doping yesterday, today, tomorrow
TRANSCRIPT
Doping
Yesterday, Today, Tomorrow
Roberto Verna MD, PhDProfessor of Clinical Pathology and
Director, Clinical Research Center, “Sapienza” University of Rome
President of the Italian Association of Clinical Pathology and
Molecular Medicine
Member of the WASPaLM Bureau
Prof. Roberto Verna
Prof. Roberto Verna
Prof. Roberto Verna
Prof. Roberto Verna
Prof. Roberto Verna
Prof. Roberto Verna
DOPING
Prof. Roberto Verna
WhatWhat isisdoping?doping?doping?doping?
Prof. Roberto Verna
Doping Doping accordingaccording toto the the ItalianItalian LawLawDecemberDecember 14th, 2000, n14th, 2000, n°°376 (art. 1) 376 (art. 1) ofof
the the MinistryMinistry ofof HealthHealth::
“doping “doping isis the the administrationadministration or or assumptionassumptionofof drugsdrugs or or biologicallybiologically and and
pharmacologicallypharmacologically activeactive substancessubstances and the and the useuse ofof medicalmedical actsacts withoutwithout anyany needneeduseuse ofof medicalmedical actsacts withoutwithout anyany needneed
justifiedjustified byby pathologicalpathological conditionsconditions and and ableabletoto modifymodify physicalphysical or or biologicalbiological conditionsconditions in in orderorder toto achieveachieve the best the best performancesperformances byby
the the athletesathletes””
Prof. Roberto Verna
The term The term dopingdoping comes from comes from ““doopdoop”,”, a mix a mix of of ergogenicergogenic substances that Dutch seamen substances that Dutch seamen used already four centuries ago before used already four centuries ago before
facing an ocean stormfacing an ocean stormProf. Roberto Verna
From From ““doopdoop””the term has the term has becomebecome“to dope”“to dope”and finallyand finally“doping”“doping”that meansthat meansthat meansthat meansa substance a substance able to modifyable to modifythe the performanceperformance
Prof. Roberto Verna
The The termterm dopingdoping comescomesalsoalso fromfrom ““oopoop””, a mix , a mix ofof opiumopium, , tobaccotobacco and and narcoticsnarcotics administeredadministeredtoto racehorsesracehorses in XIXth in XIXth centurycentury..centurycentury..
Prof. Roberto Verna
“Dope”“Dope” isis alsoalso anan ancientancient South South AfricanAfrican termtermindicatingindicating anan alcoholicalcoholic drink drink usedused toto
stimulatestimulate duringduring tribaltribal ceremonialceremonial dancesdances..Prof. Roberto Verna
Prof. Roberto Verna
•• In fact, doping substances In fact, doping substances are often drugs such as are often drugs such as Alcohol, Marijuana, Alcohol, Marijuana, Cocaine.Cocaine.
The The useuse ofof substancessubstances prohibitedprohibited forfordoping doping meansmeans beingbeing drugdrug--addictsaddicts
Cocaine.Cocaine.
•• These substances are These substances are always purchased and used always purchased and used secretly, secretly,
•• Because who uses doping Because who uses doping substances is aware of substances is aware of cheatingcheating
Prof. Roberto Verna
1. Before the match, during the training, totry to increase muscular mass andphysical strength or resistance
Types of doping related to the different moments of the agonistic
activity I
physical strength or resistance(steroids- EPO )
2. After the match, to recover strengthrapidly.
Prof. Roberto Verna
3.3. DuringDuring thethe match,match, toto::
•• DecreaseDecrease fatiguefatigue, ,
•• StimulateStimulate CNS, CNS,
TypesTypes of doping of doping relatedrelated to the to the differentdifferent momentsmoments of the of the agonisticagonistic
activityactivity IIII
•• StimulateStimulate CNS, CNS,
•• Reduce Reduce anxietyanxiety, in some , in some sportssports, ,
((cannabinoidscannabinoids, beta , beta blockersblockers, , etcetc))
•• TryTry toto increaseincrease oxygenoxygen transporttransport and and
reduce reduce fatiguefatigue ((hemotransfusionhemotransfusion))
Prof. Roberto Verna
History of History of DOPINGDOPING
Prof. Roberto Verna
Doping is an Doping is an ancient problemancient problem
Prof. Roberto Verna
From the Greeks…From the Greeks…Doping is not a recent Doping is not a recent discovery, but it was discovery, but it was already common among already common among antique antique GGreek wrestlers reek wrestlers (III century (III century b.Cb.C.) who .) who antique antique GGreek wrestlers reek wrestlers (III century (III century b.Cb.C.) who .) who used a mushroomused a mushroom--derived drug to enhance derived drug to enhance their aggressiveness.their aggressiveness.
Prof. Roberto Verna
Zeus sanctuary in Olympia
Prof. Roberto Verna
Callipateira of Rhodes
During their games, During their games, Roman athletes Roman athletes used different used different
…to the Romans…to the Romans
used different used different qualities of meat qualities of meat mixed with mixed with stimulating stimulating substancessubstances
Prof. Roberto Verna
Goat meat for the jumperGoat meat for the jumper
Antelope meat for the runnerAntelope meat for the runner
Bull meat for the wrestlerBull meat for the wrestler
…with…with breadbread and wineand wine
Milone di CrotoneMilone di CrotoneProf. Roberto Verna
The soldier of Marathon announces the victory, Jean-Pierre CORTOT, 1822-1834
Prof. Roberto Verna
The soldier of Marathon, Luc-Olivier Merson, 1869
Prof. Roberto Verna
Prof. Roberto Verna
Prof. Roberto Verna
Prof. Roberto Verna
Marathon in 1907
Prof. Roberto Verna
Prof. Roberto Verna
Leonida alle Termopili, Jacques-Louis David, 1814
Prof. Roberto Verna
Prof. Roberto Verna
Prof. Roberto Verna
Prof. Roberto Verna
Emperor Teodosio
and Holy Ambroseand Holy AmbroseAnton van Dick, 1620
Prof. Roberto Verna
An English bicycler,An English bicycler,
Arthur Linton, wins the Arthur Linton, wins the ParigiParigi--Bordeaux Bordeaux
in 1896 dying after the in 1896 dying after the race because of the use race because of the use
XIXXIXthth CenturyCentury
race because of the use race because of the use of exciting substances of exciting substances (ether(ether--cocaine)cocaine)
XXXXthth CenturyCentury
In 1904 Thomas In 1904 Thomas HicksHicks, , afterafter winningwinning the Olympic the Olympic marathonmarathonin in AthensAthens, , waswas seriouslyseriously takentaken illill byby the the useuse ofof stricnine stricnine
sulfatesulfate duringduring the racethe race
Again Again XXthXXth centurycentury
Dorando Dorando PetriPetri on on hishis marathonmarathon race race arrivalarrival, , (London 1908) (London 1908) wornworn--outout byby fatiguefatigue ‘cause ‘cause ofof the the
intakeintake ofof stricnine stricnine withwith cognaccognac
Prof. Roberto Verna
DOPING IN
SECRET SOCIETIES
Prof. Roberto Verna
Prof. Roberto Verna
Stimulating substances were
already used during WWII
Messerschmitt 109Messerschmitt 109
Messerschmitt 110Messerschmitt 110
to increase the reaction rate and decrease fear
LuftWaffeLuftWaffe fightersfighters flyingflying in British skiesin British skiesProf. Roberto Verna
BehindBehind the the strategicstrategic operationsoperations and the and the mostmost hazardoushazardousinterventionsinterventions the the useuse ofof stimulatingstimulating drugsdrugs waswas ableable toto
enhanceenhance everyevery decisiondecision and and actionaction thusthus makingmaking simplersimpler the the choicechoice toto diedie..
SoldiersSoldiers landedlanded fromfrom shipsships in in frontfront ofof NormandyNormandy shoresshorespushedpushed byby theirtheir heroismheroism, , butbut manymany withwith the the aidaid ofofchemicalschemicals usedused severalseveral timestimes byby various various armiesarmies..
