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the sports patient
Drugs used to
How drug abuse
The future of
drugs in sport
DR MICHAEL KENNEDY,
consultant physician and
clinical pharmacologist in
private practice; VMO at Manly
Hospital and Mater Hospital,
North Sydney; and research
associate, department of clinical
pharmacology and toxicology,
St Vincent’s Hospital,
in sport and exercise
MEDICAL practitioners may mended, such as avoiding injecting into
become involved in the area of med- Table 1: Clinically important drug exercise interactions the site of working muscle by changing
ication in sport in various ways. As injection sites, lowering insulin dose
doctors we are often expected to Drug Exercise effect and ensuring adequate glucose is taken
know almost everything about drugs, Insulin Increases absorption or available during exercise.
so a frequent question for the doctor
will be about the safety and efficacy Lithium Increases plasma concentration Drug distribution
of medications used by athletes. Transdermal nitrates Increases absorption Alterations in drug distribution
GPs may manage sports patients throughout the body as a result of
who present with symptoms that are Warfarin Decreases INR exercise have been studied in only a
potentially drug related, or they may Theophylline Increases plasma concentration and extends few drugs. An increase in distribution
be asked to advise patients about the half-life of digoxin results in highly significant
effects of a prescribed or comple- reductions in plasma concentrations
mentary therapy on sporting perfor- oxygen used per kilogram of body tion of transdermal nitrates and because of increased binding to stri-
mance. Less frequently there may be weight per minute exercising), gastric insulin is increased during exercise. ated muscle. However, the concentra-
a request to prescribe a drug to emptying is slowed and at this level In one study of the absorption rates tions return to pre-exercise levels one
enhance performance. of intensity there will be delayed of insulin from the arm, abdomen hour after exercise.
absorption of drugs. and leg in 11 subjects with type 1 The clinical significance of this is
Effect of exercise on Studies of a six-week exercise pro- diabetes during and after four con- uncertain and a 16-week exercise
pharmacokinetics gram have demonstrated increases in secutive periods of cycling, there was program was found to have no effect
Absorption small bowel transit time, so in some increased absorption from the leg.1 on the kinetics of digoxin when con-
Low levels of exercise have little cases, such as with slow-release for- Such effects are clearly of clinical centrations were studied in patients at
effect on gastric emptying but when mulations, drug absorption may be importance. rest.
exercise reaches 70% of maximum, impaired. Strategies to prevent hypoglycaemia Although some small decreases in
that is, 70% VO2 max (the amount of Cutaneous blood flow and absorp- from these kinds of effects are recom- cont’d next page
www.australiandoctor.com.au 14 January 2005 | Australian Doctor | 23
How to treat - medication in sport and exercise
from previous page Drug metabolism In a study of 21 patients receiv- ance of diazepam was unaffected studies on this.
the volume of distribution, with ing propranolol 80-320mg/day, by exercise.1
resulting rises in plasma concentra-
occurs in many exercise resulted in the plasma Renal blood flow falls from Therapeutic index
tions, have been found in the cases organs but concentrations rising 13-41% but 1.1L/min at rest to 0.9L/min Theophylline is a drug with a low
of atropine, theophylline, salbuta- principally through falling to pre-exercise values on during moderate exercise and therapeutic index. With exercise
mol, oxprenolol and verapamil, the liver. recovery.1 Long-term exercise does 0.6L/min in extreme exercise. its volume of distribution decreases
these are not likely to be of clinical not alter the kinetics of propra- Atenolol, a beta blocker, is but its half-life increases from 6.5
importance. nolol at rest. largely eliminated by renal mecha- hours to up to 7.2 hours.
The pharmacokinetics of nisms. When 100mg atenolol was This finding can be important
Metabolism carvedilol (Dilatrend, Kredex), a administered to 12 healthy sub- because changes in half-life may
Drug metabolism occurs in many beta-blocking agent with high first- jects, exercise was found to increase the risk of toxicity.
organs but principally through the pass metabolism, were unaffected decrease renal clearance by 8% in Warfarin is widely used and has a
liver. Hepatic blood flow falls by exercise in one study of 11 one study, 1 and in another the low therapeutic index. While there
from a normal value of 1.35L/min patients with hypertension.1 plasma concentrations rose 9% have not been any pharmacokinetic
to 0.6L/min during medium-level Hepatic drug metabolism is after exercise.1 studies carried out during exercise, a
exercise and to 0.3L/min during unaffected by short episodes of Lithium, which is also elimi- two-to-threefold increase in overall
extreme exercise. It would thus be exercise, but physical conditioning nated by the kidneys, would also walking distance has been shown to
expected that drugs with high has been shown to increase the be expected to have considerable decrease INR values, hence the need
hepatic extraction ratios would clearance of phenazone, a marker variations in its plasma concentra- to carefully monitor such patients
have decreased clearance during of drug metabolism. In one of the tions in endurance exercise, when instituting an exercise pro-
exercise. few studies in this field, the clear- although there are no specific gram (see table 1, previous page).
