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Just to clarify (using points from your own post) - newer drugs with less of the liver toxicity are now available, so its common sense to remove the old one with greater liver effects in favour of the latest medication.
In what way does any of this suggest animal research is flawed?
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quote: Originally posted by medical breakthrough:
Just to clarify (using points from your own post) - newer drugs with less of the liver toxicity are now available, so its common sense to remove the old one with greater liver effects in favour of the latest medication.
In what way does any of this suggest animal research is flawed?
I am sure if your hypothesis was correct, and the ban had nothing to do with the number of unfortunate people who died or suffered severe liver complications, the FDA and pharmaceutical company would have been at great pains to point it out. Sorry... try again...  |
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quote: Originally posted by medical breakthrough:
I'm only posting to correct your glaring errors - I'm still waiting for you to participate in the debate by addressing points put to you.
We've been through this loop before - this class of diabetes drug is inherently toxic due to its mechanism. However, the danger to life from not taking any diabetes medication is much greater. Benefits outweigh the known risks.
Liver effects were 100% accurately predicted in animal models with this medication - read Metabolism. 1995 Nov;44(11):1489-94 or Mol Pharmacol. 2001 Mar;59(3):627-35. for a review of the original studies.
However, the danger to life from not taking any diabetes medication is much greater. Now there's an interesting statement. What CAN be much more dangerous to life than dying of liver failure from taking Rezulin. You have a very ingenuous way of arguing and fantastic sense of humour sometimes, Medical Breakthrough, I have to hand it to you.  |
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quote: Originally posted by medical breakthrough:
In what way does any of this suggest animal research is flawed?
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You asked :- quote: What CAN be much more dangerous to life than dying of liver failure from taking Rezulin.
Dieing of hypoglycemia in a matter of hours following not taking medication, which would occur in nearly all diabetic patients. Conversely the liver tox occurs in a small minority of patients. I completely agree that this isn't perfect, and there is significant on going work to develop better diabetes medications, but we're currently stuck with these medications. So it's a choice of a quick death, or the outside slight chance of some toxicity - which would you choose? My point still stands that the benefits of this medication still outweight the risks. Side effects of this class of medication were very well predicted in advance, so what possible relevance does any of your ramblings have on animal research? |
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quote: Originally posted by medical breakthrough: You asked :- quote: What CAN be much more dangerous to life than dying of liver failure from taking Rezulin.
Dieing of hypoglycemia in a matter of hours following not taking medication, which would occur in nearly all diabetic patients. Conversely the liver tox occurs in a small minority of patients. I completely agree that this isn't perfect, and there is significant on going work to develop better diabetes medications, but we're currently stuck with these medications. So it's a choice of a quick death, or the outside slight chance of some toxicity - which would you choose? My point still stands that the benefits of this medication still outweight the risks. Side effects of this class of medication were very well predicted in advance, so what possible relevance does any of your ramblings have on animal research?
