Blood stream symptoms and conditions

2 genetic mutations in the gene that encodes for the transporter protein responsible for moving anti cholesterol statin drugs into the liver to be detoxified. have been identified. This gene is "SLCO1B1" (also referred to in the scientific lit as "OATP1B1"). Drugs must be "detoxified" by organs within the body and then eliminated, otherwise the drug stays in the blood stream, building up to toxic levels. With either of the 2 mutations, statins have been found to be (from various studies) anywhere from 122% to 400% ABOVE NORMAL plasma statin levels. How many people have either of these mutations? (Population genetic studies were done in Finland on Caucasian pop--so all the #'s refer to Caucasian population) 25 % to 38% of ALL Caucasian possess one of these 2 mutations. Thus, for however many yrs someone with one of these mutations has taken a statin, the level of the statin in their blood stream conceiveably could have been 400% ABOVE normal statin levels. ALll those pharmacologic effects of statins--decreased coenzyme q10, depressed manufacture of dolichols, depressed manufacture of selnproteins and thus glutathione, interrupted production of GTPases and glycoprotein function, decreased brain cholesterol levels--neuron synapses and new growth of neurons depend upon brain choelsterol--are intensified unrelentingly for the length of time the drug is taken.

As I posted earlier, I got the Mirena taken out a week ago and they told me it was normal procedure to do a culture when they remove it. Now they call me back and tell me I have MRSA which is the really bad staph infection, INSIDE me, and it was most likely caused by the Mirena IUD. This thing is so serious it's considered an infectious disease, and the 2nd doctor I saw about it literally said, "If it gets into your blood stream you can die." Wow. Thanks, Mirena.

Girls! I am so glad I am not the only one!!!!
I had Mirena right after I had my second baby (around March 2007) and I had it for 2 1/2 years. I think I was alright for the first few month (but it is hard to tell as I was quite overwhelmed with baby and toddler care). But the past year 1/2 or so It was clear to me that something was not right. I was feeling really intense mood swings, had no patience, felt angry at times, loosing interest in my job and feeling at lost with my life at times and... NO libido whatsoever!
My OB told me over and over that Mirena was not the problem! But it seemed to me that this had to be the answer. My husband did not encourage me to take any other drug to fight my mood swings and he suggested I just take this off. So, I did it... exactly 5 weeks ago! And I am so much better. My libido is back. I have not felt down. I am enjoying my work. I am loving my children and my husband!!! I am so sorry I did not take it out sooner!
Alright now... the hormones are not crossing to the blood stream... But I had NO periods and of course No ovulation! So why is this so surprising to all of those guys that there may indeed be such side effects!!!
So girls! You are not crazy! Give yourself a chance and take this IUD out!
Good luck.

Was prescribed avelox for bronchitis. Took it for the full ten days. began having diarrhea. It has been 5 weeks since i stopped taking the medication and have continued to have diarrhea, cramping, abdominal pain. The diarrhea is a loose stool. Have had stool tests done and do not have a secondary infection from this.

cannot believe how many stories I have read about mirena and hair loss etc..etc.. etc.. I have experienced many of the side effects that everyone is mentioning.. I actually feel I could live with most of them if it weren't for the hair loss. I have had ( copying from other post.. ridiculous right?)Tired all the time ~ Depression ~ Hungry all the time ~ leg cramps ~ HAIR LOSS TO THE POINT OF BALDING IN SEVERAL AREAS ~ oily skin and bad breakouts ~ Mood swings (huge...yelling fits at my husband and the kids) ~ fluttering in uterus~Sore breasts.. I have medium thick hair that is about 10 inches. I noticed a bald spot in June and now have discovered 4-5 others starting. I just had the iud removed today and my OB pretty much tried to convince me that there is no way that the IUD is causing my issues. I have never had any of these issues before. I got the Mirena on 4/30 of 08 and noticed slowly but surely all of the side effects mentioned. My OB told me that the progesterone could not be causing my issues because it is such a small dosage that it would be comparable to spitting in the ocean as far as the amount that is in my blood stream. She said because I am black and 35 that I may have an autoimmune disorder and that I should stop reading blogs. I told her that all of my research wasn't from a blog and that ALOPECIA is a side effect just not mentioned in my pamphlet that I can find. I understand what she is saying and that she is the one that is the dr. but nobody knows my body better than I do.. I am in it!! I have !never had any problems and have been healthy my entire life. There is no history of autoimmune disease in my family. I am going to my primary care doctor.. to have some blood tests done. I think that the mirena has caused an autoimmune response in my body.. it may not necessarily be the progesterone..although I don't rule it out no matter what she says . the progesterone is synthetic and has an androgynous like activity that is similar to testosterone the main thing that causes male pattern baldness. also Mirena is made out of Silicone.. perhaps those of us that are having hair loss are having it due to our body trying to fight off the foreign invader of the IUD itself. I was going to go and have the Paragard inserted.. because i was thinking it may just be the progesterone.. nope... I read that many women are complaining of ACNE and HAIRLOSS even with that because its made out of copper. So with that being said.. not sure what to do.. may have to go back on Yasmin.. didn't seem to have any problems with that.. I really just don't want to risk putting another hormone in my body.. We all need to get together and look into a class action suit because I am tired of being made to feel crazy by doctors.. sometimes what seems to not be possible is .. especially when there are so many women having the same problem. Feel free to e-mail me re: a class action suit.. if they took depo off Mirena needs to come of too. It seems like it has really screwed a lot of peoples system up.. Hopefully I won't find out I know have a thyroid problem etc.. etc..

