Constriction symptoms and conditions

I spent the weekend reading about the development of Singulair. The early studies recognized that the first phase of the acute asthma response bronco-constriction was probably not caused by leukotrienes. They identified histamines and prostaglandins as the probable sources. I don't think that changed because the Singulair literature states that it should not be considered as a treatment for that. Leukotrienes were a source of inflammation caused by eosinophils and mast cells present in greater numbers (than normal) in airway tissue. So, it was beneficial to find a way to decrease that.

The cysLT1 receptor was identified as source of the signals that tell the cells to produce leukotriene. The receptor, a gene, consist of 337 (they think) amino acids. They modified a compound that would bind to that receptor thus blocking the cells ability to produce leukotrienes. This compound is very specific. It was formulated to bind to the "model" receptor. This compound will not even bind to cysLT receptor sub-types. (That is the good thing.) There is an enormous amount of research that discusses the genetic variability of the chemical reactions that occur in the leukotriene (calling it this for simplicity) pathway. We are also seeing that a number of researchers would like to use gene profiles to predict whether patients will respond favorably to different asthma/allergy drugs. ALL PATIENTS HAVE A RIGHT TO KNOW IF IT IS INHERENT THAT SOME PEOPLE WILL NOT RESPOND TO SINGULAIR OR RESPOND ADVERSELY.

There are many studies from the 1998 era that conclude that montelukast is not effective for everyone. Those researchers stated that it can be predicted that those people who are going to respond favorably will do that within the first 14 days or so. That conclusion would be consistent with a genetic component for efficacy and safety of Singulair. Those doctors concluded that those who did not respond within that time frame should not take Singulair for fear of harming them. That makes good sense.

The Italian researchers wanted to know if there was more going on than blocking leukotrienes in the action of montelukast. They set up a "test tube" study regarding montelukast, the cysLT1 receptor, and some t-cells that they selected. Why? Researchers always have something on their minds. They observed the death of these particular t-cells.

Montelukast is a quinoline. We basically know of quinilines and quinolones as compounds that were invented as broad spectrum antibiotics. They work because they interference with bacterial DNA so they cannot replicate themselves. Montelukast is a quinoline modified to bind with the cysLT1 receptor (a gene) and prevent that gene from activating. That's consistent with what a quinoline/quinolone does.

So what does montelukast do in blood plasma if it does not bind to the receptor because of genetic mis-match? (If montelukast does bind, then a chemical reaction has occurred and the liver will break down the by-products. Montelukast metabolized in 10-12 hours.) What happens if it doesn't bind? How long before it breaks down? Does it produce toxic by-products?

I want to know what happens to lymphocytes such as t-cells just because montelukast is a quinoline. Maybe nothing but what's up with the Italians researchers? I want to know if montelukast has the capability to interfere with lymphocytes who can clone themselves. That could be a good thing under circumstances when these lymphocytes are causing inflammation. But it could be a bad thing in the case of normal individuals with no problems.

I want to know if the bad side effects are due to the fact that the body has to break down and metabolize a quinoline that did not bind to the receptor for which it was created. The side effects of Singulair are strangely similar to what is observed in the quinolones such as levaquin. I have not as yet been able to compare montelukast as a quinoline to levaquin as a quinolone. I am hoping to find something on these categories. There may be no reason to worry that they cause similar damage. But frankly, I think that there is. There is some terrible chit happening to some people. The scariest is the neurological damage.

All of these questions would be in the everybody pharma knows to ask category. I don't know where the answers are. I haven't found them as of yet. Maybe there are no answers. We have to remember that Singulair and Vioxx were released in the same year. They have continued to be drugs under the current executive management of Merck. If the Vioxx marketing promoters had their ghost writers, why not the Singulair marketing promoters. The genetic component appears to be widely accepted but we haven't heard one thing about even that.

I think that it is sad that maybe the marketing of Singulair as one stop shopping for asthma/allergies may have destroyed the original concept. I really think from reading the original work that they knew that they couldn't engineer a drug for one size fits all. Everybody gets harmed when information is withheld.

