Politics and Poisoning Part One

Poisons have been  used to change political environments since man first walked on earth.  This year we are in the midst of fierce local, statewide and national elections.   To celebrate I will write a brief entry on each presidential or vice-presidential debate day.  Tonight when President Obama squares off with Governor Romney you can sit back, enjoy the rhetoric and think poisons.

As long ago as 336 BC King Artaxeres III of Persia was murdered by his chief minister Bagoas.  Bagoas wanted to place Artaxeres IV on the throne, a king he could easily control.  When King Artaxeres IV started to push his independence Bagoas poisoned him too elevating King Darius to the Persian throne.  But Darius proved too sharp for Bagoas.  When Bagoas attempted to poison Darius the tables were turned and Bagoas drank the poison instead.    

Alexander the Great (Alexander III of Macedonia) died in 323 BC in the palace of Nebuchadnezzar II, in Babylon, at age 32.  It is said that Alexander entertained admiral Nearchus and spent the night and next day drinking wine with Medius of Larissa.  Alexander rapidly developed fever, muscle weakness and pain.  He died in agony 14 days later.  Antipater, who was recently removed as Macedonian viceroy, and at odds with Olympias, was  fingered by many as leader of the plot.  Antipater purportedly arranged for Alexander to be poisoned by his son Iollas, who was Alexander's wine-pourer. Another theory is the Alexander died of poisoning from drinking the bacteria infested water from the river Styx.   

Poisoning for political gain has existed since long before the time of Christ.  Next week we will jump ahead 1,000 years for a couple more fascinating poisonings.  

 

 

 

 

Lipid Emulsion

Today I had the opportunity to sit and listen to an Aussie talk about lipid emulsion therapy.  But he did not just talk about what we know and review the literature.  Rather he talked about lipid emulsion therapy 2.0.  He presented his research into liposome therapy.  He is using phospolipids to sequester various agents.  Imagine a sphere with a hole in the middle.  The outside is the charged, phosphate layer.  The inner ring the lipid area.  The innermost core is an area whose pH can be manipulated.  By manipulating the core pH, the charge of the phosphate layer and the size of the lipid layer a variety of drugs are trapped.  In the future will we be seeing liposomes used to increase dosages of cancer chemotherapeutic agents?  Treat toxins that today we can only weep over?  If we do; you heard it here first. 

Along the lines of lipid emulsion therapy there are no less than eight abstracts at this toxicology meeting lauding its use.  There is a wide variety of toxins that were treated.  All very fascinating.

Phenytoin Toxicity and Multidose Charcoal

Three weeks ago the toxicity of antoconvulsants was presented.  The clinical picture of a patient taking phenytoin and developing toxicity was laid out, and it was not pretty.  Initially ataxia, nystagmus and lethargy that can progress to seizures and coma.  The difference between a therapeutic serum phenytoin level and a toxic one is small.   There is some evidence that in the symptomatic patient who took an acute overdose multidose charcoal may be beneficial.  Today in my mailbox is the latest issue of Clinical Toxicology.  In it is a paper that attempts to quantify the effect multidose charcoal has on patients with a supratherapeutic serum level of phenytoin.  Clinical Toxicology Paper (Abstract).               
A few items of interest.  This is a randomized controlled study lasting 18 months involving two large teaching hospitals.  Pretty great for a tox study.  But they could only enroll 17 patients.  Pretty typical.  They showed that there was a difference in time to a sub-toxic serum concentration between the study and control groups.  Great!  With a larger number of patients they may have been able to show a significant difference.  Even better.

What to take away from this study?  Clearly more study with more patients is required.  Studies that looked at clinical parameters in addition to time to sub-toxic levels would be a plus.  Based on this paper alone is it hard to change clinical practice.  What this does do is make it easier to recommend multidose charcoal is the appropriate patient.  It is one more piece in a larger clinical puzzle. 
  

Poison Plot

My favorite headline of the week came from the San Francisco Chronicle, San Jose man accused of poison plot.  What did he do?  Put ricin in Adrian Peterson's and Christian Ponder's food after the Vikings beat the 49ers.  Or maybe gassing the Republican headquarters.  After all it is California in an election year.  But no such fun.  As with most plots this one involves love, money and nursing homes. 

It just happens that an older gentleman's girlfriend is living in a nursing home.  In order to gain control of her finances he tried the age-old trick of poisoning her.  Fortunately, he picked the wrong poison.  He snuck her bottles of water that had chlorine added to them and encouraged her to drink.   The nursing staff eventually found a bottle that smelled like pool water.  The police were notified and the poisoner is now in jail. 

