SUBSTANCE ABUSE
| PERFORMANCE-ENHANCING AGENTS —Jon S. Hallberg, MD, Assistant Professor, Family and Community Medicine,
University of Minnesota Medical School, Minneapolis, and Employee Assistance Program, Minnesota Twins baseball
team
|
| Background: many books and articles about steroid and supplement use; 50% of Americans use supplements; >600 supplement
manufacturers; ≈4000 products; $20 billion-per-year industry in 2002, probably $25 to $30 billion per year at present
|
| Ethics: level playing field (not possible if some athletes take supplements while others do not); pure sport, ie, athlete competing
for sake of competing, not to break record; integrity of game; real accomplishments; enhancement considered
cheating; rules in place against it; may be harmful to health
|
| Latin American countries: drugs easy to obtain; use of vitamin B12 injections commonplace; players may receive anabolic
steroids unknowingly
|
| Baseball Employee Assistance Programs: initially for chewing tobacco; in 1998-1999, androstenedione, creatine,
ephredra; androstenedione and ephredra taken off market
|
| Testing: before current year, could test major league players only for cause, eg, if acting erratically (could be tested for drugs
of abuse, eg, cocaine, but not for steroids); now all players tested for steroids; looking for threshold amount; ≈5% test positive
for steroids; amphetamine use currently of concern (rampant since 1960s); stimulants and caffeine thermogenic and can
cause problems during hot weather; drug access—easy on Internet and in Tijuana, Mexico; no prescription necessary
|
| Steroids: lower high-density lipoprotein (HDL), raise low-density lipoprotein (LDL); myocardial infarction (MI) seems
more prevalent in steroid users; not much research; cause liver cysts, hair loss, acne, and testicular atrophy, but build
muscle and increase speed
|
| Human growth hormone: can change bone structure
|
| Historical use: ancient Greek Olympians consumed certain mushrooms for extra power; in late 1800s, European cyclists
used heroin, cocaine, and ether-soaked tablets for performance enhancement; in 1904, men’s Olympic marathon champion
used strychnine and brandy; in 1920, 100-yd dash Olympic champion used sherry and raw eggs to augment speed; in
1940s, testosterone given to horses to increase speed and endurance; in 1950s, Soviet power lifters began using anabolic
steroids; in World War II, soldiers used amphetamines to combat fatigue and to maintain aggression (>500 major leaguers
in war, and use spread throughout game); in 1960s, 2 amphetamine-related deaths of cyclists; in 1970, United States
made amphetamines controlled substances; in 1976, International Olympic Committee (IOC) started testing for steroids
|
| Reasons for use: better strength and speed (steroids); greater endurance, less fatigue, increased energy (ephedra, caffeine);
pain reduction (nonsteroidal anti-inflammatory drugs [NSAIDs], anabolic steroids); quicker recovery (steroids, human
growth hormone); getting up (amphetamines), coming down (alcohol); marijuana—use common in minor leagues
|
| Three broad drug categories: ergogenic—improve performance, eg, steroids, amphetamines, nicotine, ephedra;
therapeutic—medications for underlying condition or healing, eg, NSAIDs, cortisone injection, steroids, human growth
hormone; recreational—drugs of abuse; legal, eg, alcohol, or illegal, eg, marijuana
|
| Creatine: composed of 3 amino acids; creatine monophosphate made in liver; found in meat and fish; not much
needed; adds extra phosphate to Krebs cycle to provide more energy (ATP) for body; could give quick burst of energy,
but no clear evidence; not harmful; not banned because endogenous, ie, normally made by body (difficult to detect in
urine; cannot differentiate from normal amounts; same for growth hormone)
|
| Stimulants: caffeine; amphetamines (“greenie”), ephedra, pseudoephedrine, and neosynephrine; similar chemical structures,
differing by ethyl or methyl group; pseudoephedrine basic ingredient in methamphetamine; sharpen focus, add
clarity
|
| Steroid precursors: androstenedione (Andro)—banned from market with 1 exception, dihydroepiandrosterone
(DHEA); women use to enhance libido; in effect, same as steroids
|
| Glucocorticoids: physicians give frequently in injections
|
| Anabolic steroids: testosterone—oral, transdermal, and injectable forms; nandralone and stanozolol 2 most common
steroids used in baseball; normal testosterone/epitestosterone (T/E ratio) 2:1 or 3:1 (6:1 in Asians); must be ≤10:1 in
baseball (higher levels indicate supplementation); efficacy—evidence from sports records that steroids work, but no
studies; injuries—increased protein synthesis leads to increased muscle mass, but tendons and ligaments remain same,
so more susceptible to injuries; incentive to use—enormous for professional athletes; steroid use found in all levels of
