Pathways symptoms and conditions

husband and brother in law both diagnosed with Parkinson's disease. dear friend's husband diagnosed with Parkinson's 3 months later . all had been on lipitor for 2-4 yrs. brother in law has died--diagnosis changed prior to death from Parkinson's to Parkinson's with lewy bodies, to Lewy body dementia to frontotemporal lobe dementia (despite NO family history of this disease entity). there are SO many metabolic substrates whose pathways are interrupted by statins--pathways to isoprenoid metabolism resulting in among many other results, a decrease in glutathione reductase; a decrease in production of coenzyme Q10; decrease in dolichol, the lipid consittuting the largest % of fats making up the substantia nigra in the brain (area diseased in Parkinson's ). and lipids constitute the substance that makes up the mylein sheath surrounding nerves, and the largest % of the dry weight content of the brain.
Tremors were the first symptoms. then non swinging arm while walking, flat affect, rigidity of muscles. all symptoms of Parkinson's...

I'm a 30 yr old healthy male. I went to the ER, and then the Dr., about 4 weeks ago after waking up with intense pain in the veins of my right arm and having pounding palps. I had just been told some extremely stressful news the night before, so I was pretty sure this was blood pressure & stress related. ... EKG showed Wolf-Parkinson-White syndrome, so that's what the Dr's assumed was the problem. I never knew what it was called, but I've had my heart race due to WPW many times since I was a young child .. this did not seem to be related. This was just pounding.

The cardiologist put me on 50mg of Toprol XL daily to control the WPW - even though that wasn't acting up. I left confused. Pharmacy issued generic Metoprolol Succinate mfg. by Sandoz.

I didn't want to be on meds, so I didn't take it for the first few days, hoping that I would return to normal. After all, I just woke up with this all of the sudden.. I had been fine the day before. Palps continued, though, so eventually I relented and started taking the meds.

The first two or three weeks were filled with ups and downs. Exhaustion, palpitations and anxiety would come and go.

This past weekend things got really bad. I began having anxiety attacks -- I think that's what it was, I'd never had one before -- and my vision was totally screwed up. I couldn't focus on anything and was sensitive to some lighting. Black text on a bright white screen (lcd monitor) was especially hard to read. I was completely in a dazed & confused state. Loud noises and crowds were bothering me... which was awful, considering it was my best friend's wedding. Also had headaches, lightheadedness & loss of appetite. These side effects came and went on Friday & Saturday and were pretty constant on Sunday & Monday.

I decided to quit Toprol cold-turkey on Sunday. I have been 2 days without. I have used L-Theamine to reduce stress and keep my blood pressure steady. It seems to be working. I also began taking CoQ10 today after reading some good things about it here.

My vision & mental focus is beginning to improve after 3 days of disabilitating problems. Anxiety has also improved. I even attempted to "get back to normal" at work today, but had to leave after only an hour of strenuous exercise in the heat. Vision problems returned, anxiety set in. It's like riding a really freaking scary roller coaster, except with a legitimate fear that this thing might kill you.

I will update this as time goes by, to let you all know how things worked out for me. I'm really hoping to be mostly back to normal in another day or two, since I haven't been on for very long. Hopefully this will be of help to someone in the future. Damn, I Wish I had never gotten on this stuff.

Below is the latest ADR report on Singulair from the United Kingdom. I deleted side effects reports by very small numbers of patients in order to keep the post briefer. This shows the total number of reports since Singulair was approved in the UK.

I don't know the total number of prescriptions for Singulair in the UK. It is considered expensive.

Drug Analysis Print
Drug name: MONTELUKAST
Drug name: MONTELUKAST Report type: Spontaneous
Report run date: 13-May-2008 Report origin: UNITED KINGDOM
Data lock date: 09-May-2008 08:00:02 PM Route of admin: ALL
Period covered: 01-Jul-1963 to 09-May-2008 Reporter type: ALL
Earliest reaction date: 01-Jan-1997 Reaction: ALL

Cardiac disorders-TOTAL 64
Palpitations 29
Myocardial infarction 6
Tachycardia 6
Diarrhoea 84
Dyspepsia 24
Abdominal pain 98
Abdominal pain upper 22
Nausea 84
Vomiting 52
Dry mouth 15
Asthenia 13
Fatigue 45
Malaise 32
Sudden death 1
Pyrexia 10
Chest discomfort 12
Feeling abnormal 16
Influenza like illness 17
Irritability 18
Drug interaction 13
Chest pain 13
Arthralgia 59
Myalgia 38
Muscle spasms 24
Pain in extremity 14
Balance disorder 10
Lethargy 16
Somnolence 23
Psychomotor hyperactivity 25
Headache 221
Dizziness 68
Neuropathy peripheral 7
Convulsion 6
Epilepsy 7
Dysgeusia 7
Hypoaesthesia 6
Tremor 18
Nervous system disorders TOTAL 526
Abnormal behaviour 13
Agitation 12
Anxiety 18
Aggression 30
Depression 23
Insomnia 58
Abnormal dreams 12
Nightmare 49
Hallucination 21
Sleep disorder 15
Psychiatric disorders TOTAL 364
Asthma 36
Allergic granulomatous angiitis 43
Angioedema 12
Swelling face 12
Erythema 13
Pruritus 32
Rash pruritic 17
Rash 55
Urticaria 33

TOTAL NUMBER OF REACTIONS 2841
TOTAL NUMBER OF FATAL ADR REPORTS* 19
TOTAL NUMBER OF ADR REPORTS* 1489

Here's a way out theory about my unique and to me mystifying medical situation....