Chlorine is in our water and used to keep our pools clean.  We use it to disinfect counters and whiten clothes.  So what's the deal?  As with everything else, "Poison is in everything and no thing is without poison.  The dosage makes it either a poison or a remedy."  In the case of chlorine it is the concentration that makes the poison.  Very dilute chlorine, as in pool water, will not do much when ingested.  Your kidneys do a good job of handling it.  But concentrated chlorine is corrosive and can cause severe oral and esophageal burns.  This victim was checked out at an ED and returned to her nursing home.    

Poison plots, love and money.  The story that always has a new chapter.

Smiles

It seems that nearly everyday I hear about a new designer drug.  One source of information is my morning paper.  The typical story is a teenager who tries the new drug and subsequently dies.  The article will quote the parents and the police.  Last week I read this  YAHOO Shine  report on 2C-I. 

"Smiles" or 2C-I is the latest designer hallucinogenic amphetamine.  It follows other designer drugs with similar names.  The effects all seem the be the same.  The users describe vivid hallucinations, or a friend finds the user dead.  These new drugs are all illegal in the US and many other countries.  Originally developed by a psychopharmacologist many years ago as new research compounds.  The compounding process has been simplified and is available for basement chemists to make their own drug.  So why did the teenager is this article die?  How about quality control.  I do not believe there is the same concerns with quality when someone is making a drug in their basement as compared with Abbott making Vicodin.  When you purchase a street drug do you really have any idea what is in it?  Does that chocolate bar have just enough drug for a nice high?  or a lethal dose.  Whereas you know every Vicodin tablet has the correct anount of hydrocodone.  I equate the use of designer drug to eating puffer fish.  Eat a meal prepared by a high quality Fugu chef and your mouth tingles from just the right amount of the neurotoxin in the fish.  Eat puffer fish prepared by some guy in an alley and you get a load of the neurotoxin and stop breathing. 

Its all about quality control.  Are designer drugs safe?  Certainly not.  Do they kill every user.  No.  Remember, its all about the dose.

Suboxone tablets

According to the American Association of Poison Control Centers (AAPCC) today Reckitt-Benckiser has decided to withdraw suboxone tablets from the market.  Suboxone is a drug used to treat opiate dependence.  It has a fascinating effectiveness profile that you will hear about in class next week.  Withdrawal of the drug was based partially on AAPCC data.  AAPCC has data from all US poison centers and includes every exposure called into a center.  Reckitt-Benckiser reviewed that data and had concerns over the number of poor outcomes following pediatric exposures to suboxone tablets. 

The AAPCC stated that, "Our analysis of the combined data sets indicated that the rate of unintentional exposure for young children is several times higher for Suboxone tablets compared to Suboxone oral film.  This effect persisted when the availability of the drug was considered.   Based on the data, RBP decided to withdraw their Suboxone tablet product from the market. We were not involved in that decision and did not know about the press release until we saw the news stories that quoted the press release."

Fascinating!  Here is an example of post-marketing surveillance and a decision based partially on a source of safety/toxicity data. 

Every call into a poison center makes a difference.   It makes a difference for the patient and in this case makes a difference for public health.

Led Zeppelin

Today is the anniversary of the death of John Bonham, drummer for Led Zeppelin (September 25, 1980).  In the 24 hours prior to his death Bonham drank 40 shots of vodka.  He drank so much that he could not protect his airway, vomited, asphyxiated and died.  Following his death Led Zeppelin disbanded, closing the door on one of the greatest rock bands of history.

Enjoy this video.

Caffeine

Like all of you I could not wait to get to my computer to read about the horrible call that gave last night’s Packer game to Seattle.  But this headline caught my eye instead.   Hamilton injury blamed on caffeine.    
 

Josh Hamilton is an amazing baseball player.  He has lead the Texas Rangers to the last two World Series.  He is fast, plays center field and can hit.  Today he is leading all of baseball in homeruns.  Josh Hamilton also has a long history of substance abuse.  It was only after he conquered his demons did his baseball career take off.  But how did he hurt himself with caffeine?  Trip on a can of Monster?  Spill coffee on his hands?  According to ESPN his caffeine consumption was so high he developed ocular keratitis.  He couldn’t focus.  Not a good thing when holding a bat while someone is throwing a 98 mph baseball at you.  It turns out Josh Hamilton drinks a lot of coffee during the day, has an energy drink before the game and tops off his evening with some theobromine (chocolate).  Caffeine is well known to cause tremor, headache, tachycardia, hypertension and GI irritation.  Now you can add ocular keratitis to the list.  Josh Hamilton may be a superb athlete but he really is just one of us. 

Do you think the NFL replacement refs get enough caffeine?

