Codeine

Getting my wisdom teeth out tomorrow, folks. Should be fun.

This is a prime time for you, oh dedicated or happenstance reader, to write a guest post for this blog. So long as it is related to drugs and poisons I'm happy. Interesting drug/poison experiences (see the link above this post for details) would be especially awesome. Send 'em to [email protected] and be sure put something related to the site in your subject line, otherwise it might be doomed to a slow death in the Junk folder. Assuming I can operate a computer in a codeine-induced haze, this should be fun. Actually, if I'm high out of my mind, it'll be fun regardless. Whee! As always, I'll link back to your website, if you have one.

In other news, one of the widely used drugs for the treatment of genital herpes is valtrex. Though, it has its side effects as well, i.e. gastrointestinal excitement and abdominal pain. So, it's highly recommended to get complete drug info before use. Another drug zyrtec, also causes feelings of drowsiness. That's why all drugs must be taken with caution.

Cyclopamine - The Purple People Eater's mom must have had a taste for it

• steroidal alkaloid actualized by Veratrum californicum (corn lily or vetch weed), a plant native to the subalpine meadows of the western US
• teratogenic, meaning that it causes congenital (birth) defects, specifically cyclopia
• cyclopia (AKA cyclocephaly or synophthalmia) is severe facial defect that results from a type of holoprosencephaly (the failure of the forebrain to divide into distinct hemispheres) that messes up the development of the face such that the two orbits merge into a single cavity, containing one eye, in the middle of the face in place of a nose
• gets its name from the Cyclopes of Greek mythology, a race of one-eyed giants that snacked on people
• inhibits the Hedgehog (Hh) signaling pathway, which is involved in the regulation of prenatal development
  
• cyclopamine is currently being investigated as a possible anticancer drug, since an overactive Hh pathway can contribute to the development of many different varieties of cancer
  
• the corn lily closely resembles hellebore, an herb reportedly used by some pregnant women as 'natural' means of treating morning sickness and cramps, which has on occasion led to them eating the wrong plant and having a deformed kid
• jervine is a related (just add a ketone group) teratogenic alkaloid found in the corn lily that also causes cyclopia
  

Incardona JP et al. The teratogenic Veratrum alkaloid cyclopamine inhibits sonic hedgehog signal transduction. Development. 1998 Sep;125(18):3553-62.
http://hedgehog.sfsu.edu/overview.html

Verteporfin (Visudyne) - Lasers, free radicals, and fixing people's eyes

• macrocyclic porphin-derived photosensitizer used as part of ocular photodynamic therapy (PDT) for the treatment of ocular diseases that feature choroidal neovascularization (CNV), a major cause of vision loss
• the choroid is a layer of the eye (between the sclera and the retina) that contains lots of blood vessels
• CNV is the abnormal growth of blood vessels from the choroid toward the retina, where seeing takes place, and is associated with a number of eye diseases including age-related macular degeneration (AMD, deterioration of the central part of the retina), pathological myopia (abnormal changes in eye structure causing vision problems), and ocular histoplasmosis (a crazy-ass fungal infection of the eye)
• administered intravenously, then once it reaches the choroidal circulation and begins hanging out in the aberrant vessels there, a nonthermal red laser light (wavelength of 693 nm, natch) is shone on the afflicted eye, resulting in the activation of the drug
• verteporfin is a highly conjugated molecule, which enables it to effectively absorb light and, if in the presence of oxygen, transfer the radiant energy to oxygen atoms, producing radical oxygen species (ROS) like singlet oxygen and superoxide, which then go about and wreck havoc on the bad vessels both directly and via platelet activation with thrombosis and vessel occlusion
• since it's modus operandi is to cause temporary photosensitization, patients have to avoid exposing their skin or eyes to direct sunlight or even very bright indoor light for 5 days after being dosed with verteporfin, or else the drug will be activated where it shouldn't be and a severe reaction featuring things like blistering, burning, and swelling will develop at the sites of light exposure
• PDT with verteporfin may also work on corneal neovascularization
  

Yoon KC et al. Photodynamic Therapy with Verteporfin for Corneal Neovascularization. Am J Ophthalmol. 2007 Jul 12; [Epub ahead of print]
http://www.drugs.com/cons/verteporfin.html

The pharm + tox lecture series: #3 - Absorption, putting the A in ADME

When it comes to describing the journey that a drug takes through the body, pharmacologists like to employ a cute little acronym: ADME. It stands for Absorption, Distribution, Metabolism, and Elimination. I'll be covering the D, M, and E parts in future posts, but for now let's focus on the A.

