drugs in sport Flashcards
what does angiotensin II do?
increases blood pressure by stimulating Gq -> IP3 -> higher [Ca2+] -> contraction
what is the effect of ACE deletions on exercise?
- higher levels of ACE
- increased angiotensin II
- increase in factors for muscle growth
- muscle hypertrophy
what type of athletes are ACE deletions found in?
short distance swimmers
what is the effect of ACE insertions on exercise?
- lower levels of ACE
- decrease in angiotensin II
- increase in bradykinin (vasodilator)
- improved vasodilation and substrate metabolism
what type of athletes are ACE deletions found in?
elite distance runners, rowers, cyclists
what are the cellular responses to IGF-1?
- activation of Akt +mTOR -> protein synthesis, growth, proliferation, metabolism and survival
- activation of ERK (MAPK) -> proliferation
how does exercise promote protein synthesis and hypertrophy?
environmental and circulating stimuli cause pituitary to secrete growth hormone, which causes the liver to secrete IGF-1, which promotes tissue growth and remodelling
what are IGF-1 polymorphisms associated with?
studies have shown IGF-1 polymorphisms to be associated with responses to strength training in the elderly
what is the impact of exercise on genes and transcription?
stimulates genes expression changes underlying structural and metabolic adaptations. this can be via alterations in gene silencing via DNA methylation, histone modification and RNA associated silencing
what is PGC-1a?
peroxisome proliferator activated receptor gamma coactivator 1. regulates genes involved with energy metabolism, mitochondrial biogenesis and function
how is VO2max affected by genetic variations?
genetic variations account for 40% of variation in VO2max with aerobic training
what was the heritage family study?
a multi-centre study on the role of genotype in cardiovascular and metabolic responses to aerobic exercise and changes to risk factors for several cardiovascular diseases and diabetes by aerobic exercise
what were the findings of the heritage study?
aerobic endurance training over 20 weeks caused
- average increase in VO2max of 19%
- greater variability in VO2max between families than within them
- there is a genetic component to VO2max and an association with muscle creatine kinase
from which endocrine glands/organs are androgens produced?
- adrenal glands
- ovaries
- testes
what type of androgens are secreted from the adrenal glands and ovaries?
weak androgens, these must undergo peripheral conversion to testosterone
what is the difference between testosterone and 5a-dihydrotestosterone?
5a-dihydrotestosterone is produced via peripheral conversion and has higher affinity for the androgen receptor
in which three forms is testosterone found in the blood stream?
- strongly found bound to sex hormone binding globulin (70%)
- found bound weakly to albumin (30%)
- unbound (0.5-0.3%)
what are the sub-families of steroid hormone receptor?
3A - estrogen receptor
3C- androgen receptor, progesterone receptor, glucocorticoid receptor
Where is androgen receptor found?
in the cytoplasm, bound to other proteins which stabilise their position
what is the effect of ligand binding to androgen receptor?
change in conformation, reducing affinity for chaperone proteins, allowing androgen receptor to act. the androgen receptor moves into the nucleus, dimerising to allow assembly of a large transcriptional compplex
what are the two types of effect of anabolic steroids?
androgenic effects
anabolic effects
how are steroids modified to improve their effects?
changes to hydroxyl group can change bioavailability
changes to cyclohexane rings can increase anabolic effects
what is the goal of making changes to anabolic steroids?
- slow inactivation
- reduce hepatic degradation
- increase lipid solubility
- increase anabolic:androgenic ratio
what morphometric changes occur upon the use of anabolic steroids?
- increased muscle volume
- increased cross-sectional area of type I and II fibres
- no difference in fibre proportions
- hyperplasia
- increased lean mass
- increased myonuclear number
what are morphometric changes caused by anabolic steroids associated with?
- increased protein synthesis
- reduced amino acid export
- increased androgen receptor expression
- fibre hypertrophy causing an increase in strength
- increase in calcium release and sensitivity of contractile proteins to calcium
increased muscle pinnation can be caused by anabolic steroid use, what is this?
when fascicles are attached to the tendon in a slanting position, allows higher force but smaller range of movement
what did measurements following intramuscular injection of nandrolone decanoate?
- decreased serum creatinine
- increase in strength
- decreased mitotic activity of satellite cells
- increased leucine uptake, increase in protein synthesis
what are the functional effects of intramuscular nandrolone decanoate injection?
- decreased damage to muscle
- increased capacity to do work
- higher fatigue resistance
- increased collagen synthesis
- increased bone mineral density
what are the complimentary effects of anabolic steroids?
- antagonism of catabolic effects of glucocorticoids
- stimulation of growth hormone insulin-like growth factor
- psychoactive effects: mood elevation, aggressiveness
what are the side effects of anabolic steroids?
- cardiovascular disease (impaired diastolic filling, dilated cardiomyopathy, increased left ventricular mass, arrhythmias)
- liver dysfunction
- cancer
what are the desired effects of stimulants?
- increased alertness, self-confidence, concentration, reduction in fatigue
- increased speed, power, endurance, and concentration
what types of stimulants are there?
- sympathomimetic amines
- CNS stimulants
- psychomotor stimulants
what effects of stimulants make their use in sport unfair?
increased cardiac output, increased blood flow to muscles, locomotor stimulation
what is amphetamine?
an indirectly acting sympathomimetic stimulant that is structurally related to monoamine neurotransmitters adrenaline and noradrenaline
why are amphetamines orally active?
they are resistant to MAO (monoamine oxidase)
what is the mechanism of action for amphetamines?
- substrates for the neuronal plasma membrane monoamine uptake transporters DAT and NET, acting as competitive inhibitors
- enter nerve terminals and interact with vesicular monoamine pump VMAT2 to inhibit uptake into synaptic vesicles of cytoplasmic dopamine and noradrenaline
- concentration of extracellular dopamine and noradrenaline in the vicinity of the synapse increases
what are the acute side effects of amphetamine use?
- increased HR, bp, restlessness, insomnia, agitation, GI upset, nausea, headache, convulsions, hallucinations, paranoia
- distortion of reality
- death due to ruptured blood vessels in the brain, heart attack due to abnormal heart rthythms
what are the chronic side effects of amphetamine use?
- dyskinesias
- compulsive and repetitive behaviour
- paranoia
what are the clinical uses for amphetamine?
- ocular actions: pupil dilation, reduction of intraocular pressure
- nasal decongestants
- narcolepsy
- ADHD
