Mast cell symptoms and conditions

Why does Singulair cause these symptoms? I am going to give my explanation which is only a HYPOTHESIS. This should not be categorized as any thing but an educated guess. This is not backed by scientific research because nobody will do any research that would appear to anger
Merck even if people are suffering in the thousands.

1. The original research that preceded the development of Singulair (montelukast) seemed to focus on the theory that asthma was caused by an unusual immune response to certain pathological stimulus. There are many references to the observation that a high percentage of asthma sufferers are people whose asthma is caused by fungus. Many people suffer from asthma and are told that they are allergic to dust mites. Dust mites can live only because the fungus aspergillus pre-digests the
food source that dust mites can then absorb. Other sources of fungus occur in the home due to dampness or problems with wood rot.

2. The body's immune system fights certain categories of pathogens such as bacteria and fungus by creating nitric oxide which kills them at the site where they try to enter the body. The mast cell is the immune cell that is responsible for the production of nitric oxide. Mast cells are found in the skin, airways, intestines etc. The mast cell is capable of many different types of biochemical functions that are designed to signal other cells or other chemical responses. When the mast cell knows that pathogens
are present and nitric oxide is NOT produced, then it signals other immune cells to be sent to the site of the infection. Thus in the case of asthma, it is known that excessive numbers of eosinophils appear in the airways and these cells create inflammation.

3. Singulair was developed for asthma and later allowed to be prescribed for other reasons. I believe that montelukast probably creates a source of nitric oxide that prevents the mast cell from signalling for other immune cells to arrive at the source of infection. I arrived at that conclusion from studying the chemical structure of montelukast, the chemical structure of the gene cysLT1 receptor, and the chemical structure of the cell wall of fungus which would be what the mast cell uses to determine "what to do in order to kill the fungus."

The researchers who invented montelukast first had to clone the gene-cysLT1 receptor meaning that they had to be able to identify the gene and replicate it. Then by trial and error they had a find a "chemical"
that would bind (connect chemically) to the cysLT1 receptor. The theory would be that montelukast would take the place of the fungus or other pathogen and thus prevent the gene from reacting to produce the
responses that the sick patient with asthma produced. Merck says in the literature that montelukast binds with the cysLT1 receptor in order to prevent the mast cell from signalling the eosinophils to arrive in excessive
numbers that cause inflammation. I believe that montelukast is also causing the production of an amount of nitric oxide that is actually killing the pathogens that are present. For one thing, I would think that it
would be dangerous to incapacitate the immune system in that way without providing a way to kill the pathogens. I don't believe that the asthma response is just allergies to something like dust. Pollen from trees and flowers is loaded with fungus spores.

4. IF, IF, IF, montelukast does actually produce nitric oxide, then it does so by binding with the gene. Any place in the body where a molecule of montelukast encounters the cysLT1 receptor (a gene) then the corresponding molecules of nitric oxide are produced before the liver enzymes break the montelukast molecules up. Nitric oxide is TOXIC and
INFLAMMATORY. So let's look at the symptoms in regard to the location of the cysLT1 receptors. The location of these symptoms would not be places in the body where the mast cells normally encounter fungus or bacteria. The cysLT1 also has other functions in that it communicates with the cysLT2 receptors. Obviously, nitric oxide
should not be produced in these locations because of the signalling effect of nitric oxide on other physiological functions.

a. intestinal pain - the cysLT1 receptors are located in the small intestines
b. leg pain actually caused by vasculitis - cysLT1 receptors are found inside blood vessels- consistent with the fact that montelukast causes
Churg-Strauss
c. some people who didn't have asthma develop asthma - the cysLT1 receptors are in the airways
d. nightmares, depression, neurological damage - when montelukast penetrates the blood brain barrier probably due to unusual conditions of blood pH or electrolyte imbalance then nitric oxide in the brain causes neuron damage and excitoxicity

5. Why do some patients not experience side effects? Probably because genetically they are completely compatible with the model that researchers created when they cloned the cysLT1 receptor gene. I didn't not find any information about whether researchers knew that there are many different variations of this gene.