cannot believe how many stories I have read about mirena and hair loss etc..etc.. etc.. I have experienced many of the side effects that everyone is mentioning.. I actually feel I could live with most of them if it weren't for the hair loss. I have had ( copying from other post.. ridiculous right?)Tired all the time
~ Depression
~ Hungry all the time
~ leg cramps
~ HAIR LOSS TO THE POINT OF BALDING IN SEVERAL AREAS
~ oily skin and bad breakouts
~ Mood swings (huge...yelling fits at my husband and the kids)
~ fluttering in uterus
~Sore breasts..

I have medium thick hair that is about 10 inches. I noticed a bald spot in June and now have discovered 4-5 others starting. I just had the iud removed today and my OB pretty much tried to convince me that there is no way that the IUD is causing my issues. I have never had any of these issues before. I got the Mirena on 4/30 of 08 and noticed slowly but surely all of the side effects mentioned. My OB told me that the progesterone could not be causing my issues because it is such a small dosage that it would be comparable to spitting in the ocean as far as the amount that is in my blood stream. She said because I am black and 35 that I may have an autoimmune disorder and that I should stop reading blogs. I told her that all of my research wasn't from a blog and that ALOPECIA is a side effect just not mentioned in my pamphlet that I can find. I understand what she is saying and that she is the one that is the doctor, but nobody knows my body better than I do.. I am in it!! I have never had any problems and have been healthy my entire life. There is no history of autoimmune disease in my family. I am going to my primary care doctor.. to have some blood tests done. I think that the mirena has caused an autoimmune response in my body.. it may not necessarily be the progesterone..although I don't rule it out no matter what she says . the progesterone is synthetic and has an androgynous like activity that is similar to testosterone the main thing that causes male pattern baldness. also Mirena is made out of Silicone.. perhaps those of us that are having hair loss are having it due to our body trying to fight off the foreign invader of the IUD itself. I was going to go and have the Paragard inserted.. because i was thinking it may just be the progesterone.. nope... I read that many women are complaining of ACNE and HAIRLOSS even with that because its made out of copper. So with that being said.. not sure what to do.. may have to go back on Yasmin.. didn't seem to have any problems with that.. I really just don't want to risk putting another hormone in my body.. We all need to get together and look into a class action suit because I am tired of being made to feel crazy by doctors.. sometimes what seems to not be possible is .. especially when there are so many women having the same problem. Feel free to e-mail me re: a class action suit.. if they took depo off Mirena needs to come of too. It seems like it has really screwed a lot of peoples system up.. Hopefully I won't find out I know have a thyroid problem etc.. etc.. ******e-mail me with Mirena in the subject line!!

I love Mirena, I am 29 years old with two children, and I had mirena twice, I actually have less cramping than usual with mirena and my periods are lights and regular. I just had it removed and I am looking forward to conceiving again.Also, I am able to conceive right after I have it taken out, I don't have any spotting or pain after removal.

