Loco
What poison makes you mad as a hatter? What’s the brand-new antidote for it hot off the presses? What medicine comes from a bean used in African witchcraft trials? Listen to find out!
This is the Pick Your Poison podcast. I’m your host Dr. JP and I’m here to share my passion for poisons in this interactive show. Will our patient survive this podcast? It’s up to you and the choices you make.
Our episode today is called Loco. What poison makes you mad as a hatter? What’s the brand-new antidote for it hot off the presses? What medicine comes from a bean used in African witchcraft trials? Listen to find out!
Today’s episode starts in the ER. You finish setting a broken wrist, then check who’s next on the list of patients waiting to be seen. Room 4. A 16-year-old with altered mental status, meaning anything from mildly agitated, psychotic or violent on one end of the spectrum, to lethargic, unconscious, or basically dead on the other end.
You walk in the room to determine what exactly the chief complaint means. The patient is sitting on the stretcher, awake. He’s alive, so it’s our job to keep him that way. You ask how he’s feeling. He turns to the sound of your voice, but just blinks a few times and doesn’t answer. His mother is sitting at the bedside. She says “he just isn’t right.”
This is one of my favorites, along with “I just don’t feel good” and “I’m dizzy”. The medical problems causing these complaints range from a cold with a runny nose to a heart attack with an impending cardiac arrest. We’re going to have to narrow it down. The patient reaches up as if to pluck something from the air, though nothing is there. He mumbles some incomprehensible words.
You ask the mother more questions. She says he has no past medical history. He was fine this morning. This afternoon, he seemed mildly confused, then progressively worsened. She keeps repeating “something’s not right.” Mom can’t give us more, so let's move on to the physical exam.
You review his vital signs. Something definitely isn’t right. His temperature is elevated at 102.8. His heart rate is 142 beats per minute, very fast. His blood pressure is high at 160/80. Not dangerously so, but high for a 16-year-old. His respiratory rate is slightly fast, his oxygen level is normal.
The patient mumbles his name when you ask, but doesn’t answer the year or the month. He has large, dilated pupils, mydriasis in medical terms. His skin is flushed. The exam is otherwise unremarkable.
In short, this is delirium. You tell the nurse to start IV fluids and give some Tylenol. The ER workup includes basic labs, a chest Xray and a urine specimen. These days for sure, a COVID swab. Fever and infection are common causes of delirium. The list of infectious possibilities is long, very, very long. Fortunately this is a toxicology podcast, not an infectious disease one.
That said, the list of toxins causing altered mental status is also huge. We could spend all day making the list, forget about treating this patient, not to mention all the other patients waiting to be seen. We need to narrow it down before we start listing the differential diagnosis. Fortunately in this case, one of the vital signs can help us focus in on the potential causes.
Question 1. Which vital sign will help us the most in figuring out what’s wrong with this kid?
A. Temperature
B. Heart rate
C. Blood pressure
D. Respiratory rate
Answer: A. The temperature is the most useful vital sign here. Yes, his heart rate is high, but the list of toxins raising the heart rate is long. His blood pressure and respiratory rate are high, but not enough to point toward a specific diagnosis. The list of toxins causing an elevated temperature, hyperthermia, is relatively small and very interesting, at least in my opinion. Let’s move right to the causes of toxicologic hyperthermia and narrow it down from there.
There are six main categories.
First, malignant hyperthermia. Very dangerous and even more rare. Basically, occurring after exposure to general anesthesia in patients with a genetic mutation of the muscles. It occasionally occurs outside of the OR, but not likely in our patient.
Categories two and three are neuroleptic malignant syndrome and serotonin syndrome. Both occur from exposure to psychiatric medicines. Neuroleptic is an old-fashioned word for antipsychotics and serotonin syndrome is often caused by antidepressants. Mom denies the patient takes any meds himself and says there are no psych prescriptions in the house. There is a physical exam finding I’d check for right away to point me toward or away from these two diagnoses.
What is it? Muscle tone.
Neuroleptic malignant syndrome causes lead-pipe rigidity, where limbs are stiff and resist movement. Serotonin syndrome causes the opposite, hyperreflexia, over reactive muscle responses. Our patient’s muscle tone is normal. This doesn’t definitely exclude categories 2 and 3, but given he doesn’t have these finding and there’s no history of exposure, also, not likely.
The next category is alcohol and benzodiazepine withdrawal. (Benzos are drugs like Xanax or valium). Alcohol withdrawal could defiantly look like this. What’s that? Did I hear you say he’s only 16