Performance enhancing drugs Flashcards
6 categories of PEDs
stimulants
pain killers
blood doping
B agonists
B blockers
AAS and hormones
AAS
anabolic/androgenic steroids
based off testosterone steroid nucleus
altered to enhance muscle building
type 1 AAS
esters
prolonged half-lives
hydrolyzed to testosterone
aromatized to estrogens by aromatase
type 2 AAS
19-nor-testosterone (nandrolone) derivatives
prolonged half-lives
reduced androgenic effects
80% less aromatization compared to type 1
type 3 AAS
17a-alkyl derivatives
greatly reduced liver metabolism
not converted to estrogen
increased anabolic effects
best for building muscles
administration
pyramiding
stacking
cycling
pyramiding
increasing dose followed by decreasing dose
stacking
using multiple steroids
cycling
alternating periods of use
co-ordinated with training or testing schedules
absorption
injection IM
ingestion
topical
distribution
lipophilic
rapid
muscle
widespread
metabolism
liver
first-pass metabolism
low bioavailability
excretion
kidney = 90%
other 10% in GI tract
physiology
sex steroids determine male and female differences
production in reproductive tissues stimulated by FSH/LH from anterior pituitary
5a-reductase
converts testosterone to DHT
aromatase
converts testosterone to estrogen
rate-limiting step for estrogen production
negative feedback
controls levels → cyclical
mechanism of action
anabolic steroids bind androgen receptor
drug-receptor complexes translocate to nucleus → bind specific DNA sequences
activates gene transcription mRNA production → make new protein
stem cell differentiation
steroids shift stem cells away from adipose and towards muscle cell differentiation
mechanism of reinforcement
euphoria
from increased beta-endorphin levels → decrease GABA release onto VTA DA-ergic neurons
steroids modulate GABAA receptors → DA-ergic mesolimbic neurons increase firing rate
animal models
with AAS
showed increased number of myonuclei; increased muscle fiber cross-sectional area
cellular memory
allows rapid muscle building after period of inactivity
more pronounced cross sectional analysis after 11 week break in steroid treated animals
trenbolone
19-nor derivative of testosterone
higher affinity for androgen receptors
not a substrate for 5a-reductase, or aromatase
induces myotrophic effects without unwanted effects
MuRF1
atrophic gene
expression reduced by trenbolone
IGF-1
anabolic gene
expression increased by trenbolone
tolerance
develops after single dose
presence of steroids inhibits their own production (neg feedback)
withdrawal
depression + mood swings
fatigue, headache
insomnia, lack of energy
no appetite
body dissatisfaction
dependence
30% of users
more likely at higher doses
psychological - cycle length
long term health risks
steroid receptors are present in multiple tissues → activation of other genes leads to unwanted, dangerous side effects
hypogonadism
masculinization
gynecomastia
heart risk
increased blood pressure
cholesterol
heart abnormalities
roid rage
increased aggression, anger, rage
psychosis and depression
GABAa, NMDA, and 5HT receptors can bind endogenous neurosteroids
anterior hypothalamus
aggression centre
activation of D2 in AH → aggression + violence
moderate doses in adolescence increases D2 expression
arginine vasopressin
excitatory
potentiates aggression
enhanced by steroid exposure
5HT
inhibitory
decreases aggression
reduced by steroid exposure
chronic nandrolone
increases aggression in mice
reduces 5HT receptor mRNA in PFC, hypothalamus, hippocampus, and amygdala
BDNF
brain-derived neurotrophic factor levels
stimulates neuronal growth in hippocampus
reduction due to abuse → correlates with depressed behaviours
CHLO treatment
chlorimipraminie
antidepressant
reverses BDNF reduction
testing
urine - test for known metabolites
HPLC, ELISA, GC-MS
assays
chemical and immunoassays
chemical haptenation
small molecule that binds a macromolecule to produce an immune reaction