sports; large studies in middle- and junior high–school students found ≈5% of boys and ≈2% of girls used performance-
enhancing drugs on regular basis; therapeutic-use exemption—amphetamine/dextroamphetamine (Adderall) prescribed
for attention-deficit/hyperactivity disorder (ADHD); used to enhance performance
|
| ABUSE OF OTC DRUGS —Barry A. Browne, PharmD, Associate Professor of Pediatrics, Texas A&M College of Medicine,
College Station, TX, and Staff Physician, Scott & White Hospital Center, Temple, TX
|
| Background: >100,000 over-the-counter (OTC) drugs; potent pharmacologic activity; easily available on Internet; limited
epidemiologic data on misuse and abuse;“pharming”—recreational use of OTCs, herbals, and prescription drugs
|
| Dextromethorphan: most frequently used and abused; found in, eg, Vick’s 44 DM, Robitussin DM, cough gels, Coricidin;
codeine analogue that suppresses cough center in medulla; found in ≈140 OTC products; syrup and gelcap formulation;
frequently combined with other cough and cold products (decongestants, antihistamines); initially
introduced as syrup (Romilar) in 1950s; abuse led to withdrawal from market; reintroduced with unpleasant taste;
abuse reports again in late 1980s; gelcaps—introduced in 1990s; no unpleasant taste; “Triple Cs”, “skittles,” “redhots”
street names for Coricidin HBP Cough and Cold; abuse reports sent to national Toxic Exposure Surveillance
System; reports on patients 13 to 19 yr of age increased from 100/mo to 350/mo from 2000 to 2003; easier to ingest
large quantities needed to produce central nervous system (CNS) effect; instructions on Internet—how to extract
dextromethorphan from syrup; tables ranking flavor; calculators providing mg/kg dosing for desired effect; instructions
for drinking 2 bottles of dextromethorphan without vomiting
|
 | Overdose: “robotripping” or “robodosing” (relates to Robitussin); produces CNS stimulation; with higher doses, common
opoid adverse effects (hyperexcitability, lethargy, ataxia, dissociative anesthesia [similar to ketamine]); CNS depression
with even higher doses; dose determines neurobehavioral outcome; plateau 1—mild CNS stimulation, 100
to 200 mg; plateau 2—opoid-induced musculoskeletal relaxation, 200 to 400 mg; plateau 3—mild dissociative
state, 300 to 600 mg; plateau 4—>600-mg dose; ketamine-type intoxication, ie, full dissociative state
|
| Metabolism: cytochrome P450 2D6 enzyme system; tolerance develops quickly, leading to dose escalation; dextromethorphan
not identified in urine drug screens; mortality rare without coingestants; drug-drug interactions—serotonin syndrome
(mental status changes, autonomic instability, and muscle hypertonicity) in patients on selective serotonin reuptake inhibitors
(SSRIs); diaphoresis with pseudoephedrine; bromism (irritability, headache, anorexia, and confusion) from long-term use of
dextromethorphan bromide (usual formulation)
|
| Antihistamines: H1 -blockers include diphenhydramine (Benadryl), chlorpheniramine (Chlor-Trimeton), others; at supratherapeutic
doses, effect more anticholinergic; “mad as a hatter” (hallucinations), “dry as a bone,” “hot as a hare” (hyperthermia),
“blind as a bat” (pupil dilation), and “red as a beet”; abusers want hallucinations primarily; hallucinations and
“tripping” major issues for teenagers; information found on Internet
|
| OTC sympathomimetics: decongestants; ephedrine, phenylpropanolamine (removed from market in 2000), and pseudoephedrine;
ephedrine-containing OTCs and herbals containing ephedra (ma huang) removed from market in 2003
because of increased risk for stroke and MI, particularly in younger patients using for performance enhancement and
weight loss; pseudoephedrine—stereoisomer of ephedrine; provides CNS stimulation; not as potent as ephedrine but
has significant toxicity and abuse potential; Sudafed PE contains phenylephrine instead of pseudoephedrine; Robitussin
PE and Tussin PE contain pseudoephedrine; pseudoephedrine more potent than phenylephrine, more easily absorbed,
and has longer duration of action, but phenylephrine cannot be converted to methamphetamine
|
| Nasal and ocular drugs: oxymetazoline (Afrin), tetradhydrozoline (Visine); α-adrenergic agonists; nasal and ocular vasoconstrictors;
abused by oral ingestion; rapid absorption in gastrointestinal (GI) tract; sympathomimetic effects; Vick’s
VapoRub and Vapor Inhaler contain L-desoxyephedrine (congener of methamphetamine; reduces fatigue); Internet
sites provide information on extraction
|
| Caffeine: 200-mg maximum per stay-alert tablet; some tablets also contain guarana (more potent source of caffeine than
coffee); caffeine, theophylline, and theobromine all methylxanthines (cause dose-dependent CNS stimulation); proposed
mechanisms of action include inhibition of phosphodiesterase, modulation of intracellular and extracellular calcium, and
blockade of adenosine receptors; actual mechanism of action unknown; has anti-inflammatory characteristics; caffeine
