Performance enhancing drugs Flashcards
What is erythropoietin
EPO is a glycoprotein hormone which can be injected to promote red blood cell
production
Naturally made in kidneys so used to be difficult to detect
Used in clinic to treat anaemia due to
- Chronic kidney disease
- Cancer chemotherapy
- HIV therapy
What are anabolic steroids
Lots of misuse of anabolic steroids amongst athletes.
Associated with violence, aggression.
Positive effects:
- Increased mass
-Increased strength
-Increased energy
- Increased self esteem
Negative effects:
- gynaecomastia (breast tissue)
-baldness
- testicular atrophy
-straie- stretch marks
-cardiovascular disease
How are anabolic steroids synthesised
Most steroid have been developed based on
testosterone modifications
Aim is to produce a steroid with much fewer
side effects
Testosterone converted to DHT by 5a-
reductase
Testosterone converted to oestrogen by
aromatase
Want to avoid these steps as they generate
unwanted side effects
In comparison to Nandrolone, this doesn’t bind as well to the aromatase enzyme so
much less oestrogen is made
No 5a-reducatse enzyme in muscle so when nandrolone is injected into the muscle it
will not be converted to DHT
If testosterone is taken alone, the hydroxyl group is oxidised and loses its effect =
need to be modified to protect hydroxyl group
If testosterone is being used as a tablet, a methyl group is added to the carbon with
the hydroxyl group = methyl testosterone
Same principle for oestrogen = needs to be modified with an ethinyl group for oral
administration
The longer the ester chain
attached to testosterone =
slower start but remains for
longer (nandrolone decanoate)
The short the ester chain
attached to testosterone = fast
peak and removed quickly
(nandrolone phenylpropionate)
What are the possible modifications of testosterone
- Add a double bond
- add a pyrazole ring
-Add methyl group
-Remove the angular methyl group - Add 17-a alkyl group - confers oral activity
What are the androgen receptors
Intracellular receptor with ligand
binding domain, DNA binding domain and N-terminal
do anabolic steroids cause dependance
- DSM criteria used to identify the factors that lead to drug depedance.
- This criteria needed to be modified for anabolic steroids in comparison for other drugs of abuse.
withdrawal symptoms characteristic of: depressive mood, prominent fatigue, insomnia, hypersomnia and loss of libido.
what are the effects on the reward system (Dopamine, endorphins and alcohol)
- Anabolic steroids affect the dopamine system. They cause a dopamine increase.
-measure d1 receptor before giving nandralone decanoate - high levels.
-After giving we can see in the brain regions that there are low levels of d1 receptors. why?- Receptors have been internalised as a compensatory response to excessive dopamine firing.
- Anabolic steroids increase the levels of endorphins
in the drug reward system
- study done on rats- gave them 5mg/kg of aas - saw that there were increased levels of endorphins. - AAS result an increase in alcohol intake.
A study was done where a group of rats were given equal doses of AAS for a period, they were placed in a cage where they had the choice of water and alcohol. The rats on steroids had a significantly greater preference for alcohol than water than control rats
Aggression with AAS use?
Study showing defensive aggression in rats:
close an inner rod to the nose of the rat and you measure the behavioural response of the rat. The control rat just moves away but the rat on AAS will bite and be aggressive.
Amygdala involved in predatory attack and defensive rage. - what are the effects on AAS
Competitiveness with AAS use?
You get a control rat and a anabolic rat are measure how much water they drink with 2 water feeders. In another experiment have one feeder of water amongst the two rats to measure competition. Anabolic steroid rat dominates .
It is not the case that the AAS rat is more muscular or bigger due to the sterioid, infact the AAS rat is slimmer and weighs less due to AAS use than the control rat. but they are more aggressive and dominating
Anxiety with AAS use?
Study where you have a control and an AAS rat. Play loud noise and assess whetehr they flee or freeze.
Normal response is to freeze for a long time then flee.
The AAS rats freeze and flee for a much shorter period and than control rats
How do anabolic steroids affect the Brain? What studies show this?
- Anabolic steroids and Opioids induce cognitive impairments in the brains of abusers
- Animal Study : Moris Water Maze ( MWM). Place a mice in water with a submerged platform and train the rat to be able to find the path.
Result: Male rats treated with AAS naladrone decanoate exhibited impaired performance on the morris water maze (MWM) compared to control mice
- Human studies: A study with 31 weight lifters using AAS and 13 NON- AAS weight lifters
AAS users showed substantial and significant deficits in visuospatial tests compared to controls.
3.Human study MRI scan: compare MRI scan of 10 Weight lifting long term users of AAS with 10 weight lifters with no AAS exposure. Result: Long term AAS use is associated with RIGHT AMYGDALA ENLARGEMENT. (right amygdala is associated with visiospiatal performance)
How does AAS and opiates affect the hippocampus
-AAS result in the reduction of neurones in the hippocampus, parietal cortex, prefrontal cortex regions and increase oxidative damage.
-The long term use of opiates may lead to negative effects on learning and memory.
How does Growth hormone improve the impaired cognition caused by opiates and AAS
GROWTH HORMONE***
Evidence:
1. Growth hormone improves short term and long term memory.
2. GH improves cognitive function in rats
GH binds to GHR, activates IGF1 which activates NMDA receptors that activate the Krebs cycle - results in the formation of new proteins, synapses, LTP and the improvement in memory.
Evidence of Growth hormone reversing brain damage
- Animal studies: GH Rats performed better in MWM than control and AAS rats
- Images of nerves cells in the hippocampus. Increased synaptic contacts, Higher density of dendritic spines in cells treated with GH compared to morphine (opioid) and control.
— Inc synaptic contacts allows for better communication between synapses and this facilitates learning and memory.
— The density of dendritic spines correlates with learning and acquired knowledge
How does Angiotensin IV improve cognition and reverse brain damage
Angiotensin IV is a modified molecule with an added ring structure.
Study: look at how the addition of Angiotensin IV affects the dendritic spines on a nerve cell.
Greater concentrations of Angiotensin IV resulted in more dendritic spines
