7. Anti-viral Agents Flashcards
Classes of anti-HIV drugs
- Nucleoside reverse transcriptase inhibitors (NRTI): abacavir, emtricitabine, lamivudine, tenfovir, zidovudine
- Non-nucleoside reverse transcriptase inhibitors (NNRTI): efavirenz
- Integrase inhibitor: dolutegravir, ratelgravir, elvitegravir
- Protease inhibitors: darunavir, lopinavir
a. Booster - Ritonavir
b. Booster - Cobicistat - Inhibition of HIV fusion with host cells: Enfurvitide
- Chemokine receptor antagonist (CCR5): Maraviroc
Antiretroviral regimen for treatment-naive patient
2 nucleoside reverse transcriptase inhibitors (NRTIs) + ARV drug from one of 3 drug classes:
a. an integrase strand transfer inhibitor (INSTI)
b. a protease inhibitor (PI) with a pharmacokinetic (PK) enhancer (booster) (cobicistat or ritonavir)
3. or a non-nucleoside reverse transcriptase inhibitor (NNRTI)
MOA of nucleoside reverse transcriptase inhibitors (NRTI)
- NRTIs are analogs of native ribosomes, lacking a 3’- OH group
- Upon cell entry → phosphorylated to the corresponding triphosphate analog → preferentially incorporated into the viral DNA by RT
- Because the 3’-OH group is not present → a 3’, 5’-phosphodiester bond between an incoming nucleoside triphosphate and the growing DNA chain cannot be formed → DNA chain elongation is terminated
Which 3 NRTIs have additional hepatitis B anti-viral activity
Emtricitabine, Tenofovir, Lamivudine
Which 3 NRTIs are category C drugs for pregnancy
Abacavir, Lamivudine, Zidovudine
Adverse effects of Emtricitabine
- Minimal toxicity
- Hyperpigmentation
- Severe acute exacerbation of hepatitis may occur in HBV-coinfected patients who discontinue emtricitabine
- Risk of lactic acidosis
Do not coadminister with lamivudine! Both are cytosine analogs
Adverse effects of Tenofovir
- Nephrotoxic
- Osteomalacia
- Severe acute exacerbation of hepatitis may occur in HBV-coninfected patients who discontinue Tenofovir
- Headache, diarrhoea, nausea, vomiting, and flatulence
Adverse effects of Abacavir
- Approved for use in adults and children > 3 months old
- GI disturbances
- Increased risk of CVD
- CNS related: headache and dizziness
- Fatal hypersensitivity syndrome
- Only use in HLA-B*5701 - negative individuals
Adverse effects of Zidovudine
- Myelosuppression → anemia and neutropenia
- CNS related → headaches, insomnia
- GIT disturbances
- Lactic acidosis
Adverse effects of Lamivudine
- Least toxic antiretroviral drug
- GIT related: abdominal discomfort
- Risk of lactic acidosis in combination
- CNS related: headache and nausea at higher doses
- Severe acute exacerbation of hepatitis may occur in HBV-coinfected patients who discontinue
- Approved for use in adults and children > 3 months old
MOA of integrase inhibitor
Binds and inhibits the catalytic site of the HIV integrase, which terminates integration of HIV DNA into host genome
Adverse effects of integrase inhibitors
- Weight gain
- Hypersensitivity reaction including rash
- Insomnia
- Depression headaches
What is cobicistat used for?
Pharmacokinetic enhancer that acts by inhibiting cytochrome P450 3A (CYP3A) that is used with Elvitegravir (EVG)
MOA of protease inhibitors
Bind to the site where protein cutting occurs, and prevent the enzyme from releasing the individual core proteins → new viral proteins are unable to mature or become infectious
What is ritonavir used for?
Pharmacokinetic enhancer (combined with another PI) to help maintain conc. of PI