tag:blogger.com,1999:blog-376239122007-08-16T22:15:10.861-04:00Drugs and PoisonsCNDBlogger136125tag:blogger.com,1999:blog-37623912.post-7624130881850126212007-08-15T20:03:00.000-04:002007-08-15T21:09:51.620-04:00Rasburicase (Elitek, Fasturtec) - 'Cause curing cancer can cause catastrophe<ul><li>recombinant form of <a href="http://en.wikipedia.org/wiki/Urate_oxidase">urate oxidase</a> (uricase), a <a href="http://en.wikipedia.org/wiki/Peroxisome">peroxisomal</a> enzyme that catalyzes the transformation of <a href="http://en.wikipedia.org/wiki/Uric_acid">uric acid</a>, a waste product of nucleic acid (<a href="http://en.wikipedia.org/wiki/Purine">purine</a>) catabolism, into a more water soluble molecule called <a href="http://en.wikipedia.org/wiki/Allantoin">allantoin</a>, thus facilitating the removal of uric acid by the kidneys</li><ul><li>this enzyme is found throughout the five kingdoms, including in most animals, but the gene that encodes it in humans is no longer functional (likely due to a sudden significant mutational event)</li></ul><li>used to treat hyperuricemia (abnormally high levels of uric acid in the blood), which can lead to kidney damage</li><ul><li>gout (a variety of arthritis) is the result of low-level, long term hyperuricemia</li></ul><ul><li>hyperuricemia is usually due to either reduced removal of uric acid by the kidneys or increased production of uric acid due to things like a deficiency in HGPRT (Lesch-Nyhan syndrome, Kelley-Seegmiller syndrome), eating too much purine-rich foods (meats, alcohol, legumes), and tumour lysis syndrome (TLS)</li></ul><li>TLS refers to a bunch of metabolic problems that can occur when chemotherapy successfully kills a bunch of cancer cells</li><ul><li>usually associated with hematologic cancers like lymphomas and leukemias</li></ul><ul><li>cells tend to concentrate certain ions within their cytoplasm, so when a whole whack of them are killed en masse, these ions are released into the blood, causing things like hyperkalemia and hyperphosphatemia (leading to hypocalcemia)</li></ul><ul><li>the degradation of all of the nucleic acid released from the destroyed cancer cells can lead to a rapid and impressively huge rise in uric acid, capable of precipitating acute renal failure</li></ul><li>since it is produced using non-human cells, the immune system can mount an allergic reaction against it, and the development of antibodies that bind it all up can lead to a reduction in efficacy<br /></li></ul><span style="font-size:85%;">- Cammalleri L, Malaguarnera M. Rasburicase represents a new tool for hyperuricemia in tumor lysis syndrome and in gout. Int J Med Sci. 2007 Mar 2;4(2):83-93. Review.<br />- Wu XW, Lee CC, Muzny DM, Caskey CT. Urate oxidase: primary structure and evolutionary implications. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9412-6. <a href="http://www.pnas.org/cgi/content/abstract/86/23/9412">[link]</a></span>CNDtag:blogger.com,1999:blog-37623912.post-77798948595698583822007-08-13T21:41:00.000-04:002007-08-14T21:43:44.886-04:00Shiga Toxin - Two words: bloody diarrheaToday's post is compliments of Toaster, who knows a whole lot about <a href="http://www.drugsandpoisons.com/2007/06/microbial-maladies-bacterial-toxins-and.html">bacterial toxins</a>. Check out his website, <a href="http://madscientistjunior.blogspot.com/">Mad Scientist, Jr.</a><a onclick="return top.js.OpenExtLink(window,event,this)" href="http://madscientistjunior.blogspot.com/" target="_blank"></a><br /><br />Background:<br />Bad-ass hexameric molecule produced by some strains of your friendly neighborhood bacteria, most notably <a href="http://textbookofbacteriology.net/Shigella.html"><span style="font-style: italic;">Shigella dysenteriae</span></a> (named after <a href="http://www.whonamedit.com/doctor.cfm/3000.html">Kiyoshi Shiga</a>, who discovered them in 1898: "Hmm...I wonder what this bloody diarrhea looks like under my microscope?") and <a href="http://en.wikipedia.org/wiki/Escherichia_coli"><span style="font-style: italic;">Escherichia coli</span></a>.<br /><br />Structure:<br />Once again, <a href="http://www.chem.duke.edu/%7Etoone/labgroup/1BOSx500.jpg">hexameric</a><a onclick="return top.js.OpenExtLink(window,event,this)" href="http://www.chem.duke.edu/%7Etoone/labgroup/1BOSx500.jpg" target="_blank"></a> (although this a picture of SLT-1, which warrants a discussion on nomenclature)<br /><br />Nomenclature:<br />This terminological mess once confused me, I hope this will make it clearer for you. True Shiga toxin is made by <span style="font-style: italic;">S. dysenteriae</span>, although several strains of <span style="font-style: italic;">E. Coli</span> (collectively termed STEC, which includes EHEC, the stuff that was on spinach <a href="http://microbiologybytes.wordpress.com/2006/09/26/e-coli-o157h7-spinach-outbreak/">recently</a>) also make very closely<br />related toxins. Shiga-like toxin 1 is made by STECs and differs from <span style="font-style: italic;">S. dysenteriae</span> by only 1 amino acid, while Shiga-like toxin 2, also made by STECs, has ~60% <a href="http://rucus.ru.ac.za/%7Ewolfman/Essays/Sequence.html">sequence homology</a> with Shiga-like toxin 1. However, most microbiologists refer to Shiga toxins interchangeably,<br />and may call any of the above Shiga toxins (abb. Stx), verotoxins, or verocytotoxins, leading to a lot of people being very often confused and frustrated, which I think that microbiologists secretly enjoy.<br /><br />Back to Structure:<br />So, Shiga toxins are <a href="http://www.chem.duke.edu/%7Etoone/labgroup/1BOSx500.jpg">hexameric</a>, with 6 distinct subunits: 5 B subunits and 1 A subunit per molecule. The whole thing is shaped like a big hook (A subunit) with a fan at one end (the B subunits).<br /><br />Genetics:<br />From what I understand, Shiga toxin generally isn't encoded in the genome of <span style="font-style: italic;">E. Coli</span> strains that produce it (I don't know about <span style="font-style: italic;">Shigella</span> strains), but is instead encoded in the genome of a <a href="http://pathmicro.med.sc.edu/mayer/phage.htm">bacteriophage</a> that infects most of the bacteria in a population of STECs. So when the<br />bacteriophage is induced from its happy little quiet <a href="http://en.wikipedia.org/wiki/Lysogenic_cycle">lysogenic phase</a> to the <a href="http://en.wikipedia.org/wiki/Lytic_cycle">lytic phase</a> it fills the bacteria up with Shiga toxins until the bacteria bursts like a sticky balloon of kidney death.<br /><br />Pathophysiology:<br />Shiga toxin will <a href="http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mmed.chapter.1257">mess</a> you up. Seriously. Like, no joke. The <a href="http://en.wikipedia.org/wiki/LD50">LD<span style="font-size:85%;">50</span></a> for Shiga-like toxin 2, calculated upwards from animal studies, for a 60kg person would be approximately 3 milligrams. Luckily, true Shiga toxin and Shiga-like toxin 1 are about 400 times less toxic.<br /><br />In any event, playing pretend is a good way to learn. So let's say you eat some undercooked beef that's been contaminated with poop. The STECs manage to colonize your digestive system and start sticking to your intestinal <a href="http://ect.downstate.edu/courseware/histomanual/epithelia.html">epithelia</a>. At this point, bloody diarrhea begins. But<br />as the bacteria pop and release Shiga toxin everywhere, some of it is going to wind up in your bloodstream. And, like anything that gets into your bloodstream, it winds up pretty much everywhere in your body. But Shiga toxin affects mostly renal tissue, hepatic tissue, <a href="http://en.wikipedia.org/wiki/Endothelium">endothelial</a> cells, and the central nervous system, where it can wreak cellular havoc.<br /><br />It's best understood how Shiga toxin affects <a href="http://dictionary.reference.com/search?q=renal">renal</a> tissue, which is to say, it targets <a href="http://www.siumed.edu/%7Edking2/crr/rnguide.htm#distal">distal tubules</a> and the <a href="http://www.siumed.edu/%7Edking2/crr/rnguide.htm#glomerulus">glomerular thingies</a> because these tissues express an abnormally large amount of globotriaosylceramide, a <a href="http://en.wikipedia.org/wiki/Lipid">lipid</a> also known as Gb3, which Shiga toxin binds to very strongly. This is highly unusual because lipids don't normally function as receptors. No one knows why this is or why it happens here. Nonetheless, it is the B subunits of the Shiga toxin that bind Gb3<br />(interestingly, Stx-B subunits have been found to be very potent <a href="http://dictionary.reference.com/search?q=adjuvant">adjuvants</a>) and somehow (once again, no one knows) get the Shiga toxin into the cell, where the A subunit dissociates from the B subunits and binds to one of the subunits of the <a href="http://en.wikipedia.org/wiki/Ribosome">ribosomes</a>, essentially shutting all protein synthesis down, which is very, very bad for your cells.<br /><br />It has been hypothesized, but not conclusively determined, that Shiga toxin plays a role in the development of HUS. HUS is not good. It stands for <a href="http://www.emedicine.com/emerg/topic238.htm">hemolytic uremic syndrome</a> and involves your red blood cells being transformed from their normal fat happy selves into ragged hunks<br />of cellular detritus. This condition is associated with infection with STECs (e.g., H7:O157) and usually only happens in those who are very young, old, or <a href="http://en.wikipedia.org/wiki/Immunodeficiency">immunocompromised</a>.