Antiretroviral Drugs Flashcards
Common opportunistic pathogens in HIV
TB CMV Candidiasis Cryptococcal meningitis Toxoplasmosis Cryptosporidiosis Karposi’s sarcoma Lymphoma
The four main classes of HIV drugs
Reverse transcriptase inhibitors (Nucleoside and Non-nucleoside)
Protease Inhibitors
Fusion Inhibitors
Integrate Inhibitors
Combinations decrease viral load and produce remission in some patients.
Goals for HIV treatment
Maintain a low viral load and a CD4+ count >200
Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
Zidovudine (AZT) - the first to be developed First choice combo: Emtricitabine Tenofovir Alternative combo: Lamivudine Abacavir
MOA for NRTIs
Nucleoside analogue, requires phosphorylation x3 (by HOST, not virus)
Incorporated into DNA, inhibits viral reverse transcriptase
Zidovudine (Retrovir,AZT)
Thymidine analogue
Oral, short acting (5x/day)
Good CNS penetration - useful for AIDS dementia
SAFE in pregnancy - decreases risk of transmission
Zidovudine toxicity
Initial: CNS (HA, etc)
Lactic acidosis and hepatotoxicity (common for the class)
Myelosuppression (neutropenia, anemia)
• Use caution when BM compromised or combined with other myelosuppression game drugs
• Counteract with Epogen (RBC) or Neupogen (WBC)
First line combo for HIV
Tenofovir and Emtricitabine
NRTIs
Major side effect = Flatulence (extreme)
Lamivudine
Cytosine analogue NRTI
Also inhibits Hep B polymerase (good combo for HepB coinfection - or as a HepB monotherapy)
Very well tolerated, SAFE in pregnancy
Huge caution for Abacavir (a NRTI)
Must screen for HLA-B-5701 —> hypersensitivity!!!
If they have rxn, must discontinue. NEVER restart —> Fatal
General rule for NRTI side effects
Lactic acidosis and hepatotoxicity
MOA for Non-Nucleotide Reverse Transcriptase Inhibitors
Bind DIRECTLY to inhibit viral reverse transcriptase. Do not require phosphorylation for activity
GREAT in combo with NRTIs because inhibiting at different points.
First choice NNRTI
Efavirenz IF not pregnant! (Very teratogenic - category X)
Alt in pregnancy = Rilpivirine
Protease Inhibitors
DarunAVIR AtazanAVIR RitonAVIR SaquinAVIR LopinAVIR IndinAVIR TipranAVIR
(Don’t try to add “abacavir” to this group)
MOA for Protease Inhibitors
Bind to proteases (duh)
Common pharmacokinetics for protease inhibitors
Never use alone - always in combo with NRTIs
Metabolized by CYP3A4 - so can’t combine them with Inducers of of CYP3A4 like RIFAMPIN
• If treating for coinfection of TB, choose Isoniazid instead
Why to be cautious with St. John’s Wort
Increases metabolism of protease inhibitors
Common toxicities for Protease Inhibitors
Altered body fat distribution (buffalo hump, truncates obesity, and facial atrophy)
Insulin resistance —> hyperglycemia
Increases in serum cholesterol but DO NOT combine with statins!
Spontaneous bleeding in patients with hemophilia A or B
Why is Ritonavir special amongst the protease inhibitors?
INHIBITS CYP3A4 - don’t relay on it as a solo PI, but give as a BOOST to protect other PIs from CYP metabolism
DO NOT combine it with saquinavir - QT
Contains ethanol, so don’t give it with metronidazole or cephalosporins
DarunAVIR
DOC amongst the protease inhibitors
Can’t be given in patients with sulfa allergies b/c of sulfa moeity
Atazenavir
Second choice to Darunavir
Less body fat redistribution but problem of increased bilirubin
SaquinAVIR
Think QT - don’t give together with ritonavir
LopinAVIR
ONLY given together with ritonavir to increase bioavailability
IndinAVIR
Some cross resistance with ritonavir so beware
Big side effect = kidney stones and hyperbilirubinema (HYDRATE)
TipranAVIR
Newer PI - non peptide
Drug of last choice - saving it for those who are treatment resistant
Increased risk for intracranial hemorrhage when given with ritonavir
Also has a sulfa moiety
Liver toxicity
Fusion Inhibitors
Enfuvirtide (Fuzeon)
• Binds to gp41 to prevent conformation change required for membrane fusion
• For treatment resistant patients
Maraviroc
• Need to know tropism of patient receptor
The only Parenteral antiretroviral agent
Enfuvirtide (Fuzeon)
Antiretroviral that is only effective in patients with CCR5-tropic HIV infections
Maraviroc (because only inhibits that receptor - patients with CXCR4 receptors will not benefit)
Dolutegravir
Integrase Inhibitor - blocks integrase enzyme needed for replication
DOC in combo with NRTIs in treatment-resistant patients from whom other drugs no longer working