most abused product in schools today; case of college student who died after ingesting dozens of caffeine pills; ready
availability and social acceptance lead to lack of concern about toxicity
|
| Laxatives: readily available; osmotic and stimulant laxatives used to prevent caloric absorption and promote weight loss;
Senokot is stimulant laxative sold as ”natural vegetable laxative”; long-term use produces profound metabolic and electrolyte
derangements, increased intestinal motility, and enhanced transport of free water and electrolytes into colon; potential
adverse effects—diarrhea (fluid and electrolyte losses), stimulation of renin/angiotension/aldosterone system, hypokalemia,
hypocalcemia, hypomagnesemia, and acid-base disturbances
|
| Antidiarrheal agents: loperamide (Imodium)—meperidine congener (opioid); same abuse potential as other opoids;
structurally similar to diphenoxylate (Lomotil) and haloperidol; initially, believed not to have opioid CNS effects because
of poor bioavailability, however, CNS effects (euphoria, drowsiness) occur with high doses; respiratory depression and
paralytic ileus occur with extremely high doses; nalaxone reverses toxicity; does not show on urine drug screen
|
| Urine drug screen: standard screen detects barbiturates, tricyclic antidepressants, benzodiazepines, opioids (codeine,
morphine, and heroin only), amphetamines, marijuana, cocaine, and phencyclidine (PCP); most OTCs do not show on
screen; dextromethorphan and diphenoxylate show no cross-reactivity with opioid screen; no urine screen for antihistamines
or caffeine; at high urine concentrations, caffeine produces false-positive for PCP; no screen for sympathomimetics,
but cross-reactivity for amphetamines when overdose significant
|
| METHAMPHETAMINE CRISIS —Carson R. Harris, MD, Associate Professor, Department of Emergency Medicine,
University of Minnesota Medical School, Minneapolis, and Senior Staff Emergency Physician, Regions Hospital, St. Paul,
MN
|
| Background: first synthesized in 1919; marketed as nasal decongestant in 1932; epidemic of use in Japan in 1940s;
given to soldiers in World War II; epidemic began in United States in 1950s; government responded by barring use of
most amphetamines and requiring prescription for methamphetamine; street names—crank, crystal meth, glass, and ice
|
| Trend: Drug Abuse Warning Network (DAWN) report—issued yearly; gathered from emergency department (ED)
records; use increasing; ≈600,000 Americans use weekly, 12.3 million used at least once; 58% of law enforcement agencies
reported methamphetatmine biggest drug problem (especially in upper Midwest and West Coast); women 38% of users
treated (highest of all drugs treated); pseudoephedrine sales limited, but supply coming from Mexico; most users 18 to 34 yr
of age (majority 18 to 25 yr), but see use in junior high and high school (4% of high school seniors have used or are using);
51% of people in prison for drug offenses there for methamphetamine
|
| Routes of administration: snorting, smoking, injection; can swallow rock or capsule, but effect decreased
|
| ED presentations: police—bring in prisoner who swallowed packets before arrest; ED physicians use polyethylene
glycol-electrolyte solution (Go-LYtely) to retrieve; emergency medical services—bring in toxic patients; friends or
relatives—worried about patients, bring them in; others—worried about toxicity or witnessed seizure
|
| Organ toxicity: most worried about CNS and cardiac toxicity; can affect every major organ system (including skin and
teeth)
|
| Pharmacology: stroke occurs from catecholamine surges; amphetamines can act as false neurotransmitters, causing severe
hypertension, stroke, MI and ventricular dysrhythmias; half-life 19 to 34 hr
|
| Toxicity: CNS—paranoid psychosis; hemorrhagic or ischemic stroke; cerebral bleeding; seizures; hyperpyrexia;
cardiovascular—increased blood pressure and heart rate, MI, myocardial rupture, aortic dissection (long-term users)
|
| Treatment: cardiovascular—large doses of benzodiazepines (“give it till they smile”); if ineffective, give nitroprusside
(Nipride); can try phentolamine, starting with 2 mg intravenously (IV); β-blocker may make hypertension and tachycardia
worse due to unopposed alpha activity; esmolol recommended β-blocker; pulmonary—occasionally see barotrauma
caused by inhaling smoke through mouth and into nose or using Valsalva maneuver while smoking (can cause pneumomediastinum
or pneumothorax); renal—may cause renal failure requiring dialysis; parenchymal infarcts and renal necrosis
also seen; skin—abscesses, cellulitis, ulcers; sensation of something crawling under skin (formication) may lead
to scratching face, neck, and sometimes eyes
|
Educational Objectives
| The goal of this activity is to discuss the abuse of performance-enhancing and over-the-counter (OTC) drugs and methamphetamines.