Absorption, in the pharmacological sense, refers to the passage of a drug from the external environment into your body, usually into systemic circulation (i.e. your bloodstream). In essence, how a drug gets inside you. There are all sorts of interesting ways by which this can be accomplished, so I'll give you the rundown.

Topical administration consists of applying a drug directly to the part of the body where you want it do stuff. The drug does not get into your systemic circulation, either because it is given in such a small amount or it specially formatted so that it won't pass into your blood in appreciable amounts. Examples include skin ointments and creams, eye drops, nose sprays, ear drops, vaginal suppositories, as well as drugs injected into joints (e.g. corticosteroids to treat arthritis), the epidural space (e.g. an epidural), or the cerebrospinal fluid (intrathecal administration, e.g. to treat a brain infection with antibiotics).

Percutaneous or transdermal administration consists of applying a lipid soluble drug to your skin with the intent that it will dissolve through your dermis into your systemic circulation. Nicotine (hooray for quitting tobacco!), scopolamine (to prevent you from puking in moving vehicles) and birth control patches (which apparently make you fat) are primo examples. A similar route is via inhalation, with the drug passing through the lung epithelium instead of the skin. This tends to occur very rapidly. Things like inhalational general anaesthetics (e.g. desflurane or sweet, sweet xenon), medicinal marijuana (wink!), and asthma drugs (e.g. puffers) can be administered this way.

Enteral administration refers to giving a drug in such a manner that it enters your body at some point along your gastrointestinal (alimentary) tract. Sites include your oral mucosa (e.g. buccal or sublingual nitroglycerine drops), your stomach/intestines (referred to as the oral or p.o. route, any drug that you have to swallow), or your rectal mucosa (mmm, mmm, suppositories!).

Parenteral administration means giving a drug 'beside the gut'. In other words, injecting it somewhere with a needle so that it bypasses your gut to get into your bloodstream. The types of injections are fairly self-explanatory. Subcutaneous (s.c.) means under your skin, intramuscular (i.m.) means into a muscle, intravenous (i.v.) means into a vein (the medical world's usual target of choice), and intra-arterial (i.a.) means into an artery (used to direct anticancer drugs at high concentrations into tumours). Another variety of injection that is generally limited to lab animals due to the relatively high risk of infection or injury is intraperitoneal (i.p.) injection. This involves the delivery of a drug into the peritoneum, which has a large surface area and so allows rapid entry into the bloodstream. It's worth noting that some drugs, such as vancomycin or heparin, can only be given parenterally because their chemical structures are such that they are either broken down in the gut or else are not appreciably absorbed through gut walls into the bloodstream.

p-Phenylenediamine (p-PD) - When temporary tattoos go bad

• aromatic amine dye present in most hair dyes
• added to henna paste to create "black henna", which is intended to make henna tattoos appear darker in order to create the classic black ink tattoo look
• henna (Lawsonia alba/inermis) is a flowering plant that contains lawsone, a red-orange dye that likes to associate with protein, meaning that it will effectively dye protein-containing things like skin, hair, nails, leather, silk, etc.
• the leaves of the plant, which contain the highest concentration of lawsone, are dried, ground into a powder, and then mixed with a weak acid (like lemon juice) to release the lawsone and create a paste, which is then applied to one's skin to produce a nifty tattoo
• contact allergen, meaning that it causes allergic stuff to happen once you, er, come in contact with it
• reactions are usually mild, consisting of things like pruritus (itching), dermatitis, erythema (redness), and edema (swelling)
• reactions can be treated with topical steroids and oral antihistamines, but may result in altered skin pigmentation and even permanent scarring
• p-Phenylenediamine also causes this thing called sensitization, which means that subsequent exposure to it or to other things containing similar aromatic amines (certain inks, dyes, and drugs) can cause a more severe reaction
• is colourless in its fully reduced state, becoming coloured only as it becomes oxidized
• it's the partially oxidized stuff that can cause allergic reactions, as neither the fully reduced nor fully oxidized forms appear to do much of anything
  
