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In light of Frostnips request I figured I would give this another go.
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Originally Posted by MissRedThumb
We seem to be talking past each other. I really don't want to be hostile. I think it's just a misunderstanding between us.
I think part of this misunderstanding is the language being used (motivate enzyme, Cellular treatment versus systemic treatment, etc). It is taking me some effort to understand what you are saying, to translate honestly. Let me know if I have this wrong.
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I did indeed use systemic in the sense of a drug targeting a body system. Many of our drugs will flood a particular system/tissue in the hopes of latching on to enough enzymes.
Ok, so in the case of linaclotide that is intended to bind to the membrane-bound guanylate cyclase receptor site- that is your "hopes of latching on to enough enzymes" comment and the flooding of a particular system...that is the cGMP signalling pathway? Is that what you mean or do you mean that linaclotide is taken orally and can potentially bind to other cellular sites it comes across that also have the GCC receptor or similar? Like promiscuous binding? Please let me know.
I have been reading about linaclotide and will post the links at the bottom of this post. Here is what I'm understanding-
The illustration below (proposed mechanism of action) shows the compound binding to the GC-C receptor site. The idea behind this, based on the paper I linked, is that ligands in the body typically bind to this site in response to a meal resulting in intestinal secretions. Linaclotide can also bind to this receptor and this, in turn, will do the same. Both the natural ligands and linaclotide activate cGMP (you can see how GTP is converted to cGMP) and as concentrations of that messenger increase the production of cGMP protein kinase is triggered. I believe the green PKGll is the enzyme and it's phosphorylating that ion channel, which results in secretions.
Are we on the same page so far?
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In my hypothetical story about Linzess, I mentioned a patient who didn't have the enzyme.
So, your hypothetical patient doesn't have the GCC receptor or the cGMP dependent protein kinases? Also, why would you refer to either as obscure?
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I did not mean to imply that they were the only individual with that problem. If that were true, Linzess would have a 99% success rate.
I did not think you were implying that.
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In fact, there is a sizable population of people who get no help from such laxatives -- and even among those who receive a benefit from it, nobody knows the toll it is taking on their enzyme supply.
I don't understand what this means either- the toll it is taking on their enzyme supply. Are you suggesting that enzymes are used up in reactions?
With that said, no doubt there are people who do not experience relief, which is likely due to a host of reasons. Keep in mind the target population are those with IBD. I do not know to what extent damage in the lumen, perhaps caused by ulcerated colitis, will have the GCC receptor site. I don't know if this compound performs better at a certain pH or if there are drug-drug interactions in the IBD population, who tend to take a lot of drugs.
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Therefore, we likely have a great many people with our hypothetical patient's problem, and this is the gap in their digestive system.
So, I'm thinking now you are using the word gap in lieu of pathology or disease?
Ok, sure. If the reason this group has constipation is because they have a gene mutation that is not coding for the GCC receptor, which would mean natural ligands cannot bind either, then linaclotide will not work. This is one of the reasons why need to understand the mechanism of action in drug development. This is about understanding the mechanistic cause of disease, which has a great many scientists busy.
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If we knew how to find that gap, it could be a standard lab test performed on all IBS-C patients, in the same way they all can have their blood checked for potassium. I'm talking about standardized methods for more precise testing.
Well, it would be wonderful if it were so easy. Establishing the cause for disease, a way to test for disease, and how to treat disease is what it's all about. I don't know what kind of blood test could be developed to determine a gene mutation coding for GCC. We have some physicians on CD, so maybe they can pipe in, but my assumption is that clinical features or symptoms are what we have for a first pass. What would you test for?
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Drugs tend to have far-reaching side effects because they will either suppress/inhibit or stimulate/motivate an entire pathway in your body. Linzess, for example, stimulates your enzyme in the hope that A will cause B and you will end up with diarrhea. A pathway of dominoes must fall for the theory to work. Each domino is another chance for something to go wrong. Meanwhile, your body has probably spent years working around those dominoes. When you insert a foreign substance to manipulate the dominoes, your body has no blueprint on how to accommodate the foreign assistance. Hence, lots of side effects.
I mostly agree here (barring motivated enzymes, dominoes, theories, etc). I had to read this paragraph several times, but I think I'm following. And sure, a drug delivered by mouth, going through first and second pass metabolism, has the potential of interfering with physiological processes. That is what we want it to do. Interfere with cancer. Interfere with MS. Interfere Alzheimer's. How do we get these drugs to only hit the target, solve the problem, without bothering the rest of the body?
That's the thread. That's what pharma is all about.
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People who are truly healed/cured do not end up with side effects. The body gets exactly what it needs. Your potassium is low, you eat bananas, problem solved. As long as you moderate your diet of bananas, you won't feel side effects from eating them. Drugs, by definition, are foreign substances that manipulate the body in unnatural ways, regardless of how much or how little you take.
