Trends in Performance Enhancing Drugs
Transcript of Trends in Performance Enhancing Drugs
Trends in Performance Enhancing Drugs
Schoen W. Kruse, Ph.D. Assistant Dean, Associate Professor of Pharmacology Kansas City University
SessionObjec,vesA/erpar,cipa,onintheTrendsinPerformanceEnhancingDrugssession,youwillbeableto:
1. Compareandcontrastthecommonperformanceenhancingdrugs.2. Compareandcontrastthemechanismsofac,onandadverseeffectsofcommon
performanceenhancingdrugs.3. Describetheassociatedrisksofperformanceenhancingdrugsandheatillness.
Togainacompe,,veadvantage…• HormonalPEDs
• Anabolicsteroids,growthhormone,erythropoie,n
• Non-hormonalPEDs• S,mulants,recrea,onaldrugs,nutri,onalsupplements,energy
beverages
• Maskingagents-hidetheuseofhormonalandnon-hormonalPEDs
HormonalPEDsforstrength1976-TheInterna,onalOlympicCommiPee(IOC)banstheuseofsteroids.
Theuseofandrogenshasspreadfromcompe,,vesportstoleisureandfitnesssports
Bodybuildersandnon-athletesuseandrogensasastrategytoincreasemusclemass,improveperformance,andenhancephysicalaPrac,veness
Meta--analysisof187studies,theoverallgloballife,meprevalencerateofanabolicsteroidusewas3.3%:6.4%inmen,1.6%inwomen
In2013,theCDCreportedthat3.2%ofhighschoolstudentshadtakenananabolicsteroidwithoutadoctor'sprescrip,onatleastonce
AnabolicsteroidsAnabolicSteroids–agonistsatandrogenreceptors• S,mulatesproteinsynthesis,bonegrowth,adiposecatabolism
• Increaseleanmusclemassandstrength
• Majormooddisorders,aggressivebehavior,hypogonadism,gynecomas,a
• Noeffectonaerobicpower,aerobiccapacity,athle,cism
Mostcommonlyusedandrogensaretestosterone,stanozolol,nandrolone,trenbolone,andboldenone(aveterinarysteroid)
Androgenprecursors• Androstenedioneanddehydroepiandrosterone(DHEA)
SARMs–selec,veandrogenreceptormodulators• Noneapprovedforhumanuseinanycountry
humanchorionicgonadotropin(hCG)SERMs(tamoxifen,raloxifene)Aromataseinhibitors(anastrozole)
Anabolicsteroids
Increaseserumtestosteroneconcentra,ons
Growthhormone,IGF-1andinsulinHumanGrowthHormone(hGH)• Cleareffectsonbodycomposi,on(moremuscle,lessfat)• Releasedfrompituitaryandac,vatesreleaseofIGF-1• Whencombinedwithtestosteronethereisagreater
performanceenhancingeffectthaneitheralone• Effectsdisappear6weeksa/erdiscon,nua,on• Adverseeffectsincludeinsulinresistance,hyperglycemia,
diabetes,sodiumreten,on,hypertension,cardiomegaly,prematureepiphysealclosure
• Detectedinbloodbecauselessthan0.1%isexcretedintheurine
Growthhormone,IGF-1andinsulinInsulin-LikeGrowthFactor(IGF-1)• EffectssimilartohGH;hypoglycemia• Commerciallyavailablerecombinantform• Onlydetectedthroughbloodbutnocommerciallyavailablescreeningtests
Insulin• Hypoglycemia• Canbedetectedinurinebutdifficulttodis,nguishhumaninsulin,insulinanalogs,and
porcineinsulin
RatesofIGF--1andinsulinuseforperformanceenhancementarelowerthangrowthhormone
HormonalPEDsforenduranceWhy• Maximalaerobicpower• Anaerobiccapacity• Aerobic/anaerobicmetabolicefficiency
How• Hemoglobin(RBC)volumeexpansion
HormonalPEDsforenduranceAthleteshaveusedmethodstoincreasetheoxygen--carryingcapacityofthebloodandtherebyathle,cperformancefordecades
Trainingathighal,tude
Transfusions
Erythropoie,ntos,mulateerythropoiesis