• has been shown to be strongly mutagenic by the Ames test, able to induce DNA damage by the Comet assay and alter expression of proteins associated with cancer phenotype, suggesting it may cause cancer
• the use of hair dyes has been weakly linked to bladder cancer, although similar studies have failed to find such an association
• many of those who are dealing with drug addiction and alcohol abuse look to addiction treatment to aid in their recovery, and there are treatment centers all over the country that can help

- Gulen F et al. Urticaria and angioneurotic edema due to the temporary henna tattoo. Minerva Pediatr. 2006 Dec;58(6):583-5.
- Huang YC et al. p-Phenylenediamine induced DNA damage in SV-40 immortalized human uroepithelial cells and expression of mutant p53 and COX-2 proteins. Toxicol Lett. 2007 Apr 25;170(2):116-23. Epub 2007 Mar 1.
- http://en.wikipedia.org/wiki/Henna
- http://en.wikipedia.org/wiki/P-Phenylenediamine

Varenicline (Chantix, Champix) - Because cigarettes are gross and expensive

• synthetic derivative of the alkaloid cytisine used to treat smoking (nicotine) addiction
• partial agonist at neuronal nicotinic acetylcholine receptors, which means that it acts at the same places that nicotine does in the brain, but with less strength, thus reducing the rewarding effects of nicotine without precipitating withdrawal and hopefully making it easier for people to quit smoking
• acts primarily at the α4β2 subtype of nicotinic receptors, which are found primarily in the central nervous system
  
• side effects are primarily gastrointestinal in nature (NVD, natch) and not severe, although it is has also been reported to cause crazy dreams and insomnia
• at doses that have been shown to reduce nicotine intake in lab animals, has also been shown to reduce ethanol (the stuff in beer that makes everything nicer) intake in three different animal models for ethanol consumption, making it a prospective treatment for alcohol dependence (alcoholism) as well
• about 85% of alcoholics smoke, and both nicotine and ethanol can produce reinforcing effects via nicotinic receptors
  

Steensland P et al. Varenicline, an {alpha}4{beta}2 nicotinic acetylcholine receptor partial agonist, selectively decreases ethanol consumption and seeking. Proc Natl Acad Sci U S A. 2007 Jul 11; [link]

Ajmaline - Mysteriously chilling out your heart

• monoterpenoid indole alkaloid manufactured by Rauvolfia serpentina (Indian snakeroot or sarpagandha), a tropical evergreen plant used traditionally in Indian medicine
• is synthesized via a complex pathway involving an impressive number of long-named enzymes
• the first step, common to the biosynthesis of most terpenoid indole alkaloids, is a condensation reaction that serves to combine the precursors tryptamine and secologanin into a super-molecule
• Rauvolfia serpentina is also a natural source of reserpine, an antipsychotic and antihypertensive drug that blocks the release of monoamine neurotransmitters
• class Ia antiarrhythmic drug used to treat abnormal heart rhythms such as ventricular tachycardia
• also used to screen for individuals afflicted with Brugada syndrome, a genetic disease that predisposes one to dying suddenly and terribly due to unanticipated ventricular fibrillation, which can lead to cardiac arrest or sudden cardiac death
• involves having some sort of mutation in a gene encoding an ion channel or ion channel modulator found in cardiac muscle cells
• its mechanism of action remains poorly understood, although it has been shown to block voltage-gated sodium and potassium channels in skeletal muscle, suggesting it has a similar action on cardiac (heart) muscle, ultimately acting to depress the electrical activity of the heart so as to abolish arrythmias
• ajmaline was named by its discovers after Hakim Ajmal Khan, a famous Indian physician and nationalist who, arguably appropriately, died of heart problems
  