Prescribing for the sports patient
IN the past, sporting activity was largely the domain of the Diuretics Lipid-lowering agents
young and fit. The situation is now very different, with almost all Diuretics are used alone and These are one of the best
age groups taking part in exercise or sporting activity. in combination formulations examples of a medication
Today exercise is recommended as part of the management of for the management of hyper- prescribed as a primary pre-
various medical conditions and even athletes with severe dis- tension and heart failure. ventive agent and taken for
abilities such as paraplegia may take part in endurance sports. They are also often used to many years by many people
With the current emphasis on drug-related prevention and ‘make weight’ in some sports who are physiologically
management of diseases, many patients participating in sport or such as weightlifting and normal.
exercise will be taking medications such as lipid-lowering agents, boxing, and can lead to severe It is well recognised that
antihypertensives, psychotropic agents or contraceptive med- dehydration resulting in syn- 3-hydroxy-3-methylglutaryl
ications. They may be taking one or more prescribed medications cope. coenzyme A (HMG CoA)
and possibly one or two complementary therapies. When used for the treat- reductase inhibitors cause
Despite the many medications consumed, there are surprisingly ment of hypertension there is myositis and even rhabdomy-
few data about their effects on sporting performance. There are an initial decrease in plasma olysis in a small percentage
several reasons for this. For example, pharmaceutical companies volume, which usually returns of patients. However, drug-
usually do not see the need for such studies in ‘normal’ subjects to normal. The therapeutic related rhabdomyolysis as a
and any adverse finding would have a negative effect on a prod- effects are largely mediated by result of exercise combined
uct’s marketing profile. Such studies are also usually have a low actions on the peripheral cir- with use of HMG CoA
priority for grant-allocating bodies. culation. reductase inhibitors has not
Studies in athletes show been reported.
Cardiovascular drugs frusemide 40mg has little Exercise results in a rise in
Nitrates effect on VO2 max, but higher creatine kinase level, which
All nitrates relax smooth muscle and hence decrease cardiac doses have an adverse reac- may be more prolonged in
preload. In patients with ischaemic heart disease, nitrates increase tion profile greater than users of these agents. Such ele-
treadmill time. There is also increased absorption of medication would be expected from dehy- vations, while infrequent, have
from transdermal patches during exercise. dration alone. also been reported in associa-
Patients using nitrates should be made aware of the possibility The carbonic anhydrase tion with the use of some of
of adverse reactions such as dizziness or presyncope during inhibitor acetazolamide is the newer antipsychotic agents
exercise. Patients with coronary disease undertaking exercise used to prevent some of the such as olanzapine and cloza-
should also be advised about the possibility of syncope when medical complications pine (see next page).
using sublingual or aerosol preparations, and also of the need to associated with high alti- At this time it is not possi-
sit down when using a nitrate formulation to relieve angina. tudes. It causes a decrease ble to implicate any specific
in exercise endurance, pos- agents, so an association
ACE inhibitors and angiotensin-II-receptor antagonists sibly because of mild acido- should be considered in cases
ACE inhibitors vary in their pharmacokinetic profiles and tissue sis inhibiting muscle glycol- in which any of these drugs is
binding. While there are differing claims about the efficacy of ysis. being administered and there
individual agents, there is no doubt about their ability to improve Most patients Most patients undertaking Diuretics are sometimes are clinical symptoms.
exercise levels in patients with heart failure. exercise in cardiac rehabilita- prescribed by doctors to Clearly, elevations greater
There are several exercise studies in both hypertensive and nor- undertaking tion programs will find beta avoid anabolic-steroid- than three times the upper
motensive subjects using treadmill and stationary exercise bike exercise in cardiac blockers do not hinder their related oedema but more limit of the reference range
protocols. When compared with placebo there is no change in rehabilitation progress. Apart from those often they are taken by persisting for several days
either VO2 max or lactate threshold on various exercise-related who develop bronchospasm, steroid users without medical after exercise has stopped
programs will the most common adverse advice. Diuretics of any type need to be considered as drug
There is a slight attenuation in the peak level of blood pres- find beta blockers reaction experienced is fatigue. are banned in various sports, rather than sport related.
sure. Some reports of decreased endurance with one agent have do not hinder because they are used as There is no indication for
yet to be confirmed with other similar studies. their progress. Calcium-channel blockers masking agents. routine testing unless there is
Angiotensin-II-receptor antagonists have clinical profiles and These fall into two broad cat- Many steroid abusers are a reasonable clinical indica-
haemodynamic actions similar to those of ACE inhibitors. egories — those decreasing aware of potassium loss that tion.
AV conduction (verapamil, occurs with diuretics and take The bile-acid-binding resins
Beta blockers diltiazem) and the dihydropy- supplements. They sometimes cholestyramine and colestid
These agents can be classified by their lipid solubility, beta1 ridines (nifedipine, felodipine, co-administer spironolactone, are hydrophilic and cause
selectivity, partial agonist activity or partial alpha-blocking amlodipine, lercanidipine) which can result in lethal constipation. It is therefore
actions. Extensive studies evaluating their effects on exercise which have no effect on AV hyperkalaemia. essential to ensure adequate
performance have shown: conduction. hydration in people who exer-
■ Attenuation of exercise-related tachycardia. All members of this group Digoxin cise and take these medica-
■ Decreased negative effect on cardiac output with increasing increase the threshold at which Cardiac glycosides increase tions.
stroke volume. angina occurs. The maximum cardiac output in patients with The fibric-acid derivatives
■ Decreased VO2 max (greater effect in trained patients). heart rate reached with exer- cardiac failure. They do not gemfibrozil, clofibrate and
■ Increased sense of fatigue. cise will be attenuated by dilti- improve sporting performance fenofibrate are unlikely to
■ Raising of the workload at which angina occurs. azem and verapamil. in normal patients. In patients have an effect on sporting
■ Apparent marginal advantages for ß1-selective agents if their Two types of adverse reac- with atrial fibrillation, digoxin performance, but elevations
doses remain low. tion commonly occur: the will not inhibit exercise- of creatine kinase may occur
■ A lesser effect on isometric exercise. dihydropyridines often pro- induced tachycardia. It can and great care should be
■ Variable effects on heat regulation. duce peripheral oedema, while alter the ST segment during taken if they are combined
■ A risk of exercise-induced bronchospasm in susceptible diltiazem and verapamil often stress testing, causing a false- with HMG CoA reductase
patients. cause constipation. positive result. inhibitors.