Oxygen-hemoglobinrela,onshipOxygentransportsystem• Themainfunc,onistotransportoxygen• Hemoglobinisatetramercomposedof4globinmolecules• 2alphaglobinsand2betaglobins
• Onehemoglobinmoleculehastheabilitytotransportupto4oxygenmoleculesboundtoferri,n
Increasetheblood’smaximumcapacitytotransportandu,lizeoxygen
Increaseaerobicpowerandphysicalexercisetolerance
Erythropoie,nuseinblooddopingErythropoie,n(EPO)• Proteinhormonesecretedbythekidneys• S,mulatesRBCproduc,on• Increasesbothmaximalaerobicpowerand
capacity• Indicatedforuseinanemiaofchronicdisease• Majoradverseeffectsofincreased
erythropoiesisincludemyocardialinfarc,on,stroke,thromboembolicdisease,andhypertension
• Numerousdetec,onmethods(directandindirect)
Erythropoie,nuseinblooddopingCERA-Con,nuousErythropoie,nReceptorAgonist• ApprovedforuseinEuropeandUSbutunavailableheredueto
legalissues• Aseffec,veaserythropoie,natmaintaininghemoglobinlevels
Transfusion• Wholeblood• Perfluorocarbons–liquidbreathing
• Synthe,cormodifiedhemoglobinandliposome-encasedhemoglobin
• Developedforprematureinfantswithrespiratorydeficits
Togainacompe,,veadvantage…• HormonalPEDs
• Anabolicsteroids,growthhormone,erythropoie,n
• Non-hormonalPEDs• S,mulants,recrea,onaldrugs,nutri,onalsupplements,energy
beverages
• Maskingagents-hidetheuseofhormonalandnon-hormonalPEDs
S,mulantsAmphetamineD--methamphetamineEphedrineCaffeineMethylphenidatePseudoephedrineDimethylamylamine(DMAA)
• S,mulantsareknowntobebothphysicalandcogni,veperformanceenhancers.• S,mulantsdecreaseappe,te,increaseenergy,improveendurance,increaseanaerobic
performance,decreasefeelingsoffa,gue,improvereac,on,me,increaseconcentra,on,improveworkingmemory,increasealertness,andcanleadtoweightloss
CocaineFenfluraminePemolineSelegilineSibutramineStrychnineModafinil
S,mulantsCatecholamines• PrimaryneurotransmiPersofthesympathe,cnervoussystem
• Epinephrine(adrenaline),norepinephrine(noradrenaline),dopamine
• Causegeneralphysiologicalchangesthatpreparethebodyforphysicalac,vity(fightorflightresponse)
• Releasedbytheadrenalglandduringperiodsofstress,bothpsychological(chasedbyabear)andphysiological(e.g.,lowbloodsugarlevels)
S,mulants–catecholaminesExogenoussourceshavethesameeffectsasendogenouscompounds(increasedsympathe,ctone)• Increasedheartrateandcardiacoutput• Prolongedrunning,metoexhaus,on• Decreasedcentralfa,gue• Improvedreac,on,me• Cogni,vefunc,onduringsleepdepriva,on
Noimprovementinaerobiccapacityorrunningspeed
Amphetamine,methylphenidate,DMAA• CommonlyusedforthetreatmentofADHD
• DMAA(1,3--dimethylamylamine)isanamphetaminederiva,vethatiswidelyusedinsportssupplementssoldintheUnitedStates
Ephedrine,pseudoephedrineEphedrineisanagonistatbothαandβreceptors;alsoenhancesreleaseofNEfromsympathe,cneurons
Marketedasadietarysupplement;bannedbytheFDAduetoriskofheartaPackandstroke
Cocaine
Blocksnorepinphrineanddopaminetransporters
Increasesnorepinephrine,dopamine,andserotonininsynapses
Caffeine• Nonspecificinhibitorofphosphodiesteraseenzyme(PDE1-5)• Increasestheconcentra,onofcAMP• cAMPincreasesstrengthofcontrac,onincardiacmuscleandrelaxes
smoothmusclesurroundingthevasculature• Enhancesprolongedandshorter,intenseac,vity• Caffeinatedproductsareo/enusedtoimproveathle,cperformance,as
wellasincreasealertnessinnon-spor,ngevents• CaffeinehasurinarythresholdssetbytheInterna,onalOlympic
