Disulfur decafluoride - Even awesome gas can't make Leno funny

The above is a video of Jay Leno (I'm a Letterman guy myself) and some dude playing with a gas called sulfur hexafluoride. It has no colour or odour and is neither toxic nor flammable. It's also denser than air, which means you can pour it into containers and float things on top of it and stuff. While this is, admittedly, pretty nifty, it also appears to have little to do with D&P. Fret not, oh reader, for if you pass high-voltage electricity through this impressively innocuous gas, it can decompose to produce disulfur decafluoride, a highly toxic phosgene-like pulmonary agent. A potential chemical weapon. Since sulfur hexafluoride is used as an insulator in electrical things like switchgear and transformers, it potentially poses a risk to lineworkers and electricians.



Monocrotaline (MCT) - The lung-killer

  • pneumotoxic macrocyclic pyrrolizidine alkaloid churned out by a number of exciting plants
  • causes a pulmonary vascular syndrome, which essentially means that a bunch of things go wrong with the blood supply to your lungs, including:
    • proliferative pulmonary vasculitis (spreading inflammation of the wall of blood vessels in the lung)
  • used to intentionally produce pulmonary hypertension in animals in order to create an experimental model for investigating the pathophysiology of pulmonary hypertension and the development of pharmacological means of treating it
  • has been hypothesized that it is biotransformed in the liver to a feisty little reactive metabolite that then travels via the blood to the lungs where it starts messing with endothelial cells, altering their function to cause detrimental structural changes in pulmonary blood vessels (particularly the arteries)
  • its selectivity for the lung likely has something to do with the way it is biotransformed by the liver and the manner in which blood circulates through the lungs (vs. any other part of the body)
Tanino Y. [Monocrotaline-induced pulmonary hypertension in animals] Nippon Rinsho. 2001 Jun;59(6):1076-80. Review. Japanese.
Wilson DW et al. Mechanisms and pathology of monocrotaline pulmonary toxicity. Crit Rev Toxicol. 1992;22(5-6):307-25. Review.


Bromethalin - Accidentally killing pets since 1985

  • bromine- and fluorine-containing diphenylamine-derived neurotoxic rodenticide
  • developed in 1985 in response to the rise of strains of rodents who were resistant to the effects of anticoagulant rodenticides (e.g. warfarin)
  • causes rodents to give up the ghost by uncoupling oxidative phosphorylation in the mitochondria of neurons, which depletes their cellular ATP stores and ultimately leads to axon damage and the disruption of normal neural communications producing paralysis, convulsions, and ultimately death
  • has been known to poison cats or dogs that eat rodents that have been killed by it (as well as those that simply eliminate the middleman by eating the rat bait itself)
  • no specific antidote, and while osmotic diuretics and corticosteroids may do something beneficial, the best way to deal with a poisoning is to eliminate it from the gastrointestinal tract (induce vomiting/give activated charcoal)
Pasquale-Styles MA et al. Fatal bromethalin poisoning. J Forensic Sci. 2006 Sep;51(5):1154-7.

Styrene (vinyl benzene) - The toxic precursor to the CD jewel case

  • sweet-smelling and rapidly-evaporating aromatic hydrocarbon used to manufacture a variety of different plastics (including polystyrene/Styrofoam), synthetic rubber, resins, and insulators
  • flammable and unstable, it likes to polymerize on its own slowly at room temperatures, and so is often stabilized with a polymerization inhibitor
  • produced au naturel by the decarboxylation of cinnamic acid, a bacteria-opposing compound found in numerous plants (including, you guessed it, cinnamon!)
  • is metabolized by the liver to, among other things, highly reactive epoxides that like to permanently bind to (by nucleophilic addition) and disrupt the function of cellular macromolecules including proteins and nucleic acids, leading to cytotoxicity, mutagenicity, and potentially carcinogenicity
  • irritates the respiratory tract, possibly by directly binding to mucosal nerve endings, and can cause bronchitis and pulmonary edema (which can kill you)
  • has been shown to cause CNS depression, impairment of long-term memory, and changes in liver histology (indicating possible liver damage) in rats
Gibbs BF, Mulligan CN. Styrene toxicity: an ecotoxicological assessment. Ecotoxicol Environ Saf. 1997 Dec;38(3):181-94. Review.