<br /><br />Then come the complications of Stx interaction with LPS, but that is an entirely different post.<br /><br /><span style="font-size:85%;">- Palermo M et al. Pretreatment of mice with lipopolysaccharide (LPS) or IL-1beta exerts dose-dependent opposite effects on Shiga toxin-2 lethality. Clin Exp Immunol. 2000 Jan;119(1):77-83.<br />- Warnier M et al. Trafficking of Shiga toxin/Shiga-like toxin-1 in human glomerular microvascular endothelial cells and human mesangial cells. Kidney Int. 2006 Dec;70(12):2085-91. Epub 2006 Oct 25.<br /><a onclick="return top.js.OpenExtLink(window,event,this)" href="http://madscientistjunior.blogspot.com/" target="_blank"></a></span>CNDtag:blogger.com,1999:blog-37623912.post-34301170496228963942007-08-12T23:15:00.000-04:002007-08-12T23:33:41.972-04:00Reader experiences: Demerol horror storyHey folks. Here's a story:<br /><br /><span style="color: rgb(255, 102, 102);">My experience with Demerol</span><br /><br /><span style="color: rgb(255, 102, 102);">When I was 14 years old, it was determined that I required a spinal fusion to correct a congenital birth defect with one of my vertebrae. (Congentical kyphosis, for those interested.) The operation itself went ok, with the possible exception that the instrumentation failed near the end of the surgery and they had to extend the fusion down one slot, resulting in only 2 vertebrae left to do my bending for me for the rest of my life. (The Xrays now, 20 years later, are not pretty. Not pretty at all.)</span><br /><br /><span style="color: rgb(255, 102, 102);">In any case, after the surgery, <a href="http://www.drugsandpoisons.com/2006/11/meperidine.html">Demerol</a> was selected as the pain killer of choice. After administration, about 10 minutes later, I basically had a low-grade heart attack. I had heart fibrillation, and they called in a heart specialist who managed to keep me alive for the short term, while I was off day-tripping some near-death light-at-the-end experience.</span><br /><br /><span style="color: rgb(255, 102, 102);">They determined that I had an extremely adverse reaction to the Demerol. As a result, they decided to eliminate all pain killers from my system for 48 hours, and then start me on straight morphine (mmmmm...smack...), since almost no one rejects the GOOD stuff. Now, my spine had been flayed open literally, metal clamps screwed down all over the place, and bone scraped from my hip to cover the instrumentation and start my body completing the fusion by itself. And staples to close it all up. With no pain killers.</span><br /><br /><span style="color: rgb(255, 102, 102);">48 hours.</span><br /><br /><span style="color: rgb(255, 102, 102);">My parents learned every single bad word I ever knew, and some I even made up. The ICU was in a children's hospital, and for some weird reason they had these recessed little panels right above each bed, with Biblical scenes of smurfs in them. (Seriously. I checked later. This is not the lack-of-smack talking.) I talked to Papa Smurf as he loaded the smurfs 2-by-2 on to the Ark. I warned him about flood plains, levees, and the force of water and riptides. I urged him to get a move-on or everyone was gonna' die. The nurses and my family had no idea what I was talking about. They assumed I had lost my mind.</span><br /><br /><span style="color: rgb(255, 102, 102);">I only remember a few things, one of which was this: I remember waking up, feeling like I had been in that bed for days and days and days. I looked over and a nurse was there, next to my bed. I asked her what day it was. She asked me what day I thought it was. (Grrrrrr...) The operation was on Sunday, so I thought I'd be conservative and say "Tuesday" even though it had to be Thursday at the earliest. She got this very sad look on her face and said "No, I'm sorry, it's been three minutes since the last time you woke up and asked me that very same question."</span><br /><br /><span style="color: rgb(255, 102, 102);">This pain would never, ever, ever, ever, ever end.</span><br /><br /><span style="color: rgb(255, 102, 102);">But, of course, it did, and they gave me morphine, and everything was coolio after that.</span><br /><br /><span style="color: rgb(255, 102, 102);">Not the best way to discover that Demerol will kill you...</span><br /><br /><span style="color: rgb(255, 102, 102);">- Trey</span>CNDtag:blogger.com,1999:blog-37623912.post-23849886046056367182007-08-11T14:20:00.000-04:002007-08-11T20:24:18.204-04:00Sanguinarine - How toothpaste can cause cancer and mustard can cause swollen limbs<ul><li>quaternary <a href="http://cancerweb.ncl.ac.uk/cgi-bin/omd?phenanthridine">benzophenanthridine</a> <a href="http://en.wikipedia.org/wiki/Glycoside">glycoside</a> alkaloid synthesized by plants belonging to the <a href="http://www.botany.hawaii.edu/Faculty/Carr/papaver.htm"><span style="font-style: italic;">Papaveraceae</span></a>, <a href="http://en.wikipedia.org/wiki/Fumariaceae"><span style="font-style: italic;">Fumariaceae</span></a>, and <a href="http://www.botany.hawaii.edu/Faculty/Carr/rut.htm"><span style="font-style: italic;">Rutaceae</span></a> families</li><ul><li>quaternary compounds possess a permanent positive charge, making them exceedingly lousy at passing through fatty things like cell membranes</li><li>specific plants include <a href="http://en.wikipedia.org/wiki/Bloodroot"><span style="font-style: italic;">Sanguinaria canadensis</span></a> (Bloodroot), <a href="http://en.wikipedia.org/wiki/Greater_celandine"><span style="font-style: italic;">Chelidonium majus</span></a> (Greater celandine), and <a href="http://en.wikipedia.org/wiki/Argemone_mexicana"><span style="font-style: italic;">Argemone mexicana</span></a> (Mexican prickly poppy)</li></ul><li>the seeds of <span style="font-style: italic;">Argemone mexicana</span> look very much like mustard seeds, which can (and <a href="http://www.ajcn.org/cgi/content/abstract/28/8/883">has</a>) lead to the <a href="http://www.itg.be/itg/DistanceLearning/LectureNotesVandenEndenE/47_Medical_problems_caused_by_plantsp8.htm">adulteration</a> of foods cooked using mustard oil with sanguinarine</li><ul><li>people consuming said foods this thing called <a href="http://en.wikipedia.org/wiki/Epidemic_dropsy">epidemic dropsy</a>, which features such exciting symptoms as your limbs swelling up (extremity swelling with pitting edema), anemia, heart failure, renal failure, and glaucoma</li></ul><li>found in some mouthwashes and toothpastes since it kills bacteria (helping to reduce <a href="http://en.wikipedia.org/wiki/Dental_caries">dental caries</a>) and has antiinflammatory effects (apparently helping to reduce gingivitis)</li><ul><li>Viadent, a toothpaste/mouthwash brand that contains sanguinarine, has been linked to oral <a href="http://www.mayoclinic.com/health/leukoplakia/DS00458">leukoplakia</a></li></ul><li>has been shown to induce <a href="http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/A/Apoptosis.html">apoptosis</a> in certain cancer cell lines, possibly related to its ability to inhibit the activation of nuclear transcription factor NF-kB (which is involved in regulating cell growth and apoptosis and stuff) or promote the production of reactive oxygen species and/or mitochondrial membrane depolarization<br /></li></ul><span style="font-size:85%;">- Allen CL, Loudon J, Mascarenhas AK. Sanguinaria-related leukoplakia: epidemiologic and clinicopathologic features of a recently described entity. Gen Dent. 2001 Nov-Dec;49(6):608-14.<br />- Chang MC et al. Induction of necrosis and apoptosis to KB cancer cells by sanguinarine is associated with reactive oxygen species production and mitochondrial membrane depolarization. Toxicol Appl Pharmacol. 2007 Jan 15;218(2):143-51. Epub 2006 Nov 1.</span>CNDtag:blogger.com,1999:blog-37623912.post-30788989077838278512007-08-01T13:52:00.000-04:002007-08-01T14:31:37.818-04:00Reader experiences: More readers respondI am pleased to announce that my mouth no longer contains any wisdom teeth. I also just misspelled wisdom as widoom three times in a row, so the codeine is definitely working it's wonders on my brain. I better stop typing while I'm ahead, so here are a couple of stories that people have sent in for you to read. Thank you, people! <a href="http://www.drugsandpoisons.com/2007/06/reader-experiences-readers-respond.html">Check out</a> the first installment. Here we go:<br /><br /><span style="color: rgb(255, 102, 102);">Steve wrote in to say, "I think it's fair to say that they're [SSRIs]</span><span style="color: rgb(255, 102, 102);"> the best thing that's ever happened to me." Well, I've got to share</span><span style="color: rgb(255, 102, 102);"> the love for my antidepressant of choice, <a href="http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a694020.html">venlafaxine</a> (a. k. a.</span><span style="color: rgb(255, 102, 102);"> Effexor), which is actually an SNRI (it affects norepinephrine as well</span><span style="color: rgb(255, 102, 102);"> as serotonin). Before, I was chronically depressed, rock-bottom</span><span style="color: rgb(255, 102, 102);"> self-esteem, apathetic, anxious, the whole shebang. Now -- well, I</span><span style="color: rgb(255, 102, 102);"> feel like things are going to turn out all right. Ordinary, everyday</span><br /><span style="color: rgb(255, 102, 102);">hopefulness. Gooooo drugs!