Paylean & Athletes

1. Paylean & Athletes

2. Paylean in Meats • 彰化地檢署曾查獲養豬業者使用禁藥「培林」瘦肉精，移送多名製售培林的業者，瘦肉精事件又死灰復燃 • 兩年養豬戶偷偷使用的「8號仔」，是含有禁藥酷特羅（COLTEROL）成份的受體素(beta2 agonist)

3. Brand Names • 一般而言, Salbutamol最為普遍,因價格便宜,它的毒性比Ractopamine高,比Clenbuterol低。不可超過十ppb, 在美國、澳洲較高, 五十ppb,加拿大則為四十ppb,而人類可以接受的Ractopamine的濃度約七萬五千ppb還不至於中毒,

4. Are a phenethanolamine salt (halogenated aromatic ring systems, e.g. clenbuterol ) or hydroxylated aromatic rings (e.g. ractopamine) • Ractopamine has four stereoisomers of the compound

5. Chemical structure of ractopamine hydrochloride

6. Beta-Adrenergic Agonists • Cardiac effects • Increase contractility (positive inotropy) • Increase relaxation rate (positive lusitropy) • Increase heart rate (positive chronotropy) • Increase conduction velocity (positive dromotropy)

7. Vascular effects • Smooth muscle relaxation (vasodilation) • Other actions • Bronchodilation • Hepatic glycogenolysis • Pancreatic release of glucagon • Renin release by kidneys

8. Pharmacology of Paylean’s Substances • Acting as beta-adrenoceptor agonist,

9. Long-acting beta-adrenoceptor agonists are usually prescribed for moderate to severe persistent asthma patients or patients with Chronic Obstructive Pulmonary Disease (COPD).

10. Effects β2 agonist (Fenoterol) on Cross-Section Area in Rats

11. Strength as a Function of Muscle Cross-Sectional Area

12. 肌肉產生肌力，一平方公分橫斷面積的肌肉，可以產生約六公斤的肌力。也就是說，肌力與肌量是成正比的。肌肉量越多，肌力越大。

13. Dosage of Ractopamine • Oral doses of 5, 10, 15, 25, and 40 mg of ractopamine, with a washout period of 48 h between doses (body-weight basis, the doses ranged from 0.063 to 0.590 mg/kg bw)

14. Metabolic effects • When given orally or parenterally, beta-agonists may increase the concentrations of glucose, lactate, and free fatty acids and decrease the concentration of potassium in plasma.

15. Orally administered ractopamine was extensively and rapidly absorbed and low systemic concentrations of parent drug were found. The urinary metabolites were monoglucuronide and monosulfate conjugates. The half-life in plasma was about 4 h.

16. Adverse Effects in Human • Are not problematic at therapeutic doses • Except perhaps in the presence of hypoxia or co-morbidity (e.g. heart failure, cardiac arrhythmias, coronary disease, diabetes). • And regular use of beta2-selective agonists may cause increased bronchial hyperreactivity and deterioration in disease (e.g. Asthma) control

17. Skeletal muscle tremor • is more likely to be seen after oral administration than after inhalation • Tremor results from an imbalance between fast- and low-twitch muscle groups of the extremities • severity varies greatly between individuals • This adverse effect is minimized at low oral doses of beta-agonists

18. Long-acting beta-agonists (e.g. formoterol, salmeterol) showing LESS pronounced adverse effects compared with short-acting agents (e.g. isoproterenol, fenoterol, salbutamol, terbutaline)

19. In general, beta-adrenoceptor agonists: • halogenated aromatic ring systems (e.g. clenbuterol) are metabolized by oxidative and conjugative pathways and have long half-lives in plasma. • hydroxylated aromatic rings (e.g. ractopamine) are metabolized solely by conjugation and have relatively short half-lives

20. The pharmacokinetic data suggest that halogenated phenethanolamine beta-adrenoceptor agonist (e.g. clenbuterol) residues comprising greater amounts of parent substance have a higher oral bioavailability and relatively slower rate of elimination and thus a greater oral potency than residues of hydroxylated beta-adrenoceptor agonists.

21. Behavioural Changes • Feelings of restlessness, apprehension, and anxiety after oral or parenteral treatment • Ractopamine showed little evidence for central nervous system stimulation

22. WADA statement on clenbuterol June 15, 2011 • Following current media interest in relation to clenbuterol, WADA wishes to clarify the following: • 1. Clenbuterol is a prohibited substance and there is no threshold under which this substance is not prohibited. • 2. At present there is no plan to introduce a threshold level for clenbuterol. • 3. It is possible that under certain circumstances the presence of a low level of clenbuterol in an athlete sample can be the result of food contamination. However, each case is different and all elements need to be taken into account. • 4. Under the World Anti-Doping Code, result management of cases foresees the opportunity for an athlete to explain how a prohibited substance entered his/her body.

23. 5. Next week, WADA laboratory experts will meet, as they do regularly, and amongst other issues will discuss the situation with regards to clenbuterol. No decision will be taken at this meeting and any recommendation will then be reviewed and discussed at the WADA Health, Medical and Research Committee in view of the preparation of the 2012 List. • 6. The power to take a decision and to adopt the 2012 List is vested to the WADA Executive Committee, composed equally of the Sport Movement and Governments, that will meet in September. • WADA will refrain from making any further comment regarding clenbuterol until the review process has been completed.

24. Discussion • What is your opinion toward the use of an ergogenic aid to elite athletes in an attempt to improve their performance. • Is there any other substance promoted muscle strength in the WADA list that can be found.