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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] 1473 Rheumatology Vol. 43 No. 12 ß British Society for Rheumatology 2004; all rights reserved R. Smith et al. 1474 (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 1475 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: 583–600. 7. Daley-Yates PT, Price AC, Sisson JR, Pereira A, Dallow N. Beclomethasone diproprionate: absolute bioavailability, pharmacokinetics and metabolism following intravenous, oral, intranasal and inhaled administration in man. Br J Clin Pharmacol 2001; 51:400–9. 8. Daley-Yates PT, Baker RC. Systemic bioavailability of fluticasone propionate administered as nasal drops and aqueous nasal spray formulations. Br J Clin Pharmacol 2001;51:103–5. 9. Thorsson L, Borga O, Edsbacker S. Systemic bioavailability of budesonide after nasal administration of three different formulations: pressurized aerosol, aqueous pump spray, and powder. Br J Clin Pharmacol 1999;47:619–24. 10. Chicharro JL, Lucia A, Vaquero AF, Perez M. Azelastine does not adversely affect aerobic performance. J Sports Med Phys Fitness 1998;38:266–71.