I have had mirena since July of 2006.. I never thought about the things I was feeling could be related until I just read your blogs! I constantly feel pregnant and I am talking all the symptoms!!! Bloating and stomach pains included! Depression, anxiety, sleepiness here lately, severe back pain, numbness.. I am almost 25 and thought some of these problems were growing pains(I know that probably sounds nuts). Please if anyone has a suggestion as far as what I should do here is my e-mail address ******! I need advice and it looks like the doctor's just want to make a buck!!
Thanks,
R.

I've been on NuvaRing for a little over a year. I've read everyone else's side effects. Mine are similar, but I have also noticed that my skin has started getting dark pigments. It started about 6 months ago, mostly on my face, but in other areas of my body as well. I went to the dermatologist this week, apparently it is from the estrogen in birth control. I've been on all sorts of birth control over the past 10 years, I've never had this problem.

I also have low blood sugar but can be controlled by eating properly. However, about the past 8 months right at the beginning of my cycle my body is out of weak. A few times it has been in the middle of the night I'll wake up nausea, weak, in a cold sweat, I'll check my blood sugar and it'll be 42, 43. I know estrogen makes your cells more sensitive to insulin, which causes more sugars to leave the blood stream and your blood sugar to drop.

After my dermatologist appointment and barley being able to walk to my kitchen this morning with out passing out, I can't help but wonder if there is too much estrogen in the NuvaRing. I do know that I wont be using the ring again SPECIALLY after reading all the other similar side effects I share with other women.

I was diagnosed with Factor V Leiden after experiencing bilateral PE's in February 2004. Since then, I have gained A LOT of weight. Not that I needed to but dang. I am at my highest ever & nothing I do will make it go down. I am almost 80 pounds heavier than I was in 2004. Something is not right. I suffer from depression (have for more than 15 years). My medication doesn't seem to have the same effect. My joints are killing me so it's hard to exercise.

A side note, shortly after being hospitalized for the PE's for a week, I noticed my hair thinning. Doctor told me it was because of the "shock" to my system due to having the PE's.

I will have to be on Warfarin for the rest of my life. I turn 45 in November. Ugh.

Has anybody had the same problem with weight gain? Is there anything to do about it? I feel I am at the end of my rope & slowing losing my grip.

I took a 10mg tablet every day for thirty days, making no connection between the dizziness and unsteadiness I was experiencing (all day) and the medication. When I finally figured it out three days ago, I stopped. I continue to have some dizziness. Does it take time to get this drug out of your blood stream? If yes, how long?

Thanks for any feedback!

Hi everyone,
I got the Mirena put in a little over 3 weeks ago and it's been nothing but trouble. I've had consistent spotting, my skin is awful---I'm getting pimples!--, I feel bloated and, worst of all, my moods are awful. I even had a fleeting thought today as I was driving about driving my car over a cliff. I would never do it of course, but the thought scared me. I'm already on a low dose of anti-depressant(Celexa) and worry that Mirena is making it worse. The weight-gain issue really worries me as well. I would like to get it removed, but worry that my doctor will tell me to give it more time. I really don't want to wait---I just want it out. I'm really kicking myself for taking my doctor's word and not researching it more before getting it.

Hi everyone. So I got the Mirena two weeks ago. I did my research on the internet before getting this put in. I did see all the bad posts and I went in and talked to my doctor about it. She told me the hormone level that reaches your blood stream is so small that it cant have effects on you. She said she just wondered if the people posting on here just had other things going on or what not. She has also had the Mirena for six years and loves it.

On the other hand when I got it in I was on like day five of my period. It did pinch a little but wasn't overly painful. I did get cramps on the way home and I did take two ibuprofen before I went in. I would get sharp pains every once in a while too. Enough to where you stopped and said " ouch. " But I wasn't bleeding until like later on that day. I bled for a week and a half. I was bleeding to where I would soak two liners per day. It seemed like a lot of blood. Plus I felt like I was on my period the whole time.

My other side effect that I just cant handle at the moment are: my hair falling out. Im talking a ton of hair. I cant believe how much hair! ****** This is a picture right after I took a shower last night. That is from only one shower. Its falling out all the time. Its been doing it for about a week. But its every where!!

Since I got this in I have been tired. I notice a huge change with that. I just have been so sleepy. I was sleeping four hours at the most with my baby and I was doing so good not looking and being tired. Then he started sleeping 6 hours through the night.... and that made me have so much more sleep. I feel so much worse. I hate it!