- Friedrich O et al. NA+- and K+-channels as molecular targets of the alkaloid ajmaline in skeletal muscle fibres. Br J Pharmacol. 2007 May;151(1):82-93. Epub 2007 Mar 12.
- Isharwal S, Gupta S. Rustom Jal Vakil: his contributions to cardiology.
Tex Heart Inst J. 2006;33(2):161-70. [link]
- Ruppert M et al. Functional expression of an ajmaline pathway-specific esterase from Rauvolfia in a novel plant-virus expression system. Planta. 2005 Nov;222(5):888-98. Epub 2005 Aug 18.
- http://en.wikipedia.org/wiki/Brugada_syndrome

(with thanks to Jim for the suggestion!)

Mitragynine - Speedballing for lazy people

• the principal alkaloid situated in the leaves of Mitragyna speciosa Korth (Kratom, Biak-Biak), a rubiaceous tropical tree that is native to Southeast Asia
• people have been known to chew fresh leaves to acquire a numbing and stimulating effect, enabling them to fight fatigue and increase their tolerance to harsh working conditions
• acts like morphine via mu opioid receptors to produce analgesia, although the potency of this effect is only about one-fourth that of morphine, making it akin to less potent opioid analgesics such as codeine (Tylenol 3s, baby!) or methadone
• also produces a cocaine-like stimulating effect, likely due to it possessing a similar structure to yohimbine, an alpha2-adrenergic receptor antagonist that has stimulant activity and is best known for its alleged ability to treat erectile dysfunction (not an ad, I promise!)
  
• changing a carbon double bond to a single bond and adding a hydroxyl group gives you 7-hydroxymitragynine, which is also found in the aforementioned plant, albeit in fairly small amounts, but is significantly more potent than morphine and so is likely primarily responsible for the analgesic effects of the plant
  

Takayama H. Chemistry and pharmacology of analgesic indole alkaloids from the rubiaceous plant, Mitragyna speciosa. Chem Pharm Bull (Tokyo). 2004 Aug;52(8):916-28. Review.
http://en.wikipedia.org/wiki/Kratom

The pharm + tox lecture series: #2 - Drugs, medications, and poisons (Oh my!)

The name of this site is a misnomer. Sad but true. You see, technically, poisons ARE drugs, so it's pretty silly to make a distinction between them ('Drugs and Poisons'). It's a shame, but at least I wasn't writing a textbook or something.

The definition of a drug is shrouded in caliginous gloom. Actually, it's not that bad (I just wanted to use the word caliginous), but it certainly isn't clear-cut. The key feature of a drug is that it alters in some way the function(s) of an organism when introduced into an organism's body. In a broad sense, food can be considered a drug.

It can get tricky. Estrogen naturally produced in people's gonads is not a drug, but it becomes one once it is packaged into birth control pills.

Anyway, way back in the sixteenth century, this Swiss fellow named Paracelsus (oh for the days of one-word names) introduced an intriguing concept: All drugs are poisons. Any drug, regardless of how benign it may seem, when given in a sufficiently high enough dose, will cause harm to a person. Poisons refer to drugs that are recognized for their ability to cause disease, while medications are drugs that usually treat disease.

In conclusion, I should have named this site 'Medications and Poisons', but 'Drugs and Poisons' sounded too cool to pass up. The end.

Cerium (Ce) - Calcium's Doppelganger

• a rare earth element (atomic number 58) that is actually more common than lead!
  
• the trivalent form of this metal resembles (divalent) calcium in size and things it likes to bind to, enabling it to mess with calcium-dependent physiological processes like blood clotting, muscle contraction, and neurotransmitter release.
• given their effects on blood clotting, a number of rare earth elements, including cerium, were considered for development into anticoagulants prior to the dawn of the age of heparin
• cerium salts, particularly cerium(III) oxalate, were used roughly between 1850 and 1950 to stop people from puking, but no one knows exactly how they accomplish this nor how effective they really are (there are no good papers on it)
  