Shame on the allergist who yelled at the mother who wanted to discuss issues. Does he know exactly who is allergic to Singulair and who isn't? Get him a dunce hat. Just because Singulair is marketed for allergies does not mean that you cannot be allergic to it. See the power of Madison Avenue? The ad agencies focus group these drugs to death. The ad agencies cleverly craft the product information. A good piece of legislation would be to prohibit consumer drugs ads.

I am starting a new post in the hopes that others will see what I am trying to say about the delayed reaction in those that took Singulair for allergies.

If it is consistent that Singulair does not stop allergy symptoms immediately, then the pathways that eventually stop allergy symptoms involve a change in the mast cell function, development and migration (or some combination).

I asked this question for a reason. Are allergy symptoms stopped immediatedly. My question below:

I have a question that will help me continuing looking for information. I can understand that in the case of asthma that Singulair would provide immediate relief. If it is used for seasonal allergies or other allergies without asthma, does it work right away or does it take a period of days or weeks to be effective? If it takes time, could you tell me how long it took in your situation?

My thinking was going in the right direction if the answer below is consistent of everyone or most.

about 2 hours ago on Apr 11, 2008 by catherineevans, #7045
My granddaughter was put on Singulair for allergy symptoms without asthma. Itching, red eyes, terrible congestion, etc. dark circles under her eyes all the time. When we first put her on this, we didn't see any consistent results for 2-3 weeks, then it seemed to 'kick in.' I don't know if this helps. By the way, she was 9, now she's almost 12 and was immediately taken off when this story came out 2 weeks ago.

Then after seeing one response, I gave my reason for asking.

I asked this question because I have a theory of how montelukast really works for allergies as compared to how it works for asthma.

Asthma is a hyper-sensitive state that gets going because the mast cell has a receptor (the leukotriene receptor that Singulair blocks) that sends a signal along a pathway that causes lung tissue to have that extreme response - the wheezing, the airway constriction.

On the mast cell is another receptor the histamine receptor that causes the secretions that make our noses runs and and stuff up. This is not the same immune response as the asthma response. When I saw a post that somebody's doctor said that Singulair is an anti-histamine, NO it is NOT.

So if Singulair does not block histamine immediately and your child's allergies did not go away immediately, then maybe Singulair is working through some other means such as changing normal mast cell homeostasis.
I know that this seems like "what does this mean?" I am really writing this hoping to God that there are people reading this site that know what I am talking about.

Thank you so much for responding. Your answer actually told me what I wanted to know and confirmed my hypothesis. More answers will help. I hope others respond.

PLEASE respond about the length of time that allergies disappeared if you took Singulair for allergies.

I have a question that will help me continuing looking for information. I can understand that in the case of asthma that Singulair would provide immediate relief. If it is used for seasonal allergies or other allergies without asthma, does it work right away or does it take a period of days or weeks to be effective? If it takes time, could you tell me how long it took in your situation.

A few weeks ago I reported many of the side effects so many of you have reported on. After several blood tests with my endocronologist, results came back normal. I have now been off Singulair for about five weeks and have noted only one improvement thus far: less headaches (especially after drinking alcohol--that being defined as one or two beers/glasses of wine. I think this has to do with less constriction of blood vessels in the brain).

I'm returning to my cardiologist next week. I'm thinking I may have what is called Postural Orthostatic Tachycardia Syndrome which can be described as a periodic low blood pressure disease that causes dizziness, faintness, ect. Many other symptoms of this disease have been mentioned on this site (including Shy-Drager Syndrome which is most scary). Doctors don't really know what brings on Pots but one suspicion is viral/bacterial or drug induced...jury is completely out on this, however).

Most notable is a sudden change in bp after stooping and standing up--bp drops, palpitations begin, extreme fatigue generally follows.

A table tilt test should help with the diagnosis.

Question: Are any of you familiar with Pots and/or have any of you experienced similar symptoms?

Thanks.

