Treatment of asthma symptoms and conditions

May 25th, 2009
11:20 A.M.

Started Singulair 5/14/09. Within last week or so started having extreme pain in shoulders, hands (especially thumbs), wrists and hips. Put ti down to arthritis. Pain has been getting worse every day. Thought it was a food allergy so stopped eating fruit and have cut out all sugar. Yesterday realized that pain has increased so it wasn't the food. It suddenly dawned on me that it could be the Singulair. Stopped taking it last night and am already much better. Still some pain but not so excruciating.

About a month before my Dr. gave me Advair. After a few days on it, I went to bed and thought I was having a heart attack. Pain across my back and down my arms, up my neck and across my chest. This happened 2 nights in a row and decided to stop taking it. Called my MD and he said to stop it immediately. However, he thought it really might be my heart so I had an echo cardiogram and stress test. They said my heart was perfect. After 2 days off the med had no more trouble..

My take is that these "air" drugs are not for me. My MD is on vacation and won't be back until Wed. I will speak with him then. Hopefully by then all paij will be gone. Will post again to report results of stopping Singulair. Reading all these posts also made me realize my depression, irritability and crying has probably been a result of this drug.

By: Fed Up

I have been doing a trial and error thing w/ all my meds and I suspect that Singulair may be the culprit in my insomnia. Since I went down on Cymbalta, it has helped but last night I did not sleep a wink. I took xanax even and was up all night. Finally got up at 4.

Singulair has some ingredients that are the same as anti-histamines which have always affected my sleep but I have copd and am afraid to not take it.It is supposed to open your airways and I use Advair which has a steroid in it and I have no appetite. I still gain weight even though I'm not eating much.Dont know what to do. jo

How does montelukast affect laminin beta2? I don't know but this came up when I cross referenced N106A.

Synthesis of tenascin and laminin beta2 chain in human bronchial epithelial cells is enhanced by cysteinyl leukotrienes via CysLT1 receptor

Cysteinyl leukotrienes (CysLTs) are key mediators of asthma, but their role in the genesis of airway remodeling is insufficiently understood. Recent evidence suggests that increased expression of tenascin (Tn) and laminin (Ln) beta2 chain is indicative of the remodeling activity in asthma, but represents also an example of deposition of extracellular matrix, which affects the airway wall compliance.

We tested the hypothesis that CysLTs affect production of Tn and Ln beta2 chain by human bronchial epithelial cells and elucidated, which of the CysLT receptors, CysLT1 or CysLT2, mediate this effect.

Methods: Cultured BEAS-2B human bronchial epithelial cells were stimulated with leukotriene D4 (LTD4) and E4 (LTE4) and evaluated by immunocytochemistry, Western blotting, flow cytometry, and RT-PCR.

CysLT receptors were differentially blocked with use of montelukast or BAY u9773.

Results: LTD4 and LTE4 significantly augmented the expression of Tn, whereas LTD4, distinctly from LTE4, was able to increase also the Ln beta2 chain.

Although the expression of CysLT2 prevailed over that of CysLT1, the up-regulation of Tn and Ln beta2 chain by CysLTs was completely blocked by the CysLT1-selective antagonist montelukast with no difference between montelukast and the dual antagonist BAY u9773 for the inhibitory capacity.

Conclusion: These findings suggest that the CysLT-induced up-regulation of Tn and Ln beta2 chain, an important epithelium-linked aspect of airway remodeling, is mediated predominantly by the CysLT1 receptor.

The results provide a novel aspect to support the use of CysLT1 receptor antagonists in the anti-remodeling treatment of asthma.

Author: Siiri Altraja, Martin Kadai, Erki Rekker and Alan Altraja
Credits/Source: Respiratory Research 2008, 9:44

Published on: 2008-05-26

CysLT1 receptor (the one that Singulair blocks) is also expressed (shows up) in the spleen. I have not seen anything yet that says what it does in the spleen. The spleen has important immune system functions especially in children. It contains B-lymphocytes that fight infection.