I recently read where Singulair, an asthma medicine, is suspected of causing suicides, obviously an effect on the brain function. The FDA notes that over the past year, Merck has updated Singulair's prescribing information and patient information to include the following post marketing adverse events: TREMOR (March 2007), (April 2007), suicidally (October 2007), and anxiousness (February 2008). (the tremor highlight is mine since this is a major symptom of Parkinson's )

Well, I took Singulair from 1998 to 2004 and I wonder if maybe, just maybe Singulair could be a contributing factor to my strange Parkinson's but not Parkinson's problems that is
gait,
balance,
freezing of gait problems

Any thoughts or ideas on how I might follow up on my hypothesis?

Singulair does interact with the astrocyte in the brain.

The role of the cysLT1 receptor (Singulair blocks this receptor) and the astrocyte in the brain has been studied. For anyone from Merck to say that there are no mechanisms by which Singulair can affect the
brain is ludicrous. If the Chinese researchers are correct, then Singulair very clearly affects the brain. Certainly, we don't know exactly how or when the effect would be good or bad. Under what circumstances would it be beneficial and under what circumstances would it be harmful.

For quite a while, researchers have been hypothesizing about the role of the astrocyte in brain function. If we go to look for theories, we will find them. Here is the theory of Dr. Dale Antanitus. I am no here to promote anyone's theory in particular but just to point out that they exist.

http://www.antanitus.com/hypothesis

We can see that the Chinese researchers have gone forward to look at potential links between the cysLT1 receptor (Singulair receptor) and inflammatory response in the brain. The 2008 study showed a link between the astrocyte and the cysLT1 receptor (Singulair receptor)

1: Glia. 2008 Jan 1;56(1):27-37. Links
Activation of CysLT receptors induces astrocyte proliferation and death after oxygen-glucose deprivation.

Huang XJ, Zhang WP, Li CT, Shi WZ, Fang SH, Lu YB, Chen Z, Wei EQ.
Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310058, People's Republic of China.

We recently found that 5-lipoxygenase (5-LOX) is activated to produce cysteinyl leukotrienes (CysLTs), and CysLTs may cause neuronal injury and astrocytosis through activation of CysLT(1) and CysLT(2) receptors in the brain after focal cerebral ischemia. However, the property of astrocyte responses to in vitro ischemic injury is not clear; whether 5-LOX, CysLTs, and their receptors are also involved in the responses of ischemic astrocytes remains unknown. In the present study, we performed oxygen-glucose deprivation (OGD) followed by recovery to induce ischemic-like injury in the cultured rat astrocytes. We found that 1-h OGD did not injure astrocytes (sub-lethal OGD) but induced astrocyte proliferation 48 and 72 h after recovery; whereas 4-h OGD moderately injured the cells (moderate OGD) and led to death 24-72 h after recovery. Inhibition of phospholipase A(2) and 5-LOX attenuated both the proliferation and death. Sub-lethal and moderate OGD enhanced the production of CysLTs that was inhibited by 5-LOX inhibitors. Sub-lethal OGD increased the expressions of CysLT(1) receptor mRNA and protein, while moderate OGD induced the expression of CysLT(2) receptor mRNA. Exogenously applied leukotriene D(4) (LTD(4)) induced astrocyte proliferation at 1-10 nM and astrocyte death at 100-1,000 nM. The CysLT(1) receptor antagonist montelukast attenuated astrocyte proliferation, the CysLT(2) receptor antagonist BAY cysLT2 reversed astrocyte death, and the dual CysLT receptor antagonist BAY u9773 exhibited both effects. In addition, LTD(4) (100 nM) increased the expression of CysLT(2) receptor mRNA. Thus, in vitro ischemia activates astrocyte 5-LOX to produce CysLTs, and CysLTs result in CysLT(1) receptor-mediated proliferation and CysLT(2) receptor-mediated death. (c) 2007 Wiley-Liss, Inc.

PMID: 17910051

The astrocyte has been studied to see how it functions in the brain. The astrocyte:

1. may perform a role in the physical structuring of the brain
2. may perform a role in providing neurons with nutrients
3. may perform a minor role in the maintenance of the blood brain barrier
4. may perform a role in neurotransmitters
5. may perform a role in the regulation of ion concentration in the extracellular spaces
6. may perform a role in neuronal regulation of blood flood
7. may perform a role in the protection and repair of neurons

TO LIE TO PEOPLE REGARDING THEIR HEALTH IS CRIMINAL AND SHOULD BE PROSECUTED. PEOPLE OUT THERE ARE GETTING SICKER IF THEY ARE EXPERIENCING SIDE EFFECTS BECAUSE MERCK IS LYING. SOME PEOPLE MAY NOT EXPERIENCE SIDE EFFECTS BUT WHY NOT TELL THE TRUTH AND SAY THAT THERE COULD BE SOME PEOPLE WHO HAVE PSYCHIATRIC SIDE EFFECTS BECAUSE THERE IS A PATHWAY FOR THAT TO HAPPEN.