CommiPee(IOC)andNa,onalCollegiateAthle,cAssocia,on(NCAA)
Non-hormonalPEDsthatimpactstrengthCrea,ne• ProvidesanATPsourcetomuscle• Increasesintracellularvolume
• Resultsin“hypertrophy”ofmuscle,ssue• Variabilitywithresponders&nonresponders
Beta-2AdrenergicAgonists• Wheninjectedortakenorallycanhaveanaboliceffectandreducebodyfat• Preventsmusclelossa/ercessa,onofanabolicsteroids(Clenbuterol,
Terbutaline,Salbutamol,Fenoterol)• NCAAandUSOConlyallowwithprescrip,on
Togainacompe,,veadvantage…• HormonalPEDs
• Anabolicsteroids,growthhormone,erythropoie,n
• Non-hormonalPEDs• S,mulants,recrea,onaldrugs,nutri,onalsupplements,energy
beverages
• Maskingagents-hidetheuseofhormonalandnon-hormonalPEDs
MaskingAgentsDiure,cs• Quicklydecreasesbodymass(sportswithweightrestric,ons)• Altersnormalurinaryexcre,onofperformance-enhancingdrugs
Probenecid• Inhibitsthereabsorp,onofuricacidattheproximalconvolutedtubule• Delaysrenalexcre,onoftestosterone
Epitestosterone• Co--administeredwithtestosteronetonormalizeurinetestosterone/
epitestosteronera,o
ExerciserelateddeathsDemandsofsportmayplaceathletesinextremeweathercondi,onsandtaxtemperatureregulatorysystems
Medicalcondi,oncouldlowerthethresholdoftemperaturecontrol
Physiologicaltera,onsenhanceriskforpoten,allylethalarrhythmias
• Bloodvolume• Dehydra,on• Electrolyteabnormali,es
Medica,oncould,pthebalance
100%preventable
HeatIllness-SymptomsFirstStage
SecondStage
• Headache• Dizziness
• Fa,gue• Irritability
• Anxiety• Chills
• Nausea• Vomi,ng
• Heatcramps
• Confusion–alteredmentalstatus• Increasedbodytemperature(may
beasymptoma,cinhealthyathletes
• RapidPulse• Hyperven,la,on• LowBloodPressure,syncope• Piloerec,on
LateStages • Markedlyincreasedbodytemperature• Greaterthan41°C(106°F)• Lackofcoolingdespitestoppingexercise
• Profuseswea,ngthatceasesdespitehighbodytemperature
Heatdissipa,onBloodvolumeCardiacoutputStrokevolume
HeartrateMuscleglycogenuseLac,cacidOnsetoffa,gue
Coretemp.Dehydra<on
MuscleEnduranceAerobicPowerWorkCapacityMentalAcuity
Effects
Results
RiskforheatillnessRiskforheatillness Notes
Anabolicagents Lowrisk MaycauseHTN;drugstotreatmayincreaseriskCrea,ne–dehydra,onandacuteinters,,alnephri,smayincreaserisk
Hematopoie,cagents
Lowrisk Canleadtohypertension,heartdisease,heatstroke,seizures,embolism
Sympathomime,cs Highrisk Increasedsympathe,ctone• Tachycardia• Hypertension• Decreasescutaneousbloodflowandimpairedheatdissipa,on
Maskingagents Moderaterisk Contributetophysiologicaltera,ons(e.g.,dehydra,on,electrolytechanges,decreasedbloodvolume)placingatriskforlethalarrhythmias
SessionObjec,vesA/erpar,cipa,onintheTrendsinPerformanceEnhancingDrugssession,youwillbeableto:
1. Compareandcontrastthecommonperformanceenhancingdrugs.2. Compareandcontrastthemechanismsofac,onandadverseeffectsofcommon
performanceenhancingdrugs.3. Describetheassociatedrisksofperformanceenhancingdrugsandheatillness.
References
1. hPp://www.cnn.com/2013/06/06/us/performance-enhancing-drugs-in-sports-fast-facts/2. www.uptodate.com3. Katzung,BGandTrevor,AJ.BasicandClinicalPharmacology.13thEd.McGrawHill.2015.4. LaurenceL.Brunton,BruceA.Chabner,BjörnC.Knollmann.GoodmanandGilman’sThe
pharmacologicalbasisoftherapeu;cs,12thEd.McGrawHill,2011.