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Lecture

chem 183 pain - anesthetics

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Department
Chemistry
Course
CHEM 183
Professor
Joe Schwarcz
Semester
Fall

Description
Lecture4 October-02-12 12:49 PM PAIN - ANESTHETICS Objectives: 1. Remarksaboutpain 2. Reliefofpain-anesthetics 3. Painresearch • Asmallnumberofpeopledonotexperiencepain-itiscalledcongenitalanalgesia • Theyoftencanfeeltouchbutnotalwaystemperature • Currentthinking:1/5personssufferfromchronicpain • 1/4persons>65 yearsinthat category • Nodevicetomeasurepain • Painiswhatthepersonsaysit is • Acutepain -resultsfromdisease,inflammationorinjury-confinedbytime • Chronicpain- persistsallthetime-representingthediseaseitself • Themore thepain - thelongerit takes to recover • "thinkofpainasa diseaseitself" • Thespinalcord"rewires"itselfwhenthereispain-paincanbecome"permanent" • Manyhospitalshavea10 pointpainscale • Maximizepainrelief ○ Goesback150 years,"Lebenswecker" ○ Painisredirectedsomewhereelse • Classicdrugforpain- MORPHINE ○ NamedafterMorpheus(GreekGod) ○ Opium(anarcotic)comesfrompoppies • ThomasDeQuinceywroteConfessionsofan Opium Eater • Goback 2000 years,mostculturesusedopium • Goback 2000 years,mostculturesusedopium • "Surgical"methodshoweverprevailedforpainreliefwheremorphinewasn'tavailable • Inmedievalagesthoughtheadwasfilledwith"evilspirits"sotheycarvedopenthehead(trepanation)torelievethepain • Allkindsof"operations"werecarriedout…. • Orthopedicsurgeonsweremanyyearsallmale • Now5-10% arefemale ○ Tookmanyyears • Anestheticswerebadlyneeded • Firstanesthetic-ether • Threepeoplemayhavefirstusedit: ○ RaymundusLullius(Spain1275) ○ ValeriusCordus(Germany1540) ○ Paracelsus  Wroteinhisowncode ○ Sweetvitriol ○ PossiblyH2SO4 • Ether • JosephPriestley(1772) ○ Workedwithoxygen ○ DiscoveredN2O • Ammoniumnitrite-crystallinesolid ○ Usedas fertilizer ○ Explosive Explosive • SirHumphrey Davy (early 1800s) ○ FoundthatN2O couldputsomeoneasleep ○ Laughinggas ○ Had"frolic"parties(gettinghighoffN2O) • Operationswereterribleforpatientspriortoanesthetics • Dr. Crawford WilliamsonLong(1842) ○ Wroteaboutuseofether ○ 2tumoursremoved ○ However,hedidn'tpublichisresultsuntil1848 • HoraceWells(1844) usedN2Oto do toothoperations • Bylate1800s N2Owas regularlyusedfordentalprocedures • WilliamT.F.Morton(1846) usedether ○ HecalleditLetheon  Lethewasa riverinHell  Ifdrunk,onewouldforgetallandspendeternityrememberingnothingoflife ○ Simplytakeaclothandsoak itin etherandput itover someone'smouthtoputsomeoneout • JohnCollinsWarren(1846) ○ Wellknownsurgeon ○ Approachedtotryout ether ○ Firsttimehetriedit,hedidn'tgivepatientenoughetherandpatientgotupfromsurgery(duringfirstknifeopening)andran outoftheroom • 2main operationsof thisera(1800s) 1. Amputation 2. Surfacetumours • Thepainproblemwas"GodsWill" • Edward GilbertAbbott(1846) ○ Patient'stumourwasremoved • Etherdome(BostonHospital) • Peopleusedtodosurgeriesintheirbesteveningclothes,didn'tevenweargloves • RobertHoudin ○ McGillstudentwhokilledHoudini  Punchedhimtwiceinthestomach,appendixruptured • JamesSimpson(1847) ○ Discoveredchloroform  Mildlycarcinogenic  Doesnotgivehigh  Effectiveanesthetic  Putsyouto sleep • ChildbirthIssue-1854QueenVictoriawasanesthetizedwith8thchild • NotdonebeforebecauseclergyinUKsaysbiblesayswomenshouldsufferduringchildbirth • Nowthoughtnottobe as muchof a controversy • Genesis2:21says it'sokay touse anestheticssoclergyhadtoback off • Dr.JohnSnowaidedtheQueeninherchildbirth • Dr.Snowdiedat 45, diedofstroke • 1852 McGill'scharter • Dr. Crawford Long has bestcreditofengagementofusinganesthetics • Potassiumbromide ○ K+Br- similartoNa+Cl- • "Topicka