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 noticed a lot of postings about weight gain on Singulair, which is nowhere listed by Merck as a possible side effect. My 15 y.o. daughter experienced sudden weight gain at the age of 9 when she was actually underweight (BMI went from 17 to 21). To make a long story short, after being off Singulair for over a year, she is now over-weight, and diet/exercise have never made a big difference (gymnastics, swim team, figure skating, trampoline, etc.) Extensive labwork is always normal & there is no family history of obesity. It's a shame the quality of life of a child is RUINED by a drug that is deemed to have "no side effects", and the many drs. & specialists out there take it very lightly. We continually worry about our daughter's self-esteem, risk of diabetes, and other complications from weight gain which is not hereditary and goes on unexplained by the drug co. Reversing this weight gain has been nearly impossible. Everytime I hear a news report about our children being overweight and obese, it makes me angry because I think about the many kids that are taking this highly prescribed drug (for even the mildest allergy or asthma) and who knows how many parents don't make the connection!

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.

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.

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.

I started taking Toprol XL after being diagnosed with SVT back in May of 2003. I was only in my late 20's & was very trusting, at the time. I was recently sent to a cardiologist because I was having horrible chest pain & the Toprol XL 50 MG wasn't working at keeping the heart rate down. The GP put me on a double dose as well as Cardizem to help with the chest pain & rapid heart rate. I was already on Lanoxin 0.5MG, the highest dose allowed. The cardiologist took me off of the Cardizem right away because he said that is was too stressful for the heart to be on that much heart medicine. I went though several tests & was told by the cardiologist that I didn't have SVT & that this was actually Postural Tachycardia (POTS) & Neurocardiogenic Syncope. I was taken off of Lanoxin, but kept on Toprol XL 100 MG. He put me on lots of salt & water to increase my blood volume which would help my blood pressure when standing. That was in June of 2007. All went pretty good, I thought, until January 18, 2008 when I was working. My heart rate went up to 136 just standing or walking across a room. I called the doctor & talked to a nurse who suggested that I take another 1/2 of a Toprol. I did that & felt better for awhile, but it was short lived. I had been having chest pain, rapid heart rate, fatigue, muscle pain, joint pain, headaches, nausea, vomiting, short term memory problems, rapid weight gain, hair loss, cold extremities, & other things I can't think of right now for what seemed like forever. My gynecologist & my cardiologist first thought that I had thyroid problems, but all tests have come back negative. They then thought that maybe it was from the birth control pills that I had been on for the ovarian cysts. I was changed from one medicine to another & at first I thought that was what was wrong. I am now certain that all of the problems that I have been having were & are a result of the Toprol XL. I was even told that all the problems were "psychiatric in nature". I know that that isn't it at all! I have never had anxiety problems & the GP now thinks that's all that is wrong with me & wants me to go on Zoloft. I tried it, but became so ill that after one pill, I quit. I now plan on weaning myself off of the Toprol XL without the GP's knowledge or consent. The cardiologist was planning on weaning me off at some time in the future, but I am starting without him knowing it at the time. I'll just tell him when I see him next month. Thanks everyone for alerting me to the facts about this medicine. If I had known then what I do now, I'd have never consented to starting it in the first place. My only question is, are some of the "side effects" going to be a permanent thing for me or will they eventually go away? Any advice would be welcome! Thanks again!

hi kim123.
i also had a lot of the symptoms of early menopause,i'm only 32 so was hoping that was not the case for me! my hormone levels came back "normal" but they were in the low end and also what is normal for one person may not be normal for the next. i also suffer from hashimotos disease and even when my blood tests say my tsh is normal i can feel really rubbish,so you can never rely on lab test results as "normal"! i also think that although your levels may have been the same last year they were naturally at that level, a lot of women pass naturally through the menopause with no effects at all. but i think the fact that yasmin is synthetic hormones and that it also messes with other hormones and androgens causes our body to react to the low levels as it drops others that would not normally be touched by a natural menopause. i am not a doctor,this is only my conclusions. hang on in there kim123. maybe try increasing your dose to 10mg lexapro if you feel no different after 2-3 weeks.you may just need a little more,it depends how badly your neurotransmitters are affected. try to keep your brain busy,the more you occupy it , the more pathways are created,the human body is an amazing thing,i never realised before all this just how complex it is! i hope that you start to get some relief soon.

sarah

Just a Note
I saw my doctor the other day and the on of the things NOT to take with Zocor is "Grapefruit". OJ is ok. It has to do with the pathways (chemically) used by the body.