PEDs and Testing Flashcards
What forms of PEDs are we interested in for this class?
Anabolic/androgenic steroids and hormones
What are some basic characteristics of AAS?
Major PEDs
Based off testosterone steroid nucleus
Altered to enhance muscle building
What is type 1 AAS?
Esters
Prolonged half lives
Hydrolyzed to testosterone
Aromatized to estrogens by aromatase
What is type 2 AAS?
19-nor-testosterone derivatives
Prolonged half lives
Reduced androgenic effects
80% less aromatization than type 1
What is type 3 AAS?
17alpha-alkyl derivatives
Greatly reduced liver metabolism
Not converted to estrogen
Increased anabolic effects
How are PEDs administered?
Pyramiding
Stacking
Cycling
What is pyramiding?
Increases doses followed by decreasing dose
What is stacking?
Using multiple steroids
What is cycling?
Alternating periods of use, co-ordinated with training or testing schedules
How are PEDs absorbed?
Injection intramuscular
Ingestion
Topical
How are PEDs distributed?
Lipophilic
Rapid
To muscle
Widespread
How are PEDs metabolized?
In the liver
Produces first-pass metabolites
Low bioavailability
How are PEDs excreted?
90% in the kidney
10% in other locations like the GI tract
What is determined by sex steroids?
Fundamental male and female differences
Where are sex steroids produced naturally?
In reproductive tissues stimulated by FSH/LH from the anterior pituitary
What is testosterone converted to in the body?
DHT by 5alpha-reductase
What is aromatase?
The rate-limiting step for estrogen production
What are natural sex steroid levels like?
Cyclical, negative feedback
What do anabolic steroids bind to?
Androgen receptors
What do higher concentrations of AAS do?
Cause additional receptor binding e.g. estrogen receptors
What are the mechanisms of AAS action?
Drug-receptor complexes translocate to nucleus, bind specific DNA sequences
Activates gene transcription mRNA production, makes new protein like for building muscle
Steroids shift stem cells towards muscle cell differentiation, as opposed to adipose cell
What are the mechanisms of AAS reinforcement?
Many users report euphoria
This may come from increased beta-endorphin levels which decrease GABA release onto VTA DA-ergic neurons
When steroids modulate GABAa receptors, DA-ergic mesolimbic neurons increase firing rate
What does AAS produce?
Massive weight gains which is virtually all muscle
What do animals treated with AAS show?
Increased number of myonuclei
Increased muscle fibre cross-sectional area
What does cellular memory allow for?
Rapid muscle building after a period of inactivity
What is trenbolone?
19-nor derivative of testosterone that has a higher affinity for androgen receptors and is also not a substrate for 5alpha-reductase nor aromatase
What is the cellular action of trenbolone?
Induces myotrophic effects without unwanted effects
Reverses expression of atrophic genes
Increases expression of anabolic genes
How fast does tolerance to anabolic steroids develop?
After 1 dose even
The presence of steroids inhibits their own production = negative feedback
What are the symptoms of AAS withdrawal?
Depression
Mood swings
Fatigue
Headache
Insomnia
Lack of energy
No appetite
Body dissatisfaction
What does dependence to anabolic steroids look like?
30% become dependent
More likely at higher doses
Mostly psychological due to cycle length, want to avoid negative effects
How do anabolic steroids affect the skin long term?
Male pattern baldness
Acne
Oily skin and scalp
How do anabolic steroids affect cognition long term?
Severe mood swings, aggression, depression, the chance of dependence
How do anabolic steroids affect muscle and fat long term?
Increased muscle mass and breakdown of fat
Breast development
How do anabolic steroids affect the circulatory system long term?
Hypertension
Increased red blood cell production
Increased blood clotting
Edema
Elevated cholesterol
Increased risk of heart attack and stroke
How do anabolic steroids affect the liver long term?
Liver damage
Increased risk of jaundice, hepatitis, and cancer
How do anabolic steroids affect the thyroid long term?
Decreased thyroid function
How do anabolic steroids affect the immune system long term?
Inhibition of immune system
How do anabolic steroids affect the reproductive system long term?
Decreased sperm production, testicular atrophy, and impotence
How do anabolic steroids affect tendons and bones long term?
Weakened tendons
Decreased bone growth during adolescence
Where are steroid receptors present?
In multiple tissues like the brain and muscles
What are risks associated with anabolic steroids?
Lack of knowledge of how many and which genes are turned on
Activation of other genes leads to unwanted, dangerous side effects
What is roid rage?
Increased aggression, anger, rage especially in dependent users
Psychosis and depression also occur more frequently
What is the mechanism behind roid rage?
GABAa, NMDA, 5HT receptors can bind endogenous neurosteroids
What is the anterior hypothalamus?
The aggression centre
What does activation of D2 in AH result in?
Aggression and violence in animal models
What do moderate doses of anabolic steroids in adolescence do to DH expression in the AH?
It increases D2 expression
What do arginine vasopressin and 5HT do to aggression?
Arginine vasopressin is excitatory and potentiates aggression
5HT is inhibitory and decreases aggression
What does steroid exposure do to arginine vasopressin and 5HT?
Enhances vasopressin and reduces 5HT effects
What does chronic nandrolone do?
Increases aggression in mice
Reduces 5HT receptor mRNA in PFC, hypothalamus, hippocampus, and amygdala
What is anabolic steroid abuse linked to in relation to depression?
Reduced brain-derived neurotrophic factor levels and correlates with depressed behaviors
What does BDNF do?
Stimulates neuronal growth in the hippocampus
Steroids reduces this
What is the issue with designer steroids?
Modified by clandestine labs
Undetectable
No one knows the mechanisms and long-term effects
How are samples tested for PEDs?
Usually urine, tested for known metabolites
Can run HPLC, ELISA, GC-MS
What assays are most common for testing?
Chemical and immunoassays
What does improved technology allow for the detection of?
Unique metabolites and lower threshold for detection
What is chemical haptenation?
A small molecule that binds a macromolecule to produce an immune reaction
