Apropos of recent FDA proceedings, I feel a rant is in order.

Although the article can be accessed in the Nouvelles section of this website, I will disclose it again below for easy-reference purposes:

6/22/07: For the first time, manufacturers of vitamins, herbal pills and other dietary supplements will have to test all of their products’ ingredients. The Food and Drug Administration said Friday it is phasing in a new rule that is designed to address concerns that existing regulations allowed supplements onto the market that were contaminated or didn’t contain ingredients claimed on the label.

Obviously, I must have been too ignorant and trusting to believe that the American federal agency in the Department of Health and Human Services was sensible enough to test the products before they are shelved for public use. According to a survey back in 2001, 59% of the population take dietary supplements, which I’m sure has only increased over the past 6 years as people’s concerns for potential risks decreased. Sure, I suppose some people may regard vitamins as inducing a placebo effect, but that doesn’t exculpate the government’s lackadaisical demeanor. Who knows what parsimonious yet greedy companies could be adding into these pills? There have been a plethora of instances where the FDA has not been careful in its regulation of pharmaceutical products whereby people taking such medications began to drop dead in the middle of the streets. If you’re interested in such details, examples are presented as follows (Or you can simply look at the pretty pictures of molecules):

Case 1: Thalidomide

Thalidomide is a hypnotic and anti-nausea drug that was given to many patients, including pregnant women, in the late 1950’s to early 1960’s.

There is one stereocenter in thalidomide. In the rotating animated views of the two thalidomide enantiomers, notice how subtle the differences are in structure between the enantiomers.

Thalidomides

The drug was given as a racemic mixture. Unknown at the time, the (S)-(-) enantiomer (but not the (R)-(+) enantiomer, although this is still controversial) is transformed in patients to two compounds that are embryotoxic and teratogenic. Regardless of whether one or both enantiomers are involved, taking thalidomide by pregnant women caused severe birth defects including abnormal (missing) limbs, as well as ear, eye, heart and gastrointestinal problems in 10,000 babies born. Interestingly, the two thalidomide enantiomers undergo interconversion in animals, so just giving the (R)-(+) isomer would metamorphose into the (S)-(-) enantiomer.

Case 2: Ecstasy

Serotonin, also known as 5-HT (5-hydroxytryptamine), is a neurotransmitter found at the synapses of certain neurons, i.e. it is released by the tip of one stimulated neuron and recognized by a specific serotonin neurotransmitter receptor on an adjacent neuron, causing it to fire. In this way, the nerve impulse is propagated throughout the nervous system. Note: After a nerve fires at a synapse, the neurotransmitter must be taken back up by the original neuron and transported back into a synaptic vesicle so that it is ready to fire again, called “re-uptake.”

Neorons that release different neurotransmitters are found in different parts of the nervous system. Serotonin is found in parts of the brain associated with memory, emotions, and feelings. It is also important for body temperature regulation among other things.

MDMA or ecstasy causes the rapid release of serotonin from neurons, in essence, causing many to fire at once due to the similarities in molecular shape. This can result in an intense feeling of well-being and is found to be pleasurable by some. Recent research reveals that the serotonin is released because the MDMA interacts with the proteins responsible for transporting serotonin around the neuron as it gets ready to fire.

Ecstasy and Serotonin

Every generation, young people have believed they have found the first truly safe recreational drug. First it was LSD in the 60’s, and then it was cocaine. Both have been shown to be harmful in numerous ways. Later, ecstasy had been touted as being safe and were, at one period, sold in stores. This is truly terrifying as ecstasy has recently been found to be extremely dangerous, causing what appears to be permanent brain damage with even a single use. No, this is not overstated propaganda to stop use of a drug. It is a scientific warning that ecstasy users are harming themselves, perhaps permanently.

Through mechanisms that are only now being understood, it turns out that the serotonin containing neurons die in response to exposure to ecstasy. They undergo programmed cell death — apoptosis. The first result of this is that users have to take more ecstasy to get the same effect, causing even more damage with subsequent use. Clinical studies have also established that this is associated with loss of memory function. It is a very long lasting effect, and it is feared to be permanent. A significant number of animals in studies die from hyperthermia when given even one dose of ecstasy, i.e. they lose control of their body temperature and die.

Case 3: Seldane 

Histamine is used as a signal in the body. Duing an allergic response, e.g. in your nose, if a pollen grain is recognized by specific receptors, that triggers release of histamine. (In hayfever, pollen is mistaken for a parasite by allergic individuals.) The histamine, in turn, causes the release of mucous to try and eliminate the invading parasite/pollen.

Seldane (terfendine) was designed to have the same pharmacophore as benadryl and introduced as a next generation antihistamine that did not cause drowsiness. Unfortunately, a few people died of heart failure when they took seldane. It was later determined that the seldane structure (with X = methyl on the uppermost structure) was not actually the antihistamine, instead, seldane was toxic to the heart.

Seldane, Benadryl, and Histamine

In normal people, seldane is circulated through the liver where it is rapidly converted to allegra (fexofenadine), with X = CO2H. The enzyme that carries out this reaction is called P450 and this is the normal mechanism by which molecules are removed from the bloodstream: oxidation. Normally, this conversion happens so fast that there are no ill effects from cardiotoxicity from seldane, and the allegra that is produced acts as an effective antihistamine. However, some patients were taking medications that blocked the action of P450, so these patients could not convert seldane to allegra. They had high levels of seldane in their bloodstream and they died from heart failure. Some common drugs such as anti-fungals and penicillins block P450. Apparently, during initial testing, seldane had never been tested on patients taking these medications.

~Les la fin~

(Why, yes, organic chemistry lecture was extremely useful for me.) If you’ve managed to comprehend all that — Splendid!

In the situations aforementioned, the FDA did implement regulations eventually; backtracking, however, does not resuscitate victims that should not have died in the first place due to the FDA’s imprudent disregard. The point here being the old adage “Once burned, twice shy” doesn’t seem to concern the FDA. Albeit they are enforcing tests now, they should have done so decades before. I’m disgusted with constantly being surrounded by incompetent fools we call “the government.”

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