: Prostaglandins Other Lipid Mediat. 2002 Aug;68-69:587-97.Links
Cysteinyl leukotriene receptors.Evans JF.
Department of Pharmacology, Merck Research Laboratories, Merck & Co., West Point, PA 19486, USA. jilly_evans@merck.com

The cysteinyl leukotrienes, leukotriene C4 (LTC4), leukotriene D4 (LTD4) and leukotriene E4 (LTE4), activate contractile and inflammatory processes via specific interaction with putative seven transmembrane-spanning receptors that couple to G proteins and subsequent intracellular signaling pathways. Pharmacological characterizations identified at least two subtypes of cysteinyl leukotriene (CysLT) receptor based on agonist and antagonist potency for biological responses. The rank potency of agonist activation for the CysLT1 receptor is LTD4 > LTC4 > LTE4 and for the CysLT2 receptor is LTC4 = LTD4 > LTE4. CysLT1 selective receptor antagonists are efficacious in the treatment of asthma. No selective CysLT2 receptor antagonists have been described. Molecular identification of the human and mouse CysLT1 and CysLT2 receptors has confirmed their structure as putative seven transmembrane domain G protein-coupled receptors and largely confirmed the previous pharmacological characterizations. The CysLT1 receptor is most highly expressed in spleen, peripheral blood leukocytes including eosinophils, and lung smooth muscle cells and interstitial lung macrophages. The CysLT2 receptor is most highly expressed in the heart, adrenal medulla, placenta and peripheral blood leukocytes. The molecular identification of the mouse CysLT1 and CysLT2 receptors show similar but not identical profiles to the orthologous human receptors.

PMID: 12432945

Hopefully this will prove to the doubters that there are genetic reasons for the variation of efficacy and adverse side effective when taking Montelukast.

I have several areas of concern (concerned citizen is concerned). One of the main areas is the reliability of Montelukast due to differences in genetics among populations. The cysLT1 (Singulair) receptor is a GENE. As I said before, it would be possible to predict those patients for which Montelukast would and would not be effective and those patients whose gene expression profile would cause them to have unwanted side effectives.

I have been looking for a way to give reasonable proof of that which could be used to convince your doctors that Montelukast is not for everybody. I happened to locate a researcher who had invented and patented methods for predicting drug sensitivity and efficacy in inflammatory disease. I have quoted below from his patent application. He intended to provide a method for determining efficacy and drug sensitivity for pharmaceuticals which include leukotriene antagonists - Montelukast.

Quoted from:

Methods for predicting drug sensitivity in patients afflicted with an inflammatory disease
US Patent Issued on December 12, 2006

Methods are disclosed for predicting the efficacy of a drug for treating an inflammatory disease in a human patient, including: obtaining a sample of cells from the patient; obtaining a gene expression profile of the sample in the absence and presence of in vitro modulation of the cells with specific cytokines and/or mediators; and comparing the gene expression profile of the sample with a reference gene expression profile, wherein similarities between the sample expression profile and the reference expression profile predicts the efficacy of the drug for treating the inflammatory disease in the patient.

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The field of pharmacogenomics measures differences in the effect of medications that are caused by genetic variations. Such differences are manifested by differences in the therapeutic effects or adverse events of drugs. For most drugs, the genetic variations that potentially characterize drug-responsive patients from non-responders remain unknown.
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In another embodiment, the invention is directed to a method for predicting the efficacy in a human asthma patient of leukotriene antagonists including, but not limited to, montelukast (a.k.a., SINGULAIR™; Merck, Whitehouse Station, N.J.), zafirlukast (a.k.a., ACCOLATE™, AstraZeneca, Wilmington, Del.), and zileuton (a.k.a., ZYFLO™; Abbott Laboratories, Chicago, Ill.), comprising: obtaining a sample of cells from the patient; obtaining a gene expression profile from the sample in the absence and presence of in vitro modulation of the cells with specific mediators; and comparing the gene expression profile of the sample with a reference gene expression profile, wherein similarity in expression profiles between the sample and reference profiles predicts the efficacy in the human asthmatic patient of leukotriene antagonists.