Asarone - I wonder what it smells like

  • volatile aromatic ether (structure) continuously brought into this cruel, cruel world by plants of the genus Acorus, particularly Acorus calamus and Acorus gramineus, and Guatteria gaumeri, a member of the Annonaceae family
    • oil of calamus, the essential oil of Acorus calamus, contains a significant amount of asarone, and has been used as a flavouring agent in the food and pharmaceutical industries and a scent in perfumes (these days the asarone is removed first)
  • comes in alpha and beta varieties (cis-trans isomers)
  • allegedly a precursor in the synthesis of 2,4,5-trimethoxyamphetamine (TMA-2), a psychedelic analog of mescaline that is used recreationally and has been sold semi-legally for “research purposes” (hehe)
  • the alpha form has been shown to inhibit a liver enzyme called HMG-CoA reductase, lowering blood cholesterol levels and increasing bile flow
    • HMG-CoA reductase is the rate-limiting enzyme in the mevalonate pathway (by which cholesterol is ultimately produced), such that when it is inhibited, the liver reacts by increasing the amount of low density lipoprotein (along with the "bad" cholesterol it carries) that is excreted via the bile (which you poop out), thus lowering LDL-cholesterol levels
    • statins (y'know, like Lipitor) also lower LDL-cholesterol levels by inhibiting HMG-CoA reductase
  • the beta form is active against a number of annoying bacterial and fungal plant pathogens as well as certain insects
  • both forms cause liver toxicity and cancer in rodents, likely as a result of their bioactivation to a reactive metabolite, putting a wee bit of a damper on drug development
- Hasheminejad G, Caldwell J. Genotoxicity of the alkenylbenzenes alpha- and beta-asarone, myristicin and elimicin as determined by the UDS assay in cultured rat hepatocytes. Food Chem Toxicol. 1994 Mar;32(3):223-31.
- Lee JY, Lee JY, Yun BS, Hwang BK. Antifungal activity of beta-asarone from rhizomes of Acorus gramineus. J Agric Food Chem. 2004 Feb 25;52(4):776-80.
- Rodriguez-Paez L et al. Alpha-asarone inhibits HMG-CoA reductase, lowers serum
LDL-cholesterol levels and reduces biliary CSI in hypercholesterolemic rats.
Phytomedicine. 2003;10(5):397-404
- http://www.inchem.org/documents/jecfa/jecmono/v16je04.htm
- http://en.wikipedia.org/wiki/Asarone


Orlistat (Xenical, alli, tetrahydrolipstatin) - Lose weight by pooping terribly and uncontrollably

I'm digging this post over at Angry 365 Days a Year. Dude basically tears the drug company a new one, which is fitting, given that this is essentially what the drug they are hawking does to you.

  • antiobesity drug derived from lipstatin, a bacterial compound that inhibits pancreatic lipase
    • pancreatic lipase is an enzyme that hangs out in your small intestine (after being secreted by your pancreas) and is responsible for breaking down (by hydrolysis) fats/oils from food that you eat into monoglycerides and free fatty acids (smaller bits of fat), which can then be absorbed and used by your body
    • so essentially, this drug acts to disrupt a perfectly normal digestive process to help you potentially lose weight
  • prevents the absorption of fats/oils from food, thus reducing the number of calories you actually rack up AND causing your poo to become oily and/or loose (this is known as steatorrhea, the fats/oils have to go somewhere!)
    • oily poo is disgusting
  • you also fart a lot, have to poo more often, and occasionally poop your pants (still interested?)
  • can disrupt the absorption of fat-soluble vitamins (A, D, E, and K) and, for some reason, cyclosporin
Bray GA, Ryan DH. Drug treatment of the overweight patient. Gastroenterology. 2007 May;132(6):2239-52.