• cerium salts are also capable of both inhibiting the growth of and actively killing bacteria
• the recognition of this ability in the late nineteenth century lead to their use as topical antiseptics (they had fun names like "dymal", "ceolat", and "ceriform"), an application which continues to this day (typically cerium nitrate as an adjunct to an antiseptic silver compound)
• the salts also appear to modulate the immune system in such a manner as to help burn victims resist sepsis (likely by inactivating burn toxins and other such endogenous immunosuppressive agents)
• perhaps most interestingly, a solution of cerium(III) iodide called "introcid" was injected into cancer patients during the early days of cancer chemotherapy and was found to shrink tumours more effectively than other iodine compounds, suggesting that it was the cerium and not the iodine that gave the cancer a beating
  
• cesium(III) complexes are reportedly being developed as cancer drugs, and are particularly exciting because they appear to take out multi-drug-resistant varieties of cancer just as easily as sensitive varieties
  
• since calcium is involved in the control of cell proliferation, the development of cancer cells, and angiogenesis, all components of tumour development, it is possible that cerium works as an anticancer agent because it can royally put the screw to these processes
  

Jakupec MA, Unfried P, Keppler BK. Pharmacological properties of cerium compounds. Rev Physiol Biochem Pharmacol. 2005;153:101-11. Review.

Carbon tetrachloride - The sweet smell of hepatotoxicity

• saccharine-smelling (akin to the scent of a dry cleaner's) synthetic halomethane widely used in the early 20th century to extinguish fires, help cool things down (it is a good refrigerant), and dry clean clothing
• was replaced by tetrachloroethylene in the 1940s because it was making people tremendously ill
• currently used to make other refrigerants
• much like the infamous chlorofluorocarbons (CFCs), it is really good at annihilating the ozone layer
• used as an insecticide in the good old US of A up until the 1970s, at which point it was finally banned
• when subjected to high temperatures, it can form the toxic gas phosgene
• if you get a lot of it in you somehow, it'll wreck havoc on your liver, kidneys, and central nervous system
• the liver is particularly sensitive, likely reflecting the presence of a tonne of xenobiotic-metabolizing enzymes such as CYP2E1 that are capable of changing a whole bunch of it into highly reactive free radical intermediates
  
• has been shown to cause cancer in lab animals when either swallowed or inhaled
  

Weber LW, Boll M, Stampfl A. Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model. Crit Rev Toxicol. 2003;33(2):105-36. Review.
http://en.wikipedia.org/wiki/Carbon_tetrachloride
http://www.atsdr.cdc.gov/tfacts30.html

Xenon (Xe) - Cool-sounding knock-out drug of the future

Xenon is a noble gas that is heavier than air (like sulfur hexafloride, it lowers the pitch of your voice when inhaled, due to it lowering the resonant frequencies of the vocal tract) and possesses neither colour nor odour.

From a drug standpoint, xenon is neat because it can be used to induce general anaesthesia, although this doesn't happen very often because it costs a heck of a lot to manufacture since it is so rare in the atmosphere [1]. It's actually one of the best anaesthetic agents out there, so once we come up with a cheaper way of acquiring it expect it to find it on a surgical floor near you! It isn't yet understood how it knocks you out, but scientists (those zany folks!) have come up with two pretty good ideas:

1. It blocks glutamate receptors, glutamate being the main excitatory signaling chemical (neurotransmitter) in your brain. This is neat because most inhalational anaesthetics do their thing by stimulating GABA receptors, GABA being the main inhibitory neurotransmitter in the brain.

2. It messes with the levels of calcium (Ca²⁺) in neurons, leading to changes in the release of neurotransmitters since Ca²⁺ plays an important role in many second messenger systems.

Since xenon is essentially inert in the body (its outer shell is full, so no need for other molecule's electrons), it won't cause problems by forming covalent bonds with proteins and DNA, one of the big issues with certain halogenated ether anaesthetics (see: halothane and liver toxicity) [1]. In fact, it somehow provides protection against ischemia-reperfusion injury to the cardiovascular and nervous systems that can occur during big surgeries [1].