Many of the cells involved in causing airway inflammation are known to produce signaling molecules within the body called "leukotrienes." Leukotrienes are responsible for causing the contraction of the airway smooth muscle, increasing leakage of fluid from blood vessels in the lung, and further promoting inflammation by attracting other inflammatory cells into the airways. Oral anti-leukotriene medications have been introduced to fight the inflammatory response typical of allergic disease. These drugs are used in the treatment of chronic asthma. Recent data demonstrates that prescribed anti-leukotriene medications can be beneficial for many patients with asthma, however, a significant number of patients do not respond to anti-leukotriene drugs.

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The genes selected are those that have been determined to be differentially expressed in either a disease, drug-responsiveness, or drug-sensitive cell relative to a normal cell and confer power to predict the response to the drug. By comparing tissue samples from patients with these reference expression profiles, the patient's susceptibility to a particular disease, drug-responsiveness, or drug-resistance can be determined.

http://www.patentstorm.us/patents/7148008-description.html

The inventor's website: Hakon Hakonarson M.D. The Children's Hospital of Philadelphia

http://stokes.chop.edu/research/profiles/?ID=251

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.

From Canada:

Leukotriene receptor antagonists: suspected adverse reactions

The cysteinyl leukotrienes are inflammatory mediators that bind to cysteinyl leukotriene receptors found in the human airway and cause a number of airway actions including bronchoconstriction, mucous secretion, vascular permeability and eosinophil recruitment.1 Zafirlukast (Accolate®) and montelukast sodium (Singulair®), marketed in Canada since November 1997 and August 1998 respectively, are competitive cysteinyl leukotriene receptor antagonists. Zafirlukast is indicated for the prophylaxis and chronic treatment of asthma in patients 12 years of age and older.2 Montelukast is indicated for the prophylaxis and chronic treatment of asthma, the treatment of asthma in ASA-sensitive patients and the prevention of exercise-induced bronchoconstriction in pediatric patients 6-14 years of age and adults 15 years of age and older.1

As of June 1, 1999, the CADRMP has received 41 reports of suspected adverse drug reactions associated with the use of zafirlukast and 22 associated with the use of montelukast. This article will discuss a serious and rare adverse reaction associated with the use of these agents, drug-drug interactions and unexpected adverse reactions that have been reported to the CADRMP.

http://www.hc-sc.gc.ca/dhp-mps/medeff/bulletin/carn-bcei_v9n4_e.html

Conditions are discussed in the article.

I am a 60 year old woman,and was on Singulair in 2000 for the treatment of asthma. At the same time I was put on inhalers Flovent and Serevent, taking the inhalers twice a day. Almost immediately, I began waking up at night, screaming my lungs out, having a very strong, vivid feeling that my heart had stopped, the blood was draining from my head and arms and this was my last breath and I was dead! It scared the hell out of me. After calming down I would go back to sleep and it would happen again. Sometimes it would happen 10 - 12 times a night, and sometimes even while I was awake. It wasn't a dream. It frequently was accompanied by a restless leg. I spoke to my allergist, my primary care doctor and a pharmacist, and all said it wasn't related to my drugs. I had a sleep test and woke up screaming my lungs out, scaring the night-shift technician, but nothing showed up on the tests. This went on for about 6 months, and then I quit taking the inhalers at night. My "night terrors" eased off a bit to only once every couple of nights, but didn't go away. I quit taking Singulair and Serevent after about 2 years, and only then did the terrors really subside. I had thought they were caused by the Serevent alone, but after reading these stories I suspect it was a combination of the 2 drugs. I still have the terrors a couple of times a year, generally preceded by a restless leg.

I am athirtysomething yr old female. I was given high dosages of predisone in an out the hospital for two years. The predisone was used for treatment of asthma. While using the drug I experienced rapid heart rate, nervousness/anxiety and my shoulder dislocated every time I used prednisone,(the shoulder had been previously dislocated due to an injury). I also am plagued with acne on my face, back and chest. Molre recently I have been diagnosed with Grave's Disease. I am wondering if my predisone usage is in anyway related to my present diagnoses.