Gossypol - How cotton plants can keep you warm, well-fed, and childless

  • polyphenolic toxin ushered into existence by cotton plants (genus Gossypium)
    • Gossypium sounds funny for some reason (am I alone in thinking this? Must cut back on the late-night blogging)
  • inhibits aldose reductase, an enzyme involved in the polyol pathway by which glucose is converted to sorbitol in the human body
    • the elevation of blood glucose levels in diabetes can lead to the accumulation of sorbitol in cells, which may contribute to diabetic complications including neuropathy, nephropathy, and retinopathy
    • therefore gossypol and other aldose reductase inhibitors could potentially be used to treat diabetic complications
  • has been and continues to be investigated as a possible male oral contraceptive, as it suppresses spermatogenesis (animation!) by some mysterious mechanism
    • lots of research was done in China during the 1970s
    • has not worked out since it has a low therapeutic index and causes things like hypokalemia (low blood potassium levels, results in fatigue and flaccid paralysis), GI upset, and permanent infertility (oops, we irreversibly damaged your testicles!) in some people
  • has been shown to inhibit the proliferation of tumour cells and the replication of HIV, making it a possible candidate for the development of new anticancer/antiviral drugs
  • some food scientists managed to figure out how to genetically engineer cotton plants so that their seeds, which are a friggin' phenomenal source of high-quality protein, contain only miniscule amounts of this toxin, thus rendering cotton plants a potential food crop!
- Kawanishi K, Ueda H, Moriyasu M. Aldose reductase inhibitors from the nature. Curr Med Chem. 2003 Aug;10(15):1353-74. Review.
- Waites GM, Wang C, Griffin PD. Gossypol: reasons for its failure to be accepted as a safe, reversible male antifertility drug. Int J Androl. 1998 Feb;21(1):8-12. Review.
- http://en.wikipedia.org/wiki/Gossypol


Alpha-Methyltryptamine (AMT) - Russian antidepressant turned American hallucinogen

  • synthetic tryptamine monoamine oxidase inhibitor invented by the Soviets (they called it Indopan) in the 1960s to treat people with depression

  • in addition to alleviating depression, it does other exciting things that have lead to its recreational use:
  • was essentially legal in the USA and available for purchase online prior to April 2003, at which point the DEA had it designated a Schedule 1 controlled substance because a college student died while on it
  • like psilocybin and DMT, acts at serotonin receptors (specifically, the 5-HT2 subtype) in the brain and disrupts serotonin breakdown (since it inhibits monoamine oxidase)
  • also called IT-290 and 3-IT
  • is closely related to alpha-ethyltryptamine (also called etryptamine, α-ethyltryptamine, α-ET, AET, and Monase), which has an ethyl group in place of a methyl group, and interestingly was initially developed in the USA as an antidepressant!
- Boland DM, Andollo W, Hime GW, Hearn WL. Fatality due to acute alpha-methyltryptamine intoxication. J Anal Toxicol. 2005 Jul-Aug;29(5):394-7.
- http://en.wikipedia.org/wiki/Alphamethyltryptamine
- http://en.wikipedia.org/wiki/Alpha-ethyltryptamine


Drugs and Poisons On Teh Interwebs

The U.S. Army 'fesses up to having secretly dumped millions of pounds of chemical weapons (arsenic trichloride, hydrogen cyanide, lewisite, mustard gas, various nerve gases, phosgene, and white phosphorus) off the coast of America
GlaxoSmithKline announces plans to introduce five new cancer drugs (cervarix, pazopanib, promacta, rezonic and ofatumumab) by 2010

Snopes determines that some crazy photographs of a tonne of cash made from illegal drug sales are authentic

A Canadian high school student gets suspended for suggesting that marijuana is safer than alcohol

Tamiflu is still making Japanese people crazy

Reader experiences: The readers respond

See my previous post for the lowdown. Much thanks to all who emailed me. If you have not, you are still welcome to do so. I'll keep posting these things until the cows come home. And trust me, cows do not come home. They just wander around and eat grass. And excrete. Anyway, dig these drug/poison stories:

When hospitalized for a serious (and ill-gotten) ankle injury that had required immediate surgery, I was given Demerol. To cut a long and disgusting story involving a rather bothersome absence of renal function short, that night I threw up 22 times before I lost count. It took the hospital staff approximately 6 hours to notice, and when they finally did, they switched me to morphine. Morphine caused me to feel as though there were ants crawling all over me under my skin, and also caused the dots on the ceiling (I still don't know if those were even real) to pulse and move around a bit. That made counting them difficult.