Evidently, the FDA doesn't agree with you about the benefits of this medication outweighing the risks. Here is what they said: ]"When considered as a whole, the pre-marketing clinical data and post-marketing safety data from Rezulin as compared to similar, alternative diabetes drugs indicate that continued use of Rezulin now poses an unacceptable risk to patients," said Dr. Janet Woodcock, Director of FDA's Center for Drug Evaluation and Research.I don't think there is any way that Rezulin posing an unacceptable risk to patients CAN be translated to your contention that "the benefits of this medication still outweight the risks"The use of the word "ramblings" in your last paragraph would seem to indicate that you are feeling a bit on the backfoot, and have resorted to very subjective comments, of the kind that I thought that you abhorred, Medical Breakthrough. It seems unfair to me that you berate others throughout the thread for what you consider subjective comments, and yet do the same yourself.  |
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Medicalbreak said: 'I referenced drug names of NCEs which were not profiled in animals when going into human trials. Read up on them all you like. They contributed to the stats you referenced as they failed in human trials.' I say: Do you mean the pharmagene ones? A drop in the ocean. ---------------------- Medicalbreak said; 'Which drug trials are you referring to? Can you highlight a couple which we can talk through and perhaps we can work out where the route of failure was?' I say: Nearly every NCE. They all have lab animal data. ------------------ Medicalbreak said that liver damage potential was known about before rezulin (or troglitazone, as it was called then) was approved for human use. Presumably, there was lab animal data to show that it could cause severe liver damage. If so, is the following accurate: 'First label change. When the FDA first approved Rezulin in early 1997, Warner-Lambert made no recommendation for monitoring liver function. There was only a precaution that troglitazone should be prescribed with caution in patients with advanced liver disease. Several months after the company launched Rezulin in March 1997, however, some cases of liver damage began to be reported. ' http://www.medlawlegalteam.com/article_jenner_rezulin.htmlIf they made no recommendation for people without liver disease to beware, did this mean that lab animals tests hadn't found the danger for these people without liver disease? ------------------------------ Below we have more from the above mentioned link. 'The newspaper quoted a March 2 e-mail message that was sent by Dr. Saul Malozowski, of the agency's diabetes drug division, to colleagues: 'My question is: How many fatal cases will suffice to put to rest [Warner-Lambert's] argument? I believe that one case will be too many. . . . The number of [liver-]associated deaths with Rezulin . . . is in excess of anything previously seen with any of the approved [diabetes] drugs . . . .We know now what has happened with Rezulin, and there is not a single piece of information to believe that either new or old patients will not develop severe or fatal complications with it. 'On March 26, 1999, the FDA's Endocrinologic and Metabolic Drugs Advisory Committee reviewed the most recent data on the safety of Rezulin. By this date, 1.5 million patients had been treated with the drug in the United States. Of concern to the FDA was the finding that some patients who took all the precautions set out by Warner-Lambert still died of severe liver toxicity that arose just weeks after they had passed a liver test.' I say: If the above is accurate, it suggests that any lab animal tests couldn't have shown how dangerous the drug would be. ------------------ More from the same link: 'On March 10, 2000, Dr. Janet McGill, a St. Louis endocrinologist who assisted in Warner-Lambert's early clinical testing of Rezulin, claimed publicly that the company "clearly places profits before the lives of patients with diabetes." McGill focused on Warner-Lambert's handling of adverse events in patients who took Rezulin in two clinical trials. "I believe that the company . . . deliberately omitted reports of liver toxicity and misrepresented serious adverse events experienced by patients in their clinical studies." ' I say: Did the company find such danger in lab animals? If they did, why did they send the drug to human trials? If they had found such danger in lab animals, and believed that lab animals are models for humans, they would have believed that very soon the dangers would be seen in humans after the drug was approved - no matter how many clinical trials they could falsify. -------------------- Medicalbreak said, about rezulin: 'Liver effects were 100% accurately predicted in animal models with this medication - read Metabolism. 1995 Nov;44(11):1489-94 or Mol Pharmacol. 2001 Mar;59(3):627-35. for a review of the original studies' I say: I couldn't find the 2001 study but found the abstract of the 1995 one. It doesn't mention severe liver disease was caused in the rats. Yes, it's only an abstract but you'd think it would mention something that serious. Do either of those two studies say that rezulin caused severe liver disease in the lab animals? |
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witch posted quote: Rezulin as compared to similar, alternative diabetes drugs indicate that continued use of Rezulin now poses an unacceptable risk to patients
I've highlighted the important part here. Are you actually failing to grasp the point here, or does it need further clarification? The original drug was approved despite known liver tox problems because there was nothing else available. When newer drugs with less liver tox became available it was only sensible to withdraw the original because it had unacceptable liver tox compared to the new drugs. When only the original drug was available the benefits most certain did outweigh the risks, and nothing you've posted suggests otherwise. Now, do you have the time to address the issues put to you, or will you simply return with further slightly altered, but essentially the same, questions for me? ======================== martin - lots or assumption, contention and opinion from yourself, but you are still failing to provide any evidence to support your claims. Please note that every point I've made has been supported by specific drug names and/or references to available material. Why can't you do the same? |
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quote: Originally posted by medical breakthrough: witch posted quote: Rezulin as compared to similar, alternative diabetes drugs indicate that continued use of Rezulin now poses an unacceptable risk to patients
I've highlighted the important part here. Are you actually failing to grasp the point here, or does it need further clarification? The original drug was approved despite known liver tox problems because there was nothing else available. When newer drugs with less liver tox became available it was only sensible to withdraw the original because it had unacceptable liver tox compared to the new drugs. When only the original drug was available the benefits most certain did outweigh the risks, and nothing you've posted suggests otherwise. Now, do you have the time to address the issues put to you, or will you simply return with further slightly altered, but essentially the same, questions for me? ======================== martin - lots or assumption, contention and opinion from yourself, but you are still failing to provide any evidence to support your claims. Please note that every point I've made has been supported by specific drug names and/or references to available material. Why can't you do the same?