6. IF, my theory is even close to being correct, then why doesn't Merck do anything about researching these side effects. Maybe because nobody in the company knows how this drug works but the researchers who created it. All of the Merck literature is very vague about any biochemical information.

Again, this is just speculation and hypothesis. I have made an attempt to put this in simplistic language and therefore sacrifice scientific accuracy. But, I think that you will get the point.

SINGULAIR IS VERY DANGEROUS TO PATIENTS WHO EXPERIENCE NEGATIVE SIDE EFFECTS. DOCTORS SHOULD JUST REALIZE THAT
THOSE PATIENTS ARE NOT COMPATIBLE WITH THE MODEL FOR THE DRUG.

Hi everyone
My little boy who is nearly two was put on Singulair as a preventative.
I did check on forums when we started using Singulair and I was concerned that there has been descriptions of negative affects. Always trying to be objective I rationalised that the people in this forum are a small part of the greater Singulair population and as a result there was a low risk of negative affects on my little boy.
I have to say I think I was wrong. As soon as he was using Singulair, he had restless nights of sleep. Every night he would cry off and on until 2am and I guess he was so tired he slept. During the day he was very short tempered and became upset very easily. We put this down to tiredness. After 10 days of the lack of sleep for parents and little one, we told our doctor.
He advised to take him off Singulair for 5 days and make observations and then put him back on. Last night, his first night off Singulair was bliss. Not a sound. He had a great sleep. As I type he is now having another great sleep.
Let us see what happens after 3 more days and after putting him back on Singulair.
It would seem that if we are correct and that Singulair is a cause of an issue for my child, am I a quasi beta testing laboratory for a drug?
We are from Australia.
Thank you for reading.

We have all been saying that our issues regard not being informed about all of the possible side effects. And, we know that Singulair works well for some people. Nobody wants to take a good drug away from those for which it probably performs miracles. People who have toxic side effects have a right to know up front.

My observations about montelukast's chemical structure are either general or not quite 100% correct or could be quite vague - so forgive me. I do not claim to be good at organic chemistry. But from doing a little work, I have come up with some observations.

1. It would seem to me that montelukast might work quite well for people who have developed mold category related asthma. I observed that chloroquinolin, a component of montelukast, is a good fungicide effective against Aspergillus, Alternaria, Cladosporium, Penicillium and Candida. Dust mites can only digest if helped by aspergillus so they go into the mold category. Molds produce millions of spores so anyone who lives in contact with mold would be chronically sick from their presence. Then people get hypersensitized to that.

I am probably wrong but I could imagine that montelukast is: 1) a ligand that binds to an empty cysLT1 receptor for a period of time 2) 7-chloroquinolin-2-yl which either acts intact or breaks down into a quinoline fungicide so that it kills the chronic mold/fungus infection and 3) a sulphur/methyl anti-inflammatory component that tells the t-cells that they are not needed so they will die. Wow, that would be great for mold asthma if it was completely non-toxic. It would be also great under controlled circumstances for many people who are mold-miserable. If I am wrong, I better go out into my garage and start inventing such a drug.

This is my visualization to try to explain the side effects of neurotoxicity. So adverse reactions could be to the quinoline component as an allergic reaction or dose related so that it just built up to a toxic level over time. There are many signs that t-cell populations are significantly reduced by montelukast. The fact that the Italians can do it in the test tube might be that it's a chemical component of montelukast designed to cause the t-cells to die.

Montelukast is a large molecule so Artie says it cannot penetrate the blood brain barrier. That would be an argument if nobody was complaining about neuro-psychiatric side effects. The neuro-psychiatric side effects are identical to quinoline and quinolones. When I read about Lariam, it just sounds like a more extreme version of Singulair side effects. Chloroquinolins were used before they invented Lariam, which is stronger. The malaria Plasmodiums became immune. Hallucinations, anxiety, depression, suicidal thoughts are completely consistent in all of the quinoline/quinolones. If montelukast breaks into sub-molecules then quinolines easily penetrate the blood brain barrier.

I find clinical evidence that montelukast may act as more than more molecule. And, that there is a rational for the existence of the chloroquinolin and evidence that it may be the source of toxicity.