- Toaster


I love reading your blog... I'm a freak that way.

Lessee... in the drug department how about my personal fave... Rebif (or for that matter any of the other interferons used to treat Multiple Sclerosis? Interesting crap to shoot as far as I am concerned. Nobody knows how it works, or even if it is working on one, but theoretically it decreases the frequency of attacks. It sure costs a pretty penny. I think the best part about Rebif is that if you look closely at the box it comes in, in tiny letters it says "Made from Chinese Hamster Ovaries." I love that part. In a very stand-up comedy technique I always comment that if that's the case... you would think that it would be in HUGE BLOCK PRINT all over the box, but go figure.

In the poison department how about Methyl Isocyanate? I really enjoyed reading about the Bhopal disaster in the book "Five Past Midnight in Bhopal" by Dominique Lapierre. I have an interest in the relation of human error and behavioral psychology and that one's a doozy.

Bob Berger


SSRIs (originally Zoloft and now Lexapro) have been effective at treating my crippling social anxiety. I think it's fair to say that they're the best thing that's ever happened to me.

As for recreational drugs, I've tried most of the common ones but only really enjoy the occasional bit of ethanol, N2O, dextro-methylphenidate and theobromine.

- Steve


I tend not to take much in the way of drugs; a bit of alcohol now and then and that's about it.

Some years back I needed a some outpatient surgery. They weren't going to put me under, just give me a some IV Valium to take the edge off any anxiety I might be experiencing.

I'm all preped for the surgery; shaved, cleaned and local adminstered. They slid a needle into my ACF vein and asked me to count back from 100. "Just like the movies" I'm thinking - what a joke... "100, 99, WHOOAAAHHHH!" Like drinking a 6 pack in 1 second. Total head rush. Eyes dialate, world gets all light and warm, head is tingly..

Daddy LIKE!

As good as the initial rush was the fact that there was no hangover.
Drunk...not drunk... Sweet!

I am SO glad this stuff isn't sold in stores otherwise I'd be high all the time.

Modern medicine; you gotta love it.

- Doug


Reader experiences: What a particular drug or poison has done for/to you

Howdy. In an effort to make my blog a little less clinical and a little more inviting, I have decided to embark on an endeavor that requires your assistance, oh devoted reader. What I want is a story; a story of how a particular drug or poison has impacted your life. Maybe your younger brother accidentally drank a bunch of antifreeze and had to have his stomach pumped. Maybe a friend has cancer and is betting on a particular anticancer drug to save their life. Maybe you just drank a couple of bottles of Robitussin and hallucinated a giant sea cucumber that knighted you and revealed why yawns are contagious (please tell me). In any event, type out an email and send it to [email protected]. Oh, and if you'd rather just write a post on a particular drug/poison in the style that I've been employing (i.e. bullet points and hopefully dry wit), you are welcome to do that as well. Much thanks! I promise to link to your website should you have one and say something nice about you.

To get the ball rolling, here is a story about my experience with a particular antibiotic. It is entitled "How amoxicillin ruined banana Popsicles forever" and here it is:

When I was but a wee lad of three, a pathogenic bacterium took a liking to my tonsils and decided to move in and have a tonne of kids. Over the course of the following year I suffered numerous bouts of tonsillitis. I got sick, recovered, and then got sick again. It sucked. My throat was sore, I ran a fever, and I either couldn't swallow because my throat was so swollen or wouldn't swallow because it hurt so darn much. Given that my tonsillitis was bacterial in origin, I was put on antibiotics. I started out with penicillin V, and when that didn't appear to be doing the job, I moved on to amoxicillin and finally ended up on pondicillin. Then a surgeon put me to sleep and cut my tonsils out with a scalpel and all was well in the world.

