Performance Enhancing Drugs Flashcards
what are anabolic steroids?
- naturally occurring steroids are substances involved in growth and maintenance of body
they are major performance enhancing drugs - they are based on testosterone includes T but also other synthetic derivatives altered to improve muscle
building - original use was for malnourished patients who needed to gain some weight
- first used by soviet athletes in 1950s spread around world rapidly
- prevalent in olympics: ben johnson and morion jones
What are the two effects that steroids can have?
androgenic effects –> promotion of male sexual characteristics (i.e. Adams apple, beards)
anabolic effects –> increase in mm. mass, increase in protein synthesis, redistribution of BF, increase calcium deposits in the bone (can result in buffalo hump or moon face)
users only want the anabolic effect but its almost impossible to separate
What are the three major anabolic steroid classes?
- Type 1 –> Testosterone Cypionate; T esters slows down metabolism for longer effect, hydrolyzed in the body for free (T). Primative derivative of Testosterone, carbon #17 contains an ester and makes it harder to break down; Hydroxyl group linked with ester, still convert to Estrogen though.
- Type 2 (Nandrolone) –> still has ester at #17, but at #19, a methyl group is removed, which extends the half life and reduces androgenic activity to estrogen; Extended half life, and only 20% aromatization; still needs to be injected
- Stanozolol –> has #19 methyl group attached but has 2 nitrogens as a ring to boost anabolic effects so it over shadows sexual effects of the compound; also added is a CH3 to the #17 hydroxyl group to make it resistant to metabolism so you can take it orally; not converted to 17-beta-estradiol
How are many steroids detected?
- many steroids that are used have been or are being used clinically
- these are easily detected but they have been tested for safety
- designer steroids are a big issue now (modification of existing steroids by illicit drug labs)
- advantage: most drug testing only identifies known drugs
- disadvantage: no safety testing and no one knows what they do
what is the mechanism of action of steroids?
genes that get activated by steroids code for proteins of mm. growth and other things (binds to androgen receptors)
Androgen receptors are not membrane bound and are either in the nucleus or cytosol
compounds of steroids pass through lipid bilayers easily because they are lipid soluble and bind to androgenic receptors
for it to bind to receptors, two receptors need to come together and form a pair, once this happens, the whole receptor heads towards nucleus
- in the nucleus, they bind to specific pieces of DNA and the DNA controls genes downstream and those genes make messenger RNA and mRNA is used to make new proteins i.e. for muscle mass
- for steroids, increase mm. mass , the receptor binds to bit of DNA that turns on genes that code for proteins that are involved in mm. formation
- proteins made are not specific to mm. growth and have long term effects we aren’t too sure about (cancer and cardiovascular problems)
- steroids also allow stem cells into muscle cells and prevent them from forming fat cells
what are some of the major problems with the mechanism of steroids?
- the proteins that are made are not just those involved in muscle
- steroid receptors are found in many different tissues, including the brain
- there is a huge gap in knowledge concerning which genes are activated by which steroids
- some of the genes other than those involved in mm. growth are responsible for unwanted and dangerous side effects
what are the effects of steroids on males and females?
males –> hypogonadism –> testes react by producing less of their own (T) and testicles shrink while sperm count is lowered and it is irreversible in some males
in females: masculinization, facial hair, balding and decreased breast size and loss of menstrual cycle
what are some problems associated with taking steroids (not a mechanism)?
- infection from injections like HIV
- male breasts enlarge (gynecomastia) because T is the precursor to estradiol (an estrogen) mediated by the aromatase enzyme… can take aromatase inhibitory to minimize conversion to estrogens
- severe ACNE –> can leave permanent scars
how does acne form in steroid users? what bacteria is involved?
steroids enlarge the sebaceous glands which are the oily glands used to keep us waterproof
- this increases the sebum (oil) production
- theres also increase in cell growth in hair follicles and while the hair follicles grow bacteria becomes entrapped
- increases PROPIONIBACTERIUM ACNES bacteria population and it is NOT common in non steroid users
what are acne fulminans?
it is a severe type of acne with bone lesion and arthritis component
- immune reaction to the P.acne bacterium
can leave residual scarring
What are the effects of Steroids on the liver?
- the liver metabolizes steroids
- increased risk of liver tumours
- bonging blood-filled cysts that can cause liver failure or bleeding out
- usually reversible upon cessation but sometimes you need to surgically remove portion of liver
What are the effects of steroids on the cardiovascular system?
- good evidence for increase BP, high cholesterol (the bad kind and heart abnormalities
- can lead to cardiac issues like heart attack and stroke
increases LDL:HDL ratio (LDL is the bad cholesterol that distributes fat everywhere)
- increased platelet aggregation (blood clots)
- immune cells stick to vessel walls increasing inflammation
- inhibits synthesis of nitric oxide a vasodialator
- steroids will increase mm. mass of the heart but not dilate blood vessels so oxygen needed to be delivered to the heart is LOW
What is “roid” range and the aggression that comes with steroid use?
“roid rage” is a term used to describe aggression and anger in users
- it is proven in many studies and is linked to psychosis and depression as well as suicide and most common in dependent users (63%) than non-dependant (16%)
- steroids have been shown to modulate the activity of GABA-A and NMDA receptors as well has 5HT receptors and this may be a link between steroids and mood disorders
these receptors have binding sites for steroids and may be normally modulated by neurosteroids produced in the brain
How is aggression linked with the hypothalamus in steroid users?
the anterior hypothalamus (AH) is the centre of aggression
stimulation of D2 receptors in the AH will results in aggression and violence in animal models
moderate doses of anabolic steroids in the adolescence increases D2 receptor expression in the AH
arginine vasopressin (AVP) is excitatory and potentiates aggression while serotonin is inhibitory and decreases aggression - exposure to anabolic steroids increases AVP effects and decreases serotonin effects
What effect do steroids have on serotonin?
chronic nandrolone (a steroid) increase aggression in mice - decreases the mRNA levels for 5HT receptors in several brain regions including prefrontal cortex, hypothalamus, hippocampus and amygdala
mostly the 5HT3A and the 5HT6 receptors that are most effected
about 80% of mice with steroids became aggressive and the attack latency (time it takes for stranger mouse to come into the cage and time of the attack) is shorter so the main mouse attacks the stranger mouse soon after it arrives
