Pharmacology- Regal/Trachte Flashcards
What viral envelope protein binds to CD4 on host T-cells?
gp120
What are the co-receptors found on T-cells that the HIV virus also needs to bind?
CXCR4 (later) or CCR5 (early)
What host transcription factor binds to LTR and acts as a promoter for the HIV viral genome?
NFkB!!!!! is a transcription factor that binds to long terminal repeats and acts as a promoter for viral genes
CD4+ count less than what is considered AIDS?
less than 200
What is the main cause of reduced T-cells in HIV?
Provirus (envelope proteins inserted in host membrane) can bind to non-infected cells to induce autophagy
What is the difference between a nuceloside reverse transcriptase inhibitor and a nucleoTide reverse transcriptase inhibitor?
The nucleoside inhibitors require phosphorylation by cellular enzymes to the triphosphate form to be active
Happens in cytosol where RT is
Zidovudine
nuscleoSide reverse transcriptase inhibitor
competitively inhibits RT and terminates DNA production
Lamivudine
nuscleoSide reverse transcriptase inhibitor
competitively inhibits RT and terminates DNA production
Emtricitabine
nuscleoSide reverse transcriptase inhibitor
competitively inhibits RT and terminates DNA production
Abacavir
nuscleoSide reverse transcriptase inhibitor
competitively inhibits RT and terminates DNA production
Tenofovir
nucleoTide reverse transcriptase inhibitor
*already phosphorylated!!
competitively inhibits RT and terminates DNA production
What are the major toxicities of NRTIs?
Mitochondrial toxicity= lactic acidosis
Hepatic steatosis = fatty liver
Fat redistribution
Hyperlipidemia
Efavirnez
Non-nucleoside RT inhibitor
Binds DIRECTLY to RT (at a site distinct from the NRTI)
- Does NOT require phosphorylation to be effective
- No cross resistance with NRTIs
Etravirine
Binds DIRECTLY to RT (at a site distinct from the NRTI)
- Does NOT require phosphorylation to be effective
- No cross resistance with NRTIs
Atazanavir
Protease inhibitor
-Inhibits the protease responsible for post-translational cleavage of the Gag-Pol polyprotein (cannot fold properly).
Ritonavir
Protease inhibitor
-Inhibits the protease responsible for post-translational cleavage of the Gag-Pol polyprotein (cannot fold properly).
Darunavir
Protease inhibitor
-Inhibits the protease responsible for post-translational cleavage of the Gag-Pol polyprotein (cannot fold properly).
Enfuviritde (T-20)
Fusion inhibitor
Binds to gp41 (transmembrane envelope glycoprotein) and prevents conformational change so fusion with host does not occur
Raltegravir
Integrase inhibitor
Binds to integrase, and inhibits strand transfer (the final step for provirus integration)
Maraviroc
CCR5 antagonist
Binds specifically and selectively to host CCR5 (one of the co-receptors used by HIV to gain entry into the host cell)
**note will not work against HIV that utilizes CXCR-4
Resistance if HIV switches chemokine receptors
Why would you add a low does of ritonavir to an HIV regimen?
- Ritonavir is a protease inhibitor that is poorly tolerated
- It is used at lower doses to increase the serum concentrations of other protease inhibitors and decrease the dosage frequency of other protease inhibitors
- POTENT INHIBITOR or CYP3A4 which is the cytochrome that metabolizes a number of other protease inhibitors and decreases their effectiveness
Rifampin
Specifically binds to and inhibits mycobacterial DNA-dependent RNA polymerase
Blocks RNA synthesis/ transcription
Most active mycobacterial agent available- bactericidial activity against dividing and non-dividing M. tuberculosis with sterilizing activity
Isoniazid
Blocks myobacterial reductase and inhibits mycolic acid synthesis (essential requirement for cell wall)
Prodrug that is activated my mycobacterial enzyme
Bactericidial
For latent and TB disease
Effects dividing cells
Pyrazinamide
Exact MOA unclear
Prodrug with metabolite active only in acidic environments
More active against slowly replicating organisms
Hepatoxicity
