最新心血管疾病中药材循证应用的最新进展-英文PPT课件 29页

心血管疾病中药材循证应用的最新进展-英文 AnOverviewofGlobalHerbalUseAllfolkmedicineincludestheuseofplantproducts.11,145speciesofherbalplantsworldwide;534speciesofplantsforChineseMedicine.WHOdefinition–botanicalorigin,withoutadulterationofanysyntheticdrugs.Legalstatus:foodsupplements(FDA&TGA)–“DSHEA”;drugs/healthfoods(SFDAofChina).>US$25billion;marketvalue1015%/peryear.>2billioninAustralia.>40%Caucasianand>80%Asiansuseorusedherbs. Dosage(mg/kg)PTTTfibAPTT Injectionrate(mg/min)PTTTFibAPTT IntegratedConc.(µg/ml)PTPTTTFibAPTT Herbalmedicinesasmulti-componenttherapeuticsItispossibletointegratePKandPDforherbalmedicines.Challenges:multi-componenttherapeutics?Whichmarkercompoundstomeasure?Howtodeterminetherapeuticwindow? Herb-DrugInteractions:UnderestimatedPatients:>70%donotrevealtheirherbalusetotheirdoctors/pharmacistsinWesterncountriesLegalissue:rigorouspreclinicalandclinicalassessmentsnotrequiredDifficultiesinthestudies;poorclinicalstudiesLackofADRreportingsystem TypesofClinicalReportsonHerb-DrugInteractionsN=85 WhatHerbsInteractwithDrugs?N=85 WhatDrugsInteractwithHerbs?N=85DrugProperties:narrowtherapeuticindex;extensivemetabolism;substratesofCYPsand/orPgP. HerbInteractingdrugsDangguiWarfarinDanshenWarfarinGarlicSaquinavir,ritonavir,warfarin,chlorpropamideGinkgoTrazodone,warfarin,digoxinGinsengAlcohol,phenelzine,warfarinHawthornDigoxin(nochange)KavaAlcohol,alprazolam,bromazepam,L-dopaMilkthistleIndinavirPiperinePropranolol,rifampin,sparteine,theophylline,phenytoin ToxicityduetoHerb-DrugInteractionsHerb+DrugToxicitySJW+cyclosporineAOrganrejectionSJW+oralcontraceptivesBreakthroughbleeding&unplannedpregnanciesGarlic+chlorpropamideHypoglycemiaKava+alprazolamSemicomaKava+L-dopa“Off”periodsinParkinsondiseaseGinseng+phenelzineManiaGinkgo+trazodoneComaGinkgo+warfarin/aspirinBleedingDanshen+warfarinBleeding SJW-DrugInteractionsAntidepressants:amitriptyline;SSRIs(sertraline–Zoloft)Anticancerdrug:irinotecan(CPT-11)Anticoagulants:warfarin(coumadin),phenprocoumonAntihistamine:fexofenadineAnti-HIVagents:PI:indinavir;RTI:nevirapineBronchodilator:theophyllineHypoglycemics:tolbutamideCardiovascualrdrugs:digoxin,simvastatinOpiates:methadone,loperamideOralcontraceptivesSedatives:alprazolam&midazolamImmunosuppressants:cyclosporine&tacrolimus MechanismsforHerb-DrugInteractionsDrugResponseMetabolizingenzymes(CYPs)IdenticalTargetsTransporters(PgP)DifferentTargetsPharmacokinetics(PK)Pharmacodynamics(PD) Herb-CYPInteractionsHerbCYPsaffectedSJWMostCYP(mainlyCYP3A4)GarlicCYP2C,2D,2E,3APiperineCYP1A,2C,3ALicoriceCYP1A,2A,2C,3AKavaCYP1A,2C,2D,3AGinsengCYP3A4,2D,2CGinkgoCYP2B,3ABaizhiCYP1A,2D,2E,3ADangguiCYP1A,3A Herb-PgPInteractionsHerbModulationofPgPCurcumininhibitionHawthorn?GarlicInhibitionGinsengMostlyinhibitionGreenteaInhibitionMilkthistleInhibitionPiperineInhibitionSJWInductionRosemaryInhibition HerbalLabelingWhat:identity,quantityofcontents,identifiedactiveingredientbycommonnameorproprietaryblend.Howtouse:route,dosedaily,etcWho:nameandplaceofmanufacturer,packerordistributor.Whattoclaim“ThisstatementhasnotbeenevaluatedbytheFoodandDrugAdministration”.“Thisproductisnotintendedtodiagnose,treat,cure,orpreventanydiseases”.-“Itisnotadvisabletouseincombinationwith…” AcknowledgmentsProf.GuangjiWangProf.XiyongYuProf.CharlieXueandChunguangLiProf.EliChanProf.WenXieProf.TonyKoonProf.JamesWPaxton&BruceBaguleyProf.JohnOMinersProf.RonaldGDickinsonProf.MinHuang&AnlongXuProf.WeiDuanProf.XiaotianLeeProf.GeLinProf.QiangZhangProf.Yi-ZhunZhuNationalUniversityofSingaporeAcademicResearchFundsSingaporeCancerSyndicateRMITUniversityGrantforNewInstituteNICMgrantofAustraliaAucklandMedicalResearchFoundationNewZealandCancerSocietyFundsMaurice&PhyllisPaykelTrustHuZepingTianQuanZhangJingSunZhumingSunFengZhangYaochungLinlinWangMeredithPayneLipingYangVivianChanYuanMingDiYanliZhouPhDstudentsDrXiaoxiaYangDrGuiJingang……Postdocfellows