The Supreme Court found in favor of the nutcase haters from the Westboro Baptist Church and its fundamentalist (and fundamentally unhinged) founder, Fred Phelps.  This is a difficult post to write, but we that love the First Amendment must honor this proper decision.

These folks are, in my opinion, fundamentally hatred filled and also love the spotlight.  But, as much as it grieves me, they have their right to spew their toxic bile.

Well, only one installment in this subseries after this one, but it will be special.  Tonight we will explore this class of drugs, what they do, and how they work.

This class of drugs also includes LSD, but that material is so culturally important that it will have a post of its own.  Thinking about it, it may deserve two posts, so there may be two installment after this one.  We will have to see.

BBC America just ran the new installment of Doctor Who.  It has surpassed my expectations, let alone hopes.  David Tennent is so well suited to the role of The Doctor (and to think that I did not like him very much at first, since Eccleston was so good) that one actually believes that he believes that he is The Doctor.

For those of you not hip to this series, I can not even begin to begin to explain.  It started as a children’s television program on BBC in 1963, starring William Hartnell as a very aged Doctor, traveling with his first companion.  She was, in the story, his granddaughter, and this has never been resolved in the years of the series.

I am not a fan of Governor Sanford.  His politics are pretty much antithetic to me, and to most of us in this community.  I also think that he would be a horrible President, but that is my own thought.

The developments today are extremely sad on many levels.  We have seen a person with a career completely destroyed, although of his own making.  But I can not condemn a man for love.

Sorry that I did not post last night.  I have been tending to more important family things.  I promise that I will post the next installment this coming Sunday.  I am getting a very intrusive signal from PC Tools Antivirus.  It will not let me go.  I suggest that you not go to that site.

Warmest regards,

Doc

Dr. Whitehead, Dean of the English Department in the Colleges of Arts and Sciences at the University of Arkansas swung a pretty big stick in his heyday there.  He was able to get important persons of letters to come and give free (well, at least to the public) readings of their material.  Notable amongst them were Ken Kesey and Allen Ginsberg.  Mrs. Translator and I went to both of those.

The fliers had been distributed around town for a week or two.  They were pretty much generic, essentially saying “Famous poet to give reading at the U of A on such and such date at 8:00 PM”.  Well, Mrs. Translator and I decided to go, as we try to be cultured individuals and I was very familiar with Allen from reading.

The psychedelic amphetamines (and I include mescaline here, although it is a methyl group away from being a true amphetamine) are many and widely encountered in what are almost always now illicit settings.  They (except for mescaline) are synthetic drugs, not found in nature.

These drugs are “true” psychedelics as opposed to the oddballs described here last week.  Many of the oddballs are dissociatives, and the true psychedelics work by a completely different mechanism.

THURSDAY NIGHT IS HEALTH CARE CHANGE NIGHT, a weekly Health Care Series (cross-posted at ePluribus Media. I have been invited to contribute this installment. I originally was going to post about high fructose corn sweetener, but between the time of the invitation and now FDA came out with a new warning about acetaminophen. Acetaminophen is one of the most widely used pain and fever relievers in the United States. Much of the widespread use has to do with the fact that it causes less stomach upset and GI bleeding than aspirin or ibuprofen. It is not linked to Reye Syndrome as is aspirin, making it a good choice for children and teens with flu. Another very large reason for widespread use is heavy marketing.

However, acetaminophen has a very dark side.  According to CDC, right at half of all cases of acute liver failure (ALF) in the United States is directly caused by acetaminophen.  I will not be as geeky in this post as I normally am in my regular Sunday evening series, Pique the Geek, where we try to delve fairly deeply into the science of various topics.  However, some scientific and historical background is necessary to understand the process of liver toxicity produced by this material.In 1887 a drug called phenacetin was first marketed for fever and pain. It is actually made from acetaminophen and is metabolized in the body to it.  It was withdrawn from the United States market in 1983 due to concerns over carcinogenicity.  However, acetaminophen had already replaced it in a large share of the market.  The reason that phenacetin was used for so long had to do with sloppy research in the early 20th century.

Acetaminophen was first introduced in 1953 by Winthrop, but in 1955 McNeil began marketing Tylenol Children’s Elixir, and the Tylenol brand is still probably the most widely recognized brand name in the United States.  Now it outsells aspirin, and I believe this is a dangerous situation.

All medications are eliminated from the body, mostly as metabolites of the parent drug.  The major site of metabolism is the great chemical factory of the body, the liver.  There are three major pathways, two of them harmless.  The first one is addition of glucuronic acid (a sugar derivative) in the liver, producing a metabolite that is nontoxic and is eliminated by the kidneys.  It is thought that, in MOST people, about 40% of the drug is eliminated that way.

A second pathway, also harmless, is addition of sulfate in the liver, forming a water soluble metabolite that is carried away by the liver.  In MOST people this accounts for around 20% to 40% of the total load.

The third pathway, accounting for about 15% of drug clearance, involves the cytochrome P450 set of liver enzymes (the ones that are increased by drinking alcohol).  A toxic intermediate called NAPQI is formed, and that is cleared by combination with the natural antioxidant glutathione and eliminated by the kidneys.  Here is where the problem arises.

NAPQI is highly reactive and combines with the lipids in liver cell membranes, killing the cells.  When combined with gluatathione, it becomes nontoxic, but glutathione is essential for liver protection from the thousands of other reactive oxidizing agents that it processes constantly.  Reduction of glutathione thus also damages the liver, since it is not available to protect the liver from other bad actors.

In most people, the recommended dose of acetaminophen does not cause any outward sign of trouble.  However, there are behaviors that increase sensitivity towards toxicity.  As mentioned before, moderate to heavy alcohol intake induces the very enzyme that is responsible for the “bad” pathway, so drinkers are naturally more susceptible.  Besides, alcohol in large doses is a liver toxin in its own right, so that is a double whammy.

Another risk factor is fasting and low protein diets.  Since glutathione is derived from protein, restriction of protein intake reduces its availability, thus decreasing its protective effect on the liver.

A third risk factor may be caffeine.  Some fairly recent work is consistent with the hypothesis that caffeine induces a liver enzyme that also causes the production NAPQI, presumably Cytochrome P450.  Now this is problematic for a couple of reasons.  First, many folks drink a lot of coffee.  Second, caffeine is often added to painkiller medications to increase their potency.  Some of these combinations include acetaminophen.

There are also other drugs that induce these enzymes, particularly anticonvulsants.  The barbiturates are potent inducers, and a few combination products contain a barbiturate, a narcotic, and acetaminophen.

In most normal people with no other risk factors, four grams of acetaminophen will show up on liver function tests after a few days for about a third of the population.  Well, four grams a day is the maximum recommended dose for Tylenol Extra Strength products according to the Tylenol website.  So, recommended doses affect liver function in one third of people with no other risk factors.  This is not good.

Six grams a day for two days can cause significant liver function disturbances in normal (that is, no other risk factor) individuals.  Now, I know a lot of folks who have the attitude, “if two tablets will help, three will help more.”  Here is how we start getting into trouble.