Another effect: About 4 days after getting this in I just was mad. I told my husband I was just so mad that I couldn't stand it. Nothing happened to me.... but I was so pissed. I can tell I have changed. My moods have changed. Im being way more honest than I normally am. Little tiny things make me mad super fast and Im being mean. My husband even approached me last weekend and said that I have said a lot of mean things over the last two weeks. I can notice that Im different but didnt realize I was being mean. He can notice a huge change.

Just One More Effect: Sex drive is gone. I was talking to my husband the weekend before about my drive being very high... then BAM I got this thing in and its gone! The sex drive being gone, being mean, and careless is enough to ruin a marriage to me.

I just called to ask if I can get this thing out. I just cant do this anymore. I have to wait four more weeks before I can get it out. Plus I have to pay 150 bucks on top of the 385 to get it put in! I have read that some people tolerate this very well... and others just don't. I rarely have found someone that has been in the middle. Its one way or the other. Dont you notice that?!

Feel free to email me if you want to talk more. I honestly don't mind.
******

I had the Mirena IUD inserted on April 1st 2009 for treament of endometriosis, nearly a month and a half ago, and I am absolutely miserable. I thought I was completely losing my mind, only to find out from finding this site and others that I am not alone. The worst of my side effects are the EXTREME anxiety and now depression. I have had a history of both from time to time in my life but nothing like what I have experienced since the Mirena. Also, my hair is falling out like crazy, my face is breaking out everywhere (never before), and worst of all I've gained 7 lbs since I got this thing put in. I felt ravenously hungry almost immediately, I never craved sugar and food like this in my entire life, not even when I was pregnant. I too was fooled by my OB in that I would experience little to no side effects as I cannot take BC due to the effect of hormones. She said that the Mirena is a localized synthetic hormone within the Uterus and would not at all enter my blood stream. ARE YOU KIDDING ME! I'm a basket case, my 3 yr old told me that she misses her mommy, that I sleep too much. That is what finally brought me to researching my symptoms and the Mirena it was the only thing new that could be related and so it was. To summarize my side effects in order from worse to much worse: weight gain, hair loss, cramping, bleeding constantly, libido decrease, extreme tiredness, severe mood swings, depression, blurred vision, sever migraines (no previous history) and the very worst of all the ANXIETY. I'm generally a very happy positive person and lately I can't even stand myself. I often times ask myself when will I ever feel normal again. My OB refused to take this thing out after I went in for an office visit a week and a half after insertion. She said let's not "throw the baby out with the bath water" and give it till 3 months before we can say for sure that I'm experiencing this from the Mirena. Whatever, it's been 6 weeks and getting worse. Finally today I took some blood tests to prove that I'm not diabetic, that I don't have a thyroid problem and that my CBC is fine. Then finally she will consider removing it, well newsflash lady, I'm going to demand it be removed immediately. If not, I'll take it out myself.

I have been on the nuvaring for almost 3 years.
The first year was great! I hated taking a pill everyday, so at first i opted for the Depo, which was great for a year, but i really didn't trust it and not having periods made me uneasy.

The nuvaring seemed like a blessing! I had no trouble for the first year and a half. I recommended it to all my friends. I didn't have any side effects, and I loved the convenience!

However, now i am experiencing some serious side effects, and thanks to this website I realize I am not the only one. I have two concerns that i link to the BC: depression and no sex drive. Some days I just want to lay in bed, and sleep. I do not want to leave the house, or see anyone. I have told my BF (of 3 years) that i just need some "me time". I am fatigued and show many symptoms of depression.
I am only 24 years old, and i have NO sex drive. It has taken a tole on the relationship with my boyfriend. Many nights i try to get in bed before him, so i can appear asleep. There have been so many nights where i would tell him "i'm sick", "i have cramps"... sooo many excuses. When we do have sex it is usually forced, and i do it because i haven't in a week!

This past year I have also had digestive problems, which seemed to have appeared out of no where. Im not sure if I blame them on the nuvaring, but I've noticed a few other people have mentioned it as well.

I Just started NR a week ago on the 1st day of my period, I have already gained 5lbs, have constant cramping (not severe but noticeable) my boobs hurt, and I have constant lethargy. Went for a walk today with my BF and could hardly stand it. Just wanted to lie down...