</span><br /><br /><span style="color: rgb(255, 102, 102);">- ap</span><br /><br /><span style="color: rgb(255, 102, 102);">P. S. Ironically, one of Effexor's most dangerous side effects is</span><span style="color: rgb(255, 102, 102);"> suicidal ideation -- which is why it's most definitely NOT recommended</span><span style="color: rgb(255, 102, 102);"> for kids and teens.</span><br /><br />---<br /><br /><span style="color: rgb(255, 102, 102);">Your blog is sweet! Ok well I've had the privilege to experience a</span><span style="color: rgb(255, 102, 102);"> multitude of drug experiences but here's one from last night which</span><span style="color: rgb(255, 102, 102);"> involved our friend <a href="http://www.erowid.org/chemicals/dxm/">DXM</a> (dextromethorphan HCL).</span><br /><br /><span style="color: rgb(255, 102, 102);">Ok so I was experiencing these very nasty coughing fits and decided it</span><span style="color: rgb(255, 102, 102);"> was worth it to bicycle in the rain to the grocery store before it</span><span style="color: rgb(255, 102, 102);"> closed to get some syrup. Being an impoverished university student I</span><span style="color: rgb(255, 102, 102);"> opted for the generic brand which contained 15 DXM/5mL plus some</span><span style="color: rgb(255, 102, 102);"> disgusting cherry flavors (read the labels kiddies, brand names are for</span><span style="color: rgb(255, 102, 102);"> suckers).</span><br /><br /><span style="color: rgb(255, 102, 102);">I drank approx 80 mL (240 mg DXM, much more than the recommended</span><span style="color: rgb(255, 102, 102);"> dosage) and the bad news was that it did absolutely nothing for my cough.</span><span style="color: rgb(255, 102, 102);"> However, I was treated to a wonderful state of</span><span style="color: rgb(255, 102, 102);"> opiated-semi-psychedelic-drunkenness, which was further complemented</span><span style="color: rgb(255, 102, 102);"> with some high-quality cannabis. This state lasted many hours and when</span><span style="color: rgb(255, 102, 102);"> I went to bed I was treated with some groovy shapes and funky colors</span><span style="color: rgb(255, 102, 102);"> behind the eyes, and a feeling I was leaving my body. Super-fun! Just</span><span style="color: rgb(255, 102, 102);"> don't tell your friends or they'll think you're huffing gas on the side</span><span style="color: rgb(255, 102, 102);"> too!</span><br /><br /><span style="color: rgb(255, 102, 102);">- Luke</span><br /><br />---<br /><br /><span style="color: rgb(255, 102, 102);">Since you ask, I am reminded of one time I was in the hospital for</span><span style="color: rgb(255, 102, 102);"> kidney stones, which ended up being one of the longest sedative</span><span style="color: rgb(255, 102, 102);"> drug-binges of my life. It began as what I hoped was a quick visit for</span><span style="color: rgb(255, 102, 102);"> some <a href="http://en.wikipedia.org/wiki/Hydrocodone">hydrocodone</a> </span><span style="color: rgb(255, 102, 102);"></span><span style="color: rgb(255, 102, 102);">to dull the relentless visceral groin pain, but ended</span><span style="color: rgb(255, 102, 102);"> up in a 3 day hospital stay and a <a href="http://www.nlm.nih.gov/medlineplus/ency/article/007113.htm">lithotripsy</a>. What follows is the</span><span style="color: rgb(255, 102, 102);"> truly amazing list of substances I was on, and my personal opinion of</span><span style="color: rgb(255, 102, 102);"> them.</span><br /><br /><span style="color: rgb(255, 102, 102);">In the ER, while hoping for <a href="http://en.wikipedia.org/wiki/Vicodin">Vicodin</a>, they instead gave me an NSAID; I</span><span style="color: rgb(255, 102, 102);"> think it was <a href="http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a684037.html">dolobid</a>, but I can't remember. I mentioned getting</span><span style="color: rgb(255, 102, 102);"> stomach upset from ibuprofen, so they gave it to me IV. That worked</span><span style="color: rgb(255, 102, 102);"> pretty well for a while, but left me a tad too alert to be entertained</span><span style="color: rgb(255, 102, 102);"> by hospital TV.</span><br /><br /><span style="color: rgb(255, 102, 102);">Once admitted, I asked for some better pain killers, and they decided</span><span style="color: rgb(255, 102, 102);"> to give me Dilaudid (<a href="http://en.wikipedia.org/wiki/Hydromorphone">hydromorphone</a>). I doubt they gave me more than</span><span style="color: rgb(255, 102, 102);"> 1mg, but even that, I realized almost immediately, was much too much.</span><span style="color: rgb(255, 102, 102);"> Pretty soon the side effects were competing with kidney stone pain to</span><span style="color: rgb(255, 102, 102);"> see which could make me more miserable. As the drug hit in a matter of</span><span style="color: rgb(255, 102, 102);"> seconds, I first felt a wave of euphoria, but this was quickly</span><span style="color: rgb(255, 102, 102);"> followed by uncomfortable flushing and profuse sweating, with severe</span><span style="color: rgb(255, 102, 102);"> nausea. I should have lain down and stopped moving, but I was stubborn</span><span style="color: rgb(255, 102, 102);"> and talking to a friend, and so soon found myself vomiting into a</span><span style="color: rgb(255, 102, 102);"> trashcan. It was at this point that I asked for something for the</span><span style="color: rgb(255, 102, 102);"> nausea.</span><br /><br /><span style="color: rgb(255, 102, 102);">They gave me Zofran (<a href="http://en.wikipedia.org/wiki/Ondansetron">ondansetron</a>), a rather expensive drug that can</span><span style="color: rgb(255, 102, 102);"> only be given every 8 hours, apparently. It worked pretty well - for</span><span style="color: rgb(255, 102, 102);"> about 4 hours. After that time, I was left to fend off the opiate</span><span style="color: rgb(255, 102, 102);"> nausea myself. It was around this time that I really wanted some</span><span style="color: rgb(255, 102, 102);"> cannabis. Make whatever dumb stoner jokes you want, but nothing that</span><span style="color: rgb(255, 102, 102);"> I've tried or heard of works as well, or faster, at treating nausea</span><span style="color: rgb(255, 102, 102);"> that cannabinoids. It's way cheaper than Zofran, too. Given my</span><span style="color: rgb(255, 102, 102);"> hospitalized state however, it was not to be.</span><br /><br /><span style="color: rgb(255, 102, 102);">After the Dilaudid fiasco, they switched me to a 1mg/hour</span><span style="color: rgb(255, 102, 102);"> self-administered morphine pump. This worked out alright, but not</span><span style="color: rgb(255, 102, 102);"> great. It didn't control the pain as well as dilaudid, and performed</span><span style="color: rgb(255, 102, 102);"> worse and worse over time, not surprisingly. The nausea left me</span><span style="color: rgb(255, 102, 102);"> feeling useless and immobile, but fortunately I never vomited again.</span><br /><br /><span style="color: rgb(255, 102, 102);">The next day, I had my lithotripsy, and being a neuroscience major, I</span><span style="color: rgb(255, 102, 102);"> couldn't resist talking to the anesthesiologist about his</span><span style="color: rgb(255, 102, 102);"> pharmacological arsenal. As it turns out, the list of drug's he'd use</span><span style="color: rgb(255, 102, 102);"> was quite impressive:</span><br /><br /><span style="color: rgb(255, 102, 102);"><a href="http://www.drugsandpoisons.com/2007/03/chloral-hydrate-aquachloral-somnos.html">chloral hydrate</a> - for initial sedation. I'm not convinced about this</span><span style="color: rgb(255, 102, 102);"> one; I thought he mentioned it, but I'm not sure.</span><br /><br /><span style="color: rgb(255, 102, 102);"><a href="http://en.wikipedia.org/wiki/Midazolam">midazolam</a> (Versed) - benzodiazepine for initial sedation, as well as</span><span style="color: rgb(255, 102, 102);"> retrograde amnesia. It worked very well in its latter role.</span><br /><br /><span style="color: rgb(255, 102, 102);"><a href="http://en.wikipedia.org/wiki/Fentanyl">fentanyl</a> - opioid for pain. I imagine it served its purpose effectively.</span><br /><br /><span style="color: rgb(255, 102, 102);"><a href="http://en.wikipedia.org/wiki/Sevoflurane">sevoflurane</a> - one of the newer halogenated ethers. Be grateful they're</span><span style="color: rgb(255, 102, 102);"> not still using halothane, like I do on my rats.</span><br /><br /><span style="color: rgb(255, 102, 102);">Some other muscle relaxants he didn't name. The urologist probably</span><span style="color: rgb(255, 102, 102);"> used some local anesthetics for the procedure as well. He may have</span><span style="color: rgb(255, 102, 102);"> mentioned <a href="http://www.erowid.org/chemicals/nitrous/nitrous.shtml">nitrous oxide</a> as well, but I can't remember.</span><br /><br /><span style="color: rgb(255, 102, 102);">Despite the high risk of such a cocktail, I made it through ok,</span><span style="color: rgb(255, 102, 102);"> although I can't remember anything after lying down on the operating</span><span style="color: rgb(255, 102, 102);"> table until I was rolling towards recovery. I woke confused, thinking</span><span style="color: rgb(255, 102, 102);"> I was a child again, being pushed in a shopping cart down a grocery</span><br /><span style="color: rgb(255, 102, 102);">store aisle. Aren't hallucinations fun?