HIV pharmacology Flashcards
Classes of drugs used for HIV
- NRTI
- NNRTI
- PI
- INSTI
- viral fusion/entry inhibitors
MOA of NRTIs
host cell purine and pyrimidine kinase enzymes must convert them into nucleotide triphosphates inside of HIV infected CD4+ cells so then gets added to viral DNA which stops the reverse transcription
Black box warning for NRTIs
Why does this happen
possibility of lactic acidosis syndrome which is potentially fatal
similarities b/t HIV reverse transcriptase and host mitochondrial DNA polymerase gamma leading to deficient proteins needed for oxidative phosphorylation
Which 3 NRTIs cause the most damage to mitochondrial polymerase
- didanosine
- Stavudine
- Zidovudine
NRTIs that are LESS BAD for mitochondrial polymerases
- Tenofovir
- Lamivudine
- Emtricitabine
- Abacavir
Which NRTI also causes pancreatitis
Stavudine
NRTI treatment should be suspended in the setting of what?
- rapidly rising aminotransferase levels
- progressive hepatomegaly
- metabolic acidosis of unknown cause
Which NRTI starts out with a phosphate and is therefore a nucleoTide instead of nucleoSide and doesn’t rely on the virus to add a phosphate
Tenofovir
What is the complication that is a result of Tenofovir being a nucleoTide instead of a side
nephrotoxicity
In patients with renal insufficiency, what alternative NRTI is preferred over Tenofovir
Abacavir
How many NRTIs do you want to use at the same time
2
What is the distinct complication associated with Abacavir
idiosyncratic, multisystem inflammatory reaction
What genetics are associated with the hypersensitivity reaction that happens sometimes with Abacavir
HLA-B*5701
NRTI combos to AVOID
- Zidovudine and Stavudine
- Lamivudine and Emtricitabine
- Stavudine and didanosine
- Didanosine and Tenofovir
- any 3 drug combo
Preferred initial combo for naive HIV patient
Tenofovir and Emtricitabine
ALTERNATIVE combo for HIV . .
Abacavir/Lamivudine
Acceptable combo for HIV but also PREFERRED in pregnancy
Zidovudine/Lamivudine
First line preferred NNRTI
Efavirenz . . . avoid in pregnancy
What is the first line ALternative NNRTI that is also the acceptable NNRTI in pregnancy
Nevirapine
complication with Efavirenz
neurotoxicity . . siezures so think occupational (don’t want a pilot having siezures)
MOA of NNRTI
bind and distort Reverse transcriptase
How are protease inhibitors metabolized and what problem does this pose
hepatic
1st pass metabolism so poor bioavailability
explain the “boosting” that is induced by giving Ritonavir with other protease inhibitors
its a a good protease inhibitor AND a strong CYP3A inhibitor so in prolongs the half life of the other protease inhibitors
it is given at low doses so the CYP3A inhibition is it’s sole purpose
What PIs will you use with caution in someone with sulfonamide allergy
- Darunavir
- Fosamprenavir
- Tipranavir
long term adverse effects of PIs
- hyperlipidemia
- lipodystrophy/fat re-distribution (increase visceral fat)
- insulin resistance
preferred PI
- Atazanavir/ritonavir
- Darunavir/ritonavir
Preferred regimen for HIV+ pregnant woman
Zidovudine/Lamivudine +Lopinavir/ritonavir
What is the Integrase Strand Transfer Inhibitor (INSTI) used for HIV
Raltegravir
What is the HIV enveloped protein that binds to the host cell?
gp120
protein on HIV that when the virus binds to the host cell, helps it fuse and enter host cell
gp41
HIV enters what cells
CD4
What coreceptors on CD4 cells do HIV cells bind to via gp120
CCR5 or CXCR4
what drug blocks CCR5 receptor but does NOT block HIV cells that bind to CSCR4
Maraviroc
What drug binds to gp41 to prevent fusion of HIV with host cell
Enfuvirtide