I am glad to risk being called crazy. That is what the internet is for. We can present our ideas and discuss. So, just take this with a grain of salt. If I am close to the truth, this post will find it's proper home.

I don't know if my 1 1 /2 year old son's being diagnosed with low igG and low IgA have anything to do with singular. He just got off it 2 weeks ago, had been on it a year. He was tested for allergies everything was negative, but tested very high positive to gliadin IgG (95.5), and positive to gliadin IgA (14.8). Is this related???? HELP!!!!!! The GI Dr want to do an endoscopy on Friday May 2. Any help, I don't want my son under anesthesia unnecessarily..................

Some common sense observations about Singulair side effects. (As everything on the internet, this is only my opinion.)

Conclusion up front: Ethics in science SUCKS these day. Put enough money on the table and what happens? I don’t mean all scientists, just the few. But, the Merck ghost writers are the tip of the iceberg for those in the schm#ck category. Maybe, if we reveal the extremes of abuse of laboratory animals, the ASPCA will organize and save us all. How about if they find out about the pharma labs that just beat the cr@p out of the lab animals to produce a stress response to find out what chemicals are produced? What was that all about?? Probably military—send our soldiers out to war over politics/oil, then we will have a pill to give them every night to put them back together again for the next day??

1.The cysLT1 receptor, which Singulair blocks, is a gene, found on the x chromosome (?), part of our inherited innate immune system. It is evolution. The hypersensitive individual overreacts to environmental stimuli causing unpleasant or dangerous symptoms. It is advantageous to intervene to prevent that. Merck’s idea was to block cysLT1 so that the chemicals secreted by the mast cell cannot reach the tissues in the lungs and nasal passages to cause the inflammatory responses-asthma being the more severe.

2.How did Merck develop such a drug? The cysLT1 receptor , a gene, has a profile, a chemical map of the components. Montelukast, was modeled to chemically bond with the receptor so that it does not function. That bond will endure until the liver enzymes break it down. Montelukast blocks the leukotriene response until it is time to take another pill. All that sounds good so far.

3.Now comes the first of the too good to be trues. Montelukast was formulated for a specific gene profile. However, cysLT1 has variations, numbers unknown, but more than several. Even Merck recognizes that it is not effective for everyone because the clinical data shows that. Mis-matches with the gene profile can cause montelukast to be recognized as an allergen. Then, the body mounts an immune response against montelukast.

4.Many of the symptoms that we see here are allergic reactions to montelukast, headache (18%), types of neuro-muscular (10%), hives, nausea, vomiting, leg pain, stomach cramps, and more. Some people will recognize montelukast instantly as an allergen. If the mis-match is slight, the allergic reaction could be acquired or build over time. Montelukast will ALWAYS be an allergen to those people. Doctors will do great harm if they treat allergic reaction to montelukast with other drugs. Those people must STOP taking montelukast.

5.The second too good to be true, is that cystLT1 receptor, involved in the leukotriene response, is only a very tiny part of the immune system, genetically programmed to function as a WHOLE. Now what? It is highly unlikely that montelukast can block the leukotriene receptor - cysLT1 in the brain, lungs, spleen, intestinal mucosa, etc. and not cause some kind of re-structuring of the immune system to compensate for that. Those who take Singulair can expect that they are a new adaptation of human being who can operate without the cysLT1 receptor. Or, they can expect long term damage. How scary is that?

6.What would happen if Merck revealed that montelukast, by definition , cannot work for everybody because it is based on a gene profile with variations? What would happen if patients and doctors started to think about the immune system as a whole? Then Singulair – which means “single thing you need for air – breathe” the logo is even Singul-AIR, would not be the huge money maker that it is. Doctors would find a way to use it, for whom it is effective, in an appropriate way to consider the long term effects. For some people, this drug could have a place. But this drug does not deserve to be a CASH COW-money, money, money!

7.What in the heck is wrong with the FDA? Are they under a spell or hiding under a rock?