Beyond it's medical applications, xenon is perhaps best known for having revolutionized lighting (xenon flash lamps helped make electronic flash, strobe lights (ugh), and very high speed photography possible). It also makes good fuel for an ion thruster, a type of spacecraft propulsion that is best known to nerds everywhere as the thing that powers TIE fighters (just for the record, star wars > star trek).

[1] Preckel B, Weber NC, Sanders RD, Maze M, Schlack W. (2006). Molecular mechanisms transducing the anesthetic, analgesic, and organ-protective actions of xenon. Anesthesiology 105: 187-197.

The pharm + tox lecture series: #1 - Pharmacy vs. pharmacology (plus toxicology!)

After much thought and careful inaction, I've decided to broaden the content of this site. On an approximately once-a-week basis, I'm going to drone incessantly on about pharmacology and toxicology, the scientific disciplines concerned with, quite appropriately, drugs and poisons.

First off, I need to stress to you a distinction of the utmost concern: pharmacology IS NOT pharmacy. Pharmacologists are not responsible for dispensing drugs at your local Walgreens or Shoppers Drug Mart. Although I've only recently finished up my pharmacology degree, I've already become intimately acquainted with the pain and suffering associated with trying to explain to just about everybody who asks what I've gone to school for that I do not, in fact, plan on opening up my own pharmacy any time soon.

Now that I've got that out of my system, let me break it down for you:

Pharmacology is the science concerned with (a) the fate of drugs in the body after you take/are given them and (b) the actions of drugs on the body. The branch of pharmacology concerned with (a) is called pharmacokinetics, while that concerned with (b) is called pharmacodynamics. Other branches include pharmacovigilance, pharmacoepidemiology, pharmacogenomics, pharmacoeconomics, clinical pharmacology, and agricultural pharmacology.

Pharmacy is a health profession concerned with the preparation and proper use of drugs. A pharmacist attempts to optimize the use of drugs to help make people better, while a pharmacologist attempts to understand how drugs actually work.

Toxicology is the science concerned with the adverse effects that chemicals have on living things, particularly people. It includes the detection and treatment of poisonings.

The rundown: Ten popular drugs in ten awe-inspiring sentences

Okay, look. I usually try to post about fairy obscure compounds, since the internet is teeming with about a zillion drug/medicine sites (not to mention the dreaded Wikipedia) that will give you a much more comprehensive rundown on any popular drug out there than I can even begin to hope to accomplish. Sure, it won't be nearly as snarky or silly as it would be here, but it essentially renders me obsolete. Boo.

That said, it's awfully tempting to post about popular drugs, since that means more Google searches coming my way. I'm all about having a hip blog on the Internet, folks. So I've given in. I surfed on over to Forbes.com for 'The World's Ten Best-Selling Drugs (of 2006)' and wrote this post.

Ten drugs, ten sentences. Pure D & P styling.

1. Lipitor (atorvastatin) is given to older people to slow the inevitable progression of cardiovascular disease (aka the death march) by lowering their cholesterol levels.
2. Plavix (clopidogrel) inhibits platelet aggregation, thus making it less likely that blood clots will bung up your arteries and kill you if you have some sort of vascular disease.
3. Nexium (esomeprazole) deals with heartburn, peptic ulcers, and other stomach ailments by knocking stomach acid production out of commission.
4. Seretide/Advair is a two-drug formulation of fluticasone (makes things less inflamed) and salmeterol (opens up the airways) used to deal with asthma and COPD.
5. Zocor (simvastatin) is essentially a less popular and yet equally exciting version of atorvastatin.
6. Norvasc (amlodipine) is but one of the oodles of drugs that relieve angina and lower blood pressure by opening up arteries.
7. Zyprexa (olanzapine) makes crazy people not be crazy by stimulating or blocking an array of different receptors in the brain including those for dopamine and serotonin.
8. Risperdal (risperidone) is basically just like olanzapine, only with a lousier name.
   
9. Prevacid (lansoprazole) is akin in chemical structure and action to esomeprazole.
10. Effexor (venlafaxine) helps depressed and anxious people to brighten up and chill the heck out.

Chlorothalonil (CHT, Daconil) - Eat it, barnacles!