Prof. Roberto Verna
DEXTROAMPHETAMINE DEXTROAMPHETAMINE isis a a drugdrug ableable toto spongespongeout out fatiguefatigue, , usefuluseful forforsoldierssoldiers in in missionmission
IRAQ IRAQ –– AFGHANISTANAFGHANISTANNew New frontiersfrontiers ofof MilitaryMilitary DopingDoping
ItsIts useuse hashas widelywidely spread non spread non onlyonly in in infantrymeninfantrymen butbut alsoalsoItsIts useuse hashas widelywidely spread non spread non onlyonly in in infantrymeninfantrymen butbut alsoalsoamongamong pilotspilots, , withwith enhancementenhancement ofof clearnessclearness and and quickerquicker
reflexesreflexes in the in the mostmost hazardoushazardous manoeuvresmanoeuvres..
Prof. Roberto Verna
In the post war In the post war periodperiod therethere waswas a a widespreadwidespread useuse ofofstimulatingstimulating drugsdrugs duringduring sport sport activityactivity. . HeavyHeavy upsetupset arosearoseforfor the the deathsdeaths ofof the the cyclistscyclists Alfredo Alfredo FalziniFalzini ((sympaminesympamineand and steanaminesteanamine) in ’49 at the end ) in ’49 at the end ofof the race the race MilanoMilano--RapalloRapallo, , KnudKnud JensenJensen ((amphetaminesamphetamines) ) OympicOympic gamesgames ’60, ’60, Tom SimpsonTom Simpson ((amphetaminesamphetamines) in ’67 Tour de France and ) in ’67 Tour de France and ofofthe the FrenchFrench soccer playersoccer player Luis QuadriLuis Quadri ((amphetaminesamphetamines) in ‘68) in ‘68
Simpson’s Simpson’s death ondeath on
Mont Mont VentouxVentoux
Prof. Roberto Verna
The The powerfulpowerful NationsNations
ForFor a long a long timetime the the powerfulpowerful NationsNations useduseddoping doping asas a State a State weaponweapontoto sorpasssorpass enemyenemycountriescountries::toto sorpasssorpass enemyenemycountriescountries::
DuringDuring the the SixtiesSixties and and the the SeventiesSeventies DDR, DDR, URSS, USA URSS, USA pushedpushed theirtheirathletesathletes toto winwin at at anyanycostcost
Prof. Roberto Verna
Former Former international international international international
efforts against efforts against dopingdoping
Prof. Roberto Verna
Prof. Roberto Verna
First cases of hematic doping
Ben Johnson lasts as Olympic champion for less than 24hs. He was suspended for the use of anabolyzing steroids
Following the dequalification, the Olympic gold has been attributed to Carl Lewis, example of honesty (15 years of career without doping).
Prof. Roberto Verna
Olympic Olympic GamesGames at Atlanta at Atlanta havehavebeenbeen namednamed “GH GAMES”“GH GAMES”
Prof. Roberto Verna
SheShe promisespromises toto
SYDNEY 2000SYDNEY 2000Cathy Freeman, Cathy Freeman, AustralianAustraliansprinter, sprinter, readsreads the the newnewOlympic Olympic oathoath::
SheShe promisespromises totoplay play withwith loyaltyloyaltywithoutwithout the the useuse ofofdoping doping toto improveimproveherher performance.performance.
Prof. Roberto Verna
RaducanRaducan, a , a RomanianRomanianathleteathlete awardedawarded withwiththe the goldgold medalmedal in in gymnasticsgymnastics isissuspendedsuspended forfor doping doping byby ephedryneephedryne, , usedusedbyby ephedryneephedryne, , usedusedtoto cure a cure a fluflu. . EphedryneEphedryne modifiesmodifiesthe the sensesense ofofequilibriumequilibrium and and isishazardoushazardous in in gymnasticgymnastic..
Prof. Roberto Verna
Three Three BulgarianBulgarianathletesathletes foundfoundpositive positive makemake allallthe the weightweight--liftersliftersteam team toto bebesuspendedsuspended..team team toto bebesuspendedsuspended..
The The RomaniansRomanians, in , in the the samesame conditioncondition, , paidpaid a fine and a fine and werewere ““forgivenforgiven””
Prof. Roberto Verna
WinterWinterOlympic Olympic gamesgames
•• First First appearanceappearance ofofNESP (NESP (DarbopoetineDarbopoetine), a ), a newnew moleculemolecule substitutingsubstitutingnewnew moleculemolecule substitutingsubstitutingEPOEPO
•• Salt Lake City Salt Lake City gamesgames: :
LazutinaLazutina, , DanilovaDanilova, , MuehleggMuehlegg ((darbopoetinedarbopoetine))
Lazutina Danilova
Prof. Roberto Verna
World World championshipchampionship ParisParis 2003 2003 –– casescases ofof doping doping byby ModafinilModafinil, a , a stimulatingstimulating moleculemolecule notnot includedincluded in in the the listlist ofof prohibitedprohibited substancessubstances; ; itit waswas includedincluded
sincesince AthensAthens 20042004
KelliKelli White White hadhad toto givegiveback 2 back 2 goldgold medalsmedals, 100 e , 100 e
200m200m
Calvin Harrison Calvin Harrison goldgold on on 4x400m4x400m
Prof. Roberto Verna
2003. New cases of positivity to Tetraidrogestrinone (THG)
Regina Regina JacobsJacobs1500m 1500m championchampion
KewinKewin TohtTohtshotshot putput
DwainDwain ChambersChambers100m 100m EuropeanEuropean
championchampion
The TGH was produced by BALCO laboratories headed
by nutritionist Victor Conte (KMA Club)Prof. Roberto Verna
ATHENS 2004ATHENS 2004Identified a significant number of doping cases that
have also led to the return of 7 illegally won medals
WilliamsRobert Fazekas
Irina Irina KorzhanenkoKorzhanenko ((StanozololoStanozololo)) goldgold medalmedalRobert Robert FazekasFazekas ((ControlControl adulterationadulteration)) goldgold medalmedalLuisa Calle WilliamsLuisa Calle Williams ((EptaminoloEptaminolo)) bronze bronze medalmedalOlenaOlena OlefirenkoOlefirenko ((EtamivanEtamivan)) bronze bronze medalmedal
Irina Korzhanenko
Prof. Roberto Verna
ATHENS 2004ATHENS 2004
Adrian Annus
Leonidas SabanisThe anti-doping controls will
have a retroactive effect and the
IOC reserves until 2012 to
withdraw the medals won in this
edition of the Games
Leonidas Sabanis ((Testosterone) bronze medalAdrian Annus (Refusal of the controls) gold medalFerenc Gyurkovics (Stanozolol) silver medal
Adrian Annus
Prof. Roberto Verna
Doping also affects the Paralympics
in Athens: two Azerbaijani
weightlifters were expelled from the
Games because positive to two
different substances. Sara Abbasov,
ATHENS 2004
Paralympics
different substances. Sara Abbasov,
28 y.o., and Gundula Ismaylov, 31
y.o. have fallen into the clutches of
the controls after a test conducted on
September 18th. The two tested
positive for nandrolone (the woman)
and stanozolol (the man).