24 | Australian Doctor | 14 January 2005 www.australiandoctor.com.au
Antidiabetic agents two amphetamines, which Anticonvulsants
Exercise results in numerous would result in a positive test Anticonvulsants must be con-
changes in glucose homeosta- for a banned drug. tinued in all patients with
sis and is a recommended Lithium poses several epilepsy who participate in
part of the management of potential problems: it has a sporting activities. Serious
most patients with diabetes. low therapeutic index and is and sometimes fatal results
Increases in cutaneous eliminated by the kidneys. can occur if medication is
blood flow plus the effects of In sporting activity during stopped or if people with
exercising muscle at the injec- hot weather, when there is poorly controlled epilepsy
tion site result in increased often considerable fluid loss undertake some sports, such
insulin absorption from a via sweat, decreased renal as surfing.
subcutaneous site. clearance may result in con- It was thought that the
This interaction and siderable alterations in ‘anxiolytic’ properties of bar-
increased uptake of insulin plasma concentrations. It is biturates may be of some
into striated muscle and other very important in such cases benefit in some sports but
metabolic changes necessitate to ensure adequate hydra- they were found to decrease
careful adjustment of insulin tion. performance in all areas.
doses before any strenuous Considerable exercise-
exercise. related elevations in creatine Antibiotics
The physiological effects of kinase level have been When an athlete is seeking
exercise last for many hours reported in association with medical advice for a febrile
after exercise, so doses need some of the newer antipsy- illness, their illness alone may
to be altered during, and for chotic agents such as olanza- predispose them to a cardiac
the day after, exercise. pine (Zyprexa) and clozapine arrhythmia or hyperthermia
Dosing will need to be indi- (Clopine, Clozapine Synthon, during extreme exercise. The
vidualised to the duration Clozaril). The mechanism is best prescription may be to
and intensity of exercise as unclear and some patients avoid exercise until symp-
well as the stability of the have elevated levels indepen- toms pass.
diabetes. Particular care is dent of exercise. While there are concerns
also needed in older people As yet there have been no about antibiotics limiting per-
receiving oral agents so as to reported cases of exercise formance, the limited avail-
avoid hypoglycaemia. rhabdomyolysis in patients able data have not shown
taking these medications, but any decrease.
Vitamin supplements it is advisable to change treat- Quinolones should be pre-
Vitamins are taken in large ment when an elevated crea- scribed with care because
quantities by athletes of all tine kinase level is found and they have been reported to
ages but they are of no value the patient is undertaking cause tendon rupture.
in enhancing performance. strenuous sporting activity.
Although they are usually There is no reason to rou- Gastrointestinal drugs
considered to be of low toxi- Sporting ration and performance in Probenecid remains on the tinely measure the creatine Antacids are used to enhance
city, unusual cases, such as those without asthma. banned list as a masking kinase level unless there is a performance by inducing
hypervitaminosis A, have
performance is Clenbuterol is a long-acting agent. clinical indication. metabolic alkalosis. How-
been reported. not improved by beta 2 agonist available in ever, the doses required to do
vitamin or Europe and used by body Oral contraceptives Stimulants this will usually result in an
Iron and ‘athlete’s mineral builders as an anabolic agent. A small number of studies There are few legitimate rea- increased osmotic load, with
anaemia’ Locally available long-acting have shown a slight decrease sons for the use of this group resulting abdominal discom-
Although endurance athletes supplements. beta2 agonists such as efor- in static muscle endurance in of frequently abused drugs. fort and increased gas pro-
increase their red cell mass moterol (Foradile, Oxis) and women taking the oral con- One of the reasons for intro- duction.
and plasma volume, the salmeterol (Serevent) do not traceptive pill. This would be ducing drug control was Antinauseants have central
plasma volume increase is appear to have been abused of little relevance to any but amphetamine-related deaths sedating properties and may
usually greater and there is a by body builders. the elite athlete. in sport. impair fine motor control,
subsequent fall in haemoglo- which can be important in
bin concentration. There is Xanthines Corticosteroids Psychostimulants activities such as gymnastics
also increased GI blood loss Caffeine has been shown to These do not enhance perfor- Methylphenydate, now or diving.
in some athletes. have a positive effect on per- mance. Corticosteroid injec- widely prescribed for atten- Antidiarrhoeal agents are a
When anaemia is first formance in some endurance tions are often used for vari- tion deficit disorder, can heterogeneous group and,
detected in an athlete, there sports. However, high con- ous sporting injuries. On cause hypertension and pre- while they have no significant
is absolutely no case for centrations can produce a occasions, tendon rupture can cipitate arrhythmias in the effect on performance, any
immediate prescription of marked tachycardia and in result from both injected and sporting situation. To my condition causing diarrhoea
iron supplements. At the ini- some people caffeine is pro- systemic corticosteroid use. knowledge, there have been will predispose to dehydra-
tial consultation take a com- arrhythmogenic. While it is no adverse cardiac events tion.
