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Monday, November 30, 2009

Majickal Elixirs

I don't have to go much farther than my Google Search History to find inspiration for something to document - I read Wikipedia like regular people read the Sports section. While most of my recent searches are stupid and pedestrian ("How long until doxycycline works?", I wondered at 12:42pm), there are a few good ones in here. Today's topic: 'elixir terpin hydrate', a medicine of years past.

Terpin hydrate is derived by high-temperature acid treatment of "oil of turpentine", which is composed mostly of alpha- and beta-pinene. These compounds are termed "terpenes", but they are more often known in science as "isoprenoids"; they share a common biosynthetic pathway in plants and some insects. Traditional biochemistry obsesses over lipids, carbohydrates, proteins, and amino acids... this is a very animal-centric perspective, and I think that isoprenoids are only excluded because they don't have a connection with the publicly well-known Big Three in nutrition (fat, carb, protein). They are the major component in all essential oils and most natural resins.

A medicine called "Elixer Terpin Hydrate" was available from the beginning of this century right up until the early 90's, and was a popular expectorant used to treat bronchitis. My parents remember the stuff fondly, but the FDA pulled it off the market because there was no indication that the active ingredient actually did anything. The original version was loaded with codeine and contained more alcohol than vodka... so that could explain why it was so popular.

See "Patent Medicine" for a fascinating look at the not-so-distant past of the pharmaceutical industry.

Sunday, November 29, 2009

A Tale of Two Antibiotics, Part Two

Doxycycline, often marked as vibramycin, is a semisynthetic tetracycline derivative that Pfizer has been pushing since 1967. It works by a mechanism similar to that of the macrolides such as azithromycin, but it binds to a different portion of the ribosome and inhibits a different step in protein synthesis (but with the same result). Because it has been around much longer than azithromycin and it does not have features that would prevent the development of resistance (taken twice a day for ten days; half life = 18 hours), it is no longer effective on some types of bacteria. However, it is still very potent against a broad spectrum of infections, including anthrax, black plague, Legionnaires' disease, syphilis, lime disease, and malaria. Tetracyclines must be taken a minimum of one hour before or two hours after eating to be well-absorbed, are inactivated by high blood levels of calcium, magnesium, or iron, and can cause severe photosensitivity, birth defects, and hepatotoxicity.

But it works!

And hey, that's what you get for getting sick in the first place.

Saturday, November 28, 2009

A Tale of Two Antibiotics, Part One

Ah, modern medicine...

Two antibiotics that I've had some recent experience with: the pharmacokinetically-curious macrolide, azithromycin, and the venerable (but still rather potent) tetracycline, doxycycline.

Azithromycin, commonly called 'Zithromax' or 'Z-Pak', is currently very popular as a broad-spectrum antibiotic that kills both Gram-positive (hard cell wall) and Gram-negative (outer membrane) bacteria. It does this by binding to the bacterial ribosome and interfering with the elongation step in protein synthesis, leading to cell degradation and death. Because bacterial and human ribosomes have slightly different structures, only bacterial cells are affected. Azithromycin is 'semisynthetic'; it is produced commercially by chemically-modifying erythromycin, another antibiotic that is produced by one species of actinomycete bacteria.

The odd thing about azithromycin: it is usually given as a single (rather gigantic) one-gram dose in powder form, but it remains effective for up to a week(!) afterwords. Like all macrolide antibiotics and many other drugs, azithromycin is involved in enterohepatic circulation: it is absorbed very readily in the small intestine and transported directly to the liver via the hepatic portal vein, where it is excreted in bile back into the duodenum (first section of the small intestine). For the chemical engineers out there, the hepatic portal-gall bladder-bile duct loop is just a recycle stream, and because it's running at a very high recycle ratio and the rate of azithromycin breakdown in the body is so low, it's easy to see how azithromycin can remain at therapeutic levels in the body for a long time on a single dose. Another form of recycle circulation further improves its half-life and effectiveness: azithromycin is preferentially taken up by white blood cells, which actively transport it to the site of infection and release it while consuming bacteria. Ion trapping and azithromycin's high lipid solubility keep its concentration at the infected site many times higher than in the blood plasma. Combined with its long half-life (68 hours) in the body and the fact that the patient doesn't have the option to discontinue the drug when they start feeling better, this helps to prevent the infecting bacteria from developing antibiotic resistance.

NEVERTHELESS, any given antibiotic will only kill certain bacteria. Azithromycin didn't work for me, so a week later I was back for a second round.