Prof. Roberto Verna
OPERATION “QUADRIFOGLIO”
CARABINIERI FOR CARABINIERI FOR HEALTH (NAS)HEALTH (NAS)
Prof. Roberto Verna
-184 soldiers involved
-507 packs of prohibited medicines seized: (stimulants,
JUNE 6th 2001JUNE 6th 2001STARTING OF OPERATION QUADRIFOGLIO
PERQUISITIONS AT HOTELS IN SANREMO AND
NEIGHBOURING TOWNS
-507 packs of prohibited medicines seized: (stimulants,
anabolic steroids, steroids, diuretics, synthetic hemoglobin,
blood products)
Sequestration of large amounts of medical material
(syringes, needle-cannulas, etc.) and anonymous substances
for laboratory analysis
-105 people reported to the Judicial Authority
In January 2003 as part of the “Hercules” operation,
the Guardia di Finanza of Como
seized a huge load of human GH
from Lithuania intended for gyms
Imperia: thirty thousand
pills and eleven thousand vials
seized (anabolic drugs)
February 2004
Operation
"HERCULES"
Conducted by the NAS
Carabinieri in Ancona
Seizure of medicines of
anabolic action
Source:
- Italy
- Greece
- Tunisia
- Spain
- Romania
LIST OF THE DRUGS FOUND DURING “HERCULES” LIST OF THE DRUGS FOUND DURING “HERCULES” CONFISCATION OPERATIONCONFISCATION OPERATION
ALDACTONEALDACTONEANAPOLON TABLET ANAPOLON TABLET OKSIMETOLONOKSIMETOLONANDRIOLANDRIOLBENADONBENADONCLOMIPHENE CITRATECLOMIPHENE CITRATEDECADECA--DURABOLINDURABOLINDIANABOLDIANABOLDEPO MEDROLDEPO MEDROLEFEDRINA LEVELEFEDRINA LEVELEPARGRISEOVITEPARGRISEOVIT
LASIXLASIXHOMEOCUR TESTERSETHOMEOCUR TESTERSETHUMOLINHUMOLINJINTROPINJINTROPINKADIURKADIURKRIPTOCURKRIPTOCURISOPURAMINISOPURAMINLIPOSTABILLIPOSTABILMASTERONMASTERONMETADIENONMETADIENONMETANABOLMETANABOL
RESTANDOLRESTANDOLSAIZENSAIZENSCHERINGSCHERINGSYNFLEXSYNFLEXSOMATOSTATINASOMATOSTATINASPASMOBRONCALSPASMOBRONCALSPIROPENTSPIROPENTSUSTENONSUSTENONTAD 600TAD 600TIOSIDETIOSIDETITI--TRE LIOTIRONINATRE LIOTIRONINAEPARGRISEOVITEPARGRISEOVIT
ESICLENEESICLENEESTRUMATEESTRUMATEEUTIROXEUTIROXEXTRABOLINEEXTRABOLINEFELDENEFELDENEFINAJECTFINAJECTFINASTERIDEFINASTERIDEGANABOLGANABOLGENOTROPINGENOTROPINGH UMATROPEGH UMATROPEGLOBURENGLOBUREN
METANABOLMETANABOLMONORESMONORESNAPOPSINNAPOPSINNEOTONNEOTONNESPO 60NESPO 60NOVALDEXTAMOXIFENNOVALDEXTAMOXIFENPARABOLANPARABOLANPLACENTEXPLACENTEXPRIMOBOLANPRIMOBOLANPROFASI HPPROFASI HPPROCAR FINASTERIDEPROCAR FINASTERIDEPROVIRONPROVIRON
TITI--TRE LIOTIRONINATRE LIOTIRONINATESTEX ELMU TESTEX ELMU PROLONGATUMPROLONGATUMTESTOSTERONE CYPIONATETESTOSTERONE CYPIONATETESTOVIRONTESTOVIRONTESTOVISTESTOVISTRANSMETILTRANSMETILVENTIPULMIN CITRATEVENTIPULMIN CITRATEVIRORMONE TESTOSTERONE VIRORMONE TESTOSTERONE PROPINATEPROPINATEWINSTROLWINSTROL
APPROXIMATE AMOUNT APPROXIMATE AMOUNT : EURO 8.970.000,00: EURO 8.970.000,00Prof. Roberto Verna
JargonJargon wordswords usedused toto orderorder drugsdrugs, , recordedrecorded duringduring tappingtapping(COMANDO CARABINIERI PER LA SANITA' (COMANDO CARABINIERI PER LA SANITA' -- N.A.S.)N.A.S.)
EFEDRINAEFEDRINA MauMau--WangWangWINSTROLWINSTROL doubledouble U U -- dressesdresses -- STROMBASTROMBAGANABOLGANABOL ((forfor veterinaryveterinary useuse))DECADECA “the “the onesones withwith the yellow the yellow capcap" " --
masterizedmasterizedANDRIOLANDRIOL the motothe motoANDRIOLANDRIOL the motothe motoDECADURABOLINDECADURABOLIN the the carscarsNANDROLONE DECAONATONANDROLONE DECAONATO lat lat extensionextensionPROVIRONPROVIRON trouserstrousersOXANDROLONEOXANDROLONE lat lat machinemachineHASHISHHASHISH smokesmoke -- chocolatechocolateGHGH “the “the coldcold oneone" " –– the the iceice –– frozenfrozen proteinsproteins
–– chewingchewing gumsgumsPRIMOBOLANPRIMOBOLAN P P -- decaffeinateddecaffeinatedPROVIRONPROVIRON PROPROTESTOVISTESTOVIS ““thosethose withwith the the blueblue box”box”
Prof. Roberto Verna
Marion Jones
Every Sport Authority is bound to: Every Sport Authority is bound to:
•• Protect athletes’ healthProtect athletes’ health
•• Enforce medical and sports ethicsEnforce medical and sports ethics
•• Maintain the same opportunities for all the Maintain the same opportunities for all the athletes during a competitionathletes during a competition
Prof. Roberto Verna
WORLD ANTIDOPING ORGANISATION
WADA, Governments and Sport Organisations
World Antidoping Code
List of the Banned Drugs and Methods
Laboratory Accreditation
Random Controls
Intergovernative Institutions
Governments
Commission for the Vigilance of Doping
International federations
National Federations
National Antidoping
Laboratories
CIO Olympic Games
National Olympic
Committees
Commissions of the Sport Federations
Random Controls
The “medicalness” of the
athlete and of the sportsman
Prof. Roberto Verna
WHY DO ATHLETES AND SPORTSMEN USE WHY DO ATHLETES AND SPORTSMEN USE DRUGS?DRUGS?
•• ToTo improveimprove athleticathletic performanceperformance•• drugsdrugs prohibitedprohibited and and notnot forfor dopingdoping
•• creatinecreatine
•• linearlinear and and ramifiedramified aminoacidsaminoacids
••ForFor a a fasterfaster athleticathletic recoveryrecovery in case in case ofof strong strong athleticathletic involvementinvolvementathleticathletic involvementinvolvement
•• ErgogenicErgogenic AidsAids
•• ToTo recoverrecover losseslosses due due toto the intense the intense physicalphysical efforteffort•• VitaminsVitamins
•• MineralMineral SaltsSalts
•• ToTo protectprotect fromfrom oxydativeoxydative damagedamage•• VitaminsVitamins
•• AntioxydantsAntioxydantsProf. Roberto Verna
Drugs used by athletes and NOT
banned for doping
• Legal drugs
• Health products (supplements)
• Herbal products
• Homeopathic preparations
Prof. Roberto Verna
Athletes subject to doping controls
who reported taking medication
= 65= 65--70% (8000 70% (8000 athletesathletes))
Types of drugs reported
1,5%1,5%Herbals / homeopathic products
17%17%Vitamin supplements
20%20%Supplements (salt, amino acids, etc.).
35%35%Non-steroidal anti-inflammatory drugs
Prof. Roberto Verna
For a medication, adverse effects are allowed
only if the ratio risk / benefit of the treatment
is favourable.
A health benefit does NOT exist
in a subject who is not sickin a subject who is not sick
Unreasonable risk of ADR occurrence
Prof. Roberto Verna
What are the factors that
favour the spread of favour the spread of
doping?
Prof. Roberto Verna
The differences in performance
among athletes are minimal
• Fractions of seconds in speed trials
• Few seconds in endurance events
Consequence
Exasperated search of the smallest
improvement through the use of drugs
believed to be capable of increasing the
performance
Consequence
Prof. Roberto Verna
The obligation of results
Entire football teams are known taking energetic
substances to complete the season
Prof. Roberto Verna
The economic benefits and
reputation
Anna
Kournikova
The sponsors pay sports champions very
well, but only as long as the champions win
Prof. Roberto Verna
The increase in training
loads
In some sports the
workload to stay at
the top can be
Nadia
Comaneci
the top can be
sustained only by
resorting to drug aid
Prof. Roberto Verna
The effect of
stress and lack of
psychological
preparation for
Michael Johnson
preparation for
sport
Prof. Roberto Verna
The pressure of parents...
Often parents demand from
children a sporting career
as champions, even
accepting the use of doping accepting the use of doping
to achieve their dreams
Prof. Roberto Verna
...Or their lack of interest
• OTHER TIMES THE
YOUNG RESORT TO
DOPING WITHOUT DOPING WITHOUT
ANYONE AROUND
HIM KNOWS IT
Prof. Roberto Verna
The The useuse ofof prohibitedprohibitedsubstancessubstances isis anan admissionadmission
ofof fearfearJenny Gale
Prof. Roberto Verna
NotNot toto acceptaccept the the duelduel, the , the defeatdefeat, the , the
victoryvictoryProf. Roberto Verna
Cases Cases ofof positivitypositivity toto some “social” some “social” drugsdrugs, , suchsuch asascannabis and cannabis and cocainecocaine in the English Premier Leaguein the English Premier League
FormerFormer Chelsea Chelsea GoalkeeperGoalkeeper Mark Mark BosnichBosnich
positive positive toto cocainecocaine
Lee Lee BowyerBowyer todaytoday at at Newcastle Newcastle UnitedUnited positive positive
toto MarijuhanaMarijuhanaProf. Roberto Verna
The “medicalization” of sports
facilities
• Some gyms are a mix
between spatial structures
and back-room
pharmacies.