</span><br /><br /><span style="color: rgb(255, 102, 102);">The real bummer was that I hadn't had a bowel movement in three days, due to opioids and Zofran. This problem plagued me for a couple days after coming home as well. Still, I much prefer my suffering to that experienced by people in the past who had to have kidney stones surgically removed with no anesthesia but strong liquor!</span><br /><br /><span style="color: rgb(255, 102, 102);">- Aaron</span>CNDtag:blogger.com,1999:blog-37623912.post-16757149582013082502007-07-31T00:36:00.000-04:002007-07-31T00:58:57.474-04:00CodeineGetting my wisdom teeth out tomorrow, folks. Should be fun.<br /><br />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 <a href="mailto:[email protected]">[email protected]</a> 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.CNDtag:blogger.com,1999:blog-37623912.post-44587782627749338182007-07-29T23:21:00.000-04:002007-07-30T00:27:36.789-04:00Cyclopamine - The Purple People Eater's mom must have had a taste for it<ul><li><a href="http://en.wikipedia.org/wiki/Steroid">steroidal</a> alkaloid actualized by <a href="http://plants.usda.gov/java/profile?symbol=VECA2"><span style="font-style: italic;">Veratrum californicum</span></a> (corn lily or vetch weed), a plant native to the <a href="http://en.wikipedia.org/wiki/Subalpine">subalpine</a> <a href="http://en.wikipedia.org/wiki/Meadow">meadows</a> of the western US</li><li>teratogenic, meaning that it causes congenital (birth) defects, specifically cyclopia</li><ul><li><a href="http://images.google.ca/images?hl=en&q=cyclopia&amp;btnG=Search+Images&gbv=2">cyclopia</a> (AKA cyclocephaly or synophthalmia) is severe facial defect that results from a type of <a href="http://www.ninds.nih.gov/disorders/holoprosencephaly/holoprosencephaly.htm">holoprosencephaly</a> (the failure of the <a href="http://en.wikipedia.org/wiki/Prosencephalon">forebrain</a> to divide into distinct hemispheres) that messes up the development of the face such that the two <a href="http://en.wikipedia.org/wiki/Orbit_%28anatomy%29">orbits</a> merge into a single cavity, containing one eye, in the middle of the face in place of a nose</li></ul><li>gets its name from the <a href="http://www.pantheon.org/articles/c/cyclopes.html">Cyclopes</a> of Greek mythology, a race of one-eyed giants that snacked on people</li><li>inhibits the <a href="http://hedgehog.sfsu.edu/overview.html">Hedgehog (Hh) signaling pathway</a>, which is involved in the regulation of <a href="http://en.wikipedia.org/wiki/Prenatal_development">prenatal development</a><br /></li><ul><li>is currently being investigated as a possible anticancer drug, since an overactive Hh pathway can produce many different varieties of cancer<br /></li></ul><li>the corn lily closely resembles <a href="http://en.wikipedia.org/wiki/Hellebore">hellebore</a>, 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</li><li>jervine is a related (just add a <a href="http://en.wikipedia.org/wiki/Ketone">ketone</a> group) teratogenic alkaloid found in the corn lily that also causes cyclopia<br /></li></ul><span style="font-size:85%;">Incardona JP et al. The teratogenic Veratrum alkaloid cyclopamine inhibits sonic hedgehog signal transduction. Development. 1998 Sep;125(18):3553-62.<br /><a href="http://hedgehog.sfsu.edu/overview.html">http://hedgehog.sfsu.edu/overview.html<br /></a></span>CNDtag:blogger.com,1999:blog-37623912.post-83912625781388335002007-07-25T21:28:00.000-04:002007-07-26T23:27:58.053-04:00Verteporfin (Visudyne) - Lasers, free radicals, and fixing people's eyes<ul><li><a href="http://en.wikipedia.org/wiki/Macrocycle">macrocyclic</a> <a href="http://en.wikipedia.org/wiki/Porphin">porphin</a>-derived <a href="http://en.wikipedia.org/wiki/Photosensitizer">photosensitizer</a> used as part of <a href="http://dictionary.reference.com/search?q=ocular">ocular</a> <a href="http://en.wikipedia.org/wiki/Photodynamic_therapy">photodynamic therapy </a>(PDT) for the treatment of ocular diseases that feature choroidal neovascularization (<a href="http://www.emedicine.com/oph/topic534.htm">CNV</a>), a major cause of vision loss</li><ul><li>the choroid is a layer of the eye (between the <a href="http://en.wikipedia.org/wiki/Sclera">sclera</a> and the <a href="http://en.wikipedia.org/wiki/Retina">retina</a>) that contains lots of blood vessels</li></ul><ul><li>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 (<a href="http://en.wikipedia.org/wiki/Macular_degeneration#Age-related_macular_degeneration">AMD</a>, deterioration of the <a href="http://en.wikipedia.org/wiki/Macula">central part</a> of the retina), pathological myopia (abnormal changes in eye structure causing vision problems), and ocular <a href="http://www.nei.nih.gov/health/histoplasmosis/index.asp">histoplasmosis</a> (a crazy-ass <a href="http://botit.botany.wisc.edu/toms_fungi/jan2000.html">fungal</a> infection of the eye)</li></ul><li>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</li><ul><li>as it is a highly conjugated molecule, it absorbs the light and, in the presence of oxygen , transfers its energy to oxygen atoms, producing radical oxygen species (<a href="http://en.wikipedia.org/wiki/Reactive_oxygen_species">ROS</a>) like <a href="http://en.wikipedia.org/wiki/Singlet_oxygen#Biochemistry">singlet oxygen</a> and <a href="http://en.wikipedia.org/wiki/Superoxide#Biology_and_superoxide">superoxide</a>, which then go about and wreck havoc on the bad vessels both directly and via platelet activation with <a href="http://en.wikipedia.org/wiki/Thrombosis">thrombosis</a> and vessel occlusion</li></ul><li>since it's <span style="font-style: italic;">modus operandi</span> 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 getting the drug, 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</li><li>PDT with verteporfin may also work on corneal neovascularization<br /></li></ul><span style="font-size:85%;">Yoon KC et al. Photodynamic Therapy with Verteporfin for Corneal Neovascularization. Am J Ophthalmol. 2007 Jul 12; [Epub ahead of print]<br /><a href="http://www.drugs.com/cons/verteporfin.html">http://www.drugs.com/cons/verteporfin.html</a><br /></span>CNDtag:blogger.com,1999:blog-37623912.post-62463868273410437032007-07-23T22:15:00.000-04:002007-07-23T23:20:36.260-04:00The pharm + tox lecture series: #3 - Absorption, putting the A in ADMEWhen 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.<br /><br />Absorption refers to the passage of a drug from the external environment into your systemic circulation (bloodstream). In essence, how you get a drug into you. There are all sorts of interesting ways by which this can be accomplished. Allow me to describe a few.<br /><br />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 body cavities (e.g. corticosteroids injected into joints to treat arthritis), the epidural space (e.g. an epidural), or the cerebrospinal fluid (intrathecal administration)<br /><br />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 (quit!), 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 general anaesthetics, medicinal marijuana, and asthma drugs (e.g. puffers) can be administered this way.<br /><br />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!).<br /><br />Parenteral administration refers, quite literally, to giving a drug 'beside the gut'. In other words, injecting it somewhere with a needle so that it gets into your blood. 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).CNDtag:blogger.com,1999:blog-37623912.post-24836467010201616272007-07-22T23:48:00.000-04:002007-07-23T00:06:30.184-04:00p-Phenylenediamine (p-PD) - When temporary tattoos go bad<ul><li><a href="http://en.wikipedia.org/wiki/Aromaticity">aromatic</a> <a href="http://en.wikipedia.org/wiki/Amine">amine</a> dye present in most hair dyes</li><li>added to henna paste to create "black henna", which is intended to make henna tattoos appear darker in order to create the classic <a href="http://flickr.com/search/?q=black+tattoo">black ink tattoo</a> look</li><ul><li><a href="http://www.hennapage.com/henna/encyclopedia/growing/">henna</a> (<span style="font-style: italic;">Lawsonia alba</span>/<span style="font-style: italic;">inermis</span>) is a flowering plant that contains <a href="http://en.wikipedia.org/wiki/Lawsone">lawsone</a>, 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.</li></ul><ul><li>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</li></ul><li>contact allergen, meaning that it causes allergic stuff to happen once you, er, come in contact with it</li><ul><li>reactions are usually mild, consisting of things like pruritus (itching), dermatitis, erythema (redness), and edema (swelling)</li></ul><ul><li>reactions can be treated with topical <a href="http://en.wikipedia.org/wiki/Glucocorticoids#Medical_uses_and_effects_of_high_dose_glucocorticoids">steroids</a> and oral <a href="http://en.wikipedia.org/wiki/Antihistamine#Indications">antihistamines</a>, but may result in altered skin pigmentation and even <a href="http://www.snopes.com/horrors/vanities/henna.asp">permanent scarring</a></li><li>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 <a href="http://en.wikipedia.org/wiki/Sulfonamide_%28medicine%29">drugs</a>) can cause a more severe reaction</li></ul><li>is colourless in its fully reduced state, becoming coloured only as it becomes oxidized</li><ul><li>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<br /></li></ul><li>has been shown to be strongly <a href="http://en.wikipedia.org/wiki/Mutagen">mutagenic</a> by the <a href="http://en.wikipedia.org/wiki/Ames_test">Ames test</a>, able to induce DNA damage by the <a href="http://en.wikipedia.org/wiki/Comet_assay">Comet assay</a> and alter expression of proteins associated with cancer phenotype, suggesting it may cause cancer</li><ul><li>the use of hair dyes has been weakly linked to bladder cancer, although similar studies have failed to find such an association</li></ul></ul><span style="font-size:85%;">- Gulen F et al. Urticaria and angioneurotic edema due to the temporary henna tattoo. Minerva Pediatr. 