We then got in a huge fight because I was freaking out about every little thing. I was crying and screaming at him, and we almost broke up. I am normally not like this. So I just took it out. Im sure my OBGYN would say to give my body a chance to adjust but I can't take another day! So Im probably messing up my Menstrual cycle but I'll take that chance especially after reading all the experiences of you other poor ladies.

I had tried to get an IUD after many of my friends recommended it. I chose Mirena although I am usually anti hormone, but my doctor says that the hormones in Mirena do not go into your blood stream but stay locally in your uterus. My friends who have Mirena love it, less periods, no cramping, no side effects. My one friend who had the non hormone one had terrible heavy bleeding, severe cramps etc. So after TWO TERRIBLY painful attempts at inserting the Mirena, ( I had to come back a second time on Valium, Vicodin, and a pill to dilate my cervix) I was told I am not a candidate because my uterus is TOO SMALL! The U.S only has two IUD's. Europe, Canada, even Mexico has smaller sizes available.

Sooooooo, long story short, I either have to fly to one of these countries, (England is farthest but will do it for free) or find another option. My friend just told me about a promising sounding option called Lea's shield- ****** which is like an updated, easy to use, strangely shaped diaphragm. Its available from Planned Parenthood, and due to its unique design is one size fits all so you don't have to get it fitted and can order it online. Hope this helps. Thanks everyone for your frank sharing, hope I have helped someone too!

My 17 year old son was diagnosed with MRSA after getting an injury on his knee from playing basketball.After the first does he had a loss of appetite, fatigue, nauseous and severe headache. By the third day he got a fever, chills, neck stiffness and a feeling of doom. We went to the ER because his blood had not been cultured and we were afraid of sepsis in the blood. The ER doctor said it was most likely viral and sent him home. The next night he had a fever of 103, sore throat, trouble swallowing, sun burnt look, swollen eyes and cracked swollen lips.The next day we went to the urgent care and they tested him for mono, strep and the flu...(all negative). He felt awful and was so tired and feverish. The next morning he woke up with a severe rash and itching all over his body and his skin looked like it was scalded. His blood culture came back negative for bacteria and his wound has healed. I have taken him off of this drug Bactrim. This is his first day. His rash is better and his fever was down for a little while. It is 101 tonight and he just feel so tired and achy. I know it will take time for this to get out of his system. Meanwhile he is missing school and is getting depressed because he feels like he will never get better. If someone told me that fever and chills were a side effect from this drug I would not have been so worried that he could die of a blood infection. Ask lots of questions or google this site before taking a new drug.

This is an update. I have experienced "some" problems trying to get Doctors to believe that my muscle problems are Lipitor related. I was sent this by a nurse. It is not the full page.

"2005 Mosby's Nursing Drug Reference (pg.155)

atorvastatin
Lipitor

Uses: As an adjunct in primary hypercholesterolemia

Interactiions:
*Risk of possible rhabdomyolysis; azole antifungaals,
cycloSPORINE, erythromycin, niacin, gemfibrozil, clofibrate".

Guess what? I have been using an azole antifungal intermittently for the entire time I was on Lipitor. It is not a medication I "take". It is used topically for a fungal nail which refuses to clear up. You may have been using it for athletes foot.
Now one pharmacist says a topical application cannot cause this interaction and another pharmacist says it is almost certain that the azole antifungal gets into the blood stream and will interact with the Lipitor. I have to laugh.
Next week I start Physical Therapy on my left elbow.

I decided to read about side effects of Welchol. I just got back from the doctor's and she gave me some free samples of this. In the past, I had been on Lipitor and Zetia but had terrible back, hip and leg pain. I went off of those and I was fine. Started on Crestor- same pain in back, hips and legs. Now my doctor says that Welchol is not absorbed in the blood stream so there should be no side effects- only possible heartburn. After reading all of these side effects that everyone is having on Welchol, I am not going to even try it.
I am going to record everything I eat and try to control my cholesterol with a good ,healthy diet. I also have heard that Red Yeast Rice- available at GNC or Health food stores can lower your cholesterol. I might try that but for now I'm doing the healthy diet and exercise.