Morning, Medical Breakthrough.  MEDICAL BREAKTRHOUGH: Rezulin as compared to similar, alternative diabetes drugs indicate that continued use of Rezulin now poses an unacceptable risk to patientsNow let's see... what did Dr Graham, the FDA's senior epidemiologist say about the drug. Oh, yes: Dr. David J. Graham, the FDA's senior epidemiologist, said he estimated that 20 Rezulin patients a month are suffering liver failure.Graham told the committee that Rezulin was one of the most dangerous prescription drugs on the market, that every patient taking the pill was at risk of liver failure and that there was no reliable way to safeguard them. This flew in the face of repeated assurances from Warner-Lambert and others at the FDA, who said that patients would be adequately protected by monthly blood tests, intended to monitor their liver functions.I think you have to perhaps convince Dr Graham of your point of view with regard to Rezulin, not me. Not too sure he would be impressed with you asking him if he had grasped the point though, or if he wants further clarification.  He seems of the opinion that Rezulin is the cause of 20 patients a month suffering liver failure, and that it is one of the most dangerous drugs on the market. |
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You obviously still aren't grasping the point here. I can't make the point any clearer.
Furthermore, none of this has anything to do with misleading animal research - are you attempting to derail the discuss to hide the fact that you are unable to provide any evidence of misleading animal research.
You've had plenty of time to do so - what's the hold-up?
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quote: Originally posted by medical breakthrough:
You obviously still aren't grasping the point here. I can't make the point any clearer.
Furthermore, none of this has anything to do with misleading animal research - are you attempting to derail the discuss to hide the fact that you are unable to provide any evidence of misleading animal research.
You've had plenty of time to do so - what's the hold-up?
You obviously still aren't grasping the point here. I can't make the point any clearer.Well, I am sorry to hear that you can't make the point any clearer because at the moment your point is quite clearly being repudiated by what Dr Graham is stating.  Furthermore, none of this has anything to do with misleading animal research - are you attempting to derail the discuss to hide the fact that you are unable to provide any evidence of misleading animal research.From my viewpoint, it appears that you are using the classical technique of derailing discussion by going on the offensive against other posters to hide the fact that you have no answers to awkward questions on Rizulin; varying toxicity levels in animals; and the fact that mental illnesses in humans can't be replicated in animals, yet animals are used for testing psychotropic drugs. It's a technique that you employ often, and therefore easy to spot. |
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No, I agree with Dr Graham, so you clearly aren't understanding.
Rizulin; varying toxicity levels in animals
where?
yet animals are used for testing psychotropic drugs
where and when?
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quote: Originally posted by medical breakthrough:
No, I agree with Dr Graham, so you clearly aren't understanding.
Rizulin; varying toxicity levels in animals
where?
yet animals are used for testing psychotropic drugs
where and when?
You've gone a bit cryptic, Medical Breakthrough.  Looking forward to an expanded version. |
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I should have stuck to my original claim. Nothing's changed.
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quote: Originally posted by medical breakthrough:
I should have stuck to my original claim. Nothing's changed.
