Lecture 25 - Growth-promoting agents for skeletal muscle Flashcards Preview

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Flashcards in Lecture 25 - Growth-promoting agents for skeletal muscle Deck (31):
1

Medical applications of anabolic agents is important for treatment of many diseases including...

MDs
HIV-AIDS
cancer cachexia
ageing (sarcopenia)
sepsis
denervation
plaster casting
enhancing regeneration after muscle injury

2

What are the hormonal therapeutic agents?

GH, testosterone, DHEA, SARMs

3

What are the hormonal therapeutic agents?

IGF-1, IL-15, TGF-Beta

4

What are the other growth promoter agents?

beta2-agonists

5

What is an Ergongenic aid?

Allows the bosy to train/perform at a higher level

6

What is the effect of endogenous levels and exogenous administration of testosterone?

endogenous levels
- responsible for male phenotype
- promotes bone and muscle growth

exogenous administration
- stimulates muscle protein synthesis

There are also synthetic analogues of testosterone and their precursors: nandrolone, oxandrolone, stanozolol

7

androgenic -anabolic steroids are synthetic derivatives of ______ capable of exerting strong effects on the body that can benefit athletic performance

androgenic -anabolic steroids are synthetic derivatives of testosterone capable of exerting strong effects on the body that can benefit athletic performance

8

True or false

testosterone replacement has been used to counteract loss of lean body mass in hypogonadal men, in older men with normal or low serum testosterone and HIV-infected men with low serum testosterone

true

muscle growth achieved

9

What are the Direct mechanisms of action for androgenic -anabolic steroids ?

Androgen receptor
- located in skeletal muscle
- stimulated by testosterone and DHT

receptor stimulation causes: increase in protein synthesis and therefore increase in muscle mass

10

What are the indirect mechanisms of action for androgenic -anabolic steroids ?

modulate gene expression of autocrine and paracrine mediators via other receptors (IFG-1)

Alter secretion of other hormones that suppress skeletal muscle growth - cortisol

11

What are the potential benefits of androgenic -anabolic steroids use?

Muscle hypertrophy
- increased protein synthesis

Ca2+ deposition in bones

lipolysis - increased lean body mass

increased RBC production - greater oxygen carrying capacity

motivation

12

what are the levels of testosterone administration and endogenous levels?

endogenous levels - 7mg testosterone/day

medicinal 4-10 mg/day

females
medicinal 0.04-0.12 mg/day

13

some studies have demonstrated enhanced muscle strength following testosterone administration, but other have reported...

n effect of androgen therapy on muscle function despite increases in muscle size

although anabolic steroids have been used for the treatment of HIV-related wasting and other wasting conditions for many years, many questions remain unanswered

e.g what are appropriate and safe doses for long-term administration and what are the associated potential risks or side-effects

14

What are the potential medical consequences of testosterone abuse?

at 100-350+ mg/day

liver dysfunction
testicular atrophy
increased body hair

male pattern baldness

gynaecomastia

acne

reduced HDL cholesterol levels

15

The abuse of testosterone in sports undermines the...

potential theapeutic applications

16

Where is growth hormone released from endogenousl and what inhibits it?

the ant. pituitary

somatostatin inhibits GH release

17

What is the mechanism of action of GH and its effects?

GH binds two receptors resulting in dimerisation

- causes the release of somatomedins = IGF-1

Effects
- lipolysis
increase lean body mass
- bone growth
protein accretion

rhGH(synthetic) has the same effect

18

Is there clinical evidence for increased performance, bone strength and decreased body fat for GH in sport?

No

19

True or false

rhGH is indistinguishable from GH

true

banned by IOC, but undetectable

20

What are the side effects of GH excess?

gigantism (pre-puberty)

acromegaly (post-puberty)

organomegaly

hypertension (increase Na reabsorbtion)

Collagen deposition

21

what is the therapeutic potential of GH?

improves muscle structure

mscuel function

numerous side effects
limited therapeutic potential

22

true or False

GH has been used by athletes since the 1980s to improve performance despite being banned for many years and appearing on the WADA list of banned substances

True

the actions of GH that interest athletes are anabolic and lipolytic

some of the anabolic GH actions are mediated through the generation of IGF-1 and there is anecdotaed evidence that this too is being abused by athletes either alone or in combination with GH

23

What does IGF-1 do?

growth factor with structural homology to insulin

involved with normal growth and repair of muscle

mediates action of GH

mechanism of Action:
Binding of IGF-1 to receptor
- increases protein synthesis
Decreases protein degradation
increase Muscle mass

24

How is IGF treated wrt sport?

what are its potential therapeutic benefits?

expensive (10,000 for 50mg)

does incerase muscle mass, strength and oxidative capacity

hence banned by the IOC

25

What are the thrapeutic benefits for Beta-agonists for sarcopenia?

increase muscle mass, Fibre size, absolutele force-producing capacity

cause slow-to-fast muscle fibre transitions (which causes hypertrophy)

enhance muscle repair after damage

26

Beta-adrenoceptor agonists (beta agonsits) are used for what?

used traditioanlly as bronchodilators for treating asthma, some have powerful anabolic effects on muscle however (when taken in higher doses and systemically rather than inhalation)

27

what is the mechanism of action of Beta-agonists?

acts through Pi3K/AKT and PKA

28

Increased levels of adrenergic stimulants reduces the response, how?

Desensitisation = same adrenoreceptor number but decreased receptor function

downregulation = decrease in adrenoceptor number, but same receptor fucntion

29

Can we separate the beneficial effects on skeletal muscle from those (delerious effects) on the heart?

all of these can be factors to deal with the CV side effect

choice of beta-agonists (clenbuterol is old, there are newer versions)
dosage
duration of treatment
mode of adminsitration

30

what family of receptors are beta-adrenoreceptors a part of?

G-protein coupled receptors (GPCRs)

31

True or False

currently in development, a synthetic receptor and an activator neither of which activates or impairs endogenous signalling

true

RASSLs and DREADDs - still in early phases of development

limits signalling to the tissue/region of interest - a result that current beta-agonists cannot achiebe

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