcriptase Inhibitors (NRTIs) and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
What is the MOA of NRTIs?
NRTIs work by mimicking nucleotides (difference is they lack 3’ OH group needed to add nucleotides to the growing dna chain) and once incorporated into viral dna, the chain stops
Can compete w/ host dna synthesis which can lead to toxicity (specifically mitochondrial toxicity. Mtoc have their own polymerase DNA polymerase gamma which can be affected by these drugs)
Name the NRTIs
Zidovudine
Lamivudine
Abacavir
Tenofovir disproxyl fumarate
Emtricitabine
Tenofovir
What are the side effects of Zidovudine?
Main side effect: bone marrow suppression (macrocytic anemia)
**can also cause lactic acidosis, lipodystrophy, myopathy, pancreatitis, peripheral neuropathy**
Which HIV drug causes mtoc toxicity manifesting as lactic acidosis, pancreatitis and peripheral neuropathy?
Stavudine, Didanosine (also Zidovudine but there’s a separate card for that)
Which 2 NRTIs are the least toxic and can be used in combination with other drugs to have activity against Hep B?
Lamivudine/Emtricitabine
Tenofovir can be used in combination with __ as PrEP for HIV
What are the side effects of the original formulation of tenofovir?
What makes the new formulation better?
Tenofovir and Emtricitabine: combo used as PrEP (pre-exposure prophylaxis)
Tenofovir disproxyl fumarate (TDF): major side effects = kidney injury, bone mineral density loss, Fanconi syndrome
Tenofovir alafenamide (TAF) is a pro-drug so it gets cleaved and active in the cell cytoplasm so less of it accumulates in the serum
*note that because this is a strong enough drug, it can also be used as a single agent against Hep B*
Which NRTI is contraindicated in persons who are HLA-B*5701 positive?
What is the reaction that these patients have to this drug?
This drug is also associated with __ (which disease? hint: most common killer in the US next to cancer)
Abacavir
These folks can have for Abacavir Hypersensitivity syndrome - need to test folks before prescribing
(fever, constitutional symptoms, GI disturbances, rash, tachycardia, hypotension – can be fatal in rechallenge)
Associated with cardiovascular disease
**
Abacavir is just a really sensitive dude. He’s one of those 5701 types and even has heart problems
Describe the MOA of NNRTIs
Basically binds at a different site on reverse transcriptase, thereby blocking it from working
Name the NNRTIs used for HIV therapy (3)
**note there’s different ones you need to know for Step**
Efavirenz
Rilpivirine
Doravirine
(2 rine’s and an enz)
What is the MOA of Integrase Strand Transfer Inhibitors (INSTIs)?
Inhibit the Integrase enzyme which blocks viral dna from being incorporated into the host genome