My 13 yr old daughter was put on Singulair along with Asmanex and Clarinex for her asthma about 6 weeks ago. Everything seemed to be going very well at first and her symptoms were starting to get controlled. I started noticing after about 3 to 4 weeks that her temper and attitude were getting much worse. Anyone with children this age knows what I mean but this was like a 180 degree turn for her. Her actions were becoming totally out of character. Before I knew it she would cry and get highly upset over the least little thing. Week 5 came around and things totally bottomed out. She came home from school and WAS NOT HERSELF. Made comments about how she hated her life and it was not worth living. Later that evening we had a big argument because I was telling her nothing was worth saying that. She went totally out of control and I had to physically restrain her to calm her down. It appeared everything was better so she went to her room. I went down to check on her and she calmly told me that she had taken advil and tylenol pm and things would be better for her forever now. We went to the ER where they made us wait for at least an hour, then finally took her back. She had to drink two cups of charcoal and was poked and prodded repeatedly. They did a catheter to get a urine sample. She was very cooperative but also was in a complete daze so who knows. The poor child couldn't even lift her head up when she started the vomiting to get rid of the drugs. It was very upsetting and sad. Her heart rate and blood pressure went very low and I really thought in the back of my mind that this was it. Finally, after several hours she started coming out of it and they sent us home. The next evening when she was starting to really come around she proceeded to tell me how she had been seeing a man walking around in her bedroom at night and she was afraid to go down there. Breaking down and crying telling me about all of the horrible nightmares she had been having recently and didn't know why. I thought what am I dealing with here? This just isn't her. Three days ago I heard about singulair in the news and looked it up on the internet. OH MY GOD THIS SOUNDED LIKE US!!!!! I immediately had her stop taking it and the next day phoned her asthma specialist who agreed she should stop now. We are going to watch her for two weeks and see if any symptoms return and then decide if she needs something else or will be fine on just the Asmanex. As a side note, she also mentioned being unable to concentrate in school (unable to do even the simplest math problems) and that her brain felt confused or like something was missing. She said this had been bothering her for several weeks. I know it was this drug. They really need to take this off the market NOW and stop flirting with disaster. The only reason I posted this was to let others know they are not alone.

Effective after two weeks for some people - not effective for others. Side effects for some people - others do not report side effects. So why does Merck have to grow their market before they have any idea what's going on?

This isn't a big group of people in the study but it makes sense from what we are reading here. These researchers did examine the mast cells. We need to know about mast cells (while suppressed by montelukast) on a longer term basis.

J Asthma. 2008 Apr;45(3):243-50. Links
The efficacy of montelukast and airway mast cell profiles in patients with cough variant asthma.Kawai S, Baba K, Matsubara A, Shiono H, Okada T, Yamaguchi E.
Division of Respiratory Medicine and Allergology, Department of Internal Medicine, Aichi Medical University School of Medicine, Aichi, Japan.

Background. Cough variant asthma (CVA) is characterized by chronic cough without apparent wheezing; its pathophysiology is considered to be similar to that of classic asthma. Objective. The clinical effects of montelukast, a cysteinyl-leukotriene receptor antagonist, on cough variant asthma were assessed, and the activation profile of airway mast cells was examined. Methods. Montelukast (10 mg/day) was given orally to 36 CVA patients (25 women and 11 men; median age, 37.5 years). Before treatment, the patients' bronchial mucosa underwent a biopsy with a fiberoptic bronchoscope. The biopsy specimens were double stained with anti-CD63 antibody and anti-human tryptase antibody. Results. After 2 weeks of montelukast treatment, cough symptoms improved in 22 patients (the effective group) but did not improve in 14 patients (the ineffective group); in the ineffective group, the symptoms disappeared 2 weeks after they were switched to fluticasone propionate (400 mug/day) inhalation therapy. In the effective group, the time interval from the onset of symptoms to the initiation of treatment was significantly shorter than in the ineffective group. The bronchial mucosa biopsy specimens showed that the proportion of CD63-positive cells in tryptase-positive mast cells was significantly higher in the effective group than in the ineffective group; although the total numbers of mast cells were not different between the two groups. Conclusion. There is a subgroup of CVA patients in whom leukotrienes are closely involved in the pathogenesis of their chronic cough; activation of airway mast cells may be an essential feature in these patients.

