LectureFourPharmacologypharmacodynamicshistaminehypothalamuspermeabilitymembraneligandbioavailabilityendogenousacetylcholineendocytosisanyman-made,naturalorendogenoustheinteractionbetweenalivingorganismandchemicalsmoleculewhichexertsabiochemicalorphysiologicaleffectonthecell,tissue,organororganismhowalivingorganismaffectsthedrughowthedrugaffectstheorganismtherateandtheamountofadrugthatisabsorbedfromthegivendosageformandreachesthesystemiccirculationreleaseofdrugfrompharmaceuticalsimplediffusionsubstanceenteringthebloodcirculationthedispersionordisseminationofsubstancesthroughoutthefluidsandtissuestherecognitionbytheorganismthatformulationandpassthroughthemembranefacilitateddiffusionactivetransporttheroutethatadrugenterstheorganismitsbioavailabilityofthebodybiotransformationinactivationforeignsubstanceispresentinanirreversibletransformationofparentcompoundintodaughtermetabolitestheremovalofsubstancefromthebodysugarnucleicacidlockandkeyhydrophilicdeoxyribonucleicacidnicotinicsodiumgradientdepolarizationdimerizationautophosphorylationeffectortranscription

Vocabularyibuprofen[a?bju??pr??f?n]n.布洛芬snare[sne?(r)]vt.設(shè)陷阱捕獲neutralize[?nju?tr?la?z]vt.中和，使無效disintegrate[d?s??nt?ɡre?t]崩解metabolite[m??t?b??la?t]代謝產(chǎn)物detach[d??t?t?]脫離，離開label[?le?bl]標(biāo)簽sprained[spre?nd]扭傷的unscathed[?n?ske?ed]

毫發(fā)無損的TrueorFalse1.Painkillersknowwherethepainisinthebodyandgettothelocationtorelievethepain.2.Apainkillerworksbypromotingtheproductionofcompoundsthatcanhelptotransmitpainsignals.3.Generally,itisbelievedthatthehigherthedose,themoreeffectivethedrug.4.Mostdrugmoleculeswillbefilteredoutbythekidneysintheurinewithoutundergoinganychanges.5.Foranydrugtakenorally,theyundergobasicallythesameprocessinthebody.6.Thedosinginstructionsonmedicinelabelscanrepresenteverypatient.7.Therearevariationsinthebody’sefficiencyofprocessingmedicineindifferentpatients,andthustheneedforpersonalizedtherapy.

1.Whenyouswallowapainkillerlikeibuprofen,howdoesitgetintothebloodcirculation?Andwhathappenswhendrugmoleculespassthroughtheliver?---Ibuprofendisintegratesintheacidicfluid.---Thedissolvedibuprofentravelsinthesmallintestineandcrosstheintestinalwallintothenetworkofbloodvessels.---Thesebloodvesselsfeedintoavein,whichcarriesthebloodtotheliver.---Drugmoleculespassthroughtheliver.---Theycontinuethejourneyoutoftheliver,throughveins,intothebodycirculatorysystem.---Whenthebloodanddrugmoleculesinittravelthroughliverbloodvessels,enzymesattempttoreactwithdrugmoleculestoneutralizethem.Thedamagedibuprofenmoleculescalledmetabolitesmaynolongerbeeffectiveaspainkillers.2.Howdoesthebodyeliminateibuprofen?Thebodystrikesefficientlyeliminatingibuprofen,withtheblooddosedecreasingbyhalfevery2hoursonaverage.Ibuprofenmoleculesdetachfromtheirtargetsandcarriedbythesystemicbloodstream.Eachtimewhenthedrugpassesthroughliver,asmallfractionofitgetstransformedintometabolitesandthenfilteredoutbythekidneys.Ineachloopfromlivertobodytothekidneys,alittlemoreofdrugisneutralizedandfilteredout.3.Whyisithardforchildrentogettherightdosage?That’sbecausehowtheyprocessthemedicinechangesquicklyasdotheirbodies.Thelevelofliverenzymesthatneutralizemedicationshighlyfluctuatesduringinfancyandchildhood.1.Whatisthefirst-passmetabolism?Drugstakenorallymaybemetabolizedbytheliverbeforetheyreachthesystemiccirculation.2.What’sthefunctionofcytochromeP450enzymesintheprocessofdrugmetabolism?CytochromeP450enzymesmetabolizedrugsthroughavarietyofprocesses.Theseincludeoxidation,hydrolysisandhydroxylation----ItishydoxylatedinphaseImetabolism;----Inphase2metabolism,,alargeglucuronicacidgroupisattachedtothedrugthroughtheactionofUDP-glucuronosyltransferase.Theglucuronicacidgrouphasmanypolargroupsattachedtoit,namely,threehydroxylgroupsandacarboxylgroup.Thismakesthemoleculeextremelywater-solubleorhydrophilic.Thusthedrugcanbeeasilyfilteredandexcretedbythekidneys.3.Howdoesthedrugmoleculebecomemorewater-solublesoitcanbeeasilyexcretedbykidneys?oxidation,reduction,hydrolysisconjugationAprodrugneedstobemetabolizedbeforeithasanyeffect.So,thetherapeuticeffectofthedrugdependsonitsmetabolites.Thephase1metabolismofaspirininvolvescytochromeP450hydrolyzingtheaspirinmoleculeandtheresultantproductissalicylicacid.SalicylicacidcanthenbeacteduponbyUDP-glucuronosyltransferasetoattachglucuronicacidgroupinplaceofhydroxylgroup.Thentheproductcanbeeasilyexcretedbykidneys.4.Whatisaprodrug?5.Whatistheprocessofaspirinmetabolism?

Vocabularyrepurpose[?ri??p??p?s]重新調(diào)整用途cocktail[?k?kte?l]雞尾酒polypharmacology多重藥理學(xué)（aconceptwhereamoleculecaninteractwithtwoormoretargetssimultaneously）withdraw[w?e?dr??]撤回leprosy[?lepr?si]麻風(fēng)病1.Whataretheadvantagesofdrugrepurposingstrategyovertraditionalnewdrugdevelopment?----Traditionalnewdrugdevelopmenttakesoveradecadeandbillionsofdollarstobringasuccessfuldrugtothemarketplace；----Drugrepurposingcanbypassalargeportionofthetimeandcostassociatedwithtraditionaldrugdevelopmentandultimatelygeteffectivetreatmenttopatientsfaster.2.Whatisspecialofthedrugcocktaildevelopedbythespeaker’slab?Thedrugcocktailonlyconsistedofrepurposeddrugs,includingaspirin,ananti-inflammatorydrug,metformin,ananti-diabeticdrug,andtamiflu,anantivrialdrug.Aspirinwasaccidentallydiscoveredtobeabletoeffectivelyshutdownacriticalcancer-promotingpathway.3.Whataretheotherexamplesofdrugrepurposingintroducedbythespeaker?Sildenafil,originallydevelopedforthetreatmentofhypertension,wasrepurposedforthetreatmentoferectiledysfunctionandfurtherrepurposedforthetreatmentofarterialhypertension.Thedrugiscurrentlybeinginvestigatedforthetreatmentofcertaintypesofcancers.Thalidomide,originallydevelopedforthetreatmentofmorningsickness,wasrepurposedforthetreatmentofleprosyandfurtherrepurposedforth