You can find anything
and almost nothing is safe
Prof. Roberto Verna
To combat doping it is
necessary to know
the effects and the effects and
damage of banned
substances
Prof. Roberto Verna
Classes of substances
prohibited in-competition only
•• STIMULANTS
• NARCOTICS• NARCOTICS
• CANNABINOIDS
• GLUCOCORTICOSTEROIDS
Prof. Roberto Verna
Classes of substances prohibited in
and out of competition
� ANABOLIC AGENTS
� DIURETICS AND MASKING AGENTS
� PEPTIDE HORMONES� PEPTIDE HORMONES
� BETA-2 AGONISTS
� ANTIESTROGENIC AGENTS
Prof. Roberto Verna
Classes of substances
prohibited only in certain
sportsALCOHOLALCOHOLAeronautics
Archery
Motoring
Billiards
BETABLOCKERSBETABLOCKERS
Football
Gymnastics
Modern Pentathlon
Motorcycling
Aeronautics
Archery
Motoring
BilliardsBilliards
Bowls
Football
Gymnastics
Karate
Modern Pentathlon
Motorcycling
Skating
Ski
Triathlon
Wrestling
Motorcycling
Bowling 9 Pins
Sailing
Shooting
Ski
Swimming
Wrestling
Billiards
Bobsleigh
Bowls
Bridge
Chess
Curling
Prof. Roberto Verna
Methods prohibited in and out competition
ENHANCEMENT OF OXYGEN TRANSFER
Blood doping: use of autologous, homologous or heterologous red blood cell
products of any origin, outside of legitimate medical treatment
Use of products that enhance the uptake, transport or delivery of oxygen (eg
erythropoietin), hemoglobin products, including but not limited to
hemoglobin-based blood substitutes, microencapsulated hemoglobin
products, perfluorochemicals, and efaproxiral (RSR13)
DRUG, CHEMICAL AND PHYSICAL HANDLING
Is the use of substances and methods that can alter the integrity
and validity of specimens collected in doping controls (intravenous
infusion, catheter and replacement of urine)
GENE DOPING
And the non-therapeutic use of genes, genetic elements and / or cells
that have the capacity to enhance athletic performance
Prof. Roberto Verna
It has recently been applied a mark on the packaging of pharmaceutical
products that contain substances prohibited for DOPING:
The mark is accompanied by the following warning:
“For those who play sports:
the use of the drug without therapeutic need
may result in positive test”
BE FAIR AND TAKE CARE OF YOUR
HEALTH!
Prof. Roberto Verna
HEMATOCHEMICAL MARKERS OF THE
PHYSICAL CONDITION OF THE ATHLETE
• Testosterone
• Dihydrotestosterone
• ACTH
• Cortisol
• Evaluation of the
agonistic stress and
involvement
• Cortisol
• DHEAs
• delta-4-
androstenedione
• GH
Prof. Roberto Verna
HEMATOCHEMICAL MARKERS OF THE
PHYSICAL CONDITION OF THE ATHLETE
• LDH
• CPK
• Study of the
muscular
characteristics of an
athleteathlete
Prof. Roberto Verna
MOUNTAIN SPORTS
• Complete Blood Count
• Iron
• Transferrin• Transferrin
• Ferritin
• Hb dissociation curve
• Diphosphoglycerate
Prof. Roberto Verna
Prohibited substances
• Stimulants
• Narcotics
• Anabolizing Agents
• Diuretics
• Peptide Hormones,
mimicking substances
Prohibited methods
• Administration of blood,
RBCs and/or similar
products)
• Administration of
INDICATORS OF THE USE OF PROHIBITED SUBSTANCES AND METHODS
mimicking substances
• Local Anestetics
• Alcohol
• Cannabis sativa and
indica
• Glucocorticosteroids
• Beta-blockers
•
artificial oxygen
transporters or plasma
substitutes
Reduced fatigue, euphoria
Increased
heart rate
Heatstroke
Excitement,
restlessness,
insomnia,
EFFECTS ADVERSE EFFECTS
Marked effect on
stimulating the central
nervous system
(increases the
competitiveness of
Central Nervous System
Tremors, Agitation,
Aggressiveness
Loss of Critical Sense
Headache
Insomnia
STIMULATING AGENTS
Amphetamine, Ephedrine, Cocaine …
Ictus
insomnia,
aggressiveness
Dependence
Addiction
Dispnea
competitiveness of
attention, sense of well
being, euphoria)
Decreased fatigue
Increased heart rate
Increased blood glucose
and free fatty acids
Reduced sense of hunger
(anorectic effect)
Vomiting, Anorexia
Hyperthermia (Heat Stroke)
Seizures
Deep depression, Psychosis
Cardiovascular System
Vasoconstriction
Hypertension
Tachycardia
Rhythm Disturbances
Myocardial Infarction
Stimulation
of energetic
metabolism
Vomiting
Prof. Roberto Verna
STIMULANTS
• Amphetamines are a class
of stimulants used in many
sports for their ability to
increase alertness,
Prohibited only in competition
increase alertness,
competitiveness, reduce
fatigue, give a sense of
euphoria by stimulating the
energy metabolism
Prof. Roberto Verna
Amphetamines damage:
Excitement
Restlessness
Insomnia
Aggressiveness
dental injury by ecstasy
Addiction
Psychosis
Convulsions
Depression
Anorexia
Prof. Roberto Verna
Effect of ecstasy on the spider’s ability to
weave the cloth
after ecstasybaseline
Prof. Roberto Verna
Side Effects
BRAIN HEMORRHAGE FROM COCAINE
Prof. Roberto Verna
� 5-HIAA 5-hydroxyindoleacetic acid - a breakdown product of
serotonin.
���� 5-HT
(levels lower in CSF during the intervals between administration)
Stimulants – blood parametersECSTASY - MDMA – Methilenedioxymethamphetamine
studies in rats
(levels lower in CSF during the intervals between administration)
���� Norepinephrine
� Epinephrine
� Dopamine
Suppression of IFN gamma and IL-10 production in coltures
Neuronal toxicity of the molecule induces serotonin depletion
� Nausea, Vomiting
Stimulants - Ephedrine
Short-term adverse effects
� Nausea, Vomiting
� Increased sweating
� Thirst
� Restlessness, Insomnia
� Tachicardy, Hypertension, Arrhythmias.
Prof. Roberto Verna
Increased
tolerance to
pain
Mood disorders
Depression of
respiratory function
EFFECTS ADVERSE EFFECTS
Interference in the
central nervous system
with increased
tolerance of pain
Bronchospasm
Depression of
respiratory function
Nausea, vomiting
NARCOTICS
Heroin, Methadone and Morphine…
Constipation
tolerance of pain Nausea, vomiting
Constipation
Decreased urine flow
Increased sweating
Drooling
Changing mood
Addiction
Nausea
Vomiting
Bronchospasm
Prof. Roberto Verna
Its removal may lead the athlete to "overdo"
Pain is a warning sign
NARCOTICS
Are taken to reduce pain perception
Prohibited only in competitionProhibited only in competition
The risks are:
worsening of existing injuries
causing permanent damage.
Prof. Roberto Verna
• Constipation;
• Nausea and vomiting;
• Insomnia and depression;
NARCOTICSADVERSE EFFECTS
Prohibited only in competitionProhibited only in competition
• Decreased ability to concentrate;
• Loss of balance and coordination;
• Addiction;
• Reduced heart rate;
• Bradypnea
EFFECTS ADVERSE EFFECTS
Increased sense
of wellbeing
Euphoria
Anxiety
Euphoria
Drowsiness
Apathy
CANNABINOIDS
Hashish, Marijuhana …
Reduced ability
to coordinate
Altered
perception
Euphoria and
wellbeing
It is hypothesized
a decrease in emotional
tension before the race
Apathy
Tachycardia
Orthostatic Hypotension
Dependence
Memory deficits
Psychosis
Schizophrenia
Teratogenic to the foetus
Carcinogen (because it is
smoked)
perception
of time
Personality
changes
Balance
disorders
Prof. Roberto Verna
CANNABINOIDSCANNABINOIDS
Marijuana and hashish
distort perceptions and do
not allow proper risk
assessment.
