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All About Salbutamol

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What will the verdict in Froome's salbutamol case?

He will be cleared
43
34%
3 month ban
4
3%
6 month ban
15
12%
9 month ban
24
19%
1 year ban
16
13%
2 year ban
21
17%
4 year ban
3
2%
 
Total votes : 126

Re: All About Salbutamol

22 Jan 2018 22:00

Robert5091 wrote:
ClassicomanoLuigi wrote:
Since Froome has no logical explanation, then maybe his last hope is: that lawyers try to subvert the courtroom process itself, with baffling maneuvers and technicalities


I expect nothing less then a full blown circus with lawyers aplenty and the Chewbacca defense https://en.wikipedia.org/wiki/Chewbacca_defense. SDB doing lots of hand waving as well. :D


The outcome of such defense in continental law system is very limited, lawyers are dealing with professionals not with dilettante (jury). Such defense may limit a bit losses, but most probably will not succeed. And even kind of such defense in Contador case did not succeed and he got the ban ... . For Froome, if I understand it properly, to found him guilty will be very damaging, he will loose his Vuelta title, WC time trial medal and possibly also option to ride Giro.
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Re: All About Salbutamol

22 Jan 2018 22:41

Here are some of the legal defenses currently being considered by Team Froome:

The lab test defense: If he can repeat it in Lausanne, you can’t give him a ban
The dehydration defense: If it’s over 1030, he can’t be so dirty.
The kidney defense: If it went to high from low, he gets to start the Giro.
The altered metabolism defense: If on diet it depends, you can’t his season suspend
The made a mistake defense: If he doesn’t try to hide it, you must let him ride it.
The innocent till guilty defense: If he’s banned but wins at CAS, we’ll bloody sue your ***.
Merckx index
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Re: All About Salbutamol

22 Jan 2018 23:42

lartiste wrote:
Robert5091 wrote:
ClassicomanoLuigi wrote:
Since Froome has no logical explanation, then maybe his last hope is: that lawyers try to subvert the courtroom process itself, with baffling maneuvers and technicalities


I expect nothing less then a full blown circus with lawyers aplenty and the Chewbacca defense https://en.wikipedia.org/wiki/Chewbacca_defense. SDB doing lots of hand waving as well. :D


The outcome of such defense in continental law system is very limited, lawyers are dealing with professionals not with dilettante (jury). Such defense may limit a bit losses, but most probably will not succeed. And even kind of such defense in Contador case did not succeed and he got the ban ... . For Froome, if I understand it properly, to found him guilty will be very damaging, he will loose his Vuelta title, WC time trial medal and possibly also option to ride Giro.


Depends on the court system and state in the US. Generally in criminal trials you are not allowed to provide an “alternate” version, you can only defend yourself against the charges. Alternate versions is what gets into Chewbacca territory and courts frown upon it. In Froome’s case he has to provide an alternate theory for his reading of Salbutamol but he also has to prove biologicallly that it’s true. That will be very difficult to do.
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Re: All About Salbutamol

23 Jan 2018 01:26

Now here's an interesting idea. Could having asthma actually benefit endurance athletes, because as with high altitude training, the body adapts to lower oxygen levels? One asthmatic claims something like this:

training with asthma is a lot like resistance training; you get used to a reduced ability to draw oxygen into your lungs, thereby restricting the supply that gets to your muscles. Its like reverse blood-doping. You get used to it and your body adjusts to the reduced supply of gun fuel. Then, on days when the air is clear and warm, you ride like you’re on EPO. I call this the “EPO-Effect”.


http://www.velominati.com/folklore/asthmatics/

There have been some studies that suggest asthmatics may actually have more efficient physiology because of this:

http://www.scielo.br/scielo.php?pid=S1806-37132011000600003&script=sci_arttext&tlng=en
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4492492/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4492492/#pone.0132007.ref006
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2150973/

It's well known that large percentages of elite athletes have asthma, and one study reported that Olympic athletes with asthma actually won more medals per group size than athletes without asthma. The usual explanation for this is that having to take in large amounts of air during training may stress the lining of the lungs, so elite athletes are more at risk for developing EIA. But is it possible that another reason is that asthmatics undergo adaptive changes that increase metabolic efficiency?