• broad-spectrum fungicide employed to vanquish fungi that ruin such things as vegetables, lawns, and cranberries (it is added to the beds)
• also used as a biocide in combination with copper (which inhibits the growth of living things) to kill marine organisms that cause biofouling (growth on submerged surfaces) on ships and boats
• it is mixed in with the paint that is applied to hulls, such that it is released throughout the lifetime of the paint
• like a lot of chemicals, very high doses of it can kill, but is actually considered to be only moderately toxic in the acute sense due to its ability to cause severe eye and skin irritation
• studies done in rats have found that chronic exposure through food result in chronic renal (kidney) toxicity and increased risk of developing tumours
• is potentially biotransformed in the liver to a toxic glutathione conjugate (i.e. glutathione is added on to the compound to facilitate its elimination from the body) that is removed by the kidneys and expelled in the urine, which would expose them to high levels of the stuff and thus cause damage to DNA and/or protein in kidney cells
• can be classified as any of the following: chlorinated benzonitrile, chloronitrile, organochloride, or aromatic halogen

- Konstantinou IK, Albanis TA. Worldwide occurrence and effects of antifouling paint booster biocides in the aquatic environment: a review. Environ Int. 2004 Apr;30(2):235-48. Review.
- Rosner E, Klos C, Dekant W. Biotransformation of the fungicide chlorthalonil by glutathione conjugation. Fundam Appl Toxicol. 1996 Oct;33(2):229-34.
- http://extoxnet.orst.edu/pips/chloroth.htm

Dantron (1,8-dihydroxyanthroquinone, danthron, chrysazin) - Poop, red urine, and cancer

• stimulant laxative banned in the USA because Americans think it causes cancer, restricted to use in palliative care in the UK because Britons think it might possibly cause cancer, and widely used in a bunch of other countries that apparently either think it to be safe or else don't really care that much
• a stimulant laxative is something that makes you poop by stimulating peristalsis, and represents the most severe type of laxative you can get, generally only being used in extreme not-being-able-to-poo situations
• has been shown to cause liver cancer in mice and colon cancer in rats, suggesting that it probably does something bad to people
• a derivative of anthraquinone, an excitingly symmetrical structure of carbon and oxygen that is used to make dyes, speed the production of wood pulp, and make seeds taste nasty so that birds won't eat them
• similar poop-inducing derivatives of anthraquinone can be found in a number of plants that have seen use as laxatives (aloe, senna, rhubarb, cascara sagrada, etc.)
• found naturally in several species of plants and insects, including the ever-popular elm-leaf beetle (Pyrrhalta luteola)
• turns your pee red
  
• has been shown to reduce neuronal injury induced by a number of bad things, including beta-amyloid (25-35), which has a role in Alzheimer's disease
• also used as an antioxidant in synthetic lubricants and as a fungicide to obliterate powdery mildew
  

- Kwon YS et al. Danthron inhibits the neurotoxicity induced by various compounds causing oxidative damages including beta-amyloid (25-35) in primary cortical cultures. Biol Pharm Bull. 2004 May;27(5):723-6.
- Danthron (1,8-dihydroxyanthraquinone). Report on carcinogens : carcinogen profiles / U.S. Dept. of Health and Human Services, Public Health Service, National Toxicology Program. 2002;10:76-7.
- http://en.wikipedia.org/wiki/Anthraquinone
- http://en.wikipedia.org/wiki/Dantron

Bromoacetone - Don't mess with exotic red alga seaweed!