I hated the amoxicillin the most. At the time of my illness, it was formulated as a thick banana-flavoured syrup. The quite evidently artificial banana taste did little to mask the underlying bitter unpleasantness of the drug, and I quickly grew to despise my daily dosings. Being too young to understand why I had to take it and utterly miserable because of my illness didn't help things along. It was a couple years post-tonsils that I tried my first banana Popsicle. And retched. It's exactly the same flavour as the amoxicillin was. And to this day, I can't eat yellow Popsicles.

Terbinafine (Lamisil, Zabel) - Because fungus-infested toenails are really gross

  • allylamine-containing antifungal/antimycotic/killer-of-fungi
  • does its thing by inhibiting squalene epoxidase, a fungal enzyme that is required for the synthesis of ergosterol, a necessary component of fungal cell membranes
  • in addition, inhibition of this enzyme results in its substrate, squalene, accumulating to toxic levels within fungal cells, providing a second avenue of destruction
  • administered topically (e.g. as a cream or ointment) to kill dermatophytes (parasitic fungi that infect the skin), including those responsible for jock itch, athlete's foot, and ringworm
  • administered orally to treat fungal nail infections, since they are usually deep beneath the nail in the cuticle and so protected from topical preparations
    • is highly soluble in fat/lipid, which means that it is rapidly absorbed and widely distributed throughout the body following administration
    • accumulates in the cuticles and kills the fungus
  • has been linked to liver toxicity, including things like cholestatic hepatitis, possibly mediated by a metabolite of the drug
    • thus it is important to monitor liver function during therapy with the drug
- Ajit C, Suvannasankha A, Zaeri N, Munoz SJ. Terbinafine-associated hepatotoxicity. Am J Med Sci. 2003 May;325(5):292-5.
- Darkes MJ, Scott LJ, Goa KL. Terbinafine: a review of its use in onychomycosis in adults. Am J Clin Dermatol. 2003;4(1):39-65.
- http://en.wikipedia.org/wiki/Terbinafine


Niacin (nicotinic acid, vitamin B3, Niaspan) - Vitamin AND lipid drug

  • water-soluble vitamin that is synthesized by the human body from tryptophan, an essential amino acid that has many dietary sources and is also a precursor to serotonin
    • this process is rather inefficient, so dietary sources are important as well
  • serves as a precursor to the coenzymes NAD+/NADH and NADP+/NADPH, which serve as electron carriers in the grand process that is cellular respiration (energy production)
  • can also be produced by the oxidation of nicotine (thus nicotinic acid), but is most commonly referred to as niacin (nicotinic acid + vitamin) to dissociate it from nicotine, which has obvious negative connotations (see: tobacco addiction)
  • a deficiency in this vitamin can result in pellagra, a disease that features "the four D's": diarrhea, dermatitis, dementia, and DEATH
  • in addition to being a vitamin (in milligram doses), is employed in gram doses as a broad-spectrum lipid drug that lowers plasma cholesterol levels
    • reduces the plasma levels of low density lipoprotein (LDL, "bad" cholesterol) by inhibiting lipolysis (breakdown of fat) in adipose tissue, which decreases plasma levels of free fatty acids, which in turn reduces the secretion of very low density lipoprotein (VLDL), the precursor to LDL, by the liver
    • also increases the plasma levels of high density lipoprotein (HDL, "good" cholesterol)
    • appears to do these things by acting via a specific receptor on fat cells and stimulating the expression of a particular cholesterol transporter
  • has been used by individuals trying to avoid a positive drug test result for fat soluble drugs like marijuana, but there is no scientific basis to this use AND you risk overdosing yourself, which can kill you or cause serious harm (liver damage, arrhythmias, metabolic acidosis, etc.)
  • has been shown to cause birth defects in lab animals at pharmacological doses
Carlson LA. Nicotinic acid: the broad-spectrum lipid drug. A 50th anniversary review. J Intern Med. 2005 Aug;258(2):94-114.