I don't know what truly healed/cured really means. If you have a gene mutation that inhibits a protein needed to signal to a cell that it needs to stop dividing, you will end up with a growing tumor. That's quite natural. It can happen from environmental exposures (UV) or aging.
As I mentioned in another post I suppose it depends on the definition of cure. If you take a person with type ll diabetes, high blood pressure, and glaucoma and treat these conditions, stop them in their tracks (low blood sugar and pressure, restored eye function) they are not going to return to the health they had prior to these conditions. Use a car as an example. You buy a new car and drive it for 10 years. You replace tires, a battery, fuel injectors, whatever. You fix the issues as they come up. No matter what you do that car is never going to be new again.
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We need to get medicine to the point that every problem can be identified as easily as potassium, and then the natural solution can fix the body. I believe that every illness known to man stems from a natural problem and be solved by a natural solution. We need to find them.
I hope this helps.
You believe this, yes. I think this is due to a lack of information. The less information a person has the less complicated it all seems. Hence, the vagueness. Hence pseudoscience. Hence a good amount of alternative medicine. Dunning-Kruger anyone? That is something we all need to be careful of.
The natural solution to natural disease are usually symptoms and death. Low potassium levels are not a disease. They can cause a disease that can inflict damage to the body and increasing your potassium will not fix the damage already done.
Bolding mine. Not saying adverse drug reactions aren't a pressing problem, but I'm not sure electronic database stats from twenty years ago are the most meaningful, let alone from fifty years ago. I'd be interested to see something more recent, and more rigorous.
I would note that fatal adverse drug reactions can include things like allergic reactions and other routine, if severe, issues which are often manageable if prompt care is provided.
The study does not appear to take into account whether any portion of fatal adverse reactions were in an already terminally ill patients, either (e.g. a patient dying of side effects from last-ditch cancer treatment for a likely fatal cancer), which to me is a rather relevant detail. To oversimplify, if I have X disease which has a 98% chance of killing me if left untreated, and the only currently available course of treatment has a 30% chance of killing me, and I choose treatment and die of it, that is lamentable and certainly a reason to push for research into more effective treatments, but I'm not sure it's fair to attribute my death to the treatment, even if the treatment is specifically what finished me off and what's listed on the death certificate.
Every study comes with that disclaimer. It's not news nor relevant, and if you are using it to discredit that particular study, you must then also discredit every single clinical trial data ever published.
That being said: If patients are terminally ill, they die from the disease, not the drug. So those patients would NOT be included in the 100,000 dead figure.
And remember this was published in JAMA. Doesn't get bigger than that. I guess JAMA is wrong? Or are they wrong because you don't want to recognize that this is a truth?
It is amazing to me the mental gymnastics people go through to deny truths that they refuse to acknowledge.
How do we get these drugs to only hit the target, solve the problem, without bothering the rest of the body?
That's the thread. That's what pharma is all about.
After several rounds going back and forth, we agree on this. It's all I intended to say from the start.
Considering your clear disinterest in taking me seriously, I won't waste my time on another detailed response. Let's agree to agree on this point. This thread is about whether pharma really wants to achieve that goal or not.
That being said: If patients are terminally ill, they die from the disease, not the drug. So those patients would NOT be included in the 100,000 dead figure.
This is the truth! Scientists are smart enough to know the difference between treatment that didn't work and treatment that backfired.
Vioxx was used to threat arthritis. People died of heart attack and stroke after taking the medicine -- taking it responsibly as prescribed. Some 27,000 people died from Vioxx alone before it was recalled.
People love to blame the victims in this case. They were drug addicts, wackos, too stupid to take their pills on a schedule, etc.
Last edited by MissRedThumb; 08-04-2017 at 11:11 AM..
Yes, we now realize viruses, bacteria, fungi, other microorganisms develop resistance to drugs. The ones that survive treatment with the standard weapons are that much harder to eradicate. One reason for combining cancer chemotherapy drugs instead of using only one. Lessening the odds that some cancer cells survive.
You're making my case for me. Finally, we're getting on the same page.
The biggest argument against herbal treatment is to say the old methods didn't work. The old methods did in fact work in old times. They're less and less effective as time goes on -- but that doesn't mean they were gobbledygook in the first place.
I'm not here to advocate a boycott of all modern medicine. It's just an observation that modern drugs continue to advance, at least in part, because of escalating illness. We shouldn't use this to slander our ancestors.
The average lifespan in 1900 was 46 years old, and now it is the 70s.
I'm not saying old remedies had NO efficacy, but obviously they weren't doing a very good job. In 1918 the influenza pandemic killed 20 to 50 million people. The flu, albeit a new strain.
