最新心血管疾病中药材循证应用的最新进展-英文PPT课件.ppt

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1、心血管疾病中药材循证应用的心血管疾病中药材循证应用的最新进展最新进展-英文英文RMIT University10th SCICC,Guangzhou,China,2008 An Overview of Global Herbal Use All folk medicine includes the use of plant products.11,145 species of herbal plants worldwide;534 species of plants for Chinese Medicine.WHO definition botanical origin,without adu

2、lteration of any synthetic drugs.Legal status:food supplements(FDA&TGA)“DSHEA”;drugs/health foods(SFDA of China).US$25 billion;market value 1015%/per year.2 billion in Australia.40%Caucasian and 80%Asians use or used herbs.RMIT University10th SCICC,Guangzhou,China,2008 RMIT University10th SCICC,Guan

3、gzhou,China,2008 RMIT University10th SCICC,Guangzhou,China,2008 RMIT University10th SCICC,Guangzhou,China,2008 RMIT University10th SCICC,Guangzhou,China,2008 RMIT University10th SCICC,Guangzhou,China,2008 RMIT University10th SCICC,Guangzhou,China,2008 Dosage(mg/kg)PTTTfibAPTTRMIT University10th SCIC

4、C,Guangzhou,China,2008 Injection rate(mg/min)PTTTFibAPTTRMIT University10th SCICC,Guangzhou,China,2008 Integrated Conc.(g/ml)PTPTTTFibAPTTRMIT University10th SCICC,Guangzhou,China,2008 RMIT University10th SCICC,Guangzhou,China,2008 Herbal medicines as multi-component therapeutics It is possible to i

5、ntegrate PK and PD for herbal medicines.Challenges:multi-component therapeutics?Which marker compounds to measure?How to determine therapeutic window?RMIT University10th SCICC,Guangzhou,China,2008 Herb-Drug Interactions:Underestimated Patients:70%do not reveal their herbal use to their doctors/pharm

6、acists in Western countries Legal issue:rigorous preclinical and clinical assessments not required Difficulties in the studies;poor clinical studies Lack of ADR reporting systemRMIT University10th SCICC,Guangzhou,China,2008 Types of Clinical Reports on Herb-Drug InteractionsN=85RMIT University10th S

7、CICC,Guangzhou,China,2008 What Herbs Interact with Drugs?N=85RMIT University10th SCICC,Guangzhou,China,2008 What Drugs Interact with Herbs?N=85Drug Properties:narrow therapeutic index;extensive metabolism;substrates of CYPs and/or PgP.RMIT University10th SCICC,Guangzhou,China,2008 HerbInteracting dr

8、ugsDangguiWarfarinDanshen WarfarinGarlic Saquinavir,ritonavir,warfarin,chlorpropamide Ginkgo Trazodone,warfarin,digoxinGinsengAlcohol,phenelzine,warfarin HawthornDigoxin(no change)KavaAlcohol,alprazolam,bromazepam,L-dopaMilk thistleIndinavirPiperinePropranolol,rifampin,sparteine,theophylline,phenyto

9、inRMIT University10th SCICC,Guangzhou,China,2008 Toxicity due to Herb-Drug InteractionsHerb+DrugToxicitySJW+cyclosporine AOrgan rejectionSJW+oral contraceptivesBreakthrough bleeding&unplanned pregnanciesGarlic+chlorpropamideHypoglycemiaKava+alprazolamSemicomaKava+L-dopa“Off”periods in Parkinson dise

10、aseGinseng+phenelzineManiaGinkgo+trazodoneComaGinkgo+warfarin/aspirinBleedingDanshen+warfarinBleedingRMIT University10th SCICC,Guangzhou,China,2008 SJW-Drug Interactions Antidepressants:amitriptyline;SSRIs(sertraline Zoloft)Anticancer drug:irinotecan(CPT-11)Anticoagulants:warfarin(coumadin),phenproc

11、oumon Antihistamine:fexofenadine Anti-HIV agents:PI:indinavir;RTI:nevirapine Bronchodilator:theophylline Hypoglycemics:tolbutamide Cardiovascualr drugs:digoxin,simvastatin Opiates:methadone,loperamide Oral contraceptives Sedatives:alprazolam&midazolam Immunosuppressants:cyclosporine&tacrolimusRMIT U

12、niversity10th SCICC,Guangzhou,China,2008 RMIT University10th SCICC,Guangzhou,China,2008 Mechanisms for Herb-Drug InteractionsDrug ResponseMetabolizing enzymes(CYPs)Identical TargetsTransporters(PgP)Different TargetsPharmacokinetics(PK)Pharmacodynamics(PD)RMIT University10th SCICC,Guangzhou,China,200

13、8 Herb-CYP InteractionsHerbCYPs affectedSJWMost CYP(mainly CYP3A4)GarlicCYP2C,2D,2E,3APiperineCYP1A,2C,3ALicorice CYP1A,2A,2C,3AKavaCYP1A,2C,2D,3A Ginseng CYP3A4,2D,2CGinkgo CYP2B,3ABaizhiCYP1A,2D,2E,3ADangguiCYP1A,3ARMIT University10th SCICC,Guangzhou,China,2008 Herb-PgP InteractionsHerbModulation

14、of PgPCurcumininhibitionHawthorn?GarlicInhibitionGinsengMostly inhibitionGreen teaInhibitionMilk thistleInhibitionPiperineInhibition SJWInductionRosemaryInhibitionRMIT University10th SCICC,Guangzhou,China,2008 RMIT University10th SCICC,Guangzhou,China,2008 RMIT University10th SCICC,Guangzhou,China,2

15、008 Herbal Labeling What:identity,quantity of contents,identified active ingredient by common name or proprietary blend.How to use:route,dose daily,etc Who:name and place of manufacturer,packer or distributor.What to claim “This statement has not been evaluated by the Food and Drug Administration”.“

16、This product is not intended to diagnose,treat,cure,or prevent any diseases”.-“It is not advisable to use in combination with”RMIT University10th SCICC,Guangzhou,China,2008 AcknowledgmentsProf.Guangji WangProf.Xiyong YuProf.Charlie Xue and Chunguang LiProf.Eli ChanProf.Wen XieProf.Tony KoonProf.Jame

17、s W Paxton&Bruce BaguleyProf.John O MinersProf.Ronald G DickinsonProf.Min Huang&Anlong XuProf.Wei DuanProf.Xiaotian LeeProf.Ge LinProf.Qiang ZhangProf.Yi-Zhun Zhu National University of Singapore Academic Research Funds Singapore Cancer Syndicate RMIT University Grant for New Institute NICM grant of Australia Auckland Medical Research Foundation New Zealand Cancer Society Funds Maurice&Phyllis Paykel TrustHu Zeping Tian QuanZhang JingSun ZhumingSun FengZhang YaochungLinlin WangMeredith PayneLiping YangVivian ChanYuan Ming DiYanli ZhouPhD studentsDr Xiaoxia YangDr Gui JingangPostdoc fellows