PMID: 18415834

I have to say this after reviewing two major areas:

1. the brain
2. mast cell homeostasis

I desperately wanted to be POLITICALLY CORRECT and say that side effects can be confined to the minority. God, how do you fight Merck?

In this case, it would seem that the real benefit of this drug is to those with the extreme type immune responses whose body chemistry has been altered by being hyper-sensitive to some type of "invader. Extreme can be defined as just not the average or beyond that.

So, if the truth comes out that essentially normal immune systems don't need Singular at all, then I have come clean. I certainly have doubts whether essentially normal systems need this at all.

One of the most important questions we should be asking as parents is:

How does Singulair - a leukotriene receptor antagonist (blocks the receptors) affect the normal function of the mast cell?

The mast cell is the FRONT LINE DEFENSE against invading micro-organisms. When Singulair was invented, there was limited knowledge regarding the mechanisms by which the mast cell performed it's function. In my opinion, the focus was very narrow - those interested zeroed in on how the leukotriene receptor performed a role in the cause of asthma attacks and how ashma attacks could be prevented. Well, that's good preventing asthma attacks. But what happens to the mast cell if that receptor is blocked on a long term basis. I am not suggesting that blocking the receptor is bad but what if the long term effect is different than what we are are lead to believe-which is this is a safe medication with no known long term effects. What if the leukotriene receptor was just blocked short term a week or two to allow the body to clean up the mess from the last attack?

I seriously question what is going on with all of these infections. Are they related to crippling the mast cell? Parents should be allowed to question. If Merck doesn't want to answer questions regarding what happens to the mast cell (including are the numbers of mast cell decreased on Singulair), then something really BIG is missing. If by any chance (unknown at the moment) that the mast cell is significantly changed and therapy by montelukast is proper on a short but not long term basis, so freakin' what if Singulair is not a huge money maker any more.

Parents deserve every answer possible when decisions regarding their child's growth and development is on the line. I hope that we get some answers.

Of course, what was there in 2002 were new questions-not necessarily answers about the mast cell. Did anybody apply this to Singulair studies?
May 2002

From Journal of Clinical Investigation

Pattern recognition receptors on mast cells
The Toll-like receptors (TLRs) fit the definition of pattern-recognition molecules, which were originally postulated to allow the innate immune system to detect the 'molecular signatures' of various infectious agents. Although the innate immune system has no memory, it shows a degree of specificity, in part because the various TLRs recognize different sets of pathogen-associated molecules. Dermal mast cells are usually associated, not with the innate immune system, but with atopic dermatitis, but Supajatura et al. have found that these cells also express TLRs. They report here that TLR4, which binds the gram-negative product lipopolysaccharide (LPS), and TLR2, which binds peptidoglycan (PGN) from gram-positive organisms like Staphylococcus aureus, induce distinct mast cell responses. Staphylococcus is known to exacerbate allergic dermatitis, but it has generally been thought to act by inducing antibacterial IgE's, which trigger mast cell degranulation by stimulating the IgE receptor. Interestingly, the authors show that the interaction between PGN and TLR2 can provoke mast cell degranulation directly, sidestepping the need for IgE receptor engagement.

Doctors should realize that we continue to learn something new every day. Nobody should ever believe that we know the answers. Everything should be constantly questioned.

My life is an example of "who knew" but I am the miracle, the lucky one. I was born pre-mature, very small for almost 60 years ago. Another baby was also born on that day pre-mature. We were placed in the incubator together. No one really knew the dangers of oxygen levels and the eyes. The baby who was next to me has lived as a permanently blind -- never saw anything about the world. I somehow never opened my eyes. I wasn't breathing well and was more knocked out. But one baby lived normally and the other didn't. So there will always be a "who knew."
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I have been concerned that the fact that Singulair binds with a leukotriene receptor on the mast cell and blocks one of it's function has possibly opened up a pandora's box of other problems. As I said before, there is communication between several receptors on the mast cell that determine how it performs it's normal function. I finally found an abstract written pretty clearly that does reference some of these concerns.