Prohibited only in competitionProhibited only in competition
assessment.
The athlete perform actions
(stunts) that would not do
under normal conditions.
Prof. Roberto Verna
A decrease of emotional tension before a race is postulated.
� Increased heart rate, blood pressure;
� Balance and coordination disorders;
CANNABINOIDS
SPECIFIC ADVERSE EFFECTS
� Short-term memory loss;
� Loss of concentration, hallucinations, psychosis;
� Subnormal body temperature;
�Abnormal spermatogenesis and ovulation.
Prof. Roberto Verna
Euphoria
EFFECTS ADVERSE EFFECTS
Powerful anti-
inflammatory action
Euphoria
Increased ability to
Alteration of
Electrolyte Balance
Hypertension
Hyperglycemia
GLUCOCORTICOSTEROIDSprohibited per oral, rectal, im. or iv. assumption
medical certification is required for other administration
Osteoporosis
Alteration of
the electrolyte
balance
HypertensionIncreased
ability to resist
to noxious Increased ability to
resist to noxious
stimuli
Hyperglycemia
Hyperlipidemia
Hyperuricemia
Increased Susceptibility
to Infections
Peptic Ulcer
Osteoporosis
Insomnia
Cataract
Peptic
Ulcer
Osteoporosis
Increased
Susceptibility
to Infections
Hyperglycemia
Anti-inflammatory action
to noxious
stimuli
Prof. Roberto Verna
GLUCOCORTICOSTEROIDSGLUCOCORTICOSTEROIDS
• Treatment of acute
pain
• Anti-inflammatory
• Euphorizing effect
Prohibited only in competitionProhibited only in competition
• Euphorizing effect
• Reducing the
perception of fatigue
Prof. Roberto Verna
• Electrolyte Disorders
• Heart Failure
• Osteoporosis
GLUCOCORTICOSTEROIDSGLUCOCORTICOSTEROIDSadverse effects
Prohibited only in competitionProhibited only in competition
• Osteoporosis
• Immunosuppression
• Renal Failure
• Amenorrhea
Prof. Roberto Verna
Insomnia;
Hypertension;
GLUCOCORTICOIDS
ADVERSE EFFECTS
Hypertension;
Cataracts;
Diabetes Mellitus;
Osteoporosis;
Immunosuppression
Prof. Roberto Verna
Tests to reveal the use
of Corticosteroids
• Blood Glucose (I)
• Blood Potassium (L)
Tests to reveal the use
of Narcotics and
Analgesics
• LH
• ADH
• GH
• Prolactin • Blood Potassium (L)
• Blood pH (I)
• Prolactin
• Testosterone
Prof. Roberto Verna
ANABOLIC DRUGS
Mr. OlympiaMr. OlympiaMs. OlympiaMs. OlympiaLenda MurrayLenda Murray
Ronald ColemanRonald Coleman
Prohibited “Prohibited “inin--out”out” competioncompetion
Are steroid hormones (testosterone, nandrolone and so on) that strengthen the
muscles and reduce fat.Prof. Roberto Verna
On the other hand,
they are carcinogenic
to the liver, addictive,
cause changes in sexual
characteristics
ANABOLIC DRUGSProhibited “in-out” competion
characteristics
producing feminization
in boys and vice versa.
Prof. Roberto Verna
Disciplines more exposed to their use:
Weightlifting
Shot put
ANABOLIC DRUGSProhibited “in-out” competion
Shot put
Discus Throw
Bodybuilding
Football
Wrestling
Prof. Roberto Verna
•• Human chorionic gonadotropin (HCG):
•���� the synthesis of testosterone
contrast to the testicular atrophy
Drugs often used in combination
ANABOLIC DRUGSProhibited “in-out” competion
contrast to the testicular atrophy
•• Diuretics:
•���� water retention
dilute the urine for drug tests
Prof. Roberto Verna
•• AntiestrogensAntiestrogens: :
• prevent gynecomastia in males
Drugs often used in combination
ANABOLIC DRUGSProhibited “in-out” competion
•• ACTH:ACTH:
• ���� endogenous steroids production
can provoke a feeling of euphoria
Prof. Roberto Verna
Long bone growth block
Acne
EFFECTS Adverse effects
Increased muscle mass
Decreased fat mass
Increased fatigue
Decreased catabolic
In males (pre-puberal)
Early epiphyseal cartilage
welding (block long bone
growth)
Inhibition of spermatogenesis
In males (adults)
Oligospermia / azoospermia
ANABOLIC AGENTS
Testosterone, Nandrolone, Stanzolol…
Increased
synthesis of
red blood cells
Increased
bone density
Impaired reproductive
function
Decreased catabolic
action of
glucocorticoids
Increased synthesis of
red blood cells
Increased bone
density
Oligospermia / azoospermia
testicular atrophy
Prostatic hypertrophy
Abnormal liver function with
the possibility of tumors
Increased plasma lipid
In women
Suppression of ovarian function
Atrophy of the mammary gland
Virilization
Abnormal liver function with
the possibility of tumors
Liver damage
Increase of TG and Chol
Muscle mass
Fat mass
Tendon injury
Prof. Roberto Verna
Testosterone increases
muscle mass and
changes the behavior
with manifestations of
Ben Johnson
ANABOLIC DRUGSProhibited “Prohibited “inin--out”out” competioncompetion
with manifestations of
irritability,
aggressiveness and
violence.
Prof. Roberto Verna
Precursors of
nandrolone
The story of the players
Guardiola, Stam, de Boer,
Monaco, Couto, Davids, Monaco, Couto, Davids,
Bucchi, (tested positive for
nandrolone for taking
supplements made in the
USA polluted with
precursors of nandrolone) is
well known.
Prof. Roberto Verna
Other and more recent cases of
nandrolone in soccer
Emanuele BlasiEmanuele BlasiMohamed KallonMohamed Kallon Saadi GheddafiSaadi Gheddafi
Prof. Roberto Verna
Bohdan UlirachBohdan Ulirach
20032003
NANDROLONE LANDS IN TENNIS
20042004
McEnroe admits that he Bohdan UlirachBohdan Ulirach McEnroe admits that he
discovered he had taken
substances used in horse
racing
Greg Rusedski in 2004, one of the 47
positive players among the top 120 of
the ATP ranking
Prof. Roberto Verna
ANABOLIC STEROIDS
Jennifer
Capriati
Can transform an athlete
in less than two years
Prof. Roberto Verna
The use of steroid hormones is so effective...
...that they can transform a woman
Heidi Krieger
transform a woman directly into a man, as Heidi Krieger.
Prof. Roberto Verna
Andreas Krieger (39) today with his wife Ute
Winter
Heidi Krieger goldmedal in putting theshot at Europeangames in 1986 whenshe was 21
Corriere della sera 4 maggio 2003
Prof. Roberto Verna
���� muscle mass
� body fat
� stamina
Anabolic Agents(testosterone, nandrolone, stanzolol…)
� stamina
� aggressiveness
� catabolic action of glucocorticoids
� synthesis of red blood cells
� bone density
Long lasting use
Mental Damage:
Dysphoria
Psychosis
Dependence
Severe Depression
ANABOLIC AGENTSProhibited “in-out” competition
Liver Damage:
Cholestasis
Hepatitis
Benign and Malignant Tumors
Cardiovascular Damage:
Cardiomyopathy
Acute Myocardial Infarction
Cerebrovascular Accident
Pulmonary Embolism
Prof. Roberto Verna
Adverse effects of using anabolic agents depend on
the age and sex of the subject, the duration of
treatment, the dose and type of steroid used
Anabolic Agents
Adverse effects can be divided into
• generic
• specific to men
• specific to women
General adverse effects
�Acne;�Damage to the Reproductive System and Sterility;�Hypertension;
Anabolic Agents
�Hypertension;�Increased Risk of Cardiovascular Disease;�Abnormalities and Renal and Liver Dysfunction;�Aggressive and Violent Behaviour;�Tendon Injury and/or Bone Microfractures
Adverse effects specific to men
Gynecomasty;
Reduced Production of Male Hormones;
Anabolic Agents
Reduced Production of Male Hormones;
Testicular Atrophy and Oligo/azoospermia;
Infertility, Impotence;
Alopecia;
Increased Risk of Prostate Cancer.
