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.