... and what was that, Medical Breakthrough? Your claim about the debating techniques of other posters; or about animal testing being 100% accurate; or that you agree with Dr Graham; or some other claim. You are evidently in a cryptic but contemplative period.  |
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Witch said: 'Thanks for more background on the Rezulin scandal.'
I say: Thanks for your thanks.
-------------------------------------------
Medicalbreak said, in reply to Witch: 'Furthermore, none of this has anything to do with misleading animal research - are you attempting to derail the discuss to hide the fact that you are unable to provide any evidence of misleading animal research.'
I say: Did the lab animals used in testing rezulin before it went to clinical trials show that there was the danger of severe liver disease in people who didn't already have severe liver disease? If they didn't show this they obviously gave misleading results.
--------------------
When Witch said that lab animals are used to test psychotropic drugs, Medicalbreak said: 'where and when?'
I say: Lab animals are used to test psychotropic drugs.
'3 Mianserin, like tricyclic antidepressants, was essentially devoid of effect on dopamine uptake both in vitro and in vivo. 4 The ability of mianserin to inhibit [3H]-5-hydroxytryptamine uptake by rat hypothalamic synaptosomes was appreciably less than that of the tricyclic antidepressants studied. Mianserin was essentially devoid of effect on rat brain 5-hydroxytryptamine uptake in vivo.'
In the Methods section of the above study it says: 'Animals used were either adult New Zealand white rabbits weighing 3.5- 4.0kg or male Wistar rats (CE/CFHB strain) weighing 200-250 grams.
British Journal of Pharmacology. 1977 October; 61(2): 307–313.
'Serotonin (5-HT) activity in vivo and in vitro was evaluated in rats following acute and chronic administration of the antidepressants nialamide (NMD) and clomipramine (CMI).'
Pharmacol Biochem Behav. 1987 Mar;26(3):593-600.
'The prediction of antipsychotic efficacy without severe motor side effects is supported by the relatively weak potency of ziprasidone to produce catalepsy in animals, contrasted with its potent antagonism of conditioned avoidance responding and dopamine agonist-induced locomotor activation and stereotypy.'
J Pharmacol Exp Ther. 1995 Oct;275(1):101-13.
And many more.
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quote: I say: Did the lab animals used in testing rezulin before it went to clinical trials show that there was the danger of severe liver disease in people who didn't already have severe liver disease?
Yes. See the evidence provided. As stated at length earlier, this class of drug is inherently toxic due to its mechanism. quote: I say: Lab animals are used to test psychotropic drugs.
And in what way was any of your references evidence of misleading animal research? |
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quote: Originally posted by medical breakthrough: quote: I say: Did the lab animals used in testing rezulin before it went to clinical trials show that there was the danger of severe liver disease in people who didn't already have severe liver disease?
Yes. See the evidence provided. As stated at length earlier, this class of drug is inherently toxic due to its mechanism. quote: I say: Lab animals are used to test psychotropic drugs.
And in what way was any of your references evidence of misleading animal research?
Martin has kindly shown that animals are used to test psychotropic drugs, and yet they are incapable of replicating human mental illness. Therefore, they are not a good model for finding out what will happen with regard to the illness when the drug is taken, as they do not have the illness to begin with. Perhaps you would like to clarify your answer with regard to Rezulin to show that animal testing did in fact show that humans would die, or suffer liver failure, in the numbers that they did, which were such that Dr Graham said that Rezulin was one of the most dangerous prescription drugs on the market, that every patient taking the pill was at risk of liver failure and that there was no reliable way to safeguard them. I am sure that if there was a drug came onto the market which said on its label "Due to animal testing, which is said to be 100% reliable, we have found that 1 in 20 people taking this drug will suffer liver failure, this is one of the most dangerous prescription drugs on the market, every user is at risk of liver failure, and there is no way to prevent this happening", the drug would not have been the blockbuster seller that it was. |
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quote: Originally posted by medical breakthrough:
I should have stuck to my original claim.
That you're not Malkie!? I dont buy that one either! |
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