plete medical, sporting and no longer banned in sporting Psychotropics and reported in association with Histamine H 1 -blocking
drug history, perform a thor- competition, a monitoring antidepressants the use of methylphenidate agents and proton-pump
ough physical examination program is being undertaken. These comprise a large and for ADD. Use of this agent inhibitors would be unlikely
and order appropriate Theophylline is dispensed heterogenous group that will result in a positive drug to alter performance.
haematological and bio- in various formulations and would not be expected to test result (see author’s case
chemical investigations. still has a place in the man- have any effects on perfor- study, page 28). Complementary therapies
When clinical evaluation and agement of respiratory dis- mance other than those asso- Athletes consume a wide
investigation do not find a ease. In one well-conducted ciated with their adverse reac- Decongestants variety of complementary
pathological cause, the diag- study examining the effect of tion profile. Most of these Ephedrine and its steroiso- medicines and dietary sup-
nosis of athletes anaemia can theophylline in athletes with- agents have not been studied mer pseudoephedrine have plements. They are even pro-
be made. out asthma, the drug had no in exercise performance, but often resulted in an athlete moted by Olympians in
In one study of elite net- effect on performance.3 tricyclic antidepressants have returning an inadvertent advertisements.
ballers with depressed ferritin been shown to decrease peak positive drug test. Pseu- There are large bodies of
levels, iron supplements were NSAIDs isokinetic (exercising at fixed doephedrine is no longer on data relating to many comple-
found to be without benefit The small body of available workload) power. the ‘banned list’ but it is mentary medicines, but most
on aerobic performance.2 In data shows NSAIDs have no SSRIs have been thought to subject to a monitoring investigations have involved
any case of an athlete pre- adverse effect on sporting have some advantage in study. small numbers and are usu-
senting with a low haemo- performance, but care is nec- enhancing performance Neither drug will enhance ally methodologically flawed.
globin level, NSAID use caus- essary to ensure there are no because of a perceived anxi- performance, but both have Some supplements may
ing blood loss should always adverse effects on the stom- olytic effect as well as some the potential to cause tachy- contain pharmacological
be excluded. ach or small bowel, leading data demonstrating increased cardia, arrhythmias and agents such as ephedrine, with
to anaemia. running time in a rat model. hypertension. predictable adverse reactions.
Respiratory drugs Subsequent human studies When taken for relief of The anabolic steroid nan-
Beta2 agonists Hypouricaemics did not show any alterations, symptoms, it should always drolone has been found in
Beta2 agonists inhibit exer- Allopurinol has no effect on positive or negative, in the be borne in mind that a some supplements, but this
cise-induced asthma and are performance. It is preferred setting of high-intensity exer- ‘mild’ respiratory or febrile has not been considered a sat-
recommended for use before to the uricosurics, such as cise. illness may be associated with isfactory defence for positive
exercise by people with probencid (Probid), which Selegiline (Eldepryl, Sel- a subclinical myocarditis. A drug tests.
asthma. They are now widely enhance urate deposition gene) is an inhibitor of febrile unwell athlete should Sporting performance is
abused on the incorrect belief when a fall in urine output monoamine oxidase type B. not undertake strenuous not improved by vitamin or
that they will improve respi- and pH occurs with exercise. Its metabolic profile includes exercise. mineral supplements.
www.australiandoctor.com.au 14 January 2005 | Australian Doctor | 25
How to treat - medication in sport and exercise
Drugs used to enhance sporting performance
DRUGS have been used in schools found 6.6% of 12th- not the sporting arena. in two well-designed studies
attempts to enhance perfor- grade students (aged 18 on ■ Normal volunteers used in to increase strength and
mance since the classical average) had or were using investigations are physio- lean body mass in men.
Olympics and will continue anabolic steroids and two- logically different to ath- ■ Erythropoietin (EPO)
to be used as long as there is thirds had started use at 16 letes, and even medium-per- increases VO2 max.
competition in sport. or younger. forming athletes are ■ Caffeine increases perfor-
Use of anabolic steroids in Despite the almost reli- different from the sporting mance in some endurance
power sports and body- gious belief of their value elite. sports, such as cross-coun-
building is widespread. A held by athletes, sports ■ Any simulated competition try skiing.
National Household Survey administrators, the public has little relationship to a ■ Beta blockers improve per-
in the US found that more and many doctors, the sci- real event, let alone a formance in some sports
than 300,000 people had entific facts are less convinc- national or international such as archery and shoot-
used anabolic steroids in the ing. event. ing.
preceding year. Erythropoi- When considering the effi- ■ Few studies have measured ■ Systemic alkalosis may
etin and stimulants are cacy of a drug in the unique individual concentrations of improve endurance.
widely used in endurance situation of sporting compe- the drug under investiga- ■ Amphetamines improve
sports such as cycling. tition, with all the associated tion. performance in some, but
Probably no sport is steroid use is in middle-level Use of anabolic psychological ‘hype’ and tac- ■ Studies often have been too not all, sports people.
exempt from drug abuse. competitors who want to tics, the doctor should small to detect an effect. For most other agents,
However, use and abuse are achieve personal bests or in
steroids in power remember the following In terms of good scientific data are lacking or at best
not the exclusive domain of people who simply want to sports and points: data, the following facts are controversial. One fact is
the elite athlete or even the improve their appearance. bodybuilding is ■ Most data relating to effi- well accepted: certain — no drug will turn
competition athlete. For Age is not a factor. A widespread. cacy come from the artifi- ■ Intramuscular testosterone a poor performer into a
example, most anabolic study conducted in US high cial area of the laboratory, enanthate has been shown champion overnight.
