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CCR5 antagonists drugs
maraviroc
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CCR5 antagonists MOA
Inhibits HIV entry into human cells by blocking HIV envelope glycoprotiens from interacting with chemokine co-receptors (specifically, CCR5 -- won't work if the HIV isn't using this mechanism but rather the CXCR4 or a combo of the two).
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CCR5 antagonists indication
not first line -- HIV-1 pts who have failed prior therapies and have CCR5 tropism.
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CCR5 antagonists interactions
metabolized by CYP3A4 (so decrease dose when given with an inhibitor)
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CCR5 antagonists SE
orthostatic hypotension. rare hepatotoxicity, cardiovascular events.
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fusion inhibitors drugs
enfuvirtide, PRO 140, ibalizumab
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fusion inhibitors MOA
competitively inhibits HIV by binding CD4 flycoprotein targets (specifically gp41).
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fusion inhibitors kinetics
IV (protein, so would be degraded if given PO)
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fusion inhibitors indications
not first line -- MDR HIV as part of combination therapy
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fusion inhibitors SE
peripheral neuropathy
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integrase inhibitors drugs
raltegravir
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integrase inhibitors MOA
prevent the virus from incorporating its DNA into the host genome by inhibiting integrase (the enzyme that binds viral DNA and joins it to host DNA).
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integrase inhibitors kinetics
metabolized by UGT1A1 (atazanavir is an inhibitor, rifampin is an inducer)
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single point mutations can knock out what classes?
integrase inhibitors, NNRTIs :(
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NRTIs MOA
Once incorporated to the cell, NRTIs are converted to nucleotides by host cell kinases. They then compete with endogenous nucleosides for incorporation into viral DNA (competitive inhibitors of reverse transcriptase).
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NRTIs kinetics
zidovudine only IV, all are PO. short elimination half life, but life in cells are much longer than that (so don't overdose based on serum levels).
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NRTIs indications
work for both HIV-1 and HIV-2
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NRTIs SE
Also inhibit host cell DNA polymerase, likely contributing to their toxic effects (specifically linked to mitochondrial toxicities). MYALGIA, HA, diarrhea. Acidosis, peripheral neuropathy, toxicities (Pancreatitis, Hepatotoxicity, bone marrow supression).
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NNRTIs drugs
efavirenz, nevirapine, 2G etravirine.
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NNRTIs MOA
bind to a site on the reverse transcriptase molecule, inducing a conformational change and reducing its activity (so also inhibits viral RNA -> DNA transformation)
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NNRTIs contraindications
pregnancy (efavirenz teratogenic)
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NNRTIs indications
works for only HIV-1 (not HIV-2)
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NNRTIs SE
rash, hepatits, transient CNS.
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protease inhibitors drugs
things that end in NAVIR.
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protease inhibitors MOA
Bind to viral proteases that typically cleave viral proteins during the maturation process. This results in the production of immature, noninfectious virus particles.
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protease inhibitors interactions
protease inhibitors are CYP inhibitors, so significant interaction potential (ritonavir most potent CYP inhibitor, therefore often combined with other 3A4 substrates to prolong their half-lifes).
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protease inhibitors SE
diarrhea, hyperlipidemia (less so with atazanavir).
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kaletra
lopinavir/ritonavir. (ritonavir has significant GI toxicity alone).
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best for pregnancy
nevirapine (NVP)
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best for HBV
tenofovir (TDF) and efavirenz (EFV)
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