Drugs
moleculeoftheday | January 5, 2007Chemotherapy, in the cancer-treatment sense, isn't very selective. Fortunately, cancer cells divide so much faster than regular cells, this imparts a measure of selectivity. All chemotherapeutic agents are poisons of one sort or another, but we continue to get better. Mechlorethamine is just an "alkylating agent," which means it will react promiscuously, forming covalent adducts with any nucleophilic species it encounters. Oftentimes, this means DNA, which means cell division will be impaired (for all cells). If this sounds a bit like carpet-bombing a knife fight, you begin to see the problem…
moleculeoftheday | January 3, 2007My dentist has an incredible knack for administering anesthetic without much pain. I'm not sure what combination of factors are at play, but getting work done there is essentially painless. My main problem for years was the fact that my mouth was numb for a good part of a day after leaving. I went today, and it had been a few years since I had anything done. For years, my dentist (and probably yours) used lidocaine, which works fine but has an elimination half-life of about 90 minutes. This time, the anaesthetic had changed.
In 1969 (20 years after lidocaine was discovered, and a mere 65…
moleculeoftheday | January 2, 2007Azelaic acid is a pretty simple small molecule:
It is used topically in dermatology.
purepedantry | December 18, 2006Yet again, a drug company is playing damage control for failing to come clean about a drug's side effects. It makes me so mad when companies do stuff like this because it is such a preventable problem. In this case, the drug in question is Zyprexa (olanzapine) -- presently one of the go-to drugs for the treatment of schizophrenia -- and the company in question is Eli Lilly:
The drug maker Eli Lilly has engaged in a decade-long effort to play down the health risks of Zyprexa, its best-selling medication for schizophrenia, according to hundreds of internal Lilly documents and e-mail messages…
moleculeoftheday | December 6, 2006As many estimable colleagues have noted, guanine's weird. It's not that soluble, which isn't too much of a problem when it's a part of your very soluble DNA, but from an origin-of-life perspective, that's a hassle. Envisioning a primordial-soup scenario with guanine is tricky, because of this low solubility. Further complicating the problem is guanine's prodigous tendency to associate with itself:
Monomers of G will do this, forming gels in solution (which exhibit repeating units of the above structure). We knew about guanine's propensity to self-associate before we even had cracked the…
moleculeoftheday | December 4, 2006Pfizer's Lipitor is the highest-grossing drug out there right now. This single molecule sells over $10B/year. As discussed in the allopurinol entry, this is another example of a small molecule enzyme inhibitor. The class to which it belongs, the statins, works on one key step of the steroid biosynthesis cycle. They do a good job lowering LDL cholesterol, but aren't so great at raising HDL cholesterol.
That's one reason drug companies have been after a different class of anticholesterol drug. Another reason for Pfizer to be worried is that in just a few years, Lipitor goes off patent.
One…
purepedantry | November 29, 2006Benjamin Zycher, fellow at the Manhattan Institute, questions of the wisdom of allowing Medicare to negotiate prices with drug companies.
Actually what I don't like about this debate is that is called "negotiating" drug prices. There is no negotiation that is going to take place. What will happen is that Medicare is going to tell the drug companies how much they are willing to pay, their opinions be damned.
Anyway, he compares the formulary in the Medicare system with the formulary in the VA system (the VA system is allowed to negotiate prices). He finds that the VA system has…
moleculeoftheday | November 21, 2006As a followup to the entry earlier today, here is a drug that is used in the treatment of gout: allopurinol.
In vivo, purines are metabolized by the enzyme xanthine oxidase to hypoxanthine and xanthine, which are converted to uric acid:
Allopurinol is a hypoxanthine mimic, which is oxidized by xanthine oxidase to alloxanthine, which is very tightly bound to xanthine oxidase.
Tie up xanthine oxidase, purines don't get metabolized to hypoxanthine and xanthine, and you don't end up with much uric acid.
Where do all the purines go? It turns out that catabolism isn't all your body can do with…
moleculeoftheday | November 17, 2006Inhalants are ubiquitous illegal drugs of abuse and a public health problem worldwide. Most lipophilic solvents have some kind of neurotoxicity (some gas anaesthetics, in fact, work based mainly on their lipophilicity, and are only special because of lower toxicity). Unavoidably, we find these in glue and, memorably, spray paint. As far as I know, in the States, you have to be 18 just about anywhere to buy spray paint (because of graffiti, as well as inhalant abuse) and solvent-based glues (because of inhalant abuse).
One thing you'll probably cover if you ever take a business ethics class is…
moleculeoftheday | November 9, 2006Another drug that can claim diphenhydramine as an ancestor is fexofenadine, sold as Allegra:
Diphenhydramine for comparison:
Fexofenadine is a member of a later generation of antihistamines. Diphenhydramine worked fine as an antihistamine (still does - you can still get the stuff OTC as Benadryl), but one big problem was the pronounced drowsiness associated with taking it. Newer antihistamines such as fexofenadine manage to exert most of their effect outside the CNS.