How drug abuse problems may present
THE most important task for the hepatitis B and C and HIV have
doctor is to take a full history and been transmitted by needle-sharing
find out what the patient does with steroid users.
the rest of their lives. Often an ath-
lete, in particular an older patient, Psychological presentations
will not mention their sporting Steroid-induced aggression, para-
activity or associated medications. noia and a dependency state are
A user of anabolic steroids will well documented and should be
probably not look like Arnold considered in an athlete presenting
Schwarzenegger and it is unusual with relevant symptoms.
for a user of illicit drugs initially In the US, a syndrome of unusual
to volunteer a history of drug use. post-game paranoia with ampheta-
Also, many adverse drug reactions mine use has been documented.
will be difficult to distinguish from The drug gamma-hydroxybu-
the multitude of symptoms that an tyrate (GHB) stimulates growth-
athlete may have as a result of their hormone release and is often
sporting activity alone. abused in sport. It may induce
coma and cause other problems
Cardiovascular presentations such as withdrawal and paranoia.
Most competitors in sporting
events will not be elite athletes but Dermatological presentations
there will be a lot of serious starters Many well-recognised skin prob-
wanting to do a personal best and lems can arise from steroid use. For
many may be taking prescribed example, men may lose hair and
drugs, illicit drugs or something women may become hirsute.
else to improve their performance. Abdominal striae, acne and periph-
Consider the basic cardiovascu- eral oedema can occur in both
lar physiology in sport. At the start sexes.
of a run there is a combination of Skin abscesses may occur at
decreased parasympathetic and injection sites, and careful exami-
increased sympathetic activity asso- nation may find small subcuta-
ciated with a host of local regula- neous lumps where agents such as
tory mechanisms. The sum of this the steroid stanozol have been
is a rise in pulse rate, a rise in sys- Steroid-induced has been normotensive develops ing sessions when the drug has injected.
tolic, but not diastolic, blood pres- elevated blood pressure. Peripheral been absorbed and inadequate glu-
sure, and redistribution of blood
aggression, paranoia vascular occlusions and pulmonary cose taken to compensate. Endocrine presentations
from the gut, liver and kidney to and a dependency emboli have also been reported Anabolic steroids produce pre-
the active skeletal muscle. state are well with anabolic steroid use. Gastrointestinal effects dictable endocrine effects, includ-
The most extreme of all presen- documented and Diuretics may be used to ‘make Up to 50% of endurance athletes ing decreased testis size and gynae-
tations in exercise or sport is weight’, increase muscle definition, complain of upper- or lower-GI comastia in men, and clitoral
sudden death. Deaths also have should be considered remove steroid-related oedema or symptoms. Often athletes under- hypertrophy and decreased breast
been associated with use of in an athlete mask agents in drug testing. taking lesser levels of activity also size in women.
amphetamines, ephedrine, the ille- presenting with complain of abdominal pain or Short-term infertility is common
gal long-acting beta2 agonist clen- Cerebral effects oesophageal reflux, probably a in men and a small number of ath-
buterol, and anabolic steroids. Ery-
relevant symptoms. Cerebral haemorrhage can occur in result of disturbances in motility. letes may develop persistent
thropoietin increases peripheral extreme isometric exercise such as When an athlete presents with hypogonadotrophic hypogonadism.
resistance, thus elevating blood inclined leg presses. The risk will anaemia, NSAID use rather than a
pressure, and has been linked to be greatly increased by the use of physiological ‘athletes anaemia’ Locomotor presentations
sudden death in cyclists. stimulants, caffeine or anabolic should be suspected. However, the Almost all sports are associated
If an athlete presents with palpi- steroids and there are reports of anaemia should always be fully with some form of overuse syn-
tations or a resting tachycardia, use stroke, haemorrhage and transient investigated. drome or muscle strain. HMG
of ephedrine, pseudoephedrine, cerebral ischaemia occurring with Bicarbonate ingestion may CoA reductase inhibitors are well
beta2 agonists, anabolic steroids or these agents. improve aerobic performance but recognised as causing myositis and
caffeine should be suspected. Insulin has been used by body the amount required will result in even rhabdomyolysis in a small
Persisting hypertension occurs builders and weightlifters because an osmotic load and increased gas percentage of patients.
with use of stimulants or high-dose of its anabolic properties. Hypo- production. Although drug-related rhab-
anabolic steroids and should be glycaemic coma has been reported Cholestatic jaundice may result domyolysis as a result of exercise
considered when an athlete who in the gymnasium and after train- from anabolic steroid use, and cont’d page 28
26 | Australian Doctor | 10 December 2004 www.australiandoctor.com.au
How to treat - medication in sport and exercise
from page 26 Disturbance in heat regulation relationship between anabolic agents
combined with use of HMG CoA When exercising, about 80% of the and malignant disease in athletes.
