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CHEM 183 (143)
Lecture

Pain Relievers (Analgesics).pdf
Pain Relievers (Analgesics).pdf

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School
McGill University
Department
Chemistry
Course
CHEM 183
Professor
Joe Schwarcz
Semester
Fall

Description
December-15-12 8:59 PM PainRelievers(Analgesics): • Tylenol,aspirin,excedrin • $3billioninNorthAmericamarketforpainrelievers • Swallow50billiontablets/yearinNorthAmerica • Incontrastto prescriptiondrugs,thereisnocontroloverwhotakesit,howmuch, underwhatsupervision • 16th centuryifyouhad a headache,itwasthoughtyou haddemonsinyour head-->so "doctors"put patientsheadinovenstoallowdemonstodie • Bestknownpainrelievingmedicationintheworldisaspirin • Closeto58billiontablets/yearworldwide • 25000 scientificpaperswrittenaboutaspirin History: • Willowtree,poplar,beech,wintergreen,meadowsweet…=Salixfamily • Aspirinassociatedwithsalicylates • Willowtreehashistoryinfolkremediesinrelievingpain • Sumerians2200BCwouldapplywillowleavestojointpainanditwashelpful • MoreSumerianfolkremedies: • Baldness-fatofsnake,lionandhippopotamus • Nightblindness-oxliver • Cryingbabies-poppyjuice,excrementofflies • Woundinflammation-willowleaves • Hippocrates400BC saidthat chewingbarkofwillowtreewouldreducechildbirthpain • 1763 ReverendEdward Stone -noticedthat peoplewhohadagueandfeverfeltbetterwhengivenextractofwillowbark • TheDoctrineofSignatures • Willowtreesgrowinmarshyareas • 1829 Henri Leroux(Frenchphysicist)extractsalicinfromwillowbark • 1838 RafaellePiriatook salicintogetsalicylicacid • Salicylicacid- analgesic,antipyretic,anti-inflammatory • SAisbittertasting,stomachirritating • CompoundW-removeswartshasSA, washard on thestomach • FelixHoffman-hisfathersufferedfromarthritis,andtookSA,butcausedstomachirritation ○ August10, 1897 -Hoffmanfounda way tochange natureofSA to makeitlessharshon stomach • • HoffmantookSAandtreatedwithaceticacid • • MadeASA • AspirinisASA,becamepopular • CarlDuisberglaunchedaspirin • InitiallyASAsoldaspowder • Australiastillusespowder • AspirinintroducedinUSAthesametimeasheroin • Heroinintroducedasasubstituteformorphine--thoughtitwaslessaddictingthanmorphine • AfterWWIinU.S., Bayerlostpatentrightto ASA • Bayerlostpatentrighttothe nameAspirin • Soanycompanycan makeASAandcall itaspirin • InCanadaafterWWI, Bayerlost patentrightASA • Bayerkeptpatentrighttothe nameAspirin • InUS, Bayeralsolostpatentrightto the nameBayer,so an AmericancompanycalledthemselvesBayer • GermanBayernothappy, • AmericancompanythatboughtBayerin1918 for $5.3 million • GermanBayerboughtUS boughtBayer companyfor$1 billionin1994 • Aspiringoodforpain,fever,inflammation • Goodformuscularpain,bad forvisceralpain • Apparentlyextrovertedpeopleismoresusceptibletopainthanintrovertedpeople • Peoplewithblondehairaremoresusceptibletopain... • ASAassociatedwithprostaglandins(discoveredinprostatebyUlfVonEuler) • JohnVaneexplainedbyASAworkedinactingonprostaglandin • Damagedcellleadstoarachidonicacidwhichreleasesprostaglandinwhichsendspainsensationtonerves • ASAblocksconversionofarachidonicacidtoprostaglandinbyblockingcyclooxygenase ○ COX-inhibitor:transmitterofpain • Feveralsoassociatedwithprostaglandins • Inflammation-Prostaglandin,Bradykinin,Histamine • Rheumatoidarthritis-inflammation • Osteoarthritis-pain,butnoinflammation • Aspirinwillworkagainstpainassociatedwithinflammation • Acetaminophenworksforpain,butnotinflammation • Aspirinandpreventionofheartdisease • ASAinsmallamountbenefitforpeoplewhosufferfromheartdisease(bloodthinner) • IdeathatASAinsmalldoseishelpfulinpreventionofheartdiseasewasbasedonstudyin1989 ○ 22,000 malephysiciansfollowed ○ Age40-84years followedfor5years • ASAdoesnotofferthesameprotectioninwomenasitdoesinmenintermsof preventionofheartattacks • ThromboxaneA2(aprostaglandin)hasclottingeffect • IfyoublockproductionofTXA2,theclottingeffectwilldiminish,andbloodwillthin • OnlyneedalowdoseofASAtothinblood(30mg) • Presenceofacetylgro
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