Dyspepsia symptoms and conditions

Leukotriene receptor cysLT1 in intestinal epithelial cells and variation in montelukast blood levels between individuals.

We know many things about this topic:

1. Montelukast enters the blood stream through the intestines
2. the cysLT1 (receptor that Singulair blocks) exists in intestinal epithelial cells
3. montelukast will bind with high affinity to the ideal gene type cysLT1 receptor
4. after montelukast enters into the blood stream is it 99% bound to plasma proteins (that point is hypothesized to be the reason that montelukast does not inhibit CYP2C8 in vivo but it does in vitro if it is true that in vivo it does not inhibit CYP2C8)
5. there is variation between individuals on how much montelukast makes it into the blood stream

Well, did anybody out there in science land think of trying to find out how much montelukast binds to the cysLT1 receptors in intestinal epithelial cells? They got all interested in transport proteins but where are the studies about the cysLT1 receptors in intestinal epithelial. And, what is the effect of montelukast if it binds to intestinal cysLT1receptors?

Now, concernedcitizen believes that if montelukast binds to intestinal epithelial cysLT1receptors that could be a BIG problem because those receptors have a different function than in respiratory tissue. In the one place, we gotta' breathe. In the other place, we gotta' digest food properly.

We have all of these children who have stomach pain. Does anybody want to find out why?

This drug belongs in the science HALL OF SHAME. Somebody please call Arnold Diaz. I am quite discussed today.

Oncogene. 2006 Oct 26;25(50):6660-5. Epub 2006 May 22. Links
Endogenous production of leukotriene D4 mediates autocrine survival and proliferation via CysLT1 receptor signalling in intestinal epithelial cells.Paruchuri S, Mezhybovska M, Juhas M, Sjölander A.
Cell and Experimental Pathology, Department of Laboratory Medicine, Lund University, Malmö University Hospital, Malmö, Sweden.

The cysteinyl leukotriene1 (CysLT1) receptor (CysLT1R) enhances survival and proliferation of intestinal cells via distinct pathways. Here, we have demonstrated that there is significant endogenous production of CysLTs from both non-tumour- and tumour-derived intestinal epithelial cells. Treatment of two non-tumour cell lines, Int 407 and IEC-6, with CysLT1R antagonists led to shrinkage and detachment of cells, confirmed as apoptotic cell death, and a dose-dependent reduction in proliferation. However, in the tumour intestinal cell lines Caco-2, SW480, HCT-116 and HT-29, treatment with CysLT1R antagonists significantly reduced proliferation, but had no effect on apoptosis. A unique characteristic of intestinal cancer cells is the presence of nuclear CysLT1Rs, which are inaccessible to receptor antagonists. In these cells, inhibition of the endogenous production of CysLTs indirectly, by 5-lipoxygenase inhibition, impaired CysLT1R signalling throughout the cell, and resulted in apoptosis of the tumour cells. These data reveal the existence of constitutive CysLT1R signalling that mediates both survival and proliferation in intestinal cells. Importantly, we propose that tumour-derived intestinal cells are resistant to CysLT1R antagonist-induced apoptosis, a phenomena that could be explained by nuclear CysLT1R signalling.

PMID: 16715140

CLINICAL TRIAL - transport proteins and montelukast

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

I believe that objective sources of information should be posted periodically so that they are not missed.

Adverse Reactions
(As reported in adults)
>10%: Central nervous system: Headache (18%)

1% to 10%:

Central nervous system: Dizziness (2%), fatigue (2%), fever (2%)

Dermatologic: Rash (2%)

Gastrointestinal: Dyspepsia (2%), dental pain (2%), gastroenteritis (2%), abdominal pain (3%)

Neuromuscular & skeletal: Weakness (2%)

Respiratory: Cough (3%), nasal congestion (2%), upper respiratory infection (2%)

Miscellaneous: Flu-like symptoms (4%), trauma (1%)

Postmarketing and/or case reports: Agitation, anaphylaxis, angioedema, arthralgia, bleeding tendency, bruising, cholestasis (rare), diarrhea, dream abnormalities, drowsiness, edema, eosinophilia, hallucinations, hepatic eosinophilic infiltration (rare), hepatitis, hypoesthesia, insomnia, irritability, muscle cramps, myalgia, nausea, palpitation, pancreatitis, paresthesia, pruritus, restlessness, seizure, urticaria, vasculitis, vomiting

http://www.umm.edu/altmed/drugs/montelukast-088375.htm

Oh my gosh, I am just shocked after reading these posts. I am taking my son off of Singulair immediatedly!!!! I knew I wasn't crazy!! My son was on Singulair for over 2 years and it was awful. He was so hyper and uncontrollable. He couldn't control his temper. He had headaches everyday. He was put on it due to severe allergies and asthma. He is on other medications as well as allergy shots. I kept telling the doctor that I think the singulair was causing his bad behavior problems. He was just so hard to handle. He couldn't sit still for anything. The teacher couldn't get him to sit still in his chair. It just wasn't normal behavior for him. The teacher even thought he had ADD!! I didn't accept that however. The doctor just thought I was crazy and told me that Singulair wouldn't cause those symptoms. She said it actually would work opposit that and cause him to be sleepy. Well I took him off of it anyways and he did get pretty sick. His asthma acted up ect. But he eventually felt better and his behavior improved drastically. He wasn't so hyper and he could actually sleep at night and wasn't so scared at night. Just within the last week he has been pretty sick due to allergy season, his asthma has been bad and the doctor told me to put him back on the Singulair. So I did he has been on it for four days now and he is HORRIBLE.. It was an instant change. My husband and I can't control him and he can't sleep at night and has headaches every day. I am so glad I found this sight. I am taking him off immediately.
Thank you all so much for your comments. This medicine should be outlawed. I don't care what the doctors say. By the way my son is 9 years old. I certainly had no idea that it has caused suicide. I am so sorry to you all that have experienced such horrible things. Come to think of it my son used to say he hated himself all of the time when he was on this medicine.
God Bless You All

I took Aciphex for 3 days and stopped. Two days later I awoke with a very scary irregular heartbeat that lasted for 2 hours and accompanied by frequent urination for the two hours. I was petrified. I thought I was dying! Now I am scared to take any more Aciphex. I only have GERD or Dyspepsia infrequently. I will try to find a natural remedy. I also had a headache every time I took the Aciphex. I did not have any bowel changes that I noticed but I was only on it for 3 days. I had none of the other symptoms mentioned.

