Download Rheumatological prescribing in athletes: a review of the new World

Rheumatology 2004;43:1473–1475
Advance Access publication 3 August 2004
doi:10.1093/rheumatology/keh338
Review
Rheumatological prescribing in athletes: a review of
the new World Anti-Doping Agency guidelines
R. Smith, L. Barnsley, S. Kannangara and A. Mace1
Rheumatologists, with their musculoskeletal background, often care for athletes. The effect of a positive anti-doping test,
whether through illegitimate use or accidental prescribing of banned drugs, is devastating to an athlete’s career. It is therefore
incumbent upon rheumatologists to be aware of issues relating to drugs in sport. This involves both therapeutic drugs and
doping. It is vital to ensure that any substance prescribed should be approved for use and should not adversely affect (or benefit)
the athlete’s performance. In March 2004, 5 months prior to the 2004 Olympic Games in Athens, the joint World Anti-Doping
Agency/International Olympic Committee published the revised list of banned substances in athletes. This article aims to
provide an overview of the current status of medications commonly prescribed in rheumatological practice.
KEY WORDS: Rheumatology, WADA (World Anti-Doping Agency), IOC (International Olympic Committee), Doping.
The term ‘doping’ first appeared in an English dictionary in
1879, its definition being ‘the use of drugs in an attempt to
enhance sporting performance’. The word ‘dope’ originated in
South Africa. Dope referred to a primitive alcoholic drink that
was used as a stimulant in ceremonial dances [1].
The results of a positive doping testing can be devastating
to an athlete’s career and the reputation of their club or country.
A positive doping test results from the ingestion or administration of a banned substance either intentionally or accidentally.
To avoid the potentially tragic error of accidental prescribing of
banned drugs, it is vital that physicians caring for athletes of
all backgrounds are fully educated. In light of the heightened
interest in sport in this Olympic year and the recent revision of
the World Anti-Doping Agency/International Olympic Committee
(WADA/IOC) guidelines [2], this article aims to serve as a review
of this important topic.
educate athletes about the harmful effects of doping, reinforce
the principles of fair play and detect those who cheat. In 2003
all major sporting federations and 73 governments approved a
resolution accepting the WADA Code as the basis for the fight
against doping.
A number of athletes who have tested positive for banned
substances have used the defence that the substance was taken
unknowingly as a nutritional substance or a prescribed or overthe-counter medicine. High-profile cases have included Alain
Baxter, the British downhill skier who, in 2002, was stripped of
his Olympic bronze medal after testing positive for methamphetamine from the US version of a ‘Vicks’ nasal inhaler. Only the
non-performance-enhancing L isomer of methamphetamine was
detected; however, the IOC does not distinguish between the two
isomers and despite appeal he received a 2-yr ban.
Testing
Drugs in sport
The use of performance-enhancing drugs by professional
athletes dates from antiquity. Roman gladiators and Greek
Olympians were known to use stimulants and hallucinogens. In
1886 an English cyclist became the first recorded fatality from
a performance-enhancing drug after an overdose of trimethyl
during a race in France [3]. The first near death in modern
Olympics occurred in 1902 when a marathon runner, Thomas
Hicks, collapsed after ingesting a mixture of brandy and
strychnine. The first actual death recorded in the modern
Olympics was in 1960 when the Danish cyclist Kurt Jensen
collapsed and died from amphetamine overdose [1].
Testing of human athletes for performance-enhancing drugs
did not begin until 1965 (over half a century after testing was
introduced in racehorses). The first IOC banned substances list
was produced in 1968, subsequently the WADA was created
in November 1999 through a collective initiative of sporting
organizations and government led by the IOC. WADA aims to
Athletes can be selected for testing at any time, anywhere,
without notice and may be asked to provide a blood or urine
specimen [4]. Failure to comply with the specified times of testing carries the same sanctions as a positive test. Specimens
are analysed at an approved WADA/IOC laboratory, usually
by gas chromatography or isotope mass spectrometry. Unless
specifically stated (e.g. ephedrine, salbutamol, morphine) there
are no threshold levels—detection of any concentration of a
banned substance is considered a positive test. Management of
the results is governed by the international federation for the
relevant sport. The athlete has a responsibility to inform any
doctor treating them that they are a competitor who is subject
to anti-doping controls; at the same time it is prudent practice
to seek this information as part of the medical history. Athletes
must also inform the international federation in advance if they
are medically required to take any substance on the prohibited
list. A medical exemption (Therapeutic Use Exemption, TUE)
must be applied for [5]. A shortened version of this form
New South Wales Institute of Sports Medicine, Concord Hospital, Sydney, Australia and 1Department of Otolaryngology, Charing Cross Hospital,
London, UK.
Submitted 20 May 2004; accepted 28 June 2004.
