Antiretroviral

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Anonymous
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298783
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Antiretroviral
Updated:
2015-03-20 14:50:46
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Antiretroviral
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Antiretroviral
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Antiretroviral
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  1. Maraviroc
    Co-receptor block
  2. enfuvirtide
    Fusion inhibitor T20, binds to gp41 preventing the creation of an entry pore for the capsid of the virus, keeping it out of the cell.
  3. nrti
    Replaces 3’ OH
  4. nnrti
    block reverse transcriptase's enzymatic function and prevent completion of synthesis of the double-stranded viral DNA, thus preventing HIV from multiplying
  5. Nevirapine
    • – binds a pocket in the
    • “palm” of reverse transcriptase
    • preventing RT from properly
    • grasping the nucleic acids
  6. integrase inhibitor
    action of integrase, a viral enzyme that inserts the viral genome into the DNA of the host cell. Since integration is a vital step in retroviral replication, blocking it can halt further spread of the virus.
  7. Protease Inhibitors
    prevent virus maturation and thus infectivity
  8. * ritonavir probs
    A PI and a p450 inhibitor and may thus influence the function of other drugs.
  9. on the horizon drugs
    • virion release inhibitors
    • HIV nuclear import blockers?
  10. Nucleoside
    = Sugar + Base
  11. Nucleotide
    = Sugar + Base +Phosphate
  12. Tenofovir probs
    :nrti nephrotoxicity
  13. Abacavir probs
    :nrti hypersensitivity reaction, cardiovascular event concerns, HLAb5701 associated
  14. Lamivudine/emtricitabine probs
    :nrti quite safe
  15. Zidovudine probs
    nrti anemia
  16. Didanosine probs
    nrti: pancreatitis, peripheral neuropathy
  17. Stavudine probs
    :nrti peripheral neuropathy, muscle wasting, hyperglycemia
  18. NRTI side affects
    • General, but higher with DDI and D4T:
    • Lactic Acidosis – mitochondrial dysfunction due to DNA polymerase inhibition by drugs-FATAL in 50% of cases
    • Abrupt onset- nausea, vomiting, abdominal pain, shortness of breath, weakness, muscle pain, liver and or renal failure, seizures, cardiac arrhythmia
    • Insidious onset- fatigue and weight loss may predominate
  19. efavirenz-
    • nnrti CNS symptoms
    • -vivid dreams
    • -drowsiness
    • Rash
    • Increased LFTs
    • Teratogenic
  20. Nevirapine
    nnrti- rash, hepatitits, hep necrosis
  21. etravirine
    • nnrti- Rash
    • Increased LFTs
  22. Ritonavir
    • protease inhibitor- at low doses enhances blood levels of co-administered drugs
    • Mechanism-inhibit P4503A4 in the liver and gut
    • Inhibition of P-glycoprotein transport
    • Benefit:Reduce frequency of dosing, pill burden
    • Improve adherence/reduce adverse reactions
    • Improved ability to suppress strains of resistant virus
    • Improves regimen efficacy
  23. ritonavir p glycoprotein
    P-GLYCOPROTEIN TRANSPORT PUMP inhibition, increase intracellular drug concentration
  24. lotanavir consideration
    when used alone low conc and short half life, in combo with RTV- much much longer half life and higher blood conc
  25. protease inhibitor side effects
    • GI intolerances- NVD
    • Metabolic Toxicities
    • Dyslipidemia
    • Hyperglycemia
    • Lipodystrophy
  26. Enfurvitide, T20 (Fuzeon®)
    • fusion inhibitor Injectable peptide
    • SE Local injection site reaction (pain, erythema, induration, nodules, and cysts)
    • bacterial pneumonia
    • Hypersensitivity reaction (<1%)
  27. Miraviroc (Selzentry®)
    • fusion inhibitor Blocks most commonly used co-receptor ccr5
    • Need tropism assay on patient’s virus to determine whether the predominant virus uses CCR5 or CXCR4
    • SE: Serious but rare: hepatotoxicity
    • Common: cough, Fever, upper respiratory tract infections, rash, musculoskeletal symptoms, abdominal pain and dizziness
  28. integrase inhibitors
    • Inhibits viral enzyme Necessary for insertion of viral DNA into human genomic DNA
    • First approved medication: Raltegravir (Insentress®)
    • Elvitegravir and Dolutegravir now also available
    • Adverse effects: Common: nausea, headache, diarrhea, pyrexia, Myopathy and rhabdomyolysis have been reported
  29. How is the armamentarium applied?
  30. Antiretroviral therapy (ART) is recommended for all HIV-infected individuals to reduce the risk of disease progression.
    ART also is recommended for HIV-infected individuals for the prevention of transmission of HIV.
  31. HAART
    • highly active antiretroviral therapy
    • Combination therapy
    • At least 3 active agents
    • Utilization of multiple classes of agents
    • Why?- keeps resistance low
    • Typically 3 agents representative of 2 classes of drugs
  32. Combination Therapy (“Cocktail”)
    • Utilize at least 3 active agents together
    • Typically a PI or NNRT + at least 2 NRTIs (backbone)
    • PI (± ritonavir boosting) + 2 NRTIs
    • NNRTI + 2 NRTIs
    • Integrase Inhibitor + 2 NRTIs
  33. SB case
    • SB diagnosed with HIV through routine testing
    • CD4 count: 650 cells/mm3
    • viral load: 75,000 copies/mL
    • no symptomatic disease to date
    • What should be done for SB regarding antiretroviral therapy?

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