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MedChem 310 HIV Drug
| Term | Definition |
|---|---|
| Maraviroc | small molecule; binds only CCR5 |
| Maraviroc | noncompetitive inhibitor and metabolized by CYP450 |
| Resistance of mech: Maraviroc | mutation of gp120 to allow binding to CCR5 even in presence of inhibitor; switch to CXCR4-tropism |
| Enfurvirtide | 36 amino acid peptide; NOT effective against HIV2; competitive inhibitor |
| Enfuvirtide | prevent gp41 folding and thus membrane fusion |
| Enfuviritide | administered twice daily subcutaneously and resistance can be due to mutation in gp41 so it's can't bind |
| Ibalizumab | human monoclonal antibody; blocks HIV binding to both co-receptors; noncompetitive inhibitor |
| Ibalizumab | PK: administered by IV for about 30 mins by healthcare provider; metabolized by CD+ receptor internalization + lysoszyme |
| NRTIs | Competitive inhibitors leading to chain termination when incorporated into viral DNA; prodrugs |
| NRTIs | used against HIV1 and 2 |
| Azidothymidine | thymine like nucleotide analog; N3 instead of OH |
| NtRTIs | competitive inhibitors that lead to chain termination when incorporated into viral DNA |
| NtRTIs | prodrug |
| Tenofovir | competes with normal dATP and through phosphorylation (twice) it gets converted to its 5'-triphosphate derivative and can act as a chain terminator |
| PK of NtRTIs and NRTIs | oral dosing and metabolism not via P450.; adverse effects include mitochondrial toxicity |
| NRTIs | causes lactic acidosis --> hepatomegaly with steatosis |
| NNRTIs | allosteric noncompetitive partial inhibitors (bind away from RT active sites); halt polymerization by causing a conformational change disrupting the catalytic site of the enzyme |
| NNRTIs | specific for HIV-1 RT |
| Nevirapine and Efavirenze | NNRTIs; can induce CYP3A4 family of phase 1 drug metabolizing enzymes thus increasing metabolism of many drugs including themselves |
| NNRTIs adverse effects | severe skin rash (e.g. stevens johnson syndrome) |
| Adverse effet of Efavirenze | gets into CNS --> dizziness, insomnia, nightmares |
| Integrase inhibitors | requires two Mg/Mn atoms; competitive inhibitor |
| Raltegravir | binds to HIV integrase and blocks strand transfer step preventing insertion of viral DNA into host DNA |
| Raltegravir | mainly metabolized by phase 2 enzymes |
| Elvitegravir | quickly metabolized by phase 1 CYP450 enzyme so co-dosed with cobicistat (potent CYP3A4 inhibitor) to boost it's levels |
| Protease inhibitors | competitive; designed as analogs of HIV-1 polyprotein substrate and replaced the cleavable Phe/Tyr-Pro amide bond with a non hydrolyzable hydroxyethylene, hydroxyethylamine, or phosphonate group |
| PK of protease inhibitors | metabolized by CYP3A4 (phase 1 enzyme) with many also being inhibitors of CYP3A4 |
| PK boosting of Protease inhibitors | use of low doses of CYP3A4 inhibitor to decrease PI metabolism |
| Adverse effects of protease inhibitors | hyperlipidemia, lipodystrophy, accumulation of fat in the base of the neck and loss of fat in face and legs and gain in abdomen and deck |
| Lencapivir | dose twice yearly and blocks virus assembly and release, production of capsid; peptidomimetic works at multiple steps in life cycle |
| PK of Lencapivir | low metabolism by phase 1 enzyme CYP3A4, subq slow release, max conc. reached in 84 days |
Created by:
rach6774