Fexofenadine is actually quite an old drug. Once upon a time, you may have taken a drug called Seldane (a very early non-…
moleculeoftheday | November 8, 2006Last night I mentioned that diphenhydramine is a somewhat promiscuous molecule, binding to a number of disparate receptors. One of its effects is some inhibition of serotonin reuptake. As you've probably read in countless pop science articles by now, this is one mechanism of action for antidepressants. Take a look at diphenhydramine again:
And Fluoxetine/Prozac:
Note the similarity in structure to diphenhydramine. Also note the trifluoromethyl group (-CF3). You don't really see organofluorine compounds in Nature (it's so reactive it's been caught up in rocks and ores for ages), but they are…
moleculeoftheday | November 7, 2006Diphenhydramine is one of the earliest antihistamines:
Being a first generation antihistamine, it has all the associated problems such as drowsiness and dry mouth. These are some of the least specific small molecule therapeutics you could hope for, which gives rise to many of the side effects. Interestingly, it has some effect on serotonin reuptake, which led to some drugs for depression with similar structure.
moleculeoftheday | October 27, 2006L-methamphetamine is a fine example of how molecules that vary only in their chirality can have very different biological effects. Chiral molecules have non-superimposable mirror images. L-methamphetamine, at left, below, is found in Vicks Vapor Inhalers. (Notice how they obfuscate the name a little bit by calling it "levmetamfetamine"). This is the mirror image of D-methamphetamine - the street drug. As you'll see, the two compounds are very different medically despite having only a subtle structural difference.
If you're having trouble working out the difference, the dashed bond is "going…
moleculeoftheday | October 26, 2006Kavain is a member of a class of compounds known as the kavalactones. (A lactone is a cyclic ester; click here for examples).
Kavain is a species found in the kava plant, which is used by the aboriginal residents of some Pacific islands and has psychoactive activity. It's attracted use as a dietary supplement lately. It's also attracted some attention for possible toxicity, particularly to the liver.
moleculeoftheday | October 25, 2006Arecoline is a compound that occurs in the seed of the betel palm. It's taken by chewing the nut.
Arecoline, like nicotine, binds to certain receptors for acetylcholine. I've grouped them together so you can note the structural similarities.
Remember all that talk about protonated amines yesterday? Here's another place where it matters.
You'll note that I've drawn arecoline and nicotine with positive charges. As I mention in this old entry about nicotine, this is the physiologically relevant form (at your cells' pH, this is what you find).
The trouble with this, though, is that charged…
moleculeoftheday | October 24, 2006It's weird drugs for the rest of the week!
Salvia probably means one of two things, if anything, to most people: a houseplant (for which purpose it is ubiquitous) or a recreational drug that you can still get your hands on legally (for which purpose it is ubiquitous). It is funny to flip back and forth between pages where people are trying to figure out exactly the best way to get this stuff in your body and pages where people are trying to figure out which plant will go best with those azaleas and think that everyone's talking about the same thing. Plants are funny that way, I guess.
Of…
purepedantry | September 22, 2006Walmart is cutting prices on generic drugs in Florida as a test program:
- Wal-Mart Stores Inc., the world's largest retailer, said on Thursday it would cut the prices of nearly 300 generic drugs to $4 per prescription starting in the retirement haven of Tampa, Florida.
Target Inc., which has faced increasingly stiff competition from Wal-Mart, said it would immediately match the drug prices in the Tampa Bay area as part of a long-standing practice of remaining price competitive with its larger rival.
Wal-Mart characterized the program as "part of its ongoing commitment to provide affordable…
scientificactivist | August 1, 2006Yesterday, the House of Commons Science and Technology Committee released a report entitled Drug Classification: Making a Hash of It?, which challenges the logic behind current drug classifications in the UK, especially when tied to legal penalities. The report discusses specific cases where drugs were misclassified or their classifications were changed for political, rather than scientific, reasons. The report is particularly critical of the Advisory Council on the Misuse of Drugs (ACMD) for not doing enough to push for a more scientifically based drug classification system.
The…
purepedantry | July 31, 2006Are we dividing drugs into illegal and legal based on a rational classification system based on risk?A British government committee says no:
The committee's report recommends that drugs be ordered on "a more scientific scale, to give the public a better sense of the relative harms involved". But Michael Gossop of King's College London, UK, who studies drug use, is not sure that drugs can be easily ranked by the harm they cause. "There are lots of different aspects to 'harm'," he says. "It's not clear that when you add them together you get a simple rating."
In seeking to compile a league…
scientificactivist | July 21, 2006This post from the archives describes a recent research finding that may be welcome news for some....
(24 May 2006) If you know what I'm talking about, and if you are in fact "cool", then you might also be interested in the findings presented Tuesday by Dr. Donald Tashkin and his coauthors at an American Thoracic Society meeting in San Diego. In short, smoking marijuana does not cause lung cancer:
The smoke from burning marijuana leaves contains several known carcinogens and the tar it creates contains 50 percent more of some of the chemicals linked to lung cancer than tobacco smoke. A…