2006 Dec;58(6):583-5.<br />- 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.<br />- <a href="http://en.wikipedia.org/wiki/Henna">http://en.wikipedia.org/wiki/Henna</a><br />- <a href="http://en.wikipedia.org/wiki/P-Phenylenediamine">http://en.wikipedia.org/wiki/P-Phenylenediamine</a></span>CNDtag:blogger.com,1999:blog-37623912.post-56993681630097669232007-07-20T18:49:00.000-04:002007-07-20T19:24:26.024-04:00Varenicline (Chantix, Champix) - Because cigarettes are gross and expensive<ul><li>synthetic derivative of the alkaloid <a href="http://en.wikipedia.org/wiki/Cytisine">cytisine</a> used to treat smoking (nicotine) addiction</li><li><a href="http://watcut.uwaterloo.ca/webnotes/Pharmacology/page-3.6.html">partial agonist</a> at <a href="http://en.wikipedia.org/wiki/Neuron">neuronal</a> <a href="http://en.wikipedia.org/wiki/Nicotinic_acetylcholine_receptor">nicotinic acetylcholine receptors</a>, 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 <a href="http://en.wikipedia.org/wiki/Withdrawal">withdrawal</a> and hopefully making it easier for people to quit smoking</li><ul><li>acts primarily at the α<span style="font-size:85%;">4</span>β<span style="font-size:85%;">2</span> subtype of nicotinic receptors, which are found primarily in the central nervous system<br /></li></ul><li>side effects are primarily gastrointestinal in nature (<a href="http://scimed.acronymfinder.com/af-query.asp?string=exact&acronym=NVD&amp;s=r">NVD</a>, natch) and not severe, although it is has also been reported to cause crazy dreams and insomnia</li><li>at doses that have been shown to reduce nicotine intake in lab animals, has also been shown to reduce ethanol (the stuff in <a href="http://www.keiths.ca/">beer</a> that makes everything nicer) intake in three different animal models for ethanol consumption, making it a prospective treatment for alcohol dependence (alcoholism) as well</li><ul><li>about 85% of alcoholics smoke, and both nicotine and ethanol can produce reinforcing effects via nicotinic receptors<br /></li></ul></ul><span style="font-size:85%;">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; <a href="http://www.pnas.org/cgi/reprint/0705368104v1">[link]</a><br /></span>CNDtag:blogger.com,1999:blog-37623912.post-52391248632087750562007-07-18T23:22:00.000-04:002007-07-20T18:24:00.093-04:00Ajmaline - Mysteriously chilling out your heart<ul><li><a href="http://en.wikipedia.org/wiki/Monoterpene">monoterpenoid</a> <a href="http://en.wikipedia.org/wiki/Indole">indole</a> alkaloid manufactured by <a href="http://www.efloras.org/object_page.aspx?object_id=45521&flora_id=110"><span style="font-style: italic;">Rauvolfia serpentina</span></a> (Indian snakeroot or sarpagandha), a tropical evergreen plant used traditionally in Indian medicine</li><ul><li>is synthesized via a complex pathway involving an impressive number of long-named enzymes</li></ul><ul><ul><li>the first step, common to the biosynthesis of most terpenoid indole alkaloids, is a condensation reaction that serves to combine the precursors <a href="http://en.wikipedia.org/wiki/Tryptamine">tryptamine</a> and <a href="http://www.phytoconsult.nl/secologanin.htm">secologanin</a> into a super-molecule</li></ul></ul><ul><li><span style="font-style: italic;">Rauvolfia serpentina</span> is also a natural source of <a href="http://www.drugs.com/pro/reserpine.html">reserpine</a>, an antipsychotic and antihypertensive drug that blocks the release of monoamine neurotransmitters</li></ul><li><a href="http://www.cvpharmacology.com/antiarrhy/Vaughan-Williams.htm">class Ia antiarrhythmic</a> drug used to treat <a href="http://www.merck.com/mmhe/sec03/ch027/ch027a.html">abnormal heart rhythms</a> such as ventricular tachycardia</li><li>also used to screen for individuals afflicted with <a href="http://www.emedicine.com/med/topic3736.htm">Brugada syndrome</a>, 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</li><ul><li>involves having some sort of mutation in a gene encoding an ion channel or ion channel modulator found in cardiac muscle cells</li></ul><li>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</li><li>named by its discovers after <a href="http://en.wikipedia.org/wiki/Hakim_Ajmal_Khan">Hakim Ajmal Khan</a>, a famous Indian physician and nationalist who, arguably appropriately, died of heart problems<br /></li></ul><span style="font-size:85%;">- 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.<br />- Isharwal S, Gupta S. Rustom Jal Vakil: his contributions to cardiology.<br />Tex Heart Inst J. 2006;33(2):161-70. <a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=16878618">[link]</a><br />- 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.<br />- <a href="http://en.wikipedia.org/wiki/Brugada_syndrome">http://en.wikipedia.org/wiki/Brugada_syndrome</a><br /><br />(with thanks to Jim for the suggestion!)<br /></span>CNDtag:blogger.com,1999:blog-37623912.post-36243822968081340332007-07-17T22:37:00.000-04:002007-07-18T00:39:04.862-04:00Mitragynine - Speedballing for lazy people<ul><li>the principal alkaloid situated in the leaves of <a href="http://www.erowid.org/plants/kratom/kratom_images.shtml"><span style="font-style: italic;">Mitragyna speciosa</span></a> <a href="http://en.wikipedia.org/wiki/Pieter_Willem_Korthals">Korth</a> (Kratom, Biak-Biak), a <a href="http://en.wikipedia.org/wiki/Rubiaceae">rubiaceous</a> tropical tree that is native to <a href="http://dictionary.reference.com/search?q=Southeast+Asia">Southeast Asia</a></li><ul><li>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</li></ul><li>acts like morphine via <a href="http://en.wikipedia.org/wiki/Opioid_receptor">mu</a> <a href="http://www.ucsf.edu/pain/orientation/opioid%20analgesics.PDF">opioid</a> 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 <a href="http://en.wikipedia.org/wiki/Codeine">codeine</a> (Tylenol 3s, baby!) or <a href="http://en.wikipedia.org/wiki/Methadone">methadone</a></li><li>also produces a cocaine-like <a href="http://en.wikipedia.org/wiki/Stimulant">stimulating</a> effect, likely due to it possessing a similar structure to <a href="http://en.wikipedia.org/wiki/Yohimbine">yohimbine</a>, an alpha2-adrenergic receptor antagonist that has stimulant activity and is best known for its alleged ability to treat <a href="http://www.merck.com/mmhe/sec21/ch240/ch240b.html?qt=yohimbine&alt=sh">erectile dysfunction</a> (not an ad, I promise!)<a href="http://www.merck.com/mmhe/sec21/ch240/ch240b.html?qt=yohimbine&amp;alt=sh"><br /></a></li><li>changing a carbon double bond to a single bond and adding a <a href="http://en.wikipedia.org/wiki/Hydroxyl">hydroxyl group</a> 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<br /></li></ul><span style="font-size:85%;">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.<br /><a href="http://en.wikipedia.org/wiki/Kratom">http://en.wikipedia.org/wiki/Kratom</a></span>CNDtag:blogger.com,1999:blog-37623912.post-74026076085787793482007-07-16T22:14:00.000-04:002007-07-17T00:16:42.670-04:00The pharm + tox lecture series: #2 - Drugs, medications, and poisons (Oh my!)The name of this site is a <a href="http://dictionary.reference.com/search?q=misnomer">misnomer</a>. Sad but true. You see, <span style="font-style: italic;">technically</span>, 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 <a href="http://www.amazon.com/gp/product/0853694737?ie=UTF8&tag=drugandpois-20&amp;linkCode=as2&camp=1789&amp;creative=9325&creativeASIN=0853694737">textbook</a><img src="http://www.assoc-amazon.com/e/ir?t=drugandpois-20&amp;l=as2&o=1&amp;a=0853694737" alt="" style="border: medium none ! important; margin: 0px ! important;" border="0" height="1" width="1" /> or something.<br /><br />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.<br /><br />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.<br /><br />Anyway, way back in the sixteenth century, this Swiss fellow named <a href="http://en.wikipedia.org/wiki/Paracelsus">Paracelsus</a> (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.<br /><br />In conclusion, I should have named this site 'Medications and Poisons', but 'Drugs and Poisons' sounded too cool to pass up. The end.CNDtag:blogger.com,1999:blog-37623912.post-46673443325553313692007-07-12T23:47:00.000-04:002007-07-13T20:17:36.064-04:00Cerium (Ce) - Stealing calcium's place in the physiological spotlight<ul><li>a paradoxically relatively common (more so than lead!) rare earth metal</li><ul><li>rare earth metals, also known as <a href="http://www.chemtopics.com/elements/lan/lan.htm">lanthanides</a> or lanthanoids, are the elements found in the first row of that cute little two-row structure situated at the bottom of the <a href="http://www.webelements.com/">periodic table</a></li></ul><li>the <a href="http://en.wikipedia.org/wiki/Valence_%28chemistry%29">trivalent</a> form of this metal resembles (divalent) <a href="http://en.wikipedia.org/wiki/Calcium">calcium</a> in size and things it likes to bind to, enabling it to mess with calcium-dependent physiological processes like <a href="http://en.wikipedia.org/wiki/Coagulation">the clotting of blood</a>, <a href="http://en.wikipedia.org/wiki/Muscle_contraction">the contraction of muscles</a>, and <a href="http://en.wikipedia.org/wiki/Chemical_synapse#Signaling_across_chemical_synapses">the release of neurotransmitters</a>.