Metaldehyde - Accidental annihilator of slimy things (and occasionally people)

  • cyclic polymer of acetaldehyde (like paraldehyde only more grandiose) that has a funky-lookin' chemical structure
  • first used as a combustible fuel ("meta-fuel" tablets) in Europe in the 1920s
  • discovered to be an effective molluscicide (murders innocent slugs and snails) by accident in the 1930s
    • how it apparently happened: "A lady who was using [metaldehyde] to heat her curling tongs threw the remains out the window afterwards and observed an assemblage of dead slugs"
  • has also been in cloud seeding experiments
  • in addition to molluscs, is toxic to all other animals, and has been reported to be responsible for poisonings of pets, wild animals, and birds
  • toxicity in humans is generally mild (gut pain, dizziness, barfing, seizures) but occasionally fatal
    • its toxic effects may be produced directly or by its metabolites, which include acetaldehyde (acetaldehyde poisoning produces a similar symptom complex)
    • death is usually the result of the depression of brain regions responsible for controlling your lungs and heart
  • has been shown to reduce brain levels of norepinephrine and serotonin in mice, and this effect was reduced with clonidine or diazepam
- Homeida AM, Cooke RG. Pharmacological aspects of metaldehyde poisoning in mice. J Vet Pharmacol Ther. 1982 Mar;5(1):77-81.
- Longstreth WT Jr, Pierson DJ. Metaldehyde poisoning from slug bait ingestion. West J Med. 1982 Aug;137(2):134-7. No abstract available.
- Shih CC et al. Acute metaldehyde poisoning in Taiwan. Vet Hum Toxicol. 2004 Jun;46(3):140-3.
- http://en.wikipedia.org/wiki/Metaldehyde


Drugs and Poisons On Teh Interwebs

Behavioral Ecology Blog - Where poison dart frogs get their poison (cool, kind of like these birds)

Instructables - DIY Kitty Crack (extraction of nepetalactone from catnip by steam distillation)

Overcompensating - Chinese Death Toothpaste (a great comic strip)

Passive-aggressive notes.com - roommate poison (guessing this was in jest, otherwise ouch!)

Los Angeles Times - A new drug may clear the haze of chemo (sweet)

MSNBC.com - Spider venom may yield virility (also sweet)

Is Britney Spears dating her drug counselor? (OMG! tell me more, useless media outlets!)


Acetohydroxamic acid (AHA, Lithostat) - Keeping pee acidic and bacteria-free

  • irreversible inhibitor of urease, an enzyme found in bacteria, yeast, and plants that hydrolyzes (breaks down) urea into carbon dioxide and ammonia
  • urea is a human waste product found in urine and sweat that has an impressive number of industrial uses
  • certain urease-producing pathogenic bacteria, including Helicobacter pylori and Proteus mirabilis, are able to infect the stomach and/or urinary tract by increasing the pH of these environments, which normally are too acidic for them to set up shop
  • since ammonia is alkaline, it neutralizes gastric (stomach) acid/urine, facilitating the invasion of stomach/urinary tract mucosa by the bacteria
  • can be used to treat urinary tract infections (UTIs), struvite stones (urinary stones associated with UTIs), and gastritis caused by urease-producing bacteria
  • also can be used to prevent the encrustation and blockage of urethral catheters in cases of UTIs caused by urease-producing bacteria, as an increase in urine pH can cause the crystallization of calcium and magnesium salts present in urine
- Griffith DP, Khonsari F, Skurnick JH, James KE. A randomized trial of acetohydroxamic acid for the treatment and prevention of infection-induced urinary stones in spinal cord injury patients. J Urol. 1988 Aug;140(2):318-24.
- Morris NS, Stickler DJ. The effect of urease inhibitors on the encrustation of urethral catheters. Urol Res. 1998;26(4):275-9.
- Ohta T, Shibata H, Kawamori T, Iimuro M, Sugimura T, Wakabayashi K. Marked reduction of Helicobacter pylori-induced gastritis by urease inhibitors, acetohydroxamic acid and flurofamide, in Mongolian gerbils. Biochem Biophys Res Commun. 2001 Jul 20;285(3):728-33.


