May 4th
2008
3:42 PM
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.
-- By concernedcitizen | Reply | (4) replies | Private Message me
February 8th
2005
3:28 AM
My daughter has been on routine nasonex for months for her (non-acute) asthma. She has been experiencing constipation, problems urinating and headaches. I'm not sure whether to blame these symtoms on this drug or more probably the guafinex she is also taking. Isn't it nice that modern pharmacueticals give us choices?
-- By rgrover | Reply | Private Message me
June 23th
2004
3:12 PM
I have been on Advair for 7 months. I started on 500, then went to 250 and now am trying 100. I have gained 30 lbs - even with going to the gym regularly and eating less than 1500 calories a day. When I tell my dtr I am gaining weight from Advair he laughs and tells me to eat less. And that any other symptoms I have are not from this medicine. I had also found a lump in my calf by my ankle and had to have an MRI. They said it is a 'limpoma', a lump attributable to steriods. So now I have to have that cut out and will not be able to run for quite some time, which means more weight gain. I don't know what to do. Since I have started taking it, I have never been able to breathe better. And I have had severe ashtma for years. When I try to wean myself off, I immediately have a bad attack. I want to stop taking it, but don't know how to get off. Even switching to the lower dosage this week has made me lethargic, dizzy and barely able to keep awake. What a nightmare. My body is so bloated and heavy, I can't fit into any clothes. And I can barely run more than 2 miles without my chest burning. This is from someone who has run a marathon before no problem. We need a new solution for asthma - Advair is NOT it.
-- By kelli_gail | Reply | (2) replies | Private Message me
September 7th
2003
6:03 AM
If children are having side effects to Advair but need a corticosteroid to help control acute asthma, you may want to ask your doctor about Pulmicort or another such inhaler or daily nebulizer treatment.
Please go to www.advair-asthma-danger.com for morte info & useful links for both children & adults.
-- By dianahollins | Reply | Private Message me
August 4th
2003
11:12 PM
my 9 yr old son has been on singulair and advair for about a year now. he has mood swings all the time. he gets so angry sometimes that he scares the heck out of me. i spoke to the doctor about this problem and he informed me that this was a side effect to the advair. i had no idea that this drug was not approved for children under the age of 12. he has acute asthma, and i`m afraid to take him off this medication.(his attacks hit him really,really hard) does anyone know of a possible alternative that i can mention to my doctor?
-- By baseballmom_9429 | Reply | Private Message me
Advair HFA (3) Nasonex (1) Nalfon 200 (1) Singulair (1) PredniSONE (1)
June 19th
2008
4:27 AM
You people are freaking me out. I just started today with my first dose of prednisone for my first bronchitis diagnosis. I've been sick for 3 months and thought this would be a good med for me to rid the coughing. I'm starting to reconsider taking any more if all I can expect is long term adverse effects. I took this once before years ago for a severe skin allergy. I got the psychosis initially but then adjusted the dose. Then, I would get euphoric and full of energy, like being on a stimulant. I had no idea the round face thing was due to this, I thought I just ate too much while I was home sick for 2 months. I think I'll try the herbal alternative route. If it works, I'll write again and let y'all know. Thanks for all the comments.
-- By suegator | Reply | (6) replies | Private Message me