Another interesting phenomenon is the refractory period that asthmatics experience. After you have an asthma attack, you are apparently protected against a further attack for a couple of hours. Posters who suffer from disorder can comment on this:

Sarah Koch and Michael Koehle at the University of British Columbia's Environmental Physiology Laboratory, funded by the World Anti-Doping Agency

…tested 42 elite cyclists, 10 of whom had "exercise-induced bronchoconstriction" (the correct term for asthma-like symptoms triggered by exercise). Each cyclist performed two 10-kilometre time trials, with or without drugs, in a double-blinded design. The result: no differences in finishing time, even for the asthmatics…

So why did the UBC study find no discernible effect? Dr. Koehle offers a surprisingly simple explanation: The subjects in his and other studies all had thorough warm-ups before their exercise tests, making them less likely to suffer an asthma attack whether they received the drugs or the inactive placebo.

It turns out that asthma attacks produce a "refractory period," during which the airways become temporarily immune from a further attack. As a result, a warm-up that is sufficiently long and intense to sensitize the airways may allow athletes to get through their competition or time trial without suffering an attack.

Most elite athletes already do this kind of warm-up as a matter of course, but others can benefit too. "With a better warm-up, you can get away with less drugs," Dr. Koehle says.


https://www.theglobeandmail.com/life/health-and-fitness/fitness/why-asthma-doesnt-stop-elite-athletes/article4445211/
Merckx index
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Re: All About Salbutamol

23 Jan 2018 02:30

Merckx index wrote:Now here's an interesting idea. Could having asthma actually benefit endurance athletes, because as with high altitude training, the body adapts to lower oxygen levels? One asthmatic claims something like this:

training with asthma is a lot like resistance training; you get used to a reduced ability to draw oxygen into your lungs, thereby restricting the supply that gets to your muscles. Its like reverse blood-doping. You get used to it and your body adjusts to the reduced supply of gun fuel. Then, on days when the air is clear and warm, you ride like you’re on EPO. I call this the “EPO-Effect”.


http://www.velominati.com/folklore/asthmatics/

There have been some studies that suggest asthmatics may actually have more efficient physiology because of this:

http://www.scielo.br/scielo.php?pid=S1806-37132011000600003&script=sci_arttext&tlng=en
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4492492/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4492492/#pone.0132007.ref006
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2150973/

It's well known that large percentages of elite athletes have asthma, and one study reported that Olympic athletes with asthma actually won more medals per group size than athletes without asthma. The usual explanation for this is that having to take in large amounts of air during training may stress the lining of the lungs, so elite athletes are more at risk for developing EIA. But is it possible that another reason is that asthmatics undergo adaptive changes that increase metabolic efficiency?

Another interesting phenomenon is the refractory period that asthmatics experience. After you have an asthma attack, you are apparently protected against a further attack for a couple of hours. Posters who suffer from disorder can comment on this:

Sarah Koch and Michael Koehle at the University of British Columbia's Environmental Physiology Laboratory, funded by the World Anti-Doping Agency

…tested 42 elite cyclists, 10 of whom had "exercise-induced bronchoconstriction" (the correct term for asthma-like symptoms triggered by exercise). Each cyclist performed two 10-kilometre time trials, with or without drugs, in a double-blinded design. The result: no differences in finishing time, even for the asthmatics…

So why did the UBC study find no discernible effect? Dr. Koehle offers a surprisingly simple explanation: The subjects in his and other studies all had thorough warm-ups before their exercise tests, making them less likely to suffer an asthma attack whether they received the drugs or the inactive placebo.

It turns out that asthma attacks produce a "refractory period," during which the airways become temporarily immune from a further attack. As a result, a warm-up that is sufficiently long and intense to sensitize the airways may allow athletes to get through their competition or time trial without suffering an attack.

Most elite athletes already do this kind of warm-up as a matter of course, but others can benefit too. "With a better warm-up, you can get away with less drugs," Dr. Koehle says.


https://www.theglobeandmail.com/life/health-and-fitness/fitness/why-asthma-doesnt-stop-elite-athletes/article4445211/


Certainly not my experience but that is with an intense warm up, only racing over 10 kms and using elite athletes. The Joe Average like myself didn't warm up like that or race like that in road races. Curious results I have to admit. The superior heart and lung function of elite athletes obviously plays a part. But not all EIA wheeze or have an attack every time they exercise either. If anything it makes me think that too many people are using asthma drugs without really needing them. Similar to other over prescribed drugs.
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Re: All About Salbutamol

