Performance and Drugs Final

Metabolism of drugs can alter

the drugs intrinsic activity, its ability to reach its site of action and its rate of elimination from the body

Michelle de bruin

used non-alcoholic beer to dilute urine

Chris Froome

B2 agonists

What is the world’s most widely consumed psychoactive drug?

caffeine

How does beet root work?

Beet root contains nitrates which are converted into nitric oxide in the body leading to vasodilation

Why is caffeine so fast acting

Rapidly absorbed in GI tract
Peaks 30-60 mins after oral ingestion
Half-life of about 4 hours

Jessica Hardy

took supplement that was contaminated with B2 agonist and got 1 year ban

Testosterone is transported in the blood in what 3 ways?

1. free testosterone (least amount)

2. bound to sex hormone-binding globulin

3. bound to albumin

Moderate drinking for men and women

Women: 1 drink or less in a day
Men: 2 drinks or less in a day

Heavy alcohol use for men and women

Women: 4 or more drinks on any day (or >8 per week)
Men: 5 or more drinks on any day (>15 per week)

Contaminants of supplements may be

Stimulants (ex. ephedrine)
AAS (ex. testosterone)
Prohormones

Why athletes may use alcohol

to calm anxiety

Athlete associated with narcotics

Kate Reed, made a bad joke

Cycling

A period of administration followed by a similar period of abstinence before the administration is recommended
People cycle bc there are negative side effects, so cycling helps reduce constant side effects

Stacking

Simultaneous use of more than one AAS at a time
Ex. taking AAS via oral administration and via injection
Or a "cocktail" of several AAS and other drugs for synergistic effects and to avoid unwanted side effects

Pyramiding

Increase dose up to a certain point, then reduce dose until abstinence
Supposed less behavioral side effects such as lowered mood, caused by withdrawal of the drug

Who is Hans-Gunnar Liljenwall

First athlete disqualified in Mexico City Olympics (1968), for drinking two beers before pistol shooting

Affinity

the chemical forces that cause a substance to bind its receptor, the attraction

Efficacy

refers to the relative ability of a drug-receptor complex to produce a maximum functional response, how good a drug is at producing a desired effect

BALCO Scandal

the production and distribution of an undetectable anabolic-androgenic steroid(THG) to professional athletes from late 1990s until 2003.

Founder and dealer and whistleblower of BALCO is

Victor Conte

Therapeutic Use Exemption (TUE)

Athletes may apply for TUE when illness or medical condition requires:
A medication containing a substance or
An administration method on the prohibited list
Allows athlete to use Rx or method to compete in a proper state of health
As long as it does not give a competitive advantage

Athlete Biological Passport

An electronic record in which biological markers are profiled.
Baseline blood/urine values are collected over time
At least 4 blood samples are needed to establish a baseline score. From this, "natural" upper and lower limits can be set.
Reveal the effects of doping, rather than trying to detect the substance itself

Athlete wherabouts/ ADAMS

Certain, high-profile, elite athletes are entered into Registered Testing Pool (RTP)
Must give whereabouts info to Anti-Doping Orgs
Including:
Home address, email, phone
Address for overnight accommodations
Regular schedule
Competitive schedule
A 1-hour available time slot to be tested
Submit via WADAS's Anti-Doping Management System

Standard Sanction means

four years ineligibility in sports

Mechanism of action of Testosterone

Testosterone diffuses through cell membrane
Binds to androgen receptor (AR)
(Induces gene transcription → protein synthesis & muscle hypertrophy)
Increases in number of myonuclei and satellite cells
Testosterone also inhibits preadipocyte differentiation into adipocytes

Site of production of testosterone for males

produced in the testes and Leydig cells

Site of production of testosterone for females

female: secreted by the adrenal and the ovary and are formed peripherally

Clinical use and side effects of testosterone and other AAS

Testosterone: primary male androgenic hormone, bone density maintenance, increase muscle strength and endurance, increase mood, libido, memory function, focus

AAS mimics the effects of testosterone and is designed to: Increase muscle mass and Help athletes train longer and more intensely
Reduce recovery time

Side effects of of Testosterone and other AAS

AAS Side effects: myocardial infarction, stroke, liver tumors, kidney failure, psychiatric problems