Centrophenoxine (meclofenoxate, Lucidril) - Stop your brain from rotting away

  • used to improve memory and general cognition in people with dementia (including dementia induced by Alzheimer's disease)
    • there is currently no cure for dementia (boo!), but a number of drugs are available to slow its progression (half-hearted yay!)
  • also has been shown to be useful for treating cerebral atrophy (i.e. your brain rotting away) as well as brain injury due to trauma, chronic alcoholism (e.g. W-K syndrome), and aluminum and barbiturate intoxication (poisoning)
  • consists of dimethylaminoethanol (DMAE) joined by an ester linkage to parachlorophenoxyacetate (pCPA)
    • DMAE is a natural compound found in things including fish and the human brain that is converted by the brain into acetylcholine, a neurotransmitter that is thought to have roles in memory and cognition
    • DMAE is also able to scavenge (detoxify) free radicals, which can potentially help to reduce brain damage following injury
    • pCPA is a synthetic compound that structurally resembles plant hormones called auxins and, being relatively lipid-lovin', is thought to improve the ability of the drug to cross the blood-brain barrier and get into the brain
  • has been shown to stimulate brain metabolism, increase the lifespan of lab animals (antiaging effects) and improve learning capacity (nootropic effects)
Nehru B, Bhalla P, Garg A. Evidence for centrophenoxine as a protective drug in aluminium induced behavioral and biochemical alteration in rat brain. Mol Cell Biochem. 2006 Oct;290(1-2):33-42. Epub 2006 Sep 13.


Alosetron (Lotronex) - Making life a little less crappy

  • used to treat the symptoms associated with the diarrhea-predominant form of irritable bowel syndrome (IBS-D), a wonderful functional bowel disorder that features gut pain and the sloppy poops
  • blocks a specific subtype of serotonin receptor (5-HT3) that is found in a number of locations in the body including the gastrointestinal (GI) tract
    • serotonin is a neurotransmitter involved in, among other things, the transmission of neural signals that control the initiation of peristalsis, GI secretory reflexes, enteric nervous system (ENS) function, and feedback to the brain and spinal cord
      • the ENS is a special little nervous system that the GI tract has all to itself
    • is thought that the 5-HT3 receptor subtype has a role in the pathophysiology of IBS, which is why this drug was developed
  • has a structure that is similar to ondansetron, a 5-HT3 blocker that is used to treat the nausea and vomiting associated with chemotherapy (alosetron does not share this antiemetic effect)
  • for some strange and utterly mysterious reason, this drug only improves IBS-D symptoms in females (tough luck, dudes)
  • the big issue with this drug is that it has two particularly terrible and potentially life-threatening GI side effects:
    1. constipation with serious complications including obstruction, perforation (my personal favourite), impaction, toxic megacolon, and secondary colonic ischemia (which is essentially #2 caused by the constipation)
    2. ischemic colitis
  • although these conditions are fairly rare, they are serious enough that the drug was removed from the US market in 2000 (it was reintroduced in 2002 with greater restrictions on its use and availability)
Gallo-Torres H, Brinker A, Avigan M. Alosetron: ischemic colitis and serious complications of constipation. Am J Gastroenterol. 2006 May;101(5):1080-3.


Microbial maladies: Bacterial toxins and the diseases they produce

Mother nature is one twisted old crone. Sure, she's all cute baby animals and pretty flowers and impressively intricate termite colonies, but mark my words, that lady's also got a toxic side. From tiny microbes to towering trees, there exists in this world a multitude of organisms working 'round the clock to synthesize substances capable of killing other living things, including us.

Take bacteria. Within a single genus, Clostridium, you've got:

Clostridium botulinum
Maker of one of the most toxic substances known to exist, botulinum toxin. This badass protein binds to and disrupts the action of nerves that control muscle movement, resulting in paralysis. Death occurs due to asphyxiation, since your diaphragm and all the other muscles that you need to inhale stop working.