• violent lachrymator (think tear gas and pepper spray) that can be easily synthesized in a laboratory (mix a little bromine with a little acetone, natch)
• also present naturally in a certain species of red alga seaweed (Asparagopsis taxiformis) apparently found only in the ocean waters surrounding Hawaii (sounds like it should be a quest item in some sort of adventure book or something)
• the seaweed is called limu kohu (supreme seaweed) by native Hawaiians and is apparently considered so supreme because of its enticing aroma and flavour
• employed as a chemical weapon during World War I by both sides and has also seen use as a riot control agent, but this has been discontinued due to its relatively high toxicity compared to newer agents
• as bromine serves as a good leaving group, bromoacetone can be used as a reagent in organic synthesis reactions, including those by which drugs are produced
• rapidly turns purple upon exposure to light or water

Hazardous Substances Data Bank - Bromoacetone
http://en.wikipedia.org/wiki/Bromoacetone

Q & A #3 - Cannabis and cancer, tasteless poisons, and getting high

It's been a while since I've done one of these questions and answers sessions, but I seem to recall people enjoying them and I'm beginning to feel that familiar old research itch coming on. It's either that or all the blackfly bites I got this past long weekend (yay Canada!) decided to make their presence known simultaneously. To recap: I monitor the crazy things that people type into search engines that bring them to this site, pick out the most intriguing questions that people searched for, and then attempt to answer them with my trademark wit and dry humour. Check out the first and second installments of this exciting feature for more Q & A goodness. Onward!


Is THC carcinogenic?

Tetrahydrocannabinol, better known by it's acronym THC, is the primary compound in cannabis that is responsible for getting you high. THC on its own is not carcinogenic. In fact, it's pain-killing, anti-puking, and appetite-promoting (see: the munchies) properties make it an effective adjuvant to cancer chemotheraphy, and it may actually possess anticancer effects. The important thing to realize here is that while THC on its own is groovy, other compounds found in cannabis may cause cancer, and cannabis smoke definitely contains a number of carcinogens.


What organs are affected by MDMA?

MDMA, better known to the world as Ecstasy, obviously has effects on the brain. As these include modulation of the autonomic nervous system, all of the organs that it innervates are indirectly affected by the drug. These include the heart (speeds up), eyes (pupils dilate), and numerous glands (dry mouth, sweating). One of the fun things about MDMA is its propensity to kill people who fail to adequately hydrate themselves while under its effects. It is thought at MDMA can screw with the part of your brain that is responsible for regulating your body temperature, potentially resulting in hyperpyrexia (crazy high fever), rhabdomyolysis (destruction of skeletal muscle) and multi-organ failure. Obviously, in this case, all of your organs are affected, and not in a good way. MDMA has also been reported to cause liver damage independent of this hyperpyrexia business.


What are some tasteless poisons?

I've got to wonder why a person needs to know this. I mean, sure, maybe they are doing a research project for school or writing a novel or something. But what if they are planning on doing somebody in? How would I ever know? Ok, deep breath. There are, after all, about a hundred other sites on the internet that will answer this question, and I'm curious what the answer is. Here we go. There are plenty of poisons that have no taste. To name a few:

• carbon monoxide
• heavy metals, including antimony, arsenic, lead, mercury, and thalium
• bacterial, shellfish, and mushroom toxins
• ricin, nicotine, and likely other plant alkaloids
• rat poisons (got to fool the rats, yo)
  

Does testosterone destroy cartilage?

I sure hope not, 'cause I'm sure going to be in trouble otherwise. Y'know, because I'm a, err, tough manly man. Testosterone is an anabolic steroid, which means that it promotes the synthesis of macromolecules like protein. It has a role in the maintenance of muscle mass and bone density in adult life. Thus, I can't see why it would destroy cartilage. However, a study published in 2005 reported an association between higher blood testosterone levels and an increased rate of cartilage loss, so there you go.


Does 'X' get you high?

I get a tonne of these ones. Might I refer to you the mighty Erowid. They will know.

If you are dealing with opiate drug addiction, treatment options such as methadone detox are available that have been shown to be effective. Another useful method is suboxone detoxification.


http://en.wikipedia.org/wiki/Health_issues_and_the_effects_of_cannabis#Cancer_risk

Hall AP, Henry JA. Acute toxic effects of 'Ecstasy' (MDMA) and related compounds: overview of pathophysiology and clinical management. Br J Anaesth. 2006 Jun;96(6):678-85.

Hanna F et al. Factors influencing longitudinal change in knee cartilage volume measured from magnetic resonance imaging in healthy men. Ann Rheum Dis. 2005 Jul;64(7):1038-42. Epub 2005 Jan 7.