reductase inhibitors use has not been energy expended goes into heat pro- The link to malignant hepatomas is
reported, an association should be duction; hence the potential for hyper- tenuous.
considered in a symptomatic patient thermia to develop. There are only single case reports
when any of these drugs have been Pseudoephedrine, antinauseants, of a Wilms tumour in an adult, ade-
used. anti-inflammatory agents, diuretics and nocarcinoma of the colon and
Tendon rupture is common in psychotropics have all been associated prostate malignancy in athletes
sport, but is well recognised in rela- with severe hyperthermia. These agents taking anabolic steroids. However,
tion to corticosteroid injection, ana- should be considered in any patient the link between the vascular tumour
bolic steroid use and quinolone use developing hyperthermia after exercise. peliosis hepatitis and anabolic steroids
in older patients. Bilateral necrosis It is also important to exclude an has been well established.
of the femoral heads has occurred infective episode because hyperthermia
with the use of anabolic steroids. is also more likely to occur when an Urological presentations
There is no evidence to recom- athlete has a febrile illness. Decreased urinary stream occurs with
mend the use of anabolic steroids as anabolic steroids. There is a case report
a means of increasing the healing Malignancy of priapism occurring with the testos-
rate of tendon or muscle damage. Much is said in the media about the terone precursor androstenedione.
Ethics of prescribing
THERE is no doubt many The athlete autonomy others. A further pressure is to
doctors prescribe steroids to argument be asked to receive team-
athletes, and others will be This argument is based on the doctor-administered injections,
approached to do so. While patient’s right to self-determi- such as vitamin B12.
medical boards and learned nation. The athletes are con- Non-compliance with such
colleges universally condemn sidered to be aware of the a regimen may be viewed
the prescription of drugs to positive and negative effects unfavourably and result in
enhance sporting perfor- of the drugs and are willing non-selection. This is a seri-
mance, it is nevertheless to take the risks: all that is ous violation of an athlete’s
important to consider the needed is the patient’s consent. autonomy. It must be resisted
arguments for and against The argument against this by doctors when they are
prescribing these medica- is that there is no obligation, made aware of, or asked to
tions to athletes. moral or otherwise, to participate in, this practice.
simply do what a patient The most extreme case
Harm minimisation asks. As doctors we are occurred in the former
Simply put, this means ath- expected to prescribe with German Democratic Repub-
letes will acquire and take the aim of producing a clini- lic, where athletes, many years
the drugs with or without a analogous to the case for many athletes. cal benefit to the patient. later, successfully lodged legal
prescription. In the latter prescribed use of heroin. A further dilemma occurs One important issue in the proceedings against some of
case they will receive illegal Against this argument is when some adverse effects area of ethics is the pressure the doctors involved in the
supplies that are not sub- the fact that little is known occur and the user then imposed on athletes by coaches administration of steroids.
jected to quality control and about the pharmacology of requests yet another drug, and others to consume various In summary, when asked
may not even contain the the multiple doses of ana- such as tamoxifen to reverse supplements. Such supple- to prescribe, a doctor must
drug listed on the label. bolic steroids that would be gynaecomastia. ments are often stated to be be non-judgmental, treat any
Whereas, if supervised, the requested. Also, it has been Finally, what is the pre- ‘natural’ compounds such as medical problems and References
supplies would be monitored found that well-meaning scriber to do when insulin, kelp, various minerals, carni- always decline the request to 1. Lenz TL, et al. Potential
and any adverse effects prescribers can be used as erythropoietin or ampheta- tine, bovine colostrum, coen- prescribe inappropriate or interactions between exer-
detected and treated. This is one source of supply by mines are also requested? zyme Q, ginseng and many illegal medications. cise and drug therapy.
Sports Medicine 2004;
2. Blee T, et al. The effects
The future of drugs in sport Author’s case study of intramuscular iron injec-
tions on serum feritin levels
and physical performance in
DRUGS have been used to enhance performance for millen- Question
elite netballers. Journal of
nia, and the practice continues to evolve with technological A 16-YEAR-old netball player
Science and Medicine in
advances. is receiving methylphenidate
Sport 1999; 2(4):311-21.
The recent Bay Area Co-Operative Laboratory (BALCO) for attention deficit disorder.
3. Morton AR, et al. The
scandal involving the use of an anabolic steroid, tetrahydro- She is in a team that has
effects of theophylline on the
gestrinone, demonstrates the availability of chemists to design reached a level at which she is
physical performance and
drugs that are difficult to detect. subject to random drug testing.
work capacity of well trained
The possibility of gene doping, using viral agents as vectors What advice should be given?
athletes. Journal of Allergy
to deliver growth-promoting genes into muscle, has been
and Clinical Immunology
foreseen in the World Anti-Doping Code. Answer
The pharmaceutical industry is developing agents for use in Use of this agent will result in a positive drug test result.
myo- and neurodegenerative disorders that will inhibit the The sporting body’s medical officer needs to be made aware
natural protein growth inhibitor myostatin. Such a drug Online resources
of the situation. Application should also be made to the Aus-
Australian Sports Drug
would be almost a Holy Grail for body builders. tralian Sports Drug Medical Advisory Committee (ASDMAC)
Fortunately, there are many pharmacologists working on (phone (02) 6206 0262; e-mail firstname.lastname@example.org).
means of detection. With rigorous out-of-competition testing This committee can review an individual case and is recog- World Anti-Doping Agency:
and blood sampling, it is hoped this will maintain a level nised under the World Anti-Doping Code as being able to www.wada-ama.org
playing field in elite sport. grant a therapeutic exemption.