25 Jan 2018 20:40

Not scientific, I know, but the fastest natural runner on least amount of training I've ever known is my asthma-suffering wife. When we lived in London and her asthma was its worse, on the few days she could train at maximum without suffering symptoms that day she would post some really incredible times. Even if she took Ventolin and felt fine, if she was asthmatic that day before the run she would always be around 5% off. I never really thought of it as the good days were way above her optimum, but looking back they might have been. She was competitive even while suffering, but when she had a good day it was always a shock, just how good her times were considering she was just running for fun and fitness after work and stuff.
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Re: All About Salbutamol

26 Jan 2018 13:40

samhocking wrote:Not scientific, I know, but the fastest natural runner on least amount of training I've ever known is my asthma-suffering wife. When we lived in London and her asthma was its worse, on the few days she could train at maximum without suffering symptoms that day she would post some really incredible times. Even if she took Ventolin and felt fine, if she was asthmatic that day before the run she would always be around 5% off. I never really thought of it as the good days were way above her optimum, but looking back they might have been. She was competitive even while suffering, but when she had a good day it was always a shock, just how good her times were considering she was just running for fun and fitness after work and stuff.


You’re right, not scientific. Lovely story though :)
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Re: All About Salbutamol

28 Jan 2018 22:54

Bardet is 2,000km down on Froome on Strava this year. Someone is really trying hard to recreate something...


Looks like Froome is trying to recreate the entire Vuelta for his submission to the UCI? :confused:
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Re: All About Salbutamol

28 Jan 2018 23:08

thehog wrote:
Bardet is 2,000km down on Froome on Strava this year. Someone is really trying hard to recreate something...


Looks like Froome is trying to recreate the entire Vuelta for his submission to the UCI? :confused:


He also recreated the crash which occured on stage 12 ?!
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Re: All About Salbutamol

28 Jan 2018 23:34

Rollthedice wrote:
He also recreated the crash which occured on stage 12 ?!


A necessary part of his defense:

[Ulissi] tested positive in the Giro’s 11th stage to Savona. His urine test showed 1900 nanograms per millilitre of Salbutamol, nearly double the limit of 1000ng/ml. His team explained at the time that he was using an inhaler with Salbutamol spray, took two puffs ahead stage and a paracetamol from the race doctor after crashing.

Ulissi and his lawyer argued that the crash at the start of the stage caused a jump in values and the resulting positive test.


http://www.cyclingweekly.com/news/latest-news/diego-ulissi-banned-nine-months-doping-152990

As I noted upthread, paracetamol, aspirin and other non-steroidal anti-inflammatory drugs can cause renal impairment. I'd love to know if Ulissi's team actually argued that--maybe they even gave Froome's team the idea--but since the case documents have never been made public, no way to tell.
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Re: All About Salbutamol

28 Jan 2018 23:42

thehog wrote:
Bardet is 2,000km down on Froome on Strava this year. Someone is really trying hard to recreate something...


Looks like Froome is trying to recreate the entire Vuelta for his submission to the UCI? :confused:


Why wouldn't he, if he thinks it will help 'prove' his argument. I have no idea whether it will or not but in his position he has to try. Obviously, the assumption most popular on here is he took an oral dose or something similar to get that test result. Perhaps, he/they think they can replicate the test result or near as possible whilst taking an allowed inhaled dose to convince the relevant bodies of his innocence.
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Re: All About Salbutamol

29 Jan 2018 00:35

bigcog wrote:
thehog wrote:
Bardet is 2,000km down on Froome on Strava this year. Someone is really trying hard to recreate something...


Looks like Froome is trying to recreate the entire Vuelta for his submission to the UCI? :confused:


Why wouldn't he, if he thinks it will help 'prove' his argument. I have no idea whether it will or not but in his position he has to try. Obviously, the assumption most popular on here is he took an oral dose or something similar to get that test result. Perhaps, he/they think they can replicate the test result or near as possible whilst taking an allowed inhaled dose to convince the relevant bodies of his innocence.