bromide" ○ There'sabromideforanysituation-there'sa solution • Dr. Harold Randall Griffith ○ Introducedmusclerelaxants ○ Usedcurare(Intocostrin)torelaxheart ○ "BeforeandafterGriffiths" ○ CurarecomesfromplantinSouthAmerica ○ UsedbynativesinSAto takedownlargegame • Anesthesiologyisasophisticatedscience ○ About12yearsof schooling-university,thenmedicineschoolandresidency • Someanestheticsareflammable Pre-anestheticMedication • Blocksecretions(Atropine) • Narcotics(Demerol) • Sedatives(Valium,Barbituries) IntravenousAnesthetics • Thiopentalsodium • Fentanyl • Botharesynthetic • Fentanyl:Chechenrebelstookoveratheatreof850 peopleandthestand-offendedwithfentanylbeingputintheventilation system. About170peoplediedincluding39oftherebels • Halflife:in2hours,halfofthat morphineisgone,andin2 moreanotherhalfofthat halfis gone • Fentanylis100xas potentas morphine • Gaseousanestheticsnotusedsomuch(i.e.N2O) • Gaseousanesthetics-veryeffectiveanesthetics • Propofolrelatedtothymol(listerineantiseptic) ○ Thymolisplantextract ○ ○ Roddickusedphenol ○ Notnaturallyoccurring ○ Anestheticofsomepotency ○ Giventoomuchto MichaelJackson,andkilledhim ○ Propofolismilky,lookswhite,liquid ○ Called"MilkofAmnesia" • Changesinchemicalstructurescanchangephysicalcharacteristicsdramatically • BHT-to maintainfreshness(preventingdecomposition) MechanismofAction • Theexactmechanismofanesthesiaispoorlyunderstoodbutitseemsthatthenervecellsabsorbtheagentandinsodoingtheir abilitytoconductimpulsestoeachotherisreduced • Generalanesthesiaisdefinedbyreversibleunconsciousnessandlackofresponsetonoxiousstimuliinducedbychemicalagents • Mechanismsunderlyingtheanestheticeffectarenot known clearly • Themostprevalentbeliefisthatanestheticdrugsacton thelipidcellmembranes,basedonthecorrelationbetweenoilsolubility andanestheticpotency andanestheticpotency • Recently,ithasbeenproposedthatanestheticagentsactonspecificproteinsofthecellularmembraneofneurons • Anesthesiacouldresultfromcombinedeffectonspecificproteinsactingonneuralcellexcitabilityaswellastransmissionand propagationofnerveimpulses • Twofeaturesofthismolecule: ○ Fatend ○ Polarend • Aftersurgeryandingeneralforpain-MORPHINE ○ Commonlyused ○ Drugof choiceformostpeople ○ Cantakemorphinedrip • Poppyisfilledwithopium ○ Extractedstraightout • LegalinIndia • Crudeopiumis~10% morphine • Morphineextractedandpurified • Morphineabout1%codeine(usedforheadaches) • Morphinesellsfor$400+ • AddictiontreatmentinMyanmarisharsh(ifaddictedtomorphineoropium) ○ Forcedtovomitinpublic ○ Humiliationwillengagethemtonottakeanymoredrugs HeroinProduction • BlueisAfghanistan • PurpleisMyanmar • 2001 suddendecrease.Why? • Banby Taliban • TheTaliban,headedbyMullahOmarsetupa banon opiumin2000 - a veryeffectiveanti-drugcampaign-thenhewasoverthrown in2001 in2001 • InUSA ○ ~60% morphineconvertedtoheroin ○ >700,000 addicts ○ >400,000 inprison Monitoring • Ifpeoplehavepoppyseedbagel,theywilltestpositiveindrugtest ○ Poppyseedhassmallamountofchemicalthatexistsinopium ○ Compoundcalled"thebain" • Opiumwars (1800s) ○ Chinawasexportingtea,silk,porcelain(export) ○ LowdemandforBritishgoods ○ Tradeimbalance ○ Britishcouldn'tsellanythinginChina,butwantedtea,silk,porcelain  StupidBritsdeclaredwar ○ Forcedopiumtradetobalancetrade ○ Consequence:morphinebecamemoreavailable • Bayerpharmaceutical'sproducedaspirin • Alsoproducedheroin(forcoughs,veryeffective) • Heroinwasbeingusedincoughmedications • Cocainewasalsoused(1900s) • UntilmagazineCollier'sstartedtogetupsetoverthesedrugs • Laudanum=opium • AndersonvillePrison-Georgia1860s • Soldiersusedmorphineforpain • Whenwarwas over,theyhadaddict
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