</li><ul><li>lanthanides were considered for development into <a href="http://en.wikipedia.org/wiki/Anticoagulant">anticoagulants</a> prior to the dawn of the age of <a href="http://www.drugsandpoisons.com/2006/11/heparin.html">heparin</a></li></ul><li>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 do this nor how effective they really are (there are no good papers on it)<br /></li><li>cerium salts are also capable of both inhibiting the growth of and actively killing bacteria, and the recognition of this ability in the late nineteenth century lead to their use as topical <a href="http://en.wikipedia.org/wiki/Antiseptic">antiseptics</a> (they had fun names like "dymal", "ceolat", and "ceriform"), a use which continues to this day (typically cerium nitrate as an <a href="http://dictionary.reference.com/search?q=adjunct">adjunct</a> to an antiseptic <a href="http://www.drugsandpoisons.com/2007/02/precious-medicines-gold-and-silver-as.html">silver</a> compound)</li><ul><li>the salts also modulate the immune system in such a manner as to help burn victims resist <a href="http://dictionary.reference.com/search?q=sepsis">sepsis</a> (likely by inactivating <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&amp;TermToSearch=7204743&ordinalpos=1&amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstractPlus">burn toxins</a> and other such endogenous <a href="http://en.wikipedia.org/wiki/Immunosuppression">immunosuppressive</a> agents)</li></ul><li>perhaps most interestingly, a solution of cerium(III) iodide called "introcid" was injected into cancer patients during the genesis of cancer <a href="http://en.wikipedia.org/wiki/Chemotherapy">chemotherapy</a> and was found to shrink tumours more effectively than other iodine compounds, suggesting that it was the cerium and not the iodine that did something<br /></li><ul><li>cesium(III) <a href="http://en.wikipedia.org/wiki/Complex_%28chemistry%29">complexes</a> 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<br /></li></ul><ul><li>since calcium is involved in the control of cell proliferation, the development of cancer cells, and <a href="http://en.wikipedia.org/wiki/Angiogenesis">angiogenesis</a>, all components of tumour development, it is possible that cerium works as an anticancer agent because it can screw with these processes<br /></li></ul></ul><span style="font-size:85%;">Jakupec MA, Unfried P, Keppler BK. Pharmacological properties of cerium compounds. Rev Physiol Biochem Pharmacol. 2005;153:101-11. Review.<br /></span>CNDtag:blogger.com,1999:blog-37623912.post-18409633594058904502007-07-11T21:30:00.000-04:002007-07-11T23:22:07.060-04:00Carbon tetrachloride - The sweet, sweet smell of hepatotoxicity<ul><li>saccharine-smelling (akin to the scent of a dry cleaner's) <a href="http://dictionary.reference.com/search?q=synthetic">synthetic</a> <a href="http://en.wikipedia.org/wiki/Halomethane">halomethane</a> widely used in the early 20th century to <a href="http://en.wikipedia.org/wiki/Fire_extinguisher">extinguish fires</a>, help cool things down (it is a good <a href="http://en.wikipedia.org/wiki/Refrigerant">refrigerant</a>), and <a href="http://home.howstuffworks.com/home-dry-cleaning.htm">dry clean</a> clothing</li><ul><li>was replaced by <a href="http://en.wikipedia.org/wiki/Tetrachloroethylene">tetrachloroethylene</a> in the 1940s because it was making people tremendously ill</li></ul><ul><li>currently used to make other refrigerants</li></ul><ul><li>much like the infamous <a href="http://www.ausetute.com.au/cfcozone.html">chlorofluorocarbons</a> (CFCs), it is really good at annihilating the <a href="http://www.nas.nasa.gov/About/Education/Ozone/ozonelayer.html">ozone layer</a></li></ul><li>used as an insecticide in the good old US of A up until the 1970s, at which point it was finally banned</li><li>when subjected to high temperatures, it can form the toxic gas <a href="http://www.drugsandpoisons.com/2007/02/phosgene.html">phosgene</a></li><li>if you get a lot of it in you somehow, it'll wreck havoc on your liver, kidneys, and central nervous system</li><ul><li>the liver is particularly sensitive, likely reflecting the presence of a tonne of <a href="http://en.wikipedia.org/wiki/Xenobiotic">xenobiotic</a>-metabolizing enzymes such as <a href="http://www.ingentaconnect.com/content/ap/to/1998/00000153/00000001/art08547">CYP2E1</a> that are capable of changing a whole bunch of it into highly reactive <a href="http://en.wikipedia.org/wiki/Radical_%28chemistry%29">free radical</a> intermediates<br /></li></ul><li>has been shown to cause cancer in lab animals when either swallowed or inhaled<br /></li></ul> <span style="font-size:85%;">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.<br /><a href="http://en.wikipedia.org/wiki/Carbon_tetrachloride">http://en.wikipedia.org/wiki/Carbon_tetrachloride</a><br /><a href="http://www.atsdr.cdc.gov/tfacts30.html">http://www.atsdr.cdc.gov/tfacts30.html<br /></a></span>CNDtag:blogger.com,1999:blog-37623912.post-1673584995450537782007-07-10T20:45:00.000-04:002007-07-10T23:35:16.997-04:00Xenon (Xe) - The cool-sounding knock-out drug of the future<ul><li>a <a href="http://en.wikipedia.org/wiki/Noble_gas">noble gas</a> that is heavier than air, possesses neither colour nor odour, and has revolutionized lighting<br /></li><ul><li><a href="http://en.wikipedia.org/wiki/Xenon_flash_lamp">xenon flash lamps</a> helped make electronic flash, <a href="http://en.wikipedia.org/wiki/Strobe_light">strobe lights</a> (ugh), and <a href="http://ocw.mit.edu/ans7870/6/6.163/f05/imagegallery/1.html">very</a> <a href="http://www.pbase.com/cerumen/waterdrops">high</a> <a href="http://users.skynet.be/fotoopa/highspeed_frame_set.htm">speed</a> photography possible</li></ul><li>makes good fuel for an <a href="http://www.nasa.gov/vision/universe/features/nep_prometheus.html">ion thruster</a>, a type of spacecraft propulsion that is best known to nerds everywhere as the thing that powers <a href="http://www.starwars.com/databank/starship/tiefighter/">TIE fighters</a></li><ul><li>just for the record, star wars > star trek</li></ul><li>can be used to induce <a href="http://en.wikipedia.org/wiki/General_anaesthesia">general anaesthesia</a>, although it isn't used very often because it costs a heck of a lot to manufacture since it is so <a href="http://en.wikipedia.org/wiki/Earth%27s_atmosphere#Composition">rare</a> in the atmosphere</li><li>is 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!</li><li>it isn't yet understood how it knocks you out, but scientists have come up with two pretty good ideas:</li><ul><li>it blocks glutamate receptors, <a href="http://en.wikipedia.org/wiki/Glutamate#As_a_neurotransmitter">glutamate</a> being the main excitatory brain signaling chemical (neurotransmitter)</li></ul><ul><ul><li>this is neat because most <a href="http://en.wikipedia.org/wiki/Inhalational_anaesthetic">inhalational anaesthetics </a>do their thing by stimulating GABA receptors, <a href="http://en.wikipedia.org/wiki/GABA">GABA</a> being the main inhibitory neurotransmitter in the brain<br /></li></ul></ul><ul><li>it messes with the levels of <a href="http://en.wikipedia.org/wiki/Calcium_in_biology#Cell_biology">calcium ion</a> (Ca<span style="font-size:85%;">2+</span>) in neurons, leading to changes in the release of neurotransmitters because Ca<span style="font-size:85%;">2+</span> plays an important role in many <a href="http://en.wikipedia.org/wiki/Second_messenger_system">second messenger systems</a><br /></li></ul><li>is essentially <a href="http://en.wikipedia.org/wiki/Inert">inert</a> in the body (its <a href="http://en.wikipedia.org/wiki/Electron_shell">outer shell</a> is full, so no need for other molecule's electrons), so it won't cause problems by forming <a href="http://en.wikipedia.org/wiki/Covalent_bond">covalent bonds</a> with proteins and DNA, one of the issues with certain <a href="http://en.wikipedia.org/wiki/Halogenated_ether">halogenated ether</a> anaesthetics (see: <a href="http://www.emedicine.com/med/topic942.htm">halothane and liver toxicity</a>)</li><li>it somehow provides protection against <a href="http://en.wikipedia.org/wiki/Reperfusion_injury">ischemia-reperfusion injury</a> to the cardiovascular and nervous systems that can occur during big surgeries</li><li>like <a href="http://www.drugsandpoisons.com/2007/06/tonight-show-jay-leno-and-josh-dumell.html">sulfur hexafloride</a>, lowers the pitch of your voice when inhaled, due to it lowering the <a href="http://en.wikipedia.org/wiki/Resonance">resonant frequencies</a> of the vocal tract<br /></li></ul><span style="font-size:85%;">Preckel B et al. Molecular mechanisms transducing the anesthetic, analgesic, and organ-protective actions of xenon. Anesthesiology. 2006 Jul;105(1):187-97. Review.<br /><a href="http://en.wikipedia.org/wiki/Xenon">http://en.wikipedia.org/wiki/Xenon</a></span>CNDtag:blogger.com,1999:blog-37623912.post-85530325524984071062007-07-09T19:15:00.000-04:002007-07-09T19:40:33.655-04:00The 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.<br /><br />First off, I need to stress to you a distinction of the utmost concern: pharmacology <font style="color: rgb(255, 102, 102);">IS NOT</font> 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.