Cool your jets BigCog. I’m not being critical of his attempt, merely observing. He needs to do something as at this point he is ****.
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29 Jan 2018 01:22

Here's a potentially very relevant paper reporting that NSAIDs (pain-killers such as aspirin and paracetamol) inhibit transport of salbutamol across bronchial epithelium by effects on organic cation transporters (OCTs):

http://sci-hub.la/10.3109/02770903.2013.773518

There are several very important implications here. First, use of these drugs, by blocking uptake of salbutamol into the lungs, would reduce the effects of inhaling, perhaps resulting in a need to take more than the usual dose. Second, if the salbutamol is retained in the lungs for a period of time, it could build up, so that when it finally passes into the blood and then the kidneys, would be at increased concentration. The third implication is that NSAID inhibition of OCTs would also be a mechanism by which these drugs could reduce salbutamol excretion by the kidneys, since OCTs are present in renal proximal tubules, and thought to play a major role in excretion of many drugs. This paper reports effects of NSAIDs on OCTs in proximal tubule cells:

http://sci-hub.la/10.3109/02770903.2013.773518

This may be what Froome's team is looking at in trying to construct a renal impairment defense. There's still a big jump between lab studies and a credible in vivo mechanism. Both of these studies were carried out using cell cultures. The first study, on bronchial epithelium, used concentrations of NSAIDs that the authors concede are far higher than in vivo plasma concentrations following the usual doses. The second study did not directly demonstrate an effect on salbutamol transport, but on a much simpler cation, tetraethylammonium. The effects were quite modest, and in fact their data suggest that at physiological doses there wouldn't be any effect at all. It should also be noted that this study transfected the transporters into the cells, i.e., inserted the appropriate gene. I think this was done to maximize the amount of transporter, so that it would be easier to detect changes produced by the NSAIDs.

I'm just speculating here, of course, but Froome may claim that after the crash on stage 12, he took paracetamol or some other NSAID or NSAID-like pain-killer for several days. The argument would be that this reduced uptake of salbutamol both in his lungs and in the kidneys, leading to elevated concentrations in the lungs and plasma. When he stopped taking the analgesic, this backlog of salbutamol was excreted.

This would require more than a week of analgesic, though, which seems unlikely, unless Froome wants to claim he was treating some additional problem. Also, of course, Froome has crashed before, as no doubt have other riders who take salbutamol, not to mention that pain-killers might be taken for some other problem. In any case, as supporting evidence, he would want to show that all his urine samples during this previous time period showed very low levels of salbutamol. And if he gave a blood sample at any point during that period, plasma concentration would be very informative. Though as noted before, all of this information has limited usefulness if Froome can't demonstrate how much salbutamol he was inhaling during this period.
Last edited by Merckx index on 29 Jan 2018 05:18, edited 2 times in total.
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Re: All About Salbutamol

29 Jan 2018 01:54

NSAIDs are anti-inflammatory based drugs often coupled with a pain killer like ibuprofen or paracetamol. They are not pain killers on their own.

NSAID = Non-Steroidal Anti-Inflammatory Drug.
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Re: All About Salbutamol

29 Jan 2018 02:16

thehog wrote:NSAIDs are anti-inflammatory based drugs often coupled with a pain killer like ibuprofen or paracetamol. They are not pain killers on their own.

NSAID = Non-Steroidal Anti-Inflammatory Drug.


Of course NSAIDs (including ibuprofen) are used to treat pain. Inflammation is painful (and there are other mechanisms). There are technical issues in the definition of NSAIDs, e.g., paracetamol is not actually a NSAID, but it works like one in some respects (which is why I said "NSAID-like"). The anti-inflammatory activity of NSAIDS results from inhibition of the cyclo-oxygenase (COX) enzymes, and paracetamol has this effect, but generally not in tissues where inflammation occurs.
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Re: All About Salbutamol

29 Jan 2018 02:44

Merckx index wrote:
thehog wrote:NSAIDs are anti-inflammatory based drugs often coupled with a pain killer like ibuprofen or paracetamol. They are not pain killers on their own.

NSAID = Non-Steroidal Anti-Inflammatory Drug.


Of course NSAIDs (including ibuprofen) are used to treat pain. Inflammation is painful (and there are other mechanisms). There are technical issues in the definition of NSAIDs, e.g., paracetamol is not actually a NSAID, but it works like one in some respects (which is why I said "NSAID-like"). The anti-inflammatory activity of NSAIDS results from inhibition of the cyclo-oxygenase (COX) enzymes, and paracetamol has this effect, but generally not in tissues where inflammation occurs.


I won’t argue with any of that :)
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29 Jan 2018 04:00

But surely if NSAIDS did this - then more athletes would go over the limit much more often. Athletes take painkillers and NSAIDS all the time ... they crash, they hurt, they are sore and exhausted ... paracetomol and Ibprofen would be part of their regular diet

so how would the sky team be able to prove that it so happened just this once?
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Re:

29 Jan 2018 04:36

AussieGoddess wrote:But surely if NSAIDS did this - then more athletes would go over the limit much more often. Athletes take painkillers and NSAIDS all the time ... they crash, they hurt, they are sore and exhausted ... paracetomol and Ibprofen would be part of their regular diet

so how would the sky team be able to prove that it so happened just this once?