I feel like my heart flutters on it and the first time I took it, I couldn't sleep for 2 days. I am giving it another try due to cedar fever.

I found this information from another site.

Post-Marketing Experience

The following additional adverse reactions have been reported in post-marketing use: hypersensitivity reactions (including anaphylaxis, angioedema, pruritus, urticaria, and very rarely, hepatic eosinophilic infiltration); dream abnormalities and hallucinations, drowsiness, irritability, agitation including aggressive behavior, restlessness, insomnia, paraesthesia/hypoesthesia, and very rarely seizures; arthralgia, myalgia including muscle cramps; increased bleeding tendency, bruising; palpitations; edema; nausea, vomiting, dyspepsia, diarrhea, and very rarely pancreatitis. Rare cases of cholestatic hepatitis, hepatocellular liver-injury, and mixed-pattern liver injury have been reported in patients treated with SINGULAIR. Most of these occurred in combination with other confounding factors, such as use of other medications, or when SINGULAIR was administered to patients who had underlying potential for liver disease such as alcohol use or other forms of hepatitis

It looks like it has many side effects.

GOOD LUCK WITH YOUR ALLERGIES!

well this is the exhaustive list of the possible side effects triggered by montelukast sodium given in the leaflet of this medicine....i am so grateful to the distributors of this medicine in my country for keeping the users of this medicine informed. I am stating the side effects as it is for every ones notice here

1. Body as whole: asthenia, fatigue, malaise, oedema, hypersensitivity reactions including anaphylaxis, angioedema, urticaria, pruritus, rash and one isolated report of hepatic eosinophilic infiltration.
2. Digestive system: thirst(pediatric patients), abdominal pain.
3. Nervous system/psychiatric: headache, dizziness, dream abnormalities including nightmares, hallucinations, drowsiness, insomnia, paraesthesia/hypesthesia, irritability, agitation including aggressive behaviour, restlessness, seizure.
4. Musculo skeletal disorders: arthralgia, myalgia including muscle cramps.
5. Hepato biliary disorders: elevated levels of serum transaminases(ALT,AST), cholestatic hepatitis.
6. Digestive system disorders: diarrhea, dry mouth, dyspepsia, nausea, vomiting.
7. Cardiovascular disorders: increased bleeding tendency, bruising, palpitations. Very rare cases of Churg-Strauss Syndrome CSS have been reported during montelukast treatment in asthmatic patients.
8. Mutagenicity and carcinogenicity: No evidence of this have been reported in montelukast treatment.
9. Pregnancy and lactation: no evidence of tratogenicity and there is no suffiecient prove for the excretion of the montelukast in the human milk as many drugs are excreted in the human milk.

I have horrible nerve pain in my right leg from the knee down into my foot after laminectomy and diskectomy 8 months previously. I began taking Neurontin, and experienced dizziness, lack of coordination the first week or two, but a dramatic decrease in the numbness, tingling and pain in my leg and foot. I have stopped taking Neurontin because of stomach pain, bloating, dyspepsia, really miserable, this was while I was on 40mg of Prilosec. I am now on Amytriptyline. It helps somewhat, but not nearly as much as the Neurontin. I am frustrated, because I don't know how to live with this constant distracting and painful condition. It's difficult to walk because of the severe pain in the ball of my right foot. I would really like to take the Neurontin, because I saw such improvement with it, but there always seems to be a side effect that makes it impossible to take a drug that helps. Same with anti-inflammatories, that also rip my stomach apart. Please help with any suggestions.

Dukes

I have been taking 10 mg Paxil at night and 150 mg Wellbutrin daily for the past 6 months. I was still feeling a bit low energy wise and decided to ask my doctor to ratchet up the Wellbutrin to 300mg. He prescribed the XL formulation.

First day was fine. On the second day, I had a strong cappuccino for breakfast and two diet cokes (at lunch). Also had 3 shots of scotch at a dinner party. I woke up with severe diarrhea and nausea. For the next 3 days, I stopped all caffeine and alcohol intake but my digestive upset has not gone.

The symptoms are very similar to the Irritable Bowel Disorder I suffered for years before Paxil. Alternating diarrhea and Constipation with concommitant dyspepsia.

I am now seeing my doctor today to see what he thinks. I have a suspicion that Wellbutrin and Caffeine do not mix well. Almost a year ago when I first started Wellbutrin (300 mg) and drank 2 diet cokes, I felt very weird. I immediately cut the dose down to 150 mg. Maybe that is all my body can tolerate.

On the plus side, when I started Wellbutrin, I was feeling extremely low energy-wise and was sleeping a lot. At that time I was on 20 mg of Paxil. I have felt much better after adding 150 mg Wellbutrin and cutting the Paxil down to 10 mg.

My original problem was essentially chronic anxiety throughout childhood (a family condition) accompanied by a variety of psychosomatic illnesses like mild Psoriasis, back pain and IBD. I also had a mild stuttering problem that has now almost disappeared. Paxil has been responsible for alleviating all these conditions.

Unfortunately, as is well known Paxil is no panacea and it makes me very drowsy.