Case study steroids or testosterone. cled, had slight acne but was other- gynaecomastia. I also explained the
SD, 22, is an enrolled nurse. He first I told him I would be happy to talk wise well. possible negative effects on fertility
presented to our practice six months with him and provide information I went on to explain that side effects and coronary heart disease.
ago requesting a “Sustanon script” about the effects and side effects of of steroids are common and can be I suggested he read the booklet from
(testosterone) and asking if it was pos- anabolic steroids and testosterone, but serious (eg, mood swings). I told him Sports Medicine Australia, think about
sible to have this drug regularly explained to him that I could not ethi- that I have had female patients com- our consultation and return in couple
injected by our practice nurse. cally or legally prescribe for purposes plain that they had been physically of weeks.
He looked like, and admitted to that were not medically indicated. abused or feared being abused by their On return he had read the booklet
DR MARTINE WALKER being, a body builder and openly I gave him an information booklet steroid-using boyfriends. and admitted to using steroids for
Mosman, NSW told me that the Sustanon was for from Sports Medicine Australia and We also discussed the less common about the past six months. He said he
bodybuilding purposes. I suspected performed a physical examination, but perhaps more worrying side wanted to continue and hoped to do it
he was already using anabolic which revealed that he was well mus- effects of testicular atrophy and cont’d page 30
28 | Australian Doctor | 14 January 2005 www.australiandoctor.com.au
How to treat - medication in sport and exercise
from page 28 enough to treat) and his liver When a doctor’s actions are Often in the past, football illnesses can also predispose
in a “medically safe” way. function is normal. His acne brought to the attention of the players appeared in the media, patients to malignant hyper-
We discussed why he used has worsened and we are treat- relevant medical board on the having had marijuana use thermia. The best advice is: “If
steroids and he admitted ing this with minomycin. He matter of prescribing or sup- detected on drug screens. Is sick, don’t compete.”
having poor self-esteem. He had also started taking plying anabolic steroids, it tetrahydrocannabinol per-
said he lived a “healthy” life Nolvadex (tamoxifen) obtained may result in a decision that formance enhancing? If not, You discuss the risk of tendon
— he did not smoke or drink, through the gym to counter the doctor is guilty of unsatis- why the concern? rupture in association with oral
but said using steroids helped gynaecomastia. factory professional conduct, Cannabinoids impair aero- corticosteroid use. Is this a risk
in his part-time work in secu- and in some cases even pro- bic performance. The reason we should be discussing with
rity at nightclubs. Questions for the author fessional misconduct. for bans will depend on the patients taking short-term oral
I reiterated that I could not Is there any evidence about sport, but are usually in keep- steroids such as for asthma,
prescribe them and discour- the cardiovascular risk of General questions for the ing with the philosophy of a croup or severe sinusitis?
aged him from using steroids long-term high-dose steroid or author drug free sport and society. No.
from the gym (he was not sure androgen use? At what levels of competition
what he was taking, but knew There have been several does drug testing begin? In what types of acute illness Serious female runners often
it included Stanazolol). case reports in Australia and Any sporting body can should we counsel athletes become amenorrhoeic but are
I suggested he continue to overseas of AMIs and car- request the Australian Sports such as runners not to com- reluctant to use pharmaceuti-
come for monitoring of blood diomyopathies being caused Drug Agency to conduct pete? What are the risks? cals such as the oral contra-
pressure, liver function and by steroids. The risk must be drug testing on a fee-for-ser- In any serious cardiac or sys- ceptive pill. What arguments
lipids every three months. I small when you consider their vice basis. Testing is almost temic illnesses, such activity is can we use in discussion with
suggested a referral for fur- widespread use. Steroids universal at a national level an absolute contraindication. our patients for and against
ther counselling, but he decrease HDL-cholesterol and What are the penalties for and is sometimes present at In the case of less severe ill- the use of the pill in this situa-
declined. increase LDL-cholesterol doctors for prescribing ana- state levels of competition. nesses advice should be given tion?
Since that time he has levels, which, combined with bolic steroids or androgens for Often a world record can that a ‘mild’ febrile illness may Sporting performance is
returned occasionally. His an increase in blood pressure, non-medical uses? only be recorded if there is be associated with a subclinical unaffected by the use of the
blood pressure is normal, lipids increases the risk of vascular All Australian states adopt documentation of drug-free myocarditis with the potential pill but the risk of pregnancy
slightly raised (but not high events. a similar position on this issue. status. for serious arrhythmias. Such is not.
How To Treat CPD
Instructions may compete. Which antibiotic would you be d) Caffeine . . . . . . . . . . . . . . . . . . . . . . . .❏
unlikely to use in this situation (choose
Earn 2 CPD points by completing this quiz online or on the attached card. Mark your
ONE)? 8. Nigel’s haemoglobin is 120g/L. Which
answers on the card and drop in the post (no stamp required) or fax to (02) 9422 2844.