Cutoff for testosterone : epitestosterone ratio AAF

ratio of 4:1

How testosterone is carried in the blood and bioavailibility of each form

is secreted into the blood and carried to target cells in the male reproductive organs
All non-SHBG bound testosterone is therefore considered bioavailable

Gynecomastia and how athletes attempt to avoid it with drug use

AAS users often take tamoxifen (estrogen blocker) during post-cycle therapy
Decreases estrogen biosynthese, which increases testosterone biosynthesis

Justin Gatlin

Testosterone

Mechanism of action of Growth hormone

• Stimulates IGF release from the liver

• increases linear bone growth in children

• stimulates anabolism

• Alters metabolism to ↓fat mass and ↑lean mass

Clinical use and misuse in sport of HGH

clinically used to promote growth especially in children and at puberty
Misused in sport to decrease fat mass and increase lean mass, stimulates anabolism

Why is HGH difficult to detect

short half-life and low concentration in urine

Growth hormone disorders

Growth hormone deficiency: Drawfism, deficiency during pre-pubertal stage
Pituitary tumor: most common cause of excess growth hormones
Giantism: short lifespan b/c tumor eventually destroys the pituitary gland (BEFORE epipyseal plate closure)
Acromegaly: excess GH AFTER epipyseal plate closure

Side effects of growth hormones

Skeletal changes
Enlargement of fingers and toes, orbit, lengthening of jaw
Internal organ enlargement
Muscle weakness
Cardiovascular disease worsening
Altered regulation of glucose
Insulin resistance

What is Somatocrinin

growth hormone-RELEASING hormone

What is Somatostatin

growth hormone-INHIBITORY hormone

Myostatin

gene controlling musculature, inhibits muscle growth, causing muscle breakdown, acts to balance

What happens without myostatin

extreme muscle growth

Effects of insulin

increased glucose uptake by skeletal muscle
Inhibit protein breakdown
Anabolic agent

Mechanism of action of beta-2 agonists

β2 receptor activation =
ATP conversion to cyclic AMP (cAMP)
Decrease myosin light chair kinase activity (MLCK)
Decrease intracellular calcium (Ca**) concentration
Thus, smooth muscle relaxation and bronchodilation

Types of beta-2 agonists and their use

All B2 agonists are potent bronchodilators used for treatment of asthma
Short acting (quick relief) - 4 hours: salbutamol, terbutaline, fenoterol, reproterol, bitolerol, pibuterol
Long acting (relax muscles, last longer) - 12 hrs: Formoterol, salmeterol, bambuterol, indacterol, oldaterol, tulobuterol, procaterol, vilanterol

Beta-2 agonist side effects

side effects: headache, muscle cramps, tachycardia, tremor, sweating, HTN, anxiety

Management of Asthma

Chronic inflammatory disorder of airways
Non-drug treatment involves avoiding known trigger factors
Drug treatment: aim to stop/reverse inflammatory phase
B2 agonists only relieve symptoms
Combine B2 agonists and corticosteroids to decrease inflammation and bronchoconstriction

Why athletes may use diuretics

Little evidence of performance enhancement
Misused for weight class sports, and to release bloating from other drugs
Polypharmacy
Masking agent

Sports more likely to use diuretics

weight class sports

Chris “Cyborg” Justino

diuretics

Mechanism in which blood doping increases oxygen carrying capacity

More hemoglobin(Hb) = more oxygenated blood carrying capacity

methods of autologous blood doping

Draw 1-4 units of blood from athlete

Treated/packed RBCs stored at 4 degrees C

Return to baseline blood levels for 8-12 weeks

Reinfused prior to competition

Autologous transfusion

transfusion of one’s own blood

timeframe of aerobic performance enhancement for blood doping

effects last 10-12 days, return to baseline after 8-12 weeks

Effectiveness of altitude-simulating tents, technology, and masks

contradictory results - masks dont work

which sports/athletic events are more prone for blood doping

aerobic sports (like cycling)

Notable athlete associated with blood doping

Tyler Hamilton (American cyclist)

Hematocrit cutoff for males (EPO)