<br /><br />Now that I've got that out of my system, let me break it down for you:<br /><br /><font style="color: rgb(255, 102, 102);">Pharmacology</font> 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 <a href="http://en.wikipedia.org/wiki/Pharmacovigilance">pharmacovigilance</a>, <a href="http://www.pharmacoepi.org/aboutpe.cfm">pharmacoepidemiology</a>, <a href="http://www.ornl.gov/sci/techresources/Human_Genome/medicine/pharma.shtml">pharmacogenomics</a>, <a href="http://www.dundee.ac.uk/memo/memoonly/PHECO0.HTM">pharmacoeconomics</a>, <a href="http://cancerweb.ncl.ac.uk/cgi-bin/omd?query=clinical&action=Search+OMD">clinical</a> pharmacology, and agricultural pharmacology.<br /><br /><font style="color: rgb(255, 102, 102);">Pharmacy</font> 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.<br /><br /><font style="color: rgb(255, 102, 102);">Toxicology</font> is the science concerned with the adverse effects that chemicals have on living things, particularly people. It includes the detection and treatment of poisonings.CNDtag:blogger.com,1999:blog-37623912.post-45681557850381685582007-07-08T22:30:00.000-04:002007-07-11T21:23:57.128-04:00The rundown: Ten popular drugs in ten awe-inspiring sentencesOkay, 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 <a href="http://www.wikipedia.org/">Wikipedia</a>) that will give you a much more comprehensive rundown on any popular drug out there. Sure, it won't be nearly as snarky or silly as it would be here, but it essentially renders me obsolete.<br /><br />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 '<a href="http://www.forbes.com/2006/03/21/pfizer-merck-amgen-cx_mh_pk_0321topdrugs.html">The World's Ten Best-Selling Drugs (of 2006)</a>' and wrote this post.<br /><br />Ten drugs, ten sentences. Pure D & P stylings.<br /><span style="font-size:100%;"><br /></span><ol><li><span style="font-size:100%;">Lipitor (</span><span style="font-size:100%;"><span style="color: rgb(255, 102, 102);">atorvastatin</span>)</span><span style="font-size:100%;"> is given to older people to slow the inevitable progression of <a href="http://en.wikipedia.org/wiki/Cardiovascular_disease">cardiovascular disease</a> by lowering their <a href="http://www.cbc.ca/news/background/health/cholesterol.html">cholesterol</a> levels.</span></li><li><span style="font-size:100%;">Plavix (</span><span style="font-size:100%;"><span style="color: rgb(255, 102, 102);">clopidogrel</span>)</span><span style="font-size:100%;"> inhibits <a href="http://www.fi.edu/biosci/blood/platelet.html">platelet</a> aggregation, thus making it less likely that <a href="http://www.nlm.nih.gov/medlineplus/ency/article/001124.htm">blood clots</a> will bung up your arteries and kill you if you have some sort of <a href="http://www.netdoctor.co.uk/diseases/facts/vasculardiseases.htm">vascular disease</a>.</span></li><li><span style="font-size:100%;">Nexium (</span><span style="font-size:100%;"><span style="color: rgb(255, 102, 102);">esomeprazole</span>)</span><span style="font-size:100%;"> deals with <a href="http://en.wikipedia.org/wiki/Heartburn">heartburn</a>, <a href="http://www.mayoclinic.com/health/peptic-ulcer/DS00242">peptic ulcers</a>, and <a href="http://en.wikipedia.org/wiki/Dyspepsia">other stomach ailments</a> by knocking <a href="http://en.wikipedia.org/wiki/Gastric_acid">stomach acid</a> production out of commission.</span></li><li><span style="font-size:100%;">Seretide/Advair is a two-drug formulation of <span style="color: rgb(255, 102, 102);">fluticasone</span> (makes things <a href="http://en.wikipedia.org/wiki/Glucocorticoids#Antiinflammatory_effects">less inflamed</a>) and <span style="color: rgb(255, 102, 102);">salmeterol</span> (<a href="http://en.wikipedia.org/wiki/Bronchodilator">opens up</a> the airways) used to deal with asthma and <a href="http://www.lung.ca/diseases-maladies/copd-mpoc_e.php">COPD</a>.</span></li><li><span style="font-size:100%;">Zocor (</span><span style="font-size:100%;"><span style="color: rgb(255, 102, 102);">simvastatin</span>)</span><span style="font-size:100%;"> is essentially a less popular and yet equally exciting version of atorvastatin.</span></li><li><span style="font-size:100%;">Norvasc (</span><span style="font-size:100%;"><span style="color: rgb(255, 102, 102);">amlodipine</span>)</span><span style="font-size:100%;"> is but one of the oodles of drugs that relieve <a href="http://www.nhlbi.nih.gov/health/dci/Diseases/Angina/Angina_WhatIs.html">angina</a> and lower blood pressure by <a href="http://en.wikipedia.org/wiki/Calcium_channel_blocker#Mechanism_of_action">opening up</a> arteries.</span></li><li><span style="font-size:100%;">Zyprexa (</span><span style="font-size:100%;"><span style="color: rgb(255, 102, 102);">olanzapine</span>)</span><span style="font-size:100%;"> renders <a href="http://en.wikipedia.org/wiki/Schizophrenia">crazy</a> people not crazy by stimulating or blocking an array of different receptors in the brain.</span></li><li><span style="font-size:100%;">Risperdal (</span><span style="font-size:100%;"><span style="color: rgb(255, 102, 102);">risperidone</span>)</span><span style="font-size:100%;"> is just like olanzapine, only with a lousier name.</span></li><li><span style="font-size:100%;">Prevacid (</span><span style="font-size:100%;"><span style="color: rgb(255, 102, 102);">lansoprazole</span>)</span><span style="font-size:100%;"> is akin in chemical structure and action to esomeprazole.</span></li><li><span style="font-size:100%;">Effexor (</span><span style="font-size:100%;"><span style="color: rgb(255, 102, 102);">venlafaxine</span>)</span><span style="font-size:100%;"> helps <a href="http://www.nlm.nih.gov/medlineplus/depression.html">depressed</a> and <a href="http://www.cmha.ca/bins/content_page.asp?cid=3-94">anxious</a> people to brighten up and chill out.</span></li></ol>CNDtag:blogger.com,1999:blog-37623912.post-73323689576815254232007-07-06T14:56:00.000-04:002007-07-06T16:23:13.543-04:00Chlorothalonil (CHT, Daconil) - Eat it, barnacles!<ul><li>broad-spectrum fungicide employed to vanquish fungi that ruin such things as vegetables, lawns, and cranberries (it is added to the <a href="http://en.wikipedia.org/wiki/Cranberry#Cultivation_and_uses">beds</a>)</li><li>also used as a <a href="http://en.wikipedia.org/wiki/Biocide">biocide</a> in combination with copper (which inhibits the growth of living things) to kill marine organisms that cause <a href="http://en.wikipedia.org/wiki/Biofouling">biofouling</a> (growth on submerged surfaces) on ships and boats</li><ul><li>it is mixed in with the paint that is applied to <a href="http://en.wikipedia.org/wiki/Hull_%28watercraft%29">hulls</a>, such that it is released throughout the lifetime of the paint</li></ul><li>like a lot of chemicals, very high doses of it can <a href="http://www.snopes.com/horrors/poison/golftee.asp">kill</a>, but is actually considered to be only moderately toxic in the <a href="http://cancerweb.ncl.ac.uk/cgi-bin/omd?query=acute&action=Search+OMD">acute</a> sense due to its ability to cause severe eye and skin irritation</li><li>studies done in rats have found that chronic exposure through food result in chronic renal (kidney) toxicity and increased risk of developing tumours</li><ul><li>is potentially <a href="http://www.agls.uidaho.edu/etoxweb/lectures/etox_sub/lect8/L8_BIOTR_files/v3_document.htm">biotransformed</a> in the liver to a toxic <a href="http://en.wikipedia.org/wiki/Glutathione">glutathione</a> conjugate (i.e. glutathione is added on to the compound to facilitate its elimination from the body) that is removed by the <a href="http://en.wikipedia.org/wiki/Kidney">kidneys</a> 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</li></ul><li>can be classified as any of the following: chlorinated <a href="http://en.wikipedia.org/wiki/Benzonitrile">benzonitrile</a>, chloronitrile, <a href="http://en.wikipedia.org/wiki/Organochloride">organochloride</a>, or aromatic halogen</li></ul><span style="font-size:85%;">- 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.<br />- Rosner E, Klos C, Dekant W. Biotransformation of the fungicide chlorthalonil by glutathione conjugation. Fundam Appl Toxicol. 1996 Oct;33(2):229-34.<br />- <a href="http://extoxnet.orst.edu/pips/chloroth.htm">http://extoxnet.orst.edu/pips/chloroth.htm</a><br /></span>CNDtag:blogger.com,1999:blog-37623912.post-83434948540218815932007-07-05T22:24:00.000-04:002007-07-05T23:59:46.728-04:00Dantron (1,8-dihydroxyanthroquinone, danthron, chrysazin) - Poop, red urine, and cancer<ul><li>stimulant <a href="http://en.wikipedia.org/wiki/Laxative">laxative</a> banned in the USA because Americans think it causes cancer, restricted to use in <a href="http://en.wikipedia.org/wiki/Palliative_care">palliative care</a> 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</li><ul><li>a stimulant laxative is something that makes you poop by stimulating <a href="http://en.wikipedia.org/wiki/Peristalsis">peristalsis</a>, and represents the most severe type of laxative you can get, generally only being used in extreme not-being-able-to-poo situations</li></ul><ul><li>has been shown to cause liver cancer in mice and colon cancer in rats, suggesting that it probably does something bad to people</li></ul><li>a derivative of <a href="http://en.wikipedia.org/wiki/Anthraquinone">anthraquinone</a>, 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</li><ul><li>similar poop-inducing derivatives of anthraquinone can be found in a number of plants that have seen use as laxatives (<a href="http://en.wikipedia.org/wiki/Aloe">aloe</a>, <a href="http://en.wikipedia.org/wiki/Senna_%28genus%29">senna</a>, <a href="http://en.wikipedia.org/wiki/Rhubarb">rhubarb</a>, <a href="http://en.wikipedia.org/wiki/Rhamnus_purshiana">cascara sagrada</a>, etc.)