Adverse effects specific to women
� Hirsutism and Hair Loss;� Menstrual Irregularities and Amenorrhea;
Anabolic Agents
� Menstrual Irregularities and Amenorrhea;� Atrophy of the Mammary Glands;� Voice Change;� Clitoris-megalia
���� Haematocrit���� Platelets
���� Levels of FSH and LH
Anabolic Agents
General Haematochemical Alterations
���� Levels of FSH and LH
���� Testosterone levels
���� HDL-cholesterol and total cholesterol
���� Glycemia, Insulinemia
���� Liver enzymes and indices of cholestasis
Analytes specific for anabolyzing substances
• FSH ↓
• LH ↓
• PT ↓
• PTT ↓
• Tot. Chol. ↓
• Testosteron ↓
• Estradiol ↓
• Estrone ↓
• LDL Chol ↑
• C- Prot
Prof. Roberto Verna
• Tot. Chol. ↓
• HDL Chol ↓
• GH
• CPK ↑
• AST - ALT ↑
• LDH ↑
• Total Proteins
• C- Prot
• S-Prot
• D-Dimer
• PAI-1
• ATIII
• APO A ↓
Alterated
hydro-saline
balance
Dehydration
Collapse
EFFECTSADVERSE EFFECTS
Decreased excretion of
other prohibited
substances in the urine,
masking the presence
Alteration of the hydro-
saline equilibrium
Dehydration, collapse
muscle cramps
Fatigue
Alteration of the
MASKING AGENTS
Diuretics, Epitestosterone, Probenecid,
Plasma expanders (dextran, hydroxyethyl-starch)
Alterated
hormonal
haematological
parameters
Increased
urine
excretion
Collapsemasking the presence
Alteration of the
hormonal and
hematological
parameters
Removal of fluid
resulting in loss of body
weight (sport weight
category)
Alteration of the
metabolism of sugars
and fats
Increased uric acid
Formation of kidney
stones, Kidney damage
Hypersensitivity reactions
Renal
lesions
Muscle cramps and
fatigue
Prof. Roberto Verna
They have the ability to
• alter the excretion of
prohibited substances,
mask their presence in urine
Zhang Yi
MASKING AGENTS
Prohibited “in-out” competition
• mask their presence in urine
or other samples used in
doping control,
• or modify the hematological
parameters
Prof. Roberto Verna
Useful to decrease weight in the orders divided by classes
• Dehydration
• Amenorrea
Ivan Ivanov
MASKING AGENTSProhibited “in-out” competition
• Amenorrea
• Anemia
• Electrolyte Dysequilibrium
• Osteoporosis
• Hypotension
Prof. Roberto Verna
Tests able to detect the use of diuretics
• Na
• K
• Cholesterol
• Ht
• Uric acid
• Glucose
• Urinary aldosterone
• Na, K Pump
• Na, K Cotransport• Plasma and
Urine electrolytes
• 17-OH corticosteroids
• Urine pH (or blood)
• Na, K Cotransport
Prof. Roberto Verna
• Small protein molecules made by biotechnology:
• GH
• GONADOTROPINS
PEPTIDE HORMONESProhibited “in-out” competition
• GONADOTROPINS
• ERYTHROPOIETIN
• INSULIN
THE DARKER SAMPLE CONTAINS BLOOD SO DENSE THAT IT DOES NOT COME DOWN ON TURNING THE TUBE UPSIDE DOWN
Prof. Roberto Verna
GH and gonadotropins have the same effects as testosterone: they are anabolizing agents but
PEPTIDE HORMONESProhibited “Prohibited “inin--out”out” competitioncompetition
anabolizing agents but block growth of long bones, generate gynecomasty, depression, testicular atrophy and hepatic tumors.
Prof. Roberto Verna
Long bone
growth block
Euphoria
Depression
EFFECTS ADVERSE EFFECTS
•In males promote the
production of
testosterone by the
In pre-puberal
Early epiphyseal cartilage
welding (block long bone growth)
Inhibition of spermatogenesis
in adulthood
Oligospermia / azoospermia
Testicular atrophy
PEPTIDE HORMONES
Chorionic gonadotropin (HCG) and synthetic pituitary hormone (LH)
Stimulation of
testosterone production
Damage
to reproductive
function
testosterone by the
testisTesticular atrophy
Prostatic hypertrophy
Abnormal liver function with the
possibility of tumors
Increased plasma lipid
States of euphoria and depression
Gynecomastia
Precocious puberty in adolescents
Liver damage
Increased
triglyceride
and cholesterol
Prof. Roberto Verna
Dizziness
Euphoria
Headache
Insomnia
EFFECTS ADVERSE EFFECTS
Increases the ability to
withstand stress
Anti-inflammatory
action
Hypertrophy of the adrenal
cortex
Osteoporosis
Myopathies
Damage to the gastro-
intestinal Peptic ulcer
PEPTIDE HORMONES
Corticotropin (ACTH)
Gastritis
Tendency
to diabetes
action intestinal Peptic ulcer
Shiny skin
Headache
Reduced tolerance to
carbohydrates
Dizziness
Euphoria, insomnia
Obesity
Gastritis
Ulcer
Muscular and bone fragility
Hypertrophy
of the
adrenal cortex
Increased
stress tolerance
Anti-inflammatory
action
Prof. Roberto Verna
CardiopathyHypertension
EFFECTS ADVERSE EFFECTS
Increased protein
synthesis
Increased muscle
tissue growth
Acromegaly in adults
Fluid retention and edema
(generalized and
peripheral)
Arthritis, carpal tunnel
PEPTIDE HORMONES
Growth hormone (GH) growth factor (IGF-1)
Increased protein synthesis
Diabetes
Muscular and joint damage
tissue growth
Increased height
growth in the young
(gigantism)
Increased lipolysis
Increased blood
glucose
Arthritis, carpal tunnel
syndrome
Cardiomyopathy
Hypertension
Hyperglycemia Diabetes
Increased hands and feet size
Increased volume oforgans
Stimolated bone growth
Increased release
of circulating
energy intake
Diabetes
Prof. Roberto Verna
Tests able to detect the use of GH
• GH
• LH
• FSH
• Cholesterol
• IGF-1
• IGF- BP2
• IGF – BP3
• NEFA • Cholesterol
• TG
• Creatinine Clearance
• BUN
• Glucose
• Insulin
Prof. Roberto Verna
Death for doping“Flo Jo” Griffith (1959-1998) caught an infectious disease because of the abuse of growth hormone extracted from corpses.
She said:“when you always get second, you can accept it or try to become the number one”.
Prof. Roberto Verna
EFFECTS ADVERSE EFFECTS
•Enhances glucose
uptake by the tissues
(mainly muscle,
adipocytes and liver)
•Hypoglycemic crisis (Arrhythmias, Cardiomiopathy, Coma, Death)
PEPTIDE HORMONES
Insulin
Stimulates protein synthesis
Hypoglycemia
adipocytes and liver)
•Stimulates protein
synthesis
•Hypoglycemia
induces GH release
Coma, Death)
• Inhibition of endogenous production
•Hepatic damage
Endogenous synthesis inhibition
Increases tissue uptake of glucose
Prof. Roberto Verna
•Stimulus to
erythropoiesis
•Increases oxygen
•Polyglobulia
• Increase of blood viscosity
•Myocardial Infarction
PEPTIDE HORMONES
Erythropoietin (EPO)
PoliglobuliaThrombosis
EFFECTS ADVERSE EFFECTS
•Increases oxygen
transport capacity •Thrombosis
• Ictus
•Pulmonary embolism
•Seizures
ThrombosisCardiac failure
Stimulates erythropoiesis
Prof. Roberto Verna
Prof. Roberto Verna
EPO increases erythrocyte
production thus oxygen
transport.
