医学期刊的投稿的方法与技巧.ppt

Antiretroviral Pharmacology Amanda H. Corbett, PharmD, BCPS Clinical Assistant Professor UNC School of Pharmacy Oct 19, 2007 Antiretroviral Classes NRTIs (Nucleoside OR Nucleotide Reverse Transcriptase Inhibitors, aka “Nukes”) NNRTIs (Non-Nucleoside Reverse Transcriptase Inhibitors, aka “Non-Nukes”) PIs (Protease Inhibitors) Fusion Inhibitors Chemokine Receptor Antagonists Integrase Inhibitors Antiretroviral Drug Approval:1987 - 2007 NRTIsMechanism of Action Nucleoside analogs (like AZT below) Analog of thymidine, cytosine, adenine, or guanine Triphosphorylated inside lymphocytes to active compound Incorporate into the growing HIV viral DNA strand by reverse transcriptase Nucleotide analog Currently only tenofovir (TDF) Does NOT need to be tri-phosphorylated only di-phosphorylated to active compound After incorporation of the NRTI, viral DNA synthesis will be terminated. NRTI Class Toxicities Lactic Acidosis Damage to mitochondria in cells Elevated lactate, low pH/bicarbonate, N/V, shortness of breath, if untreated can lead to death Hepatomegaly with Steatosis Build up of fat droplets inside liver cells Enlarged liver NRTIs NRTIs NRTI Combinations Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs) These agents directly bind to reverse transcriptase to inhibit transcription NNRTIs do not require phosphorylation to be active NNRTIs Protease Inhibitors (PIs):Mechanism of Action Protease enzyme cleaves HIV precursor proteins (gag/pol polyproteins) into active proteins that are needed to assemble a new, mature HIV virus. PIs bind to protease preventing the cleavage and inhibiting the assembly of new HIV viruses Lipids, Insulin Resistance (Lypodystrophy) Hypercolesterolemia Usually hypertriglyceridemia, can have increased LDL and decreased HDL Treat with Fibric acid derivatives and certain HMGCoA reductase inhibitors Insulin Resistance Treat with diet/exercise, metformin, TZDs, insulin, sulfonylureas Lipodystrophy Illustratio