Correspondence to: L. Barnsley, New South Wales Institute of Sports Medicine and Department of Rheumatology, Concord Hospital, NSW 2139,
Australia. E-mail: [email protected]
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R. Smith et al.
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(Abbreviated Therapeutic Use Exemption, ATUE), formally
known as a medical notification, is only available to athletes
requiring inhaled salbutamol or for non-systemic administration
of corticosteroids during competition.
Drugs used for crystal arthritis
Colchicine is permitted for the treatment of acute gout.
Allopurinol is also permitted for gout prophylaxis; however,
probenecid may be used as a masking agent and is therefore
banned.
Rheumatology and drugs in sport
Rheumatologists are likely to see athletes in two circumstances.
Firstly, as patients with athletic or sports-related injuries and
secondly as athletes with coincidental rheumatic disease [6].
Although the responsibility lies with the athlete to be aware of
the substances prohibited in their sport, the devastating affect
of a positive doping test on an athlete’s career and reputation
mean that great care must also be taken by those who prescribe
for them. This article aims to act as a guide for rheumatologists
prescribing not just specialist medications but also drugs commonly encountered in daily practice (Table 1). The following list
is not exhaustive but covers the most routinely prescribed classes
of medications.
Corticosteroids
Systemic administration of corticosteroids is banned in competition. This includes oral, intramuscular and intravenous routes;
if required a regular TUE must be granted. Most commonly
prescribed topical corticosteroids have some systemic bioavailability and are liable to be detected when used at normal
therapeutic doses [7–9]. Non-systemic administration of corticosteroids, topical, inhaled, rectal and intra-articular, may only
be administered providing an abbreviated TUE is granted.
Local anaesthetics and adrenaline
Local anaesthetics are permitted when administered by local
or intra-articular injection. Adrenaline is banned in competition;
however, it may be used in emergency settings (haemorrhage
or anaphylactic shock). If a medical team has to administer
adrenaline during a competition, the completion of a TUE will
be required.
Anabolic steroids
Anabolic steroids are occasionally used for management of
osteoporosis in hypogonadal males (e.g. sustanon) and stanazol
is occasionally indicated for vascular manifestations of Behçet’s
disease and hereditary angioedema. All anabolic steroids are
prohibited.
Agents with anti-oestrogenic activity may be illegally used
to counteract undesirable side-effects associated with anabolic
steroid use, such as gynaecomastia (development of breast tissue). Therefore agents such as aromatase inhibitors and tamoxifen
are banned in males, but not females.
Drugs used for management of osteoporosis
All NSAIDs and the newer selective cyclo-oxygenase 2 inhibitors
are permitted orally, intramuscularly or topically.
As stated above, anabolic steroids and drugs masking their
side-effects are banned in males. Bisphosphonates, calcitonin,
recombinant parathyroid hormone, strontium, fluoride, calcium
and vitamin D are all permitted.
Disease-modifying anti-rheumatic drugs (DMARDs)
Narcotics
These drugs act via mechanisms that neither enhance or detract
from performance and are therefore freely permitted. New
treatments for inflammatory diseases classified as ‘biologicals’
such as etanercept, adalimumab and infliximab do not appear on
the WADA prohibited list and are therefore freely permitted.
Dextromoramide, morphine,
buprenorphine, methadone,
diamorphine, oxycodone oxymorphone, hydromorphone, pentazocine and pethidine are all prohibited. However, codeine,
dihydrocodeine and dextropropoxyphene are allowed but the
risk of adverse effects on performance must be considered.
Non-steroidal anti-inflammatory drugs (NSAIDs)
TABLE 1. Commonly prescribed drugs in rheumatology and their current WADA/IOC status
Drug
Permitted
Banned
Corticosteroids
NSAIDs/COXIBs
DMARDs
Gout medications
Vasodilators
Osteoporosis
medications
Opiates
Simple analgesia
Asthma
medications
Antimicrobial agents
TUE
Oral,
intravenous,
intramuscular
All permitted
Methotrexate, sulphasalazine,
plaquenil, cyclosporin,
azathioprine, penicillamine,
gold, biologicals
Allopurinol, colchicine
Nifedipine, losartan, irbesartan,
perindopril
Bisphosphonates, calcitonin, fluoride,
calcium, vitamin D
Codeine, dihydocodeine,
dextropropoxyphene
Paracetamol, codydramol, coproximal
Ipratropium bromide, sodium
chromoglycate
All antibiotics, terbinafine, acyclovir
Abbreviated TUE
Topical,
intra-articular
Probenicid
Irbesartan and perindopril
combinations with thiazides
All anabolic steroids, tamoxifen
(males only)
Morphine, dextromoramide,
buprenorphine,
methadone, diamorphine
Salbutamol, formoterol,
salmeterol, terbutaline
Miconazole
Fluconazole
Rheumatological prescribing in athletes
Vasodilators and other antihypertensive agents
All diuretics including frusemide and thiazides are considered
masking agents and prohibited unless a TUE is accepted. A
TUE for diuretics is invalidated if found in association with
a prohibited substance. Vasodilators such as calcium channel
blockers and ACE inhibitors are permitted, although care must be
made when prescribing some compound antihypertensives which
may contain banned diuretics; examples include irbesartan–hydrochlorothiazide and perindopril–indapamide combinations.