Yes, I pointed this problem out above. But keep in mind that different individuals will react differently to drug interactions, so assuming there really is an effect, the magnitude of the effect will vary between individuals as well as at different times for the same individual. Any effect that did occur might not be enough, by itself, to raise urine levels above the threshold most of the time, but might combine with other causes in exceptional circumstances. E.g., if Froome took all of the maximum 800 ug allowed within a couple of hours of the finish, without urinating; if he was somewhat dehydrated; if NSAID use went on every day during a period when he was also taking near-maximum allowed amounts of salbutamol.

Any case his team develops is probably going to have to involve multiple factors. I still think it's a stretch, but this is the way it would probably be presented.

Edit: I should have mentioned above that while those studies show that salbutamol excretion can be inhibited by NSAIDs, this effect is not selective. Excretion of other substances, such as creatinine, would also be affected. So as someone pointed out previously, unless Froome's samples show a significant effect on markers like this, pointing to lower salbutamol levels probably wouldn't help him.

More edit: On looking at those studies more closely, I see that the effect of NSAIDs on organic cation transporters (OCTs; the class that would be relevant to salbutamol uptake and excretion) really is not that great; the needed concentrations are too high. They seem to be more potent at OATs, the anion transporters. But I found a very recent study--it was just accepted a few weeks ago--which reports effects of eighteen commonly used antibiotics on transporters. Again, the greater effect is generally on OATs, but there is a significant effect of several of these antibiotics on OCTs, i.e., effects at physiologically relevant concentrations.

http://sci-hub.la/10.1016/j.ejps.2018.01.002

There is irony in this approach, because to the extent that substances like NSAIDs or antibiotics inhibit excretion of salbutamol, they are in effect masking agents, much like probenecid, which Impey tested positive for. Indeed, now that I think about it, this is another possible explanation for Froome's positive. If he used a masking agent during the Vuelta--not to mask use of salbutamol, but of some other drug, such as a steroid--but then forgot to use it before stage 18, he could get a back-up of salbutamol that was later excreted in high concentration. In fact, he wouldn't even have had to forget to use it. If, with the end of the GT approaching, he decided he didn't need to use the steroid or whatever any longer, he would have also stopped using the masking agent, without realizing this could have an effect on salbutamol.
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Re: Re:

29 Jan 2018 07:19

[quote="Merckx index

There is irony in this approach, because to the extent that substances like NSAIDs or antibiotics inhibit excretion of salbutamol, they are in effect masking agents, much like probenecid, which Impey tested positive for. Indeed, now that I think about it, this is another possible explanation for Froome's positive. If he used a masking agent during the Vuelta--not to mask use of salbutamol, but of some other drug, such as a steroid--but then forgot to use it before stage 18, he could get a back-up of salbutamol that was later excreted in high concentration. In fact, he wouldn't even have had to forget to use it. If, with the end of the GT approaching, he decided he didn't need to use the steroid or whatever any longer, he would have also stopped using the masking agent, without realizing this could have an effect on salbutamol.[/quote]

The doc c**k up theory ... but his samples from 19 & 20 would show this?
"Are you going to believe me or what you see with your own eyes?"

“It doesn’t matter what I do. People need to hear what I have to say. There’s no one else who can say what I can say. It doesn’t matter what I live.”
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Re:

29 Jan 2018 11:30

AussieGoddess wrote:But surely if NSAIDS did this - then more athletes would go over the limit much more often. Athletes take painkillers and NSAIDS all the time ... they crash, they hurt, they are sore and exhausted ... paracetomol and Ibprofen would be part of their regular diet

so how would the sky team be able to prove that it so happened just this once?


Wasn't Ibuprofen part of Lance's diet as advised by Ferrari?

I could imagine a paracetamol / ibuprofen being used quite a lot - as a combination its very good at pain relief, and also for relief from colds & flu.

Could be that Sky are using NSAIDs - perhaps prescription ones (in the UK at least) like Naproxen. Its an effective pain reliever and doesn't appear on any list as far as I know especially if they are no longer using Tramadol (although lets not confuse those two in terms of their potency).
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