It's hard to say meds don't extend our life and quality of life, especially considering the obesity rate and the processed foods so many eat.
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After several rounds going back and forth, we agree on this. It's all I intended to say from the start.
Considering your clear disinterest in taking me seriously, I won't waste my time on another detailed response. Let's agree to agree on this point. This thread is about whether pharma really wants to achieve that goal or not.
I think I gave you quite an involved response, which indicates that I did take our conversation seriously. I'm not sure what you mean by taking you seriously. Seriously as what? I think it would behoove you to learn the science. You seem to have enough interest in it and a pretty good general grasp of why side effects arise.
Every time a needle biopsy is done, it move cells around, which can promote new cancer growth.
Now, if a needle biopsy is positive, why on earth would the lump be left in place? It is removed (unless the patient refuses) and an additional margin of tissue around it is as well. If the cancerous tissue is removed how does the biopsy spread it?
A needle biopsy isn't the only tool used to diagnose breast cancer. It is one of several methods used to CONFIRM a suspicion in conjunction with a mammogram and/or ultrasound.
Most people die from the treatment of cancer than the cancer itself. That means, that yes, they would have died from cancer eventually. But the combo of surgery/chemo/radiation kills them quicker.
SOME people die as a result of treatment certainly. As we all keep saying, humans are individual and there are so many other processes going on during a person's subsequent life it would be very hard to isolate cancer treatment as the cause.
Think about it.
Of course I think about it and did think about it when I was diagnosed.
1 Shock the body with trauma (surgery),
Of course its a shock. But, I would also say to interrupt an ongoing disease process usually requires a shock of some sort. You could even say this resulting shock ends up kicking the immune system into higher gear. Even a herbal treatment is trying to "shock" or interrupt an unwanted process.
2 followed by severely immunosupressive drugs that do not allow it to heal and invite all bacteria and viruses in, backstage pass no blockers, get the person sick as possible with all sorts of infections.
I seem to recall not starting chemo for at least a couple of months after surgery to allow healing. I'm sure some people do end up fighting off infections.
3 add in the vomiting that chemo causes so no food can be digested for strength to fight off pathogens,
For most (no one can claim all including myself) vomiting/nausea is transient (hours to days followed by weeks of none) and treatable. There are several excellent anti-nausea meds, both herbal and prescription available to prevent or alleviate it.
4 then radiate, which causes secondary cancer (that's why everyone always leaves the room)
Remember, the people leaving the room are the techs who would otherwise be exposed to rads for 8 hours every day for years. I don't recall seeing random bystanders in the treatment room. No patient would ever receive such exposure. In addition, except for system-wide cancers (I don't know about those), radiation exposure is limited to a very precise area using lead shielding. And that shielding is specifically designed for each patient. The total rads are calculated ahead of time and not exceeded.
That's why the survival rate is clocked at 5 years after diagnoses. They KNOW after five years, people start dying. It's shocking to me that people still don't question this process.
Not all cancers use the 5 year survival "clock". Breast cancers don't. There are so many variables that can affect outcomes during those 5 years. Sure, some people die after 5 years. Many don't. Let's see....my treatment ended about 25 years ago and I'm still around and I had the full gamut of what was standard treatment at the time, based on the specific tumor type, hormonal sensitivity, etc.
If jamin wants to avoid all medicines with side effects, she can always try to pray the illness away. It has a 0% proven success rate. But then again, she won't be contributing to big pharma's greed and won't take any risk from possible medication interactions/problems. Taking medication is a personal decision. Does the person want to risk living with the disease that causes pain/further illness/death?
Why so obsessed with pharmaceutical companies making a profit? Their profits/lack thereof are part of a bigger issue: our messed up healthcare system. But people don't understand it costs BILLIONS of dollars to even get a drug to market. There is extensive health testing involved: scientific experiments with bacteria, viruses, fungi, etc, followed by multiple animal trials, human trials, ethics committee hearings, approval (or not) by the FDA, etc. It's not just one test, one month, and done. I don't understand why drug companies are so demonized. We live in a capitalistic society. We can't have a double standard where Walmart deserves to make a profit but hospitals and other healthcare entities shouldn't. Even drug companies deserve to make a profit.
Everyone is in business to MAKE profits even vit/supp companies, believe it or NOT.
Pharma are hogs and would love to destroy the vit/supp companies, they've worked on this end for years. Glad there are lobbyists on our side too. And activists who walk the talk.
You want to pray, go ahead I'm not so much into prayer.
Everyone is in business to MAKE profits even vit/supp companies, believe it or NOT.
Pharma are hogs and would love to destroy the vit/supp companies, they've worked on this end for years. Glad there are lobbyists on our side too. And activists who walk the talk.
You want to pray, go ahead I'm not so much into prayer.
A large portion of supplement companies are owned by pharma companies.
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