Clostridium tetani
Responsible for tetanus (i.e. rusty nail disease), due to its production of tetanospasmin. This downright sinister protein binds to neurons in your brain and spinal cord, preventing the release of inhibitory chemicals that normally keep them from becoming overactive. Hence, your central nervous system goes loco, leading to seizures and tetanic muscle spasms (your muscles contract for long periods of time, during which you are paralyzed) that are so friggin' strong that they can snap your bones. The muscle paralysis occurs first in your face and jaw, producing a characteristic face paralysis (risus sardonicus) and lockjaw.

Clostridium difficile
The scourge of hospitals everywhere, this mofo produces two toxins called enterotoxin and cytotoxin that destroy the cells lining your intestine, resulting in diarrhea and inflammation. Responsible for a very considerable number of hospital deaths and resistant to lots of antibiotics.

Clostridium perfringens
Produces toxins that can cause exciting things like food poisoning and severe infections featuring gas gangrene.

I'm telling you, bacteria are a venerable gold mine of toxic compounds. Some other bacteria and their toxins that are worth noting:

Vibrio cholerae
Causer of cholera, which features intense bouts of diarrhea. So intense, in fact, that if left untreated, you can die within hours of the first squirt since you become so severely dehydrated. The trots are the work of cholera toxin, an enterotoxin that acts on the lining of the small intestine.

Bacillus anthracis
Produces three distinct proteins that together are referred to as anthrax toxin. None of the three cause problems on their own, but when they are brought together they become a neigh-unstoppable force of utter pestilence. Anthrax is interesting because it comes in three different flavours, depending on how the bacteria gets into you. You breathe it in, you get pulmonary anthrax. You eat an infected cow, you get GI anthrax. You smear some bacterial spores in a cut, you get cutaneous anthrax. All three forms can kill you dead.

Corynebacterium diphtheriae
Diptheria comes in respiratory and cutaneous forms. The cutaneous form is pretty gross. Google it if you dare. Diptheria toxin gets into cells and inhibits their ability to make proteins, which is a pretty essential part of being a healthy and normal cell, resulting in cell death. As this is a generally bad thing, you get sick.

Streptococcus pyogenes
Not content to just produce a single toxin, this bacterium produces a whole wack of 'em. The most exciting of these are streptolysin O and S, which destroy blood cells. Toxins from this bacterium are responsible for a number of diseases, including strep throat, impetigo, scarlet fever, necrotizing fasciitis, and toxic shock syndrome.


Grayanotoxin - Turkish mad honey and third-degree heart block

  • also called andromedotoxin, acetylandromedol, and rhodotoxin by science people who can't seem to agree on one name (seriously, form a committee and get this sorted out, science people! I don't indirectly pay for some of your research for nothing, you know! I want clarity!)
  • sublimely synthesized by a considerable number of plants belonging to the family Ericaceae, in particular, several of those of the genus Rhododendron
  • is occasionally found in honey from Turkey (especially around the Black Sea) as a result of bees collecting nectar from certain species of Rhododendron that grow in the area
    • this honey is called 'mad honey' ('deli bal' in Turkish) and people have been reporting that it makes them puke since 401 BCE
    • mad honey is still a common source of food poisoning in Turkey, likely because it is also used as an alternative medicine AND there is an increasing demand for 'natural' products
    • the locals can apparently tell when the honey is poisonous, as it causes a burning sensation in the throat following consumption
  • binds to and inhibits the closing of (i.e. persistently activates) sodium channels, causing excitable tissues (muscle and nerve) to become overexcited (due to sustained depolarization)
    • this can lead to things like muscle weakness, puking, excess sweating and salivating, and in cases of more severe poisoning, potentially life-ending heart problems like third-degree atrioventricular (AV) block as well as seizures and hypotension
Gunduz A, Turedi S, Uzun H, Topbas M. Mad honey poisoning. Am J Emerg Med. 2006 Sep;24(5):595-8.