Ocular Keratitis:  Keratitis is an inflammation of the cornea — the clear, dome-shaped tissue on the front of your eye that covers the pupil and iris. Keratitis may or may not be associated with an infection.  Noninfectious keratitis can be caused by a relatively minor injury, wearing your contact lenses too long or other diseases. Infectious keratitis can be caused by bacteria, viruses, fungi and parasites.  (www.mayoclinic.com)

 

Ban on booze

Government bans hard liquor! That is a headline that grabs my attention. In Texas we lived in a dry county.  Is Ozaukee County now going dry!?  Is prohibition back?  Most importantly, can I still buy beer before tonight's Packer game?

The Czech Republic has banned the sale of any liquor with an alcohol content of greater than 20 %.  They are having a moonshine problem.  Many people around the world make their own alcoholic beverages.  Home brewed beer and wine is pretty common in this country.  But distilling hard liquor in your backyard is little different.  The problem in the Czech Republic is that the homemade hard liquor is being made, labeled and sold are the real deal.  Someone is making a buck, what's the big deal?    Check out this link.    The tox problem is that the counterfeiters are adding methanol to their liquor. The methanol adds to the alcohol content, stretches the volume produced, and is cheap and tasteless.  Perfect.  But it causes blindness and death. Over 20 people have died and many more are sick and/or blind.  

Methanol is a toxic alcohol that in the body metabolizes to formic acid and formaldehyde. The formic acid causes a severe metabolic acidosis, blindness and death. Clearly, "stretching" your moonshine with a little methanol is a big deal. Methanol outbreaks from tainted alcohol have happened before, and will happen again.

Arsenic and Rice

Judy Buenoano, aka the “Black Widow” decided that arsenic was her friend.  She used it to poison her husband and a boyfriend and collect life insurance money.  Obviously, arsenic is horrible.  But wait, we use arsenic (Trisenox®) to treat cancer.  So it must be good for us.  So what is it, a horrible poison or a lifesaving pharmaceutical? 

 This week I have had two family members ask me about the report of arsenic in rice.  According to Consumer Reports arsenic has been found in high levels in rice.  (ABC News report)  Brown rice more than white.  Arkansas rice more than California.  Urvashi Rangan, director of consumer safety and sustainability at Consumer Reports, said "we think that consumers ought to take steps to moderate their consumption."  Consumer Reports even threw chickens under the bus for having arsenic in their feed.  For a more balanced report read this FDA update.    “It is critical to not get ahead of the science,” says Michael R. Taylor, FDA’s deputy commissioner for foods. “The FDA's ongoing data collection and other assessments will give us a solid scientific basis for determining what steps are needed to reduce exposure to arsenic in rice and rice products.”  Good, now I can get back to eating more than just Raisin Bran Crunch.  

 Arsenic is a naturally occurring element that is ubiquitous in the environment.  It is in our soil, our water and our food.  We breathe it and ingest it every day.  In large doses it can kill and it is a known carcinogen.  But at what dose is it a problem?  As with everything the “dose makes the poison”.  The FDA is continually investigating to set safe levels.  But logic tells me we are safe where we are at.  Rice is a food staple worldwide.  Eat in Uganda, Mexico or China and rice will be on your plate.  So how is it the world is over-populated if rice is so bad for you? 

By now you are totally confused.  To eat rice or not?  Here is one more item for you to read to help you make up your mind.    Maybe my dinner tonight will be a chicken breast on a bed of rice.  Yum.  But I will not be drinking apple juice for breakfast, there’s poison in it! 

Drugs and self-portraits

On the first day of class we defined toxicology as "a science that deals with poisons and their effect and with the problems involved (as clinical, industrial, or legal)".  Of course there are many ways to study poisons.  Analytically and clinically are the first that come to mind.  But personal experience can be fascinating.  My favorite website (www.erowid.org) is full of descriptions of drug experiences.  This person goes one step further.  Brian Lewis Saunders is an artist who is painting self-portraits of himself while on different drugs. Some of the drugs are prescription, and some are not. Check it out, the paintings are great!

Toxic Tattoo

For years where toxic and tattoo were used in the same sentence it was an urban myth.  Supposedly drug dealers hung around schools to give kids little stick on tattoos that contained LSD.  Not true.  So today I was a surprised to see something about toxic tattoos in my in-box. 

The American Academy of Clinical toxicology sent our this tidbit...

"A 19-year-old female calls the poison center stating she received a tattoo on her upper arm one month ago and now has what sounds like red papules in and around the site of the tattoo. The tattoo consists of a large red rose and most of the ink used was bright red in color. What is the likely source of these red papules?"

Good question.  The tattoo below has a red rose, but it looks clean.  So what is the problem?  I doubt it is LSD.  Maybe hepatitis?  Interesting?