50%

Clinical uses for EPO

Treatment of severe cases of anemia

chronic kidney disease, myelodysplasia from cancer treatment, HIV infection, prematurity, bone marrow transplantation, autologous blood transfusion

Danger of synthetic EPO use

blood may become too thick and cause heart failure

2001 Findland Skier Scandal (plasma expanders)

Jari Isometsa, misplaced medical bag found near gas station (EPO/plasma expanders), six skiers tested positive

Lance Armstrong in trouble for

EPO

RBC production from EPO

EPO stimulates production of pronormoblasts that develop into normoblasts, which lose their nucleus to become reticulocytes that then enter the blood system and develop into RBCs

Types of manipulation

Tampering with samples and intravenous infusions and/or injections

Most common form of manipulation

sharing urine samples

When does WADA prohibit gene doping

At all times (in and out of competition)

2 basic mechanisms of actions of stimulants

1. mimic neurotransmitter effects

2. increase secretion of these neurotransmitters

Side effects of ephedrine

anxiety

dysrhythmias

HTN

Addiction

Seizure

Psychosis

Death

side effects of amphetamines

Anxiety, indifference, irresponsible behavior, irritability, restlessness, dry mouth, tremors, insomnia, confusion, delirium, sweating, palpitations, rapid breathing, tachycardia, HTN, chronic use may lead to decrease libido, withdrawal associated with mental and physical depression

Different types of stimulants:

Caffeine, amphetamines, cocaine, sympathomimetics, modafinil

Types of sympathomimetics

ephedrine, pseuduoephedrine, phenylephrine (more of a placebo), phenylpropanolamine (PPA)

Performance enhancing effects of caffeine & ephedrine

increases muscular endurance

enhances anaerobic exercise performance

small amount of weight loss

Performance enhancing effects of cocaine

increased HR and TTE and blood lactate

epinephrine use (heat stroke and cardiac events) athlete

Knud Jensen (1960)

stimulant use (heat stroke and cardiac events) athlete

Tom simpson (1967)

When does WADA prohibit stimulants

in competition

Types of narcotics

Analgestic, Non-narcotic/opioid, Narcotic (opioid), morphine, diamorphine (heroin), codeine, dihydrocodeine

Physiological effects of narcotics

stimulate the same receptors endorphins act upon to induce similar or more profound analgesia and euphoria > nociception and sense of well being

Mechanism of action of opioids

Inhibits the generation and transmission of nerve impulses in the peripheral pain fibers

When opioids bind to receptor:

inhibits adenylate cyclase and calcium channels

leads to decrease excitability of neurons/pain signals

Clinical uses for narcotics

post injury for pain management, acute diarrhea( anti-motility-shuts down GI tract), antitussives (for dry, nonproductive cough)

Statistics of opioid-related drug overdoses

over 75% of deaths in 2021

When WADA prohibits narcotics

prohibited in competition

Tested positive for morphine in 2007

Ethiopian runner, Ambesse Tolosa

Cannabinoid receptors:

CB1 and CB2

Stimulation of CB1 and CB2 effects

acetylcholine in hippocampus (learning and memory) and noradrenaline in cerebral cortex (alertness and motor coordination)

Cannabinoids are likely more ______ than ________

ergolytic than ergogenic

CB1 is more

psychoactive

CB2 is more

anti inflammatory/ anxiety

Mode of action of THC

tends to accumulate in adipose tissue, slowly released

AAF for THC metabolites

Ross Rebagliati in 1998

American sprinter positive for THC metabolites

Sha’Carri Richardson

CBD vs THC

CBD lacks psychoactive effects while THC does not

Potential performance-enhancing effects of glucocorticoids

endurance performance and strength

When does WADA prohibit glucocorticoids

Prohibited in competition

Effects of glucocorticoids

anti-inflammatory
Increasing transcription of genes for gluconeogenesis, proteolysis, and lipolysis
Immunosuppresive
Metabolic

Definition of one drink and guidelines for consumption

12 fl oz beer = 8-9 fl oz of malt liquor = 5 fl oz of table wine = 1.5 fl oz of distilled spirits

Metabolism of alcohol happens primarily in

the liver

Rate of alcohol metabolism

about 100 mg/kg body weight per hour