J Allergy Clin Immunol. 2004 Jul;114(1):21-7. Links
Mast cells in innate immunity.Marshall JS, Jawdat DM.
Dalhousie Inflammation Group, the Departments of Pathology and Microbiology & Immunology, Dalhousie University, Halifax, Nova Scotia, Canada. jean.marshall@dal.ca

Mast cells have been most extensively studied in their traditional role as an early effector cell of allergic disease. However, in the majority of individuals, it might be the role of this cell as a sentinel in host defense that is most important. Mast cells have been repeatedly demonstrated to play a critical role in defense against bacterial infections, and evidence for their involvement in early responses to viral and fungal pathogens is growing. Mast cells are activated during innate immune responses by multiple mechanisms, including well-established responses to complement components. In addition, novel mechanisms have emerged as a result of the explosion of knowledge in our understanding of pattern-recognition receptors. The mast cell shares many features with other innate immune effector cells, such as neutrophils and macrophages. However, a unique role for mast cells is defined not only by their extensive mediator profile but also by their ability to interact with the vasculature, to expedite selective cell recruitment, and to set the stage for an appropriate acquired response.
Copyright 2004 American Academy of Allergy, Asthma and Immunology

In other words, mast cells play a key role in the development of the immune system. The child's immune system is changing and developing every day. If we block one of the mast cell's receptors, what are we doing to the entire system.

I have been looking for studies that addressed the long term effects of Singulair on the immune system in other animals like pigs. I am still searching.

I am repeating one of my post regarding the Swedish study of the side effects of Singulair. When I read that parents have complained to their doctors about side effects and been dismissed, and told to continue the medication, I truly questions whether these doctors are giving their patients the right to INFORMED CONSENT.

I have been told by doctors before something like this "That is my professional opinion - I stand by it ." And I have said right back-- I understand that is your opinion. But if you don't have the time to tell me what I need to know then I am not giving you my informed consent. I get an entirely different attitude after that point. Because, that is how doctors get sued. Parents/patients didn't understand.

1. Have parents been told the complete reasons why it would be absolutely necessary, just necessary, or desirable to take Singulair and why?
2. Have parents been told what the alternative treatments are and the possible side effects of those treatments?
3. Have parents been given an option of another treatment when they complaint about the side effects of Singulair?
4. Do parents know that headache is a side effect that occurs in 18% of patients? These headache have indicated some serious events in European hospital reports. They are not just sinus headaches.
5. Do parents know that Singulair can cause serious events that require hospitalization as referenced in European hospital reports? These reports have described the event and provided laboratory test results that prove that Singulair was the cause.
6. Singulair in NOT an anti-histamine. Can your doctor fully explain to you how Singulair interacts with the receptors on the mast cell (cell part of the immune system)? Can your doctor fully explain how the mast cell will be changed by this? The mast cell has a number of receptors that interact with each other to tell the mast cell how to function normally; when it's time to die; when it's time to be replaced; and when to tell the bone marrow to send a replacement mast cell. Singular CHANGES the immune system---- good or bad???

So here is the report from Sweden to take to your doctors. Would your doctor give consent for his/her children after reading this? Maybe he/she would BUT at the very least that doctor would be looking for side effects that could mean trouble.

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Update: I have spent hours searching scientific data bases for articles on Singulair. So far this is the most direct reference to adverse drug reactions and Singular.

For anyone who wanted to print the article from the Swedish researchers that stated that their study suggested that montelukast (singulair) should be investigated for adverse psychiatric drug reactions, I was able to find a link with open access to the public. So far, this is the only article that I have found. I am still searching through databases. This link should work if you cut and past. I am sure that all doctors would appreciate the opportunity to read it for themselves to see what they think.

PRINT REPORT.

http://www.biomedcentral.com/1472-6904/8/1

Individual case safety reports in children in commonly used drug groups – signal detection Gertrud Brunlöf , Carina Tukukino and Susanna M Wallerstedt Department of Clinical Pharmacology and Regional Pharmacovigilance Centre, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden author email corresponding author email BMC Clinical Pharmacology 2008, 8:1doi:10.1186/1472-6904-8-1 Conclusion In conclusion, the present study indicates that ADRs are reported for commonly used drugs in children. The number of ICSRs varies in different groups of drugs. A possible signal for montelukast and psychiatric adverse drug reactions was found, which should be further explored.