Fortuna

feels like the inside of my mouth is sloughing skin.constriction in my throat.short of breath

I began taking Yasmin Dec. 2004 on my ob-gyn's advice. (My previous pill, which I had been on for years before and between pregnancies, was making my breasts very tender and sore but otherwise was OK to be on.) Within one month, I noticed several changes in my health and mood that I initially thought might go away after my body "got used to" the new birth control pill. Unfortunately, the symptoms did not go away and other even worse symptoms appeared. These symptoms included the following:

1. feelings of chest constriction and tightening
2. heart pounding/racing for no reason
3. inability to sleep (and thus fatigue and tiredness all the time)
4. severe changes in skin texture (esp. facial)--leathery and sallow
5. excessive anxiety, worry, depression, and feelings of panic (NOT AT ALL my personality prior to taking Yasmin)
6. development of asthma-like symptoms that turned out to be symptoms of acid reflux disease (which I had NEVER had before in my life!)
7. a general and pervasive sense that I was just not the normal me--I know this is not very "clinical" but it was very very disturbing to me and my family--everyone noticed changes in me
8. a dangerous jump in my blood pressure--prior to Yasmin my blood pressure was never higher than 120/70 (which is about what it was in Dec. 2004 at the office visit where I got my first pack of Yasmin)--not even at any point in my two preganancies! Yet in Feb. 2005, my resting blood pressure was 160/90 and was even higher (180/100) at times!
9. From Dec. 2004 through March 2005 (which is when I got off of this terrible medication), I was sick virtually non-stop with some type of cold or flu every 2 weeks--yet no one else in my household was getting sick!
10. a near complete loss of sex drive

As I have read from women in other postings, both my GP and ob-gyn (both of whom are women incidently) also said these effects could NOT be because of Yasmin. The only doctor that indicated he believed there might be a link between my symptoms and Yasmin was the ear-nose-throat guy who diagnosed my reflux.

I am writing to tell other women that I do firmly believe these health problems were DIRECTLY related to taking Yasmin--I noticed improvement in my health in all areas within about 6 weeks of stopping Yasmin--now several months later, I have normal blood pressure once again and my reflux has resolved itself, I'm the old "me" again (my Dad especially was terribly bothered by how my outlook on life had changed in just a couple of months after starting this pill). I'm 41 years old and have never had any type of emotional or health problems prior to taking Yasmin.

I contacted the manufacturer of Yasmin (Berlex) and made a report about the adverse effects I believe were attributable to taking Yasmin--I urge anyone who feels this drug has impacted their lives in a negative way to also do so. I have also made clear statements to my docs about what I believe happened to me in the 3-4 months I was on this stuff.

I felt such a wave of relief when I first found this Web site--it was like reading 100s of e-mails that could have been written by me!! I actually called my Mom sobbing on the phone after reading several pages from this listing on Yasmin--everything that was happening to me had happened to other women also, and I stopped taking Yasmin immediately.

I wish anyone who has gone down this road the best of luck--while doctors are usually good, educated people who try to improve people's lives, they are NOT infallible--if you believe Yasmin or any drug is affecting you negatively, be proactive about your own health no matter what your doc says--there are always options. To this day, despite how dramatically different my health is compared to earlier this year, my docs still will not say that they feel Yasmin was the root cause of my problems. (I guess it is the price you pay when so many people are afraid of lawsuits and such.)
Connie

I have been on Yasmin for about 2 1/2 years. I have a nagging 15 pounds that won't go away, chest pain/a feeling of constriction, and terrible bloat. I actually feel less bloated during my period week because I am not taking the Yasmin! I think it's time to get rid of this pill. I am only 23... I don't need chest pains and palpitations. Any alternative pills out there?

Omeprazole was successful in relieving excess stomach acid but unfortunately some severe unwanted side effects were developing after the first two weeks of administration.

The most prominent side effect was constriction and tenderness in the chest cavity which was affecting breathing ability at the height of these episodes. A second side effect was the gradually increasing levels of numbness and tingling sensations on the left side of my body in the arm and leg. A third effect was progressively increasing weakness developing in my legs which at times caused tremors and shakyness which affected my endurance during activity levels.