On the other hand, EPO makes
PEPTIDE HORMONESProhibited “in-out” competition
blood dense like marmalade:
the risk of death by thrombosis
increases by 400%
Prof. Roberto Verna
Tests revealing the use of EPO and analogues
• Peripheral blood examination
including RBC indices
• Reticulocytes ↑
• Transferrin
• Ferritin
• Folic Acid• Folic Acid
• Vitamin B12
• Iron
• CD 71
• Glycophorin A
• Bilirubin
• CFU-E
• BFU-EProf. Roberto Verna
Broncodilation
Cardiostimulatingaction
Agitation
Irritability
Insomnia
Heart rhythm
disorders
EFFECTS ADVERSE EFFECTS
Bronchodilation
Increasing the efficiency
of Myocardial Contractility
Lipolytic Action
(Increase of Free Fatty
Tremors, Agitation,
Irritability and Insomnia
Hyperhidrosis
Drooling
Urinary Retention
Beta 2 agonists
Stimulating and Anabolic Action
disorders
Urinary retention
(Increase of Free Fatty
Acids)
Hypertrophy
of Type II Muscle Fibers
Urinary Retention
Anorexia
Hypokalemia
Alterations in Blood Pressure
Tachycardia and
Rhythm Disturbances
Dyspnea
Hyper
hidrosis
Type II muscle
fiber hypertrophy
Lipolytic action
Prof. Roberto Verna
BETABETA--2 AGONISTS2 AGONISTS
THESE DRUGS HAVE AN EFFECTIVE
ACTION ON THE MUSCLE MASS WITHOUT
DETERMINING THE MANY SIDE EFFECTS
RELATED TO THE USE OF STEROIDS.
They are also used to prevent asthma triggered by
exercise
Prohibited “Prohibited “inin--out”out” competioncompetion
Growth in mass and
increased muscle strength
exercise
Clenbuterol produces a specific
protein anabolism in both normal
muscle and in the catabolic phase
through the activation of beta-2
adrenergic receptors present in
skeletal muscles themselves
Prof. Roberto Verna
Therapeutic dose range:
20-80 micrograms per day
Doses in doping:
100-140 micrograms per day
BETABETA--2 AGONISTS2 AGONISTSProhibited “Prohibited “inin--out”out” competioncompetion
SIDE EFFECTS: Tremor (very marked), and
cardiovascular effects such as tachycardia, palpitations,
arrhythmias, hypertension. Anxiety, dizziness, headache,
insomnia and muscle spasms were also observed.
Prof. Roberto Verna
Alopecia
Liver anomalies
EFFECTS ADVERSE EFFECTS
Indirect
anabolyzing
capacity
Nausea and vomiting
Headache and dizziness
Leukopenia
Thrombocytopenia
AGENTS WITH ANTIESTROGEN ACTIVITY
Aromatase inhibitors, clomiphene, cyclophenil
Nausea andVomiting
capacityThrombocytopenia
Severe skin reactions
Alopecia
Liver impairment
LeucopeniaThrombocytopenia
Indirect anabolyzing capacity
Prof. Roberto Verna
ANTIESTROGEN AGENTSANTIESTROGEN AGENTS
Prohibited in and out competition,
exclusively for men
Clomiphen
Prohibited in and out competition
Cyclophenil
Raloxifen
Tamoxifen
Toremifen
Aromatase inhibitors (Aminoglutethimide, Anastrozole, Exemestane,
Letrozole, Fludrocortisone and Desossicortone)
Prof. Roberto Verna
EFFECTS ADVERSE EFFECTS
Taken in small doses
it reduces anxiety and
nervous tension Depression of the
ALCOHOL
Depression of reflex activities
Reduced
anxiety and
nervous
tension
nervous tension
Increased self
confidence
Depression of the
nervous system
Impaired coordination
Liver damage
Altered coordination
Prof. Roberto Verna
ALCOHOLALCOHOL
Alcohol activates the
ventral area of the
brain and releases
Prohibited in particular sportsProhibited in particular sports
brain and releases
dopamine by
changing all the
positive feelings
Prof. Roberto Verna
Damage from alcohol
include severe liver
disease and risk for
infants of drinker
ALCOHOLALCOHOLProhibited in particular sportsProhibited in particular sports
infants of drinker
mothers: the foetal
alcohol syndrome
Prof. Roberto Verna
Anxiety decrease
EFFECTS ADVERSE EFFECTS
Reduction in blood
pressure
Decreased heart rate
Reduced contractility of
Negative effect on
aerobic performance
Increased perceived
exertion
BETABLOCKERS
Lightheadedness
Increased fatigue
Reduced contractility of
the heart
Reduction of oxygen
consumption
Reduction of tremor
Reducing anxiety
exertion
Bronchospasm in
patients with asthma
Bradycardia
Hypotension
Insomnia
Impotence
Possibility of
cardiac arrest
of bronchospasm
and hypoglycemia
Reduced cardiovascular activity
Reduced
aerobic
performance
Prof. Roberto Verna
BETABLOCKERSBETABLOCKERS
Beta-blockers reduce tremor with great
effectiveness, and are used in shooting
competitions
Prohibited in particular sportsProhibited in particular sports
Prof. Roberto Verna
• On the other hand, beta
blockers may cause heart
failure, bronchospasm
and even death.
BETABLOCKERSBETABLOCKERSProhibited in particular sportsProhibited in particular sports
and even death.
• Depression,
hallucinations, seizures
and alopecia are also
reportedProf. Roberto Verna
Tests to detect the use of beta-blockers
• TSH
• fT3
• fT4
• HDL-Chol
• TG
• Insulin
• Renin
• Emogas analysis
Prof. Roberto Verna
• TG
• NEFA
• Glucose
SPORTS YES, DOPING NO
DOPING IN SPORT IS A CRIME
AND MAY SERIOUSLY HARM
YOUR HEALTH
Prof. Roberto Verna
Prof. Roberto Verna
Genetic DopingGenetic Doping
chromosomes
genes
cell
genome
DNA
genes contain
instructions for
protein productionDNA
proteins
The proteins act alone or
in many cellular
functions in order to
explain complex
Prof. Roberto Verna
Genetical manipulation.Genetical manipulation.Which should the limit be?Which should the limit be?
Prof. Roberto Verna
• Based on the manipulation of genes.
• Using the results obtained in gene
therapy.
Genetic DopingGenetic Doping
therapy.
• Is it a future threat for athletes?
Prof. Roberto Verna
Gene TherapyGene Therapy• Artificial insertion of genes into the body of the patient.
Purpose:
• Kill or weaken cancer cells.• Kill or weaken cancer cells.
• Making the body able to reproduce on its own substances now available only on administration.
• Replace defective genes with healthy copies.Problems: lack of control on the expression of artificial gene.
Prof. Roberto Verna
The structure of a Gene
DNADNA
Control regioncoding region
RNARNA
ProteinProtein
Prof. Roberto Verna
How is an artificial gene
introduced ?