Please don't forget to PRINT the Tables which open on a separate page. Table 2 lists the specific side effects that they found which include anxiety, aggression, night mares, pain, and several others.

I just got a very condescending private message from a doctor on this site who said that while my articles from Europe are very helpful that I don't know what I am talking about and that I could mislead the public. Then I see how many parents and patients got a condescending attitude from their own doctors.

Well the public has been mislead but it is not my fault. I don't see any experts in this field stepping up to the plate to acknowledge that these side effects exist, have been reported by authorities in other countries, and that these experts are interested in learning why they are happening. This is an extremely widely prescribed medication that involves the lives of millions.

Merck's research director was quoted as saying that they know of no mechanisms by which these side effects could be related to psychiatric adverse drug reactions. That was a flat out LIE. So what if I quoted you a research article from China that was very complicated and yes, could possibly be misinterpreted by somebody? I just needed to give you an example. The only expert so far that had the guts to give you a truthful statement was Dr. J. Douglas Bremner. Thankfully, he corrected a misunderstanding about saying that it was "unclear."

I hope that we will all hang in there and something will be said by somebody, anybody on this site that will make the FDA listen and investigate Singulair (montelukast) all the way back to the very original studies done in test tubes not on people. And, then take a new look at it from the standpoint of what we now know about human genetics. I guess I will keep repeating myself about one size does not fit all.

I would also PRAY that all clinical studies on Singulair (montelukast) would be suspended until the FDA decides why these side effects occur. And that they would issue a statement to doctors to make conservative decisions regarding treatment with Singulair until the results of the investigation have been reported.

I hope that nobody thinks that I am trying to mislead anyone. The answers are either unknown or being hidden by Merck. How would I know the answers? I don't work for Merck. How many other people are out there trying to translate articles in foreign languages to see what's going on? American doctors are calling Merck and being assured that there is nothing to these claims.

I wonder how many experts there are that just don't want to be another Jeffrey Wigand or don't know what is wrong?

I know that I am ranting but somebody should do it.

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.

Have any of you seen this site: http://www.askapatient.com/viewrating.asp?drug=20829&name=SINGULAIR - the side effects we all recently began discussing is documented from users and parents of users as far back as seven years ago!
Why is it that the FDA just became concerned and Merck had no clue of these reports?? Interesting and distressing wouldn't you say?

I just visited Merck's Singulair website and spent a long time really, really thinking about everything that they had for physicians. After thinking about the pathways for myself from the standpoint of chemical interactions, I wanted to know what was explained to the physician. I approached the site from the standpoint of -- if one of my patients was overdosing, how could I recognize that. What would happen? Merck's site has diagrams and movies on the nasal passages and the lungs. You get a picture of a mast cell producing-- doing it's thing. That was it. And on every page, this...

SINGULAIR is indicated for relief of symptoms of allergic rhinitis (seasonal allergic rhinitis in adults and children aged 2 years and older and perennial allergic rhinitis in adults and children aged 6 months and older).

In clinical trials, SINGULAIR was generally well tolerated, with a safety profile similar to that of placebo. Adverse events varied by age. The most commonly reported adverse events, occurring at a frequency of ≥1% and at an incidence greater than placebo, regardless of causality assessment, were sinusitis, upper respiratory infection, sinus headache, cough, epistaxis, headache, otitis media, pharyngitis, and increased ALT.

SINGULAIR is contraindicated in patients with hypersensitivity to any component of this product.

Okay, let's talk about headache at greater than 1%. Headache is 18-19%. How do I know that from what they put on their website?

It might be a very good question to ask your doctor if they could go to the Singulair website and be able to know what would happen if they had a group of children or adults that liked to take pills. Yum, one of good, more is better. I had no clue from that website if there was a risk of overdose or not.

This is not my area. I am trying to help. I am essentially as in the dark as you are.

Here is another who might know how to help.

I got stuck on trying to understand IgE. Here is somebody else who might know something.

