时间药理学和时间治疗学

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1、时间药理学与临床合理用药CHRONOPHARMACOLOGYANDRATIONALMEDICATION2021/10/51时间药理学Chronopharmacology研究药物的体内过程和药物效应与机体生物周期的相互关系生物周期性(bioperiodicity)机体的功能状态随时间推移所呈现的规律性变化，包括近日节律(昼夜节律circadianrhythm)和近年节律(circannualrhythm)2021/10/52ThedistinguishontheeffectofdrugwhileusingindifferenttimeThesamedisease,samemedi

2、cine,samedose,takeindifferenttimeofaday,therearedifferenteffectandtoxicity.Thedegreeofthedifferencemaybetwofold,orevendecadestimes.2021/10/53Therevolvingcirclingmovementoftimewhichcanbecomparedtothecircadianrhythmsthatregulatethebehaviour,physiologyandfunctionoflivingorganismsatmanybiochemical

3、levels.Thedailypatternsofhormonereleaseresultindifferentbodytemperatures,pulseandbloodpressuredependingonthetimeoftheday.Thiscanbeappliedtotheunderstandingandtreatmentofdisease.2021/10/54Effectivetreatmentmustworkwiththebody’sclocksnotagainstthem.Theevidencesuggeststhetreatmentofdiseasecouldbe

4、improvedbygivingdrugsatcarefullyselectedtimesoftheday.Chronopharmacologyaimsatachievingoptimumdrugeffectandminimumadverseeffectwithoutalteringthefunctioningofthedruginthebody.Modernchronopharmacologyinvestigatesdrugeffectsasafunctionofbiologicaltiming.2021/10/55影响药物作用的时间因素Chronopharmacokinetic

5、sChronopharmacodynamicsE=F(,C,S)E：药效及毒性作用的强度：常数：药物的内在活性C：作用部位的药物浓度S：机体对药物的反应性2021/10/56Theeffectofbioperiodicityontheabsorptionofmedicine药物吸收与机体节律性的关系9时与21时口服氨茶碱的血药浓度比较，尽管AUC和t1/2相同，但9时的tmax短；Cmax高2021/10/57Theeffectofbioperiodicityonthedistributionofmedicine9时与21时口服地西泮的血药浓度比较：9时的Cmax高；tm

6、ax短禁食状态下给药仍然存在这种差异在静脉注射给药时，仍然表现出这种差异提示：这种变化与血浆蛋白含量的节律变化有关(地西泮的血浆蛋白结合率为99％)2021/10/58Theeffectofbioperiodicityonthemetabolismofmedicine肝脏酶的活性具有昼夜节律性肝脏酶活性低时，药物代谢慢，作用维持时间长肝脏酶活性高时，药物代谢快，作用维持时间短肾上腺皮质激素的昼夜节律性也会影响药物代谢(晨后高午后低)2021/10/59TheeffectofbioperiodicityontheexcretionofmedicineTherhythmoftheaci

7、dandbaseflowoftheurineThemostacidat2:00A.M.(pH5.0to6.8)Themostalkalineat2:00P.M.(pH7.0to8.5)Twotimesadaytheurineshouldbealkalinecorrespondsto10A.M.and2P.M.,thealkalinetideaftermeals.2021/10/510Theeffectofbioperiodicityonthepharmacodynam