After hearing and assimilating this program, the clinician will be able to:
|
| 1. Explain the background and widespread use of performance enhancing drugs at all levels of athletic competition.
|
| 2. List the 3 categories of drugs used to enhance athletic performance and describe their effects on the human body.
|
| 3. Review the abuse potential of dextromethorphan and the effects of overdose.
|
| 4. Discuss the signs and symptoms of abuse of OTC sympathomimetics, laxatives, and antidiarrheal agents.
|
| 5. Describe the presentation of methamphetamine toxicity.
|
Discussed on this Program
Amphetamine/dextroamphetamine [Adderall, Adderall XR]
Chlorpheniramine maleate (several trade names)
Creatine monohydrate
Dextromethorphan HBr (several trade names)
Diphenhydramine HCl (several trade names)
Diphenoxylate HCl with atropine sulfate [Logen, Lomanate, Lomotil, Lonox]
Ephedra sinica (ma huang)
Esmolol HCl [Brevibloc]
Loperamide HCl [Diar-aid Caplets, Imodium, Imodium A-D Caplets, Kaopectate II Caplets, Maalox Anti-Diarrheal
Caplets, Neo-Diaral, Pepto Diarrhea Control]
Ketamine HCl [Ketalar]
Methamphetamine HCl (desoxyephedrine HCl) [Desoxyn]
Naloxone HCl [Narcan]
Nitroprusside sodium [Nitropress, Sodium Nitroprusside]
Oxymetazoline HCl
Phencyclidine HCl (PCP) [Sernylan] (withdrawn 1978)
Phentolamine [Phentolamine Mesylate for Injection, Regitine]
Phenylephrine HCl (several trade names and formulations)
Phenylpropanolamine HCl (withdrawn)
Polyethylene glycol electrolyte solution [Go-LYTELY]
Pseudoephedrine HCl (d-isoephedrine HCl) (several trade names)
Somatropin (human growth hormone; several trade names)
Stanozolol [Winstrol]
Tetrahydrozoline HCl (several trade names)
Theophylline (several trade names and formulations)
Suggested Reading
Baker SD, Borys DJ: A possible trend suggesting increased abuse from Coricidin exposures reported to the Texas Poison
Network: comparing 1998 to 1999. Vet Hum Toxicol 44:169, 2002; Calfree R, Fadale P: Popular ergogenic drugs
and supplements in young athletes. Pediatrics 117:e577, 2006; Carr BC: Efficacy, abuse, and toxicity of over-the-
counter cough and cold medicines in the pediatric population. Curr Opin Pediatr 18:184, 2006; Climstein M et al: The
effects of anabolic-androgenic steroids upon resting and peak exercise left ventricular heart wall motion kinetics in male
strength and power athletes. J Sci Med Sport 6:387, 2003; Dhar R et al: Cardiovascular toxicities of performance-enhancing
substances in sports. Mayo Clin Proc 80:1307, 2005; Juhn M: Popular sports supplements and ergogenic aids.
Sports Med 33:921, 2003; Ling W et al: Management of methamphetamine abuse and dependence. Curr Psychiatry
Rep 8:345, 2006; Rawson RA: Treatment of methamphetamine use disorders: an update. Subst Abuse Treat 23:145,
2002; Roehr B: Half a million Americans use methamphetamine every week. BMJ 331:476, 2005; Schwartz RH: Adolescent
abuse of dextromethorphan. Clin Pediatr 44:565, 2005.
Faculty Disclosure
In Adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial
relationship with the manufacturer or provider of any commercial product or service discussed. For this issue, the faculty
reports nothing to disclose.
Dr. Hallberg was recorded at Family Medicine Review-Update 2006, sponsored by University of Minnesota Medical
School, on May 1-5, 2006, in Minneapolis, MN. Dr. Browne was recorded in San Antonio, TX at the Adolescent Health
Conference, sponsored by The Children’s Hospital at Scott & White, Temple, TX and Texas A&M University Health Science
Center, on April 27-29, 2006. Dr. Harris was recorded in St. Paul, MN, at Family Medicine Today, sponsored by
HealthPartners Institute for Medical Education, on March 9-10, 2006. The Audio-Digest Foundation thanks the speakers
and sponsors for their cooperation in the production of this program.
|