Immunol Res. 2007;37(1):1-16.Links
Decoding IgE Fc receptors.Zhang M, Murphy RF, Agrawal DK.
Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE 68178, USA.

Immunoglobulin E (IgE) plays a central role in the pathogenesis of allergic diseases by interacting with two membrane receptors: high-affinity FcepsilonRI and low-affinity FcepsilonRII (CD23). Allergeninduced IgE-occupied FcepsilonRI aggregation on the mast cell or basophil cell surface leads to the activation of intracellular signaling events and eventually the release of pre-formed and de novo synthesized inflammatory mediators. The role of FcepsilonRII in allergic diseases has been proposed to include regulation of IgE synthesis, enhanced histamine release from basophils, and a contribution to Ag-IgE complex presentation but the exact function of CD23 remains poorly understood. This review summarizes some new developments in IgE Fc-receptor studies with an emphasis on regulation of FcepsilonRI expression and signal transduction, including monomeric IgE, lipid raft segregation, and some recently identified negative regulators. A better understanding of signaling events following IgE FcR aggregation will shed new light on how allergy patients might be treated more safely and effectively.

I know that many here would like the FDA to take a very serious took at the problem. I personally don't see how a review of their data is going to make any difference at all. But, if there are experts who can propose a model of the pathways of cell signalling that include the possibility that these symptoms can occur (and under what circumstance), then maybe the problem will look like something much more than statistics.

This is not my field. But I tried to follow the possible pathways to see if I could identify a possible area of concern. Then I looked for someone who had written in the area and read their abstract. A place to start may be to get an opinion from those who know something about "normal homeostasis of the mast cell." Singular blocks the cysteinyl leukotriene receptor 1 which is a site on the outer membrane of the mast cell (other cells also). The mast cell which is produced in the bone marrow is released in a immature state and matures after it arrives at it's destination. The mast cell does not become active unless it's receptor sites come in contact with the activating agent. So, what happens when a receptor site on the mast cell is suppressed by Singular, a receptor antagonist.

You see, I don't have a clue what the signals are that tell the bone marrow to make mast cells (or what the signals are that tell them where to go after they are made in the bone marrow). Does Singular interfere with something that tells the bone marrow what to do? If Singular does interfere with that process, then what is happening and what period of time does it take to happen? Could we wonder whether Singular is interfering with the NUMBER of mast cells that are produced over time? And, of course, maybe there is some OTHER kind of explanation for why the adverse drug reactions are happening. But, at this level, I got lost and can't go any further.

Maybe this group would be interested in the Singulair problems or could suggest somebody else?

http://www.edata-center.com/journals/2ff21abf44b19838,0a1257122f661a7e,0d8ee7116ef23452.html

I apologize if this lead doesn't produce any results but at least it could be a place to start.

1500mg/day for 2 yrs now and it's been a lonnnnng road with this flushing and itching. The typical avoidance foods, hot showers, spicy foods..etc..all help to aoid the side effects. However, if you still get that flushing/itching effect, take some antihistamine medication. Benedryl works, although it will make you drowsy, but it's worth it ! It relieves the itching !

Why does this happen ? it's NOT niacitic poisoning like some on this site suggest. Niaspan causes vasodilation of your the blood vessels in your skin. This causes your mast cell to increase thus triggering a production of histamine in your skin receptors. This is what causes the unbearable itching to occur. It is completely harmless, however, it can be un-bearable at times when the flushing/itching become severe. So taking an ANTI-histamine works well. Time on the medication helps. Reducing the dosage may help as well, however, you will most likely see a drop in your HDL levels by 5-7% for every 500mg drop in dosage.

Hang in there, hopefully big Pharm will come up with a new drug to increase HDL.. I know they are working on it as we speak, but may take a few more years.

I am a registered respiratory therapist and like to read about side effects of respiratory medications. For those of you who are suffering from these harsh side effects know that there are alternatives to steroids. Ask your doctors about mast cell stabilizers or leukotriene inhibitors...
Please remember to wash your mouths thoroughly after adminstering Advair to prevent what is called Candida (thrush) an oropharyngeal fungal infection.