</li></ul><li>found naturally in several species of plants and insects, including the ever-popular <a href="http://ohioline.osu.edu/hyg-fact/2000/2036.html">elm-leaf beetle</a> (<span style="font-style: italic;">Pyrrhalta luteola</span>) </li><li>turns your pee red<br /></li><li>has been shown to reduce <a href="http://en.wikipedia.org/wiki/Neuron">neuronal</a> injury induced by a number of bad things, including <a href="http://en.wikipedia.org/wiki/Amyloid_beta">beta-amyloid</a> (25-35), which has a role in <a href="http://en.wikipedia.org/wiki/Alzheimer%27s_disease">Alzheimer's disease</a></li><li>also used as an <a href="http://en.wikipedia.org/wiki/Antioxidant">antioxidant</a> in synthetic lubricants and as a fungicide to obliterate <a href="http://en.wikipedia.org/wiki/Powdery_mildew">powdery mildew<br /></a></li></ul><span style="font-size:85%;">- 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.<br />- <a href="http://ntp.niehs.nih.gov:8080/cs.html?charset=iso-8859-1&url=http%3A//ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s055dant.pdf&amp;amp;qt=danthron&col=005main&amp;n=1&la=en">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.</a><br />- <a href="http://en.wikipedia.org/wiki/Anthraquinone">http://en.wikipedia.org/wiki/Anthraquinone</a><br />- <a href="http://en.wikipedia.org/wiki/Dantron">http://en.wikipedia.org/wiki/Dantron</a></span>CNDtag:blogger.com,1999:blog-37623912.post-84053108370785400262007-07-04T23:33:00.000-04:002007-07-06T00:06:25.034-04:00Bromoacetone - Don't mess with exotic red alga seaweed!<ul><li>violent <a href="http://en.wikipedia.org/wiki/Lachrymatory_agent">lachrymator</a> (think tear gas and pepper spray) that can be easily synthesized in a laboratory (mix a little <a href="http://en.wikipedia.org/wiki/Bromine">bromine</a> with a little <a href="http://en.wikipedia.org/wiki/Acetone">acetone</a>, natch)</li><li>also present naturally in a certain species of red alga seaweed (<a href="http://www.horta.uac.pt/species/algae/Asparagopsis_taxiformis/Asparagopsis_taxiformis.htm"><span style="font-style: italic;">Asparagopsis taxiformis</span></a>) 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)</li><ul><li>the seaweed is called <a href="http://www.hawaii-seafood.org/compete/salad_ahi_poke.html">limu kohu</a> (supreme seaweed) by native Hawaiians and is apparently considered so supreme because of its enticing aroma and flavour</li></ul><li>employed as a chemical weapon during World War I by both sides and has also seen use as a <a href="http://en.wikipedia.org/wiki/Riot_control_agent">riot control agent</a>, but this has been discontinued due to its relatively high toxicity compared to newer agents</li><li>as bromine serves as a good <a href="http://en.wikipedia.org/wiki/Leaving_group">leaving group</a>, bromoacetone can be used as a reagent in <a href="http://en.wikipedia.org/wiki/Organic_synthesis">organic synthesis</a> reactions, including those by which drugs are produced</li><li>rapidly turns purple upon exposure to light or water</li></ul><span style="font-size:85%;"><a href="http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?HSDB">Hazardous Substances Data Bank</a> - Bromoacetone<br /><a href="http://en.wikipedia.org/wiki/Bromoacetone">http://en.wikipedia.org/wiki/Bromoacetone</a></span>CNDtag:blogger.com,1999:blog-37623912.post-27698445524467258682007-07-03T23:26:00.000-04:002007-07-04T00:21:55.869-04:00Q & A #3 - Cannabis and cancer, tasteless poisons, and getting highIt'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 <span style="font-style: italic;">simultaneously</span>. 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 <a href="http://www.drugsandpoisons.com/2007/01/q.html">first</a> and <a href="http://www.drugsandpoisons.com/2007/02/q-2.html">second</a> installments of this exciting feature for more Q & A goodness. Onward!<br /><br /><br /><span style="color: rgb(255, 102, 102);">Is THC carcinogenic?</span><br /><br /><a href="http://www.drugsandpoisons.com/2007/02/delta-9-tetrahydrocannabinol-thc.html">Tetrahydrocannabinol</a>, 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.<br /><br /><br /><span style="color: rgb(255, 102, 102);">What organs are affected by MDMA?</span><br /><br />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.<br /><br /><br /><span style="color: rgb(255, 102, 102);">What are some tasteless poisons?</span><br /><br />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:<br /><ul><li>carbon monoxide</li><li>heavy metals, including antimony, arsenic, lead, mercury, and thalium</li><li>bacterial, shellfish, and mushroom toxins</li><li>ricin, nicotine, and likely other plant alkaloids</li><li>rat poisons (got to fool the rats, yo)<br /></li></ul><br /><span style="color: rgb(255, 102, 102);">Does testosterone destroy cartilage?</span><br /><br />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.<br /><br /><br /><span style="color: rgb(255, 102, 102);">Does 'X' get you high? </span><br /><br />I get a tonne of these ones. Might I refer to you the mighty <a href="http://www.erowid.org/">Erowid</a>. They will know.<br /><br /><br /><span style="font-size:85%;"><a href="http://en.wikipedia.org/wiki/Health_issues_and_the_effects_of_cannabis#Cancer_risk">http://en.wikipedia.org/wiki/Health_issues_and_the_effects_of_cannabis#Cancer_risk</a><br /><br />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.<br /><br />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.<br /></span>CNDtag:blogger.com,1999:blog-37623912.post-22047640748668347362007-06-29T14:41:00.001-04:002007-07-05T14:17:31.135-04:00Disulfur decafluoride - Even awesome gas can't make Leno funny<div xmlns="http://www.w3.org/1999/xhtml"><p><object height="350" width="400"><param value="http://youtube.com/v/5LZ7vystdkA" name="movie"><embed type="application/x-shockwave-flash" src="http://youtube.com/v/5LZ7vystdkA" height="350" width="400"></embed></object></p></div><br />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&amp;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 <a href="http://www.drugsandpoisons.com/2007/02/phosgene.html">phosgene</a>-like <a href="http://en.wikipedia.org/wiki/Pulmonary_agent">pulmonary agent</a>. A potential chemical weapon. Since sulfur hexafluoride is used as an insulator in electrical things like <a href="http://en.wikipedia.org/wiki/Switchgear">switchgear</a> and <a href="http://en.wikipedia.org/wiki/Transformer">transformers</a>, it potentially poses a risk to <a href="http://en.wikipedia.org/wiki/Lineman_%28occupation%29">lineworkers</a> and <a href="http://en.wikipedia.org/wiki/Electrician">electricians</a>.<br /><br /><a href="http://en.wikipedia.org/wiki/Sulfur_hexafluoride">http://en.wikipedia.org/wiki/Sulfur_hexafluoride<br /></a><a href="http://en.wikipedia.org/wiki/Disulfur_decafluoride">http://en.wikipedia.org/wiki/Disulfur_decafluoride</a>CNDtag:blogger.com,1999:blog-37623912.post-75741398122099192652007-06-28T15:10:00.000-04:002007-07-06T01:30:42.086-04:00Monocrotaline (MCT) - The lung-killer<ul><li><a href="http://en.wikipedia.org/wiki/Pulmonology">pneumo</a>toxic <a href="http://en.wikipedia.org/wiki/Macrocycle">macrocyclic</a> <a href="http://www.itmonline.org/arts/pas.htm">pyrrolizidine</a> <a href="http://en.wikipedia.org/wiki/Alkaloid">alkaloid</a> churned out by a number of exciting plants<span style="font-style: italic;"><br /></span></li><li>causes a pulmonary vascular syndrome, which essentially means that a bunch of things go wrong with the blood supply to your lungs, including:</li><ul><li>proliferative pulmonary <a href="http://en.wikipedia.org/wiki/Vasculitis">vasculitis</a> (spreading inflammation of the wall of blood vessels in the lung)<br /></li></ul><ul><li><a href="http://en.wikipedia.org/wiki/Pulmonary_hypertension">pulmonary hypertension</a><a href="http://en.wikipedia.org/wiki/Pulmonary_hypertension"><br /></a></li></ul><ul><li><a href="http://en.wikipedia.org/wiki/Cor_pulmonale">cor pulmonale</a> with <a href="http://en.wikipedia.org/wiki/Right_ventricular_hypertrophy">right ventricular hypertrophy</a><br /></li></ul><li>used to intentionally produce pulmonary hypertension in animals in order to create an experimental model for investigating the <a href="http://en.wikipedia.org/wiki/Pathophysiology">pathophysiology</a> of pulmonary hypertension and the development of pharmacological means of treating it</li><li>has been hypothesized that it is <a href="http://www.eoearth.org/article/Biotransformation">biotransformed</a> in the liver to a feisty little reactive <a href="http://en.wikipedia.org/wiki/Metabolomics#Metabolites">metabolite</a> that then travels via the blood to the lungs where it starts messing with <a href="http://en.wikipedia.org/wiki/Endothelium">endothelial cells</a>, altering their function to cause detrimental structural changes in pulmonary blood vessels (particularly the arteries)<br /></li><li>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)<br /></li></ul><span style="font-size:85%;">Tanino Y. [Monocrotaline-induced pulmonary hypertension in animals] Nippon Rinsho. 2001 Jun;59(6):1076-80. Review. Japanese.<br />Wilson DW et al. Mechanisms and pathology of monocrotaline pulmonary toxicity. Crit Rev Toxicol. 1992;22(5-6):307-25. Review. </span>CND