1. Direct injection of DNA into muscle structures
2. By inserting genetically modified cells2. By inserting genetically modified cells
3. Introduction of the gene in the organism using a virus
as a vector
Prof. Roberto Verna
Direct injection of DNA into a
muscle
Prof. Roberto Verna
Direct injection of DNA into a
muscle
Prof. Roberto Verna
Quadriceps mouse Quadriceps mouse muscle after a single muscle after a single
Direct injection of DNA into a
muscle
Danko et al. Human Molecular Genetics (1997) 6:1435-1443
muscle after a single muscle after a single injection of a plasmid injection of a plasmid containing a gene, containing a gene,
evidenced by the blue evidenced by the blue color (color (lacZlacZ))
Prof. Roberto Verna
Inserting genetically modified
cells
Prof. Roberto Verna
Inserting genetically modified
cells
Prof. Roberto Verna
Inserting genetically modified
cells
Prof. Roberto Verna
Inserting genetically modified
cells
Prof. Roberto Verna
Inserting genetically modified
cells
Prof. Roberto Verna
Inserting genetically modified
cells
Prof. Roberto Verna
Using a virus as a vector
Prof. Roberto Verna
Using a virus as a vector
Prof. Roberto Verna
The prospect of gene
doping
• An alternative to the administration of drugs
that the body can produce itself
• Changing the natural regulation of genes
• Enhancement of proteins in the body
Prof. Roberto Verna
Examples of the potential of
gene doping
• Increase in hematocrit by EPO
• Increased muscle strength by IGF-1
• Increased muscle mass by the removal of • Increased muscle mass by the removal of
myostatin
• Increased blood flow through VEGF
Prof. Roberto Verna
Gene therapy using EPO
Monkeys
EMATOCRITO
Zhou et al. Gene Therapy (1998) 5:665-670
Monkeys
inoculated with a
virus carrying the
gene for EPOEMATOCRITO
WEEKS AFTER INOCULATION
Prof. Roberto Verna
Mice inoculated with a
virus carrying the gene
for IGF-I
Gene therapy using IGF-I
Barton-Davis et al. Proc.Natl.Acad.Sci. (1998) 95:15603-15607
Prof. Roberto Verna
Removing the gene that controls the
growth of muscle mass (myostatin)
Foreleg of a Foreleg of a Foreleg of a
normal mouse
Lee et al. Curr. Opin. Gen. Dev. (1999) 9:604-607
Foreleg of a
mouse lacking
the myostatin
gene
Prof. Roberto Verna
Prof. Roberto Verna
Prof. Roberto Verna
Prof. Roberto Verna
VEGF gene therapy on
humans
Blood vessels of a patient
Baumgartner et al. Circulation (1998) 97:1114-1123
AfterAfter
Blood vessels of a patient
who received the
inoculation of a virus
carrying the gene for
VEGF
BeforeBefore
Prof. Roberto Verna
Can we discover
genetic doping?• The protein produced is equal to the endogenous
protein
• The artificial DNA is present only locally after an
injection with pure DNA or genetically modified
cellscells
• You should know the sequence of artificial DNA
to be able to detect it
Prof. Roberto Verna
POSSIBLE COUNTERMEASURES
• Making the gene doping illicit
• Establish close contacts with companies that
produce gene therapies
• Developing DNA tests that can detect artificial
genes used in gene therapygenes used in gene therapy
• Developing indirect methods to detect gene doping,
if possible
Prof. Roberto Verna
WHEN?WHEN?• Gene doping is already present and it
constitutes a serious risk to the athlete
• It will be easier when gene therapy
becomes a standard procedure
(in 10-20 years)
Prof. Roberto Verna
THANK YOU FOR YOUR
ATTENTIONATTENTION
THE PROBLEM OF FOOD
SUPPLEMENTS
The world of sport, professional or not, looks for a
"magic" and harmless ingredient that can improve
physical performance and increase the level of
competitiveness
Companies promote the spread of specialized
products designed specifically for sports
These substances are not always safe
Prof. Roberto Verna
Recently, the European Directive on food supplements
(46/2002/EC of June 10th, 2002) has been transposed
in Italy
FOOD SUPPLEMENTSFOOD SUPPLEMENTS
products capable of performing
nutritional effects physiological effects
Prof. Roberto Verna
FOOD SUPPLEMENTS:FOOD SUPPLEMENTS:(46/2002/CE 6(46/2002/CE 6--1010--2002)2002)
in particular, but not limited to, vitamins, minerals,
capsules, tablets, bars, vials, bags
in particular, but not limited to, vitamins, minerals,
amino acids, fatty acids, fibers and herbal extracts
Prof. Roberto Verna
Guidelines on foods intended to meet
intense muscular effort, especially for sportsmen
Products aimed at energy integration
Products with minerals designed to restore salt and
water losses (...)water losses (...)
Products for the integration of proteins
Products for the integration of amino acids and
derivatives (creatine)
Other products with nutritional value, adapted to an
intensive muscular effort
Combination of the above products
Prof. Roberto Verna
VITAMINS AND MINERAL SUPPLEMENTS
Supplementation of vitamins in the diet, in most cases, is
incongruous and unnecessary
Minerals replenish salt and water losses resulting from
physical activity
incongruous and unnecessary
Sportsmen seldom have a vitamin deficiency
Moreover, if vitamins are “good”, it doesn’t
mean they can’t become “bad” if abused
Prof. Roberto Verna
Even among sportsmen the culture of “natural
supplement” is becoming more widespread
The erroneous belief that, being natural, must necessarily be
harmless
The effect of word of mouth propagation, especially in clubs
HERBAL PRODUCTS
The effect of word of mouth propagation, especially in clubs
and gyms
Advertising campaigns not subject to controls
The wide availability on parallel sales channels (internet)
self-medication w/out supervision
Prof. Roberto Verna
A scientific demonstration of effectiveness
Correct information of the action on the body and
on the performance
Certainty of the content of products
Is the use of supplements “safe”?
ARE MISSINGARE MISSINGARE MISSINGARE MISSING
- Health risks
- Commercial fraud
- Positivity to antidoping tests
Prof. Roberto Verna
Incongruous / Hazardous
use of supplements and health products
Raw materials and production processes are not
always controlled.
Extreme vagueness in the indication of the dosages.Extreme vagueness in the indication of the dosages.
Lack of references to age, sex, body weight, in place to
pathological situations (hypertension)
Belief that the dosages are not critical as for medicines.
There isn’t any real assessment of the effectiveness and toxicity
of such products
Prof. Roberto Verna
Presence of pharmacologically active
molecules that have names quite often
misleading:
Incongruous / dangerous use of
supplements and health products
misleading:
ma-huang, guarana, pullulan, etc. ...
Different composition versus the one
shown on the label(contamination, whether deliberate or accidental)
Prof. Roberto Verna
“ETERNAL LIFE” (slimming)
Dictamnus dasycarpus plant contains numerous toxins
3 cases of liver failure, 1 death
Incongruous/hazardous use ofsupplements and health products.
“JIN BU HUAN ” (sedative, analgesic)
Lycopodium serratum plant containing
a morphin-like alkaloid
7 cases of hepatotoxicity and acute liver failure
Prof. Roberto Verna
Different composition from the one declared on
the label (contamination, whether deliberate or
accidental, with doping substances or their
precursors)
Potential risk of
positive drug test
precursors)
Active ingredients contained in herbal products
marked with an “unusual” name (eg, ephedrine
/ ma huang-...)
Unknown interactions with other drugs /
metabolites and / or endogenous substances
Prof. Roberto Verna
� Product based on a mixture of herbs, free for
sale
� Declared ingredients: Cola nut, Passiflora, Ma-
Potential risks of a positive doping
test: an example...
� Declared ingredients: Cola nut, Passiflora, Ma-
huang, Siberian Ginseng, Chinese Dandelion,
Ginger, Seaweed, Pullulan, Gymnema sylvestre
� The analysis showed the presence of ephedrine
(ephedrine, methylephedrine).
Prof. Roberto Verna
The presence of anabolic steroids was found in
some packages of food supplements
in individual packages, NOT all
Potential risks of a positive doping test:
a further example...
The contaminated products are often of U.S. production, almost
always not available over the counter, but on safe parallel channels
particularly Internet
Contaminated capsules contained steroids
in amount ranging from 0.3 to 500 micrograms
in individual packages, NOT all
the capsules were contaminated
Prof. Roberto Verna
Supplements and herbal products
should be considered as drugs?
YES, YES, accordingaccording toto WHOWHO
Editorial in JAMA, March 26th, 2003: supplements
should be considered in all respects and consequently
medication should be adequate evidence available on
their validity.
Prof. Roberto Verna
It has been proposed the use of a mark
(Green Seal?)
to be applied to these products,
with the indication of:
ABSENCE OF SUBSTANCES
PROHIBITED FOR DOPING
Prof. Roberto Verna
The administration of medications,
including supplements, to people
without disease, as in the case of
athletes, is always dangerous because
there is no therapeutic need, that is thethere is no therapeutic need, that is the
main purpose of a medication.
Prof. Roberto Verna
The excessive "medicalization",
represents a serious danger for the athlete,
NOT ONLY FOR THE POSSIBILITY OF A
POSITIVITY TO DOPING TESTS,
BUT ALSOBUT ALSO
FOR THE POSSIBLE OCCURRENCE OF
ADRs
ADR: ���� Adverse Drug Reaction
Prof. Roberto Verna
The ADRs in the U.S. (JAMA 1998; 279: 1200-05)
are, incidentally, the fourth leading cause of death
after cardiovascular diseases, cancer and stroke:
more than 100,000 deaths / year.more than 100,000 deaths / year.
The data comes from a meta-analysis of 39 prospective
studies in hospitalized patients:
��������2.216.000 2.216.000 patients with serious non-fatal ADRs
�������� 106.000 106.000 patients with fatal ADRs
Prof. Roberto Verna
DoubtsDoubts ofof Sport MedicineSport Medicine
Can the sports physician, motivated by the need for prevention
(no disease) administer drugs without violating the law and
professional ethics?
The physician of professional societies should make a note of
the use of supplements/health products
TUE: Therapeutical Use Exemption
Prof. Roberto Verna