Chantix Can Lead To Mania, Depression, Suicidal Thoughts…So It Gets The Black Box

In a move that was not unexpected, the FDA has given Chantix, a popular smoking cessation drug, a black box warning; the strongest warning level a drug can get. This black box warning concerns adverse neuropsychiatric symptoms brought on by the use of varenicline (Chantix), most commonly in those with a previous psychiatric disorder. Surprisingly the anti-depressant Welbutrin (commonly used as a smoking cessation drug) also received the mandate for a black box warning. This was a little more surprising but nonetheless I think a good move to clue those in who don’t know this possible interaction.

Back in my younger days when I knew much less about drugs and their side effects I had a friend (we’ll call him Charles for anonymity’s sake) who suffered through a manic episode brought on by Chantix use. He was a 25 year old male with bipolar disorder II (BP) who was on the mood stabilizer Seroquel and a minimal dose of Zoloft. As with most people diagnosed with a personality disorder he was an avid smoker and upon hearing about the success people were having with Chantix (it really is effective to help people stop smoking) decided to ask his psychiatrist if using it was an option.

There were already warnings against prescribing Chantix to those with previous psychiatric problems, specifically those with suicidal thoughts or being previously diagnosed with BP or schizophrenia. Although Charles did bring his concerns to the table (he is constantly hypomanic and was afraid of the induced mania he had read about) the decision was to begin the treatment. After one week he suffered a tremendous manic episode and managed to piss off everyone within a 20ft radius as well as mangle some good personal relationships. Luckily he did not have to be hospitalized, but

 

Using long-range missiles to attack the kidneys, E. coli O157: H7’s offensive strategy

Since the FDA recalled Nestle’s cookie dough products E. coli O157:H7 is again in the news.  Today I thought I’d cover a topic that I am pretty familiar with, exactly how this strain of E. coli can be so damaging to the body.

E. coli O157:H7 is  a nasty little bacteria that I worked with quite a bit in my microbiology days. The letter/number combination after E. coli just indicate its strain.  Just as all dogs are the same species but can be classified into breeds, bacteria have this distinction as well.

This particular strain of E. coli produces a protein (Shigella-like toxin) that causes damage and death to cells in our body and has been in the news a lot as it has broken out in the food chain from several different locations. Usually patients will have diarrhea and recover just fine, but in some patient the infection can lead to a condition called Hemolytic Uremic Syndrome (HUS), which in severe cases can require long-term dialysis or a kidney transplant. So exactly what is going on when you get infected with this strain of E. coli and how is it that a bacteria in the gut can cause kidney damage?

After you ingest the bacteria it begins a search for a suitable home along the lining of the intestine.  By employing a protein called intimin to bind the inestinal mucosa the bacteria can resist attempts of the host to expel it.  As the little bugger becomes attached to the intestinal cells it disrupts the brush border which leads to the most common symptom, diarrhea.

After the colony has settled in, the production of Shigell-like toxin 2 (Stx-2) begins and the real damage can start.  Stx-2 migrates across the intestinal cells and is released into the blood stream.  Here it binds with polymorphonuclear leukocytes (PMNs) and is carried around in the blood stream on these cells.  The Stx-2 receptor on PMNs isn’t very strong though and as they are pushed passed the glomerulus in the kidneys a new player emerges.

The Stx-2 receptor on glomerular endothelial cells (Gb3) has a much higher affinity (100-fold) for the Stx-2 protein than do the receptors on the PMNs, so as the PMNs wizz past these Gb3 containing cells the Stx-2 changes dance partners and attaches to the much stronger receptor in the kidney cells.  The E. coli hanging out in your intestines have sent a long-range missile with an advanced targeting system directly to your kidneys endothelial cells.

Once docked onto the cell membrane Stx-2 is endocytosed and moves towards its target inside the cell, the ribosome.  By attaching to the 28S rRNA compnoent it can affectively alter and shut down protein production within the cell.  There are a few ways that this can cause damage to the endothelial cells; one way is by shutting down protein production enough that the cell cannot maintain its metabolism and eventually dies, or certain mediators which are vasoactive can become disregulated (such as Nitric Oxide) which can cause microvascular damage.

As the regulation of these mediators is thrown off a cascade of events starts, including abnormal leukocyte-endothelial adhesion and misregulated production of the coagulation cascade proteins.  This all leads to complications in the microvasculature of both the gastrointestinal and renal system.

It is fascinating that a bacteria who reside in the gut (which is technically outside of the body) can have some wide reaching effects without actually entering the body proper.  This is a great example of the extremely complicated processes that can occur during infections in the body.

 

FDA recalls Nestle Cookie Dough due to E. coli OH 157:H7 contamination

Uh-oh, another outbreak of E. coli so avoid the Cookie Dough for a little bit.  The FDA is reporting 66 reported cases in 28 different states.

And don’t think that thourougly cooking the product will get rid of it because most likely you’ll pick it up on your hands and get infected.

Hopefully this will stay under 100 cases or so, and maybe make us start reconsidering mass distribution systems for our food?

 

Homeopathy Works…when its not really homeopathy (The FDA and how pseudoscience has made a mockery of safety guidelines)

Yesterday the FDA advised the public not use use three Zicam products because they have been related to nerve damage and loss of smell.

• Zicam Cold Remedy Nasal Gel
• Zicam Cold Remedy Gel Swabs
• Zicam Cold Remedy Swabs, Kids Size

Debrorah Autor, Director of the FDA’s Office of Compliance, laid out a pretty firm statement today when she said “consumers should stop using these products immediately and should discard or return them.”  Here’s a copy of the FDA’s letter to Matrixx Initiatives, the company who markets Zicam and other homeopathic “drugs”.

Zicam was an over-the-counter (OTC) product that had applied to the FDA as a homeopathic drug which means that it didn’t have to go through FDA approval to get put on the shelves.  Here’s the FDA’s Compliance Policy Guide (CPG) concerning homeopathy, I recommend you do not read it.  Well maybe if you’re a policy buff you would get into this but it really makes my head spin.

Homeopathy is truly a pseudo-science.  Many physicians and senior researchers attack the practice with more vitriol than a Hitler speech and even in my young scientific career I can easily see how the goal of homeopathy is to co-opt scientific ideals into a completely mystic form of treatment.  You can go all over the internet and find out why homeopathy is ridiculous but I feel the need to torture myself and look into the policy of homeopathy and how it relates to the FDA, specifically OTC products.