I am 33 years old and have tried numerous forms of birth control. I have been taking yaz for 9 months and just decided to stop taking it after my last cycle. I have tried birth control pills before, but I really think the side effects were worse with this pill. I had absolutely NO sex drive and felt very apathetic and listliss all the time. I described to my husband that I felt "empty" inside. I was mildly depressed and experienced a great amount of anxiety. The only good thing was the light periods and I had great skin! I have since decided to try the nuvaring, but I am having some of the same problems with that one too. My doctor suggested it since it doesn't have to go through the liver like pills do, but it still sends these hormones into your blood stream. If you have problems with hormonal birth control methods, I highly suggest trying the copper iud or other non hormonal forms of control. The only bad thing about the copper iud was the heavy periods. I have also tried the mirena iud and didn't seem to experience as severe of emotional symptoms with that one, since it only contains progesterone. But for the first several months after you have it inserted you have a constant light bleeding. Plus it caused acne problems, which I never had to worry about before. But I would take those side effects over the emotional roller coaster I was on when taking the pill.

Well.... I wrote earlier about the 13th of October...since then I have had the Mirena REMOVED and I feel a VERY BIG DIFFERENCE! It was nothing to having it put in. Very fast to get out and was ok! Around day three I flooded, I guess it was my body's way of trying to get back to normal. I feel better. Not a 100% but better. The doctor said it would take a month till the hormones were out of my body WHICH made me mad because when I had it put in they were so confident with Mirena because the hormones stayed in one spot and didn't go throughout your body. NOW they tell me it will take time to get out of my blood stream!!!!!????? Glad I did what I did and hope to start enjoying life like I used too! WOULD NOT RECOMMEND TO ANYONE!!!!!!! May God bless you all!

I cant thank you all enough THANK YOU. I am 45, have 4 older children and have had the mirena for twelve months. the nurse who encouraged me to have the mirena and fitted it told me to ignore the booklet , that side effects were very rare as the drugs don't go into your blood stream. I cant believe i fell for that, i mean it doesn't make sense. since having it in i haven't stopped bleeding bits,im covered in a rash that the doc says is a viral infection, i have incredible mood swings, joint pains, cramps, depression which i have been taking st johns wort for, shakes,headaches,dermatitis on my hands, forgetfulness, crying, numb hands and feet,weak ankles that tend to just go all of a sudden which makes me feel really stupid. Blurry vision and feeling a inner hotness behind my eyes,some mornings i feel like ive got a hangover even though i don't drink. As for sex forget it i mean why would my hubby want me!! and its the last thing i feel like. I cant believe hes put up with me and my nasty moods. Ive been married for 24 years. I never thought that all these systems were due to the mirena, until i looked it up and stumbled onto this site, i must of read all of the posts, and look twice a day to see if there are any new ones.I have had to wait 2 weeks to get an appointment to have it taken out, but thank god i had it taken out this morning. I couldn't believe how easy, quick and painless it was, maybe i was lucky that the strings were easily found. I feel sooo relieved to finally have it out and only feel slightly crampy. I cant wait to get back to normal. This is the fist time i have ever posted anything on the internet so please forgive me if my typing isnt up tp scratch, its taken half an hour to write this. I feel i have a lot to make up for with my family and my very lovely hubby and hope that these systems go quickly. I will let you know and please keep up the posts i need the encouragement, and im sure others do too.!!

I had the mirena put in in june after my third child. I did feel a bit dizzy when it was first put in but did not cramp at all. I was still spoting then from giving birth, so it just continued for about 3 more weeks the stopped altogether. I have not had a period since, woooooooohooooooooooo!!!!!!!! I don't feel bad about that at all. I did have a day when I woke up cramping and thought I was going to start but never did. My doctors nurse told me everything I needed to know about the mirena long before i had it put in. I actually made the appointment to discuss it with her. Everyone should have been smart enough to ask questions before it was done, not the day it is. You cant think straight when someone is getting ready to put a device in you. I have to say I love my mirena and would not trade it for a pill, a shot, or any other birth control method. Ladies know your gyn very well before trusting them. I think most of you just think it is your doctors fault. It is not it is yours for not researching it more. And come on what women is not moody a day in her life, not many. How many headaches did you get before the mirena? How were your sinuses before mirena? Probably the same. Some womens health simply changes after having a baby. I also advise against you removing these mirenas yourselves. It is not smart, you could get a bad infection from not being in a sterile environment.

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