In certain weight-classified sports and sports where weight
loss can enhance performance a TUE for diuretics will not be
granted. This includes ski jumping, weight lifting, rowing and
judo, amongst others.
Decongestants
Imidazole preparations such as oxymetazoline, xylometazoline
(Otrivine, Vicks Sinex, Dristan) and tramazoline (Dexarhinaspray Duo) are likely to be found in over-the-counter
combination remedies which athletes may not consider to be
drugs. They may also be prescribed in the short term for
exacerbations of rhinitis and rhinosinusitis, otitis media and
prior to flying. These and ‘other substances with similar chemical
structure or pharmacological effects’ are, however, considered
stimulants and permitted only for topical use. Even with topical
use a test is considered positive for ephedrine and methylephedrine if urinary concentrations greater than 10 mg/ml are
detected. Phenylephrine and pseudoephedrine (Sudafed) have
recently been removed from the banned list and transferred to
the 2004 monitoring programme (a programme where a samples
are tested for the substance to monitor and detect potential
misuse in sport) and are therefore permitted at present.
Antihistamines
Antihistamines are not prohibited; however, an important
principle of prescribing to athletes is that no medication should
adversely affect the athlete’s performance. First-generation antihistamines may have undesirable sedating and anticholinergic
side-effects, such as decreased sweating, if taken orally. Intranasal azelastine (Rhinolast), however, has been shown to have no
adverse affect on performance [10] and may be used to manage
seasonal allergic rhinitis.
Antimicrobial drugs
All antibiotics are freely permitted, as is acyclovir; however,
some antifungal agents are banned. Miconazole (Daktarin Oral
Gel) is an imidazole and therefore a potential stimulant. It is
prohibited unless used solely as a topical agent. There is
obviously potential for systemic absorption across the buccal
mucosa and by ingestion and a TUE should be applied for. Nonimidazole antifungals are permitted.
Peptide hormones
Erythropoeitin, insulin, growth hormone, insulin growth factor
(IGF1), corticotrophins and gonadotrophins are all prohibited
unless elevated levels can be proved to be due to pathological or
physiological condition.
Asthma medications
2 agonists are prohibited in and out of competition except
formoterol, salbutamol, salmeterol and terbutaline which may
be used in conjunction with an abbreviated TUE. A urinary
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salbutamol concentration greater than 1000 ng/ml is considered an
adverse finding. The inhaled medications ipratropium bromide
and sodium chromoglycate, often used for exercise-induced
asthma, are all permitted.
Other considerations
Certain substances are prohibited in competition only in
particular sports. Beta-blockers and alcohol are banned in any
sport where their systemic effects may convey benefit. These
include archery, billiards, football, skiing and automobile/
aeronautic sports amongst others.
Caffeine, a common component of over-the-counter coryzal
remedies, was removed from the prohibited list in 2003 and
transferred to the 2004 monitoring programme.
To facilitate compliance with the WADA guidelines prescribers should ensure that adequate supplies of medications of
known composition are available. This is particularly important
for athletes training or competing abroad where locally available
drugs may differ from similarly named medications from the
athlete’s home country.
Summary
Care should be taken when prescribing medications to athletes.
Drug testing can occur at any time, both in and out of
competition. The onus is on the athlete to be aware of any
doping regulations in their particular sport but the prescribing
physician should be aware of both the general and specific issues
in prescribing to athletes. Compliance with the regulations
governing drugs in sport should be considered part of sound
clinical practice.
The authors have declared no conflicts of interest.
References
1. Australian Sports Drug Agency (ASDA). www.asda.org.au
2. World Anti-Doping Agency. World Anti-Doping Code—the
Prohibited List 2004. International Standard, 17th March 2004.
www.wada-ama.org
3. Walder GI, Hainline B. Drugs and the Athlete. Philadelphia: Davis
Co., 1989.
4. Athletes Guide to WADA’s Out of Competition Doping Control
Programme, 2003. www.wada-ama.org
5. International Standard for Therapeutic Use Exemption, Section 8.
http://www.wada-ama.org/docs/web/standards_harmonization/code/
tue/tue_v3.pdf
6. Gibson T. Sports injuries. Baillieres Clin Rheumatol 1987;1:
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