"Based on recent reports and cautions issued by the FDA, these red papules likely represent nontuberculous mycobacterial infection from contaminated tattoo ink. The caller should be referred to a knowledgeable dermatologist or other physician for treatment. The cited reference points out that “Antibiotic choices are limited by the susceptibility profile of the organism and prolonged treatment may be necessary to clear the infection.” They go on to note that many persons treated with macrolides have had “favorable response” to this therapy. A recently reported outbreak found contaminated ink in an unopened contained and “thus, contamination could have occurred at various points in the ink-production process-for instance, from unsanitary manufacturing processes or the use of contaminated ingredients such as water, glycerin or pigments." (LeBlanc PM et al. Tattoo ink-related infections-awareness, diagnose, reporting and prevention. 2012 NEJM 367(11):985-987)" 

Toxic tattoos from contaminated ink!  Thank you AACT for the fun note.  

Vitas Gerulaitis

Vitas Gerulaitis?  Even I have to think for a minute about that name.  As I recall he was a tennis "star" in the late 70's and early 80's.  He was far more famous for his blond hair (google his hair, its 70's amazing) and reputation as a partier.  What does he have to do with today? 

This morning I went out for an early morning run and was a little surprised at the temp.  It was chilly.  As I look out the window I see trees turning color.  For many that means fall.  For toxicologists it means carbon monoxide season.  Carbon monoxide is an odorless, tasteless, invisible gas that is a by-product of incomplete combustion.  Burn wood, charcoal, gasoline or propane and carbon monoxide results.  When sitting around a campfire or tailgating at a Brewers game, no problem.  When the carbon monoxide builds up in your home, that is a different story.  Carbon monoxide first displaces oxygen off your hemoglobin.  Your blood carries carbon monoxide instead of oxygen, not good.  Even worse, as levels in your body increase carbon monoxide eventually blocks cellular respiration.  Thankfully the antidote is close by, fresh air. 

Why is fall CO season?  As people fire up their furnaces for the first time some are bound to fail.  Others heat their homes with poorly vented fireplaces.  Calls to poison centers regarding CO greatly increase in fall and winter.  Patients show up in emergency departments with headaches, dizziness and other vague symptoms.  Low level CO poisoning.

Vitas Gerulaitis?  He was staying in a summer cottage of a friend's in Long Island.  To prepare for winter the owner had a new propane heater installed.  On the morning of September 18, 1994 the heater failed and a tennis star died of carbon monoxide poisoning. 

Flumazenil and Lifetime Learning

Every practicing professional has their own way of keeping informed on the latest and greatest in their chosen field.  The desire for lifetime learning is one of the cornerstones of higher education.  Some use journals, others electronic newsletters.  But it seems that everyday there is another paper published that impacts pharmacy.  As a member of the American Academy of Clinical Toxicology I receive a monthly "Current Awareness" newsletter that lists important papers published in the last month.  My September current awareness includes, "A Poison Center's Ten-year Experience with Flumazenil Administration to Acutely Poisoned Adults".  Perfect timing!  Last Wednesday I talked about the use of flumazenil as a benzodiazepine antagonist in the poisoned patient.  This paper is now posted on Angel in the "readings" folder.  The conclusion you heard last week was that the flumazenil is rarely used due to the risk of seizures.  This paper reviewed 904 patients who received flumazenil.  Of those patients 13 had a seizure and one died.  So the seizure rate is actually low.  The authors conclude that only 13/904 (1.3 %) of patients developed seizures and that those seizures were significantly associated with the ingestion of a medication that is pro-convulsants.  The authors also also note that most of the patients had an improved mental status after flumazenil administration.  So what did I learn from this that I can carry into my practice?  Flumazenil does work, but its risks are significant.  Each patient must be very carefully screened before it can be administered.  The ingestion of a pro-convulsant drug would be an absolute contraindication to flumazenil. 

Lifetime learning, so what are your plans?          

Botulism

Botulism, the grandaddy of food poisoning.  Botulism is the reason we don't buy dented cans.  And, more importantly, where Botox come from.  When people get botulism the outcome is not always good.  As with any potentially fatal illness early diagnosis is important. 

To help clinicians diagnose botulism we have the "Dozen D's":

1. Dry mouth;
2. Diplopia;
3. Dilated pupils;
4. Droopy eyelids;
5. Droopy face;
6. Diminished gag reflex;
7. Dysphagia;
8. Dysarthria;
9. Dysphonia;
10. Difficulty lifting head;
11. Descending paralysis; and
12. Dyspnea from diaphragmatic paralysis.

In any patient who displays three or more of the "Dozen D's" botulism should be considered.   Just the kind of thing we should be injecting to take care of wrinkles!  

Thank you to the AACT question of the day and Zane Horowitz.  (Horowitz BZ. Botulinum toxin 2005 Crit Care Clin 21:825-839)