For immediate feedback click the ‘Earn CPD pts’ link at www.australiandoctor.com.au
a) Cephalexin . . . . . . . . . . . . . . . . . . . . . .❏ ONE statement is incorrect regarding
Note that some questions have more than one correct answer. The mark required for CPD
b) Amoxicillin-clavulanate . . . . . . . . . . . . .❏ anaemia in this situation?
points is 80%. Your CPD activity will be updated on your RACGP records every January,
c) Trimethoprim . . . . . . . . . . . . . . . . . . . .❏ a) The anaemia may be
April, July and October.
d) Ciprofloxacin . . . . . . . . . . . . . . . . . . . .❏ physiological . . . . . . . . . . . . . . . . . . . . . . .❏
b) Iron should be given immediately . . . . .❏
5. Which ONE substance is not on the c) The anaemia should be
‘banned list’ for athletes? investigated . . . . . . . . . . . . . . . . . . . . . . .❏
1. Peta, 54, has diabetes and competes in b) The dose of oral hypoglycaemics a) Probenecid . . . . . . . . . . . . . . . . . . . . . .❏ d) Blood loss should be considered . . . . .❏
cross-country running. She takes a statin for should remain unaltered . . . . . . . . . . . . . .❏ b) Pseudoephedrine . . . . . . . . . . . . . . . . .❏
hypercholesterolaemia. Her routine tests c) Insulin should be injected into the c) Tetrahydrogestrinone . . . . . . . . . . . . . .❏ 9. Paul, 36, a competitive cyclist, attends
show a creatine phosphokinase (CPK) of 850 thigh . . . . . . . . . . . . . . . . . . . . . . . . . . . . .❏ d) Amphetamines . . . . . . . . . . . . . . . . . . .❏ your surgery with a laceration. Blood
U/L. She was in a competition 24 hours d) Ensure an adequate amount of glucose pressure is 150/100mmHg, compared with
before her test. What TWO actions would is used or available during exercise . . . . .❏ 6. The clinical effects of which TWO drugs 125/80mmHg four months ago. Which
you advise? may be significantly affected by endurance THREE drugs would you consider as
a) The statin should be stopped 3. Peta asks for advice about enhancing her exercise? possible causes?
immediately . . . . . . . . . . . . . . . . . . . . . . .❏ performance. Which ONE statement is a) Propanolol . . . . . . . . . . . . . . . . . . . . . .❏ a) High-dose anabolic steroids . . . . . . . . .❏
b) Repeat CPK in several days . . . . . . . . .❏ correct? b) Warfarin . . . . . . . . . . . . . . . . . . . . . . . .❏ b) Ephedrine . . . . . . . . . . . . . . . . . . . . . . .❏
c) The troponin level should be a) Iron supplements may be beneficial . . .❏ c) Verapamil . . . . . . . . . . . . . . . . . . . . . . .❏ c) Erythropoietin . . . . . . . . . . . . . . . . . . . .❏
checked and an ECG recorded . . . . . . . .❏ b) Erythropoeitin may be beneficial . . . . .❏ d) Lithium . . . . . . . . . . . . . . . . . . . . . . . . .❏ d) Citalopram . . . . . . . . . . . . . . . . . . . . . .❏
d) Repeat CPK the following day . . . . . . .❏ c) Mega-doses of vitamins should be
used routinely . . . . . . . . . . . . . . . . . . . . . .❏ 7. Nigel, 28, swims long distances 10. Paul tells you he uses antacids to
2. Secondary therapy with oral d) Oral corticosteroids may be competitively. He is seen in casualty with improve his performance, but no other
hypoglycaemics fails, and insulin is added. beneficial . . . . . . . . . . . . . . . . . . . . . . . . .❏ supraventricular tachycardia. Which drug is drugs. Which TWO side effects might he
What advice are you most likely to give Peta least likely to induce arrhythmias in a experience from high doses of antacids?
about adjusting her medications when 4. One month later, clinically Peta has mild sporting situation (choose ONE)? a) Chest pain . . . . . . . . . . . . . . . . . . . . . .❏
training and competing (choose ONE)? pyelonephritis 48 hours before a a) Metoprolol . . . . . . . . . . . . . . . . . . . . . .❏ b) Abdominal pain . . . . . . . . . . . . . . . . . .❏
a) Decrease the insulin dose only on the competition. You advise her to withdraw b) Pseudoephedrine . . . . . . . . . . . . . . . . .❏ c) Headache . . . . . . . . . . . . . . . . . . . . . . .❏
day of training or competing . . . . . . . . . .❏ from the competition, but she indicates she c) Methylphenidate . . . . . . . . . . . . . . . . . .❏ d) Increased gas production . . . . . . . . . . .❏
HOW TO TREAT NEXT WEEK
Editor: Dr Lynn Buglar The next How to Treat looks at the management of chronic pelvic pain in women. The authors are Dr David Knight, senior staff specialist in obstetrics and
Co-ordinator: Julian McAllan gynaecology, The Canberra Hospital, and clinical lecturer in obstetrics and gynaecology, Australian National University, Canberra; and Dr Steve Robson,
Quiz: Dr Marg Tait director, department of obstetrics and gynaecology, The Canberra Hospital, and senior lecturer in obstetrics and gynaecology, Australian National University.
That’s How to Treat. Now for the ‘How to’ guide to your practice. • Legal
In Practice • Business
Don’t miss Australian Doctor’s new dynamic section on page 35
30 | Australian Doctor | 14 January 2005 www.australiandoctor.com.au