Pathway symptoms and conditions

I am a 21 year old female. I have been on 25mg Toprol (twice a day) for over a year now. I was having intense heart palpitations from scary panic attacks... this drug basically cured my heart irregularity. When I first started taking Toprol I experienced some muscle cramps but that lasted less than a week. Overall I have NOT experienced ANY negative side effects from this drug. It is one of the best things I have ever done for myself. I was so scared before due to having at least 5 ‘episodes’ a day with my heart… now I may only have 2 – 3 per week. Such a wonderful improvement! It has really changed my life for the better.

Since HTML is not allowed...need you to find the links to the following:

"whether an oral contraceptive (OC) containing drospirenone (DRSP) (3 mg) + ethinyl estradiol (EE) (30 μg) (DRSP + EE) could modify psychological symptoms and whether it could modify steroids interfering with the γ-aminobutyric acid (GABA)-A receptors.

Conclusion(s): The results suggest beneficial effects of DRSP + EE on psychological symptoms by

decreasing DHEAS."

Beneficial to lower the levels of DHEAS?!

"Women With Higher Levels Of DHEAS Have Better Cognitive Function"

"dehydroepiandrosterone sulfate (DHEAS), inhibit the production of TNF in vitro and in vivo."

Who is at greater risk?

Those who have the HLA-DR gene type and already have allergies/asthma.

Adrenergically blockaded conditions = AdBCs include the following: respiratory allergies, skin allergies, and asthma.

IgE will go thru the roof. Allergic reaction. Th2 pathway.

""It has also been shown that young women exposed to intensive stress situations,

with low plasma of dehydroepiandrosterone
sulfate (DHEA-S),

and a recent use of contraceptive pills are most at risk for

onset of autoimmune disease."

"Montelukast (Merck brand name Singulair) is a selective Cys-LT1 receptor antagonist that is used to control asthma symptoms in children and adults. Although safe and effective, the inter-patient variability in response is substantial (25-60% response rate), which is due in part to genetic variability. For example, we recently reported that polymorphisms in candidate genes that encode proteins in the LT pathway influence responsiveness to the drug."

Co-sponsored by Merck

http://clinicaltrials.gov/ct2/show/record/NCT00513760

More evidence of what I have been saying about genetics and the leukotriene pathway that Singulair blocks. FLAP's as mentioned below are actually the same era as Singulair (late 90's)--many scientists were looking at this pathway.

The genetic component is so "in your face" every where that I am quite appalled that Merck has not at least addressed that issue by now.

Monday, June 02, 2008
Amira Pharmaceuticals Achieves Milestones in FLAP Inhibitor Program With GlaxoSmithKline
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SEND ComtexDigg It StumbleUpon Newsvine Reddit SAN DIEGO, Jun 02, 2008 (PR Newswire Europe via COMTEX) ----GSK exercises option for AM803, a FLAP inhibitor which recently completed phase I studies

Amira Pharmaceuticals today announced that under the terms of a worldwide exclusive agreement entered into in Feb 2008, GlaxoSmithKline (GSK: 43.65, -0.88, -1.97%) will exercise its right to a second FLAP compound, AM803. Under the original agreement, GSK has rights to develop, manufacture and commercialize FLAP (5-Lipoxygenase Activating Protein) inhibitors for the treatment of respiratory and cardiovascular disease. The decision to develop AM803 follows the successful completion of a phase I study by Amira, which demonstrated its potential as a once-daily FLAP inhibitor.

"Exercise of this option by GSK caps a productive first few months during which Amira has hit a number of near term milestones. Hitting these milestones early has not only further strengthened our relations with GSK, but has resulted in meaningful economic benefit to Amira," said Hari Kumar, Chief Business Officer, Amira. "The project has started extremely well and we are very pleased at the commitment of GSK and the progression of development."

About FLAP Inhibitors

FLAP (5-Lipoxygenase Activating Protein) is a key component early in the leukotriene pathway, a complex signaling process that exerts control over biological processes, such as inflammation and immunity. Excessive production of leukotrienes exacerbates inflammatory diseases, such as asthma; the FLAP gene has also been linked to a significant increase in the risk of myocardial infarction and stroke. AM103 and AM803 bind to FLAP, inhibiting the synthesis of leukotrienes that cause inflammation.

About Amira

Founded in 2005 and headquartered in San Diego, Amira Pharmaceuticals is a small molecule pharmaceutical company focused on the discovery and early development of compounds to treat inflammatory disease linked to the eicosanoid pathway.

The company combines the rigor of a big pharmaceutical company with the ingenuity and energy of a small company, creating an environment for efficient and effective pre-clinical and clinical program decisions. Its scientific founders have successfully worked together for more than a decade and were pivotal in the discovery of a number of inflammatory drugs, including Singulair(R: 73.05, -0.38, -0.51%). The drug hunters at Amira are now actively leveraging their history of success to create high-value compounds for the future. For more information, visit http://www.amirapharm.com.

Web site: http://www.amirapharm.com

I already posted about my son's behavioral changes while on the drug from the time he was 4-7. He is now 9 years old and has been back to "normal now for 18 months. BUT- we recently had his immune system checked though a blood test and he does not have sufficient immunity for ANY viruses. My 6 year old could fight 8 out of the 14, but my son who was on Singulair for almost 4 years has a severely depleted immune system. And from what I have read, could clearly be attributed to the drug. BUYER BEWARE~!

I don't think that anyone can predict a time frame for getting over an adverse drug reaction. Below is my opinion but I see a lot of evidence that it is basically shared by other people maybe not exactly as I state it.

Adverse drug reactions deplete many essential nutrients from our systems. Inflammatory response is very stressful on the body. It is sometimes a very big effort to work on the diet to put back what has been taken away. It can take a long time.

Quinolines particularly deplete B-vitamins, folic acid (B-9), calcium/magnesium/zinc and omega-3 fatty acid. Sometimes the blood-lab work shows elevated homocysteine which proves that the body has suffered inflammation. Cardiologists now use homocysteine levels to show whether someone is at risk for heart disease due to inflammation. Deficiencies of B-6, B-9, and B-12 are known to cause elevated homocysteine.

Here is the pharmaceutical company ZINGER. Now companies such as Merck and Pfizer are going to offer niacin products to lower cholesterol. Well, yeh, duh !. All of these drug reactions are causing depleted B vitamins which elevate cholesterol. Then after they have tried to kill us by depleting our B - vitamins, they want to sell us another pill to give the B vitamins back to us. How many people out there are on some kind of a pill with side effects that cause inflammation? What a business? It is win, win, win.

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.

Some of you who are following this site may remember that I posted that when I was following the pathways of the leukeotriene receptor antagonist Singulair that I got to a point where I concluded that there has to be a genetic component (meaning that there are different gene groups of people) and that the efficacy of Singulair (and possibly safety) can vary depending upon what gene group people are in. So I took a little time to see if anybody else was already studying that issue. And YES, they are -- including Merck.

quote:

" However, logically one might predict that it will be the combination of the polymorphisms in these different key regulatory enzymes and receptors that may ultimately determine treatment response. There have been some attempts to tease out the possible contribution of different genes important in this pathway for treatment response to a Cys leukotriene receptor 1 antagonist.18 However, because of the number of potential gene variants that may contribute to efficacy, large studies will be needed to fully evaluate the potential contribution of pharmacogenetic variability in this pathway to treatment response to Cys leukotriene receptor 1 antagonists. Work in the cardiovascular field has demonstrated the potential importance of genetic variants in this pathway to disease risk and also to treatment response,19 suggesting the potential for important effects to be defined in asthma."

(Chest. 2006;130:1873-1878.)
© 2006 American College of Chest Physicians

Pharmacogenetics of Asthma
Ian P. Hall, DM
* From the Division of Therapeutics and Molecular Medicine, University Hospital of Nottingham, Nottingham, UK.
Correspondence to: Ian P. Hall, DM, Division of Therapeutics and Molecular Medicine, University Hospital of Nottingham, Nottingham NG7 2UH, UK; e-mail: Ian.Hall@nottingham.ac.uk

http://www.chestjournal.org/cgi/content/full/130/6/1873

And Merck sponsored a study on this which is now completed.

http://clinicaltrials.gov/ct2/show/NCT00116324?intr=%22Montelukast%22&rank=79

Of course, it was sponsored by Merck and paid for by Merck.

I don't know if the study discovered anything but I believe this is an indication that Merck acknowledges genetic differences in populations that may predict the success of montelukast.

I am not any where close to being an expert in this field. I have another background but I believe that there are experts who can tell you exactly why you had side effects from Singulair.

My husband started taking Simvastatin about 6 weeks ago. Since taking it he has been experiencing sexual problems. Is this related to the drug? It has never been an issue before.

Hello fellow sufferers,
Several years ago I had a CT of my face and head due to frequent migraines...They had thought maybe there was a tumor or blocked blood vessels, but to my complete surprise all of that was normal, but I had all the sinuses on the right side of my face completely blocked...The doctor @ that time asked me some questions about my breathing and pain...Of course my breathing through the nose wasn't that great, but I had always taken that as a bonus since I work in the hospital...NO pain really either...Due to the fact that sinus infections have a direct pathway to the brain they decided that I needed Levaquin...On the second day of taking the medication I was in complete tears...The bottom half of my body ached like someone had kicked the %^&* out of me...First off I thought that maybe it was because I had my leg in a full cast and that had just been adjusted so stupidly I continued with the med another 2 days and the symptoms got to the point that I couldn't walk...I called the pharmacy right away and told them of my symptoms and they said they had no documentation of such side effects so I continued thinking it was something else ( they always tell you to complete the full course of an antibiotic so you don't kill off half the "bug" and the other half goes resistant)....Stupid....I finally made an appointment and had my husband literally carry me cast and all down there...The doctor had no explanation for the symptoms I had but did lab work to kinda shut me up and low and behold it reviled that I had full blown arthritis so off to a rheumatoid specialist...We went through my health history and other that the sinus infection, migraines and a broken leg I was fine except for the constant pain from the waist down........It took 7 months to return to "normal" blood test went back to normal too...I had made a second trip to the pharmacy and insisted on filling out a form for side effects and had proof of it with the weird lab tests that had since gone back to normal...This form was supposed to be sent to the drug company (not sure if it ever was).....Thought I would just share my experience with you and hope it helps others...I am an RN with 15 yrs surgical experience and thought I was going nuts when on this stuff...Since then I have always included this as an ALLERGY since it is one of the best and most common drugs used for things like sinus infections and I don't ever want to take this again.
Sincerely,
Debbie

Anaphylactic reaction, blood pressure dropped to 70/40, flushing, generalized hives/angioedema, tightness in throat, diaphoresis, palpitations, and lightheadedness(even near syncope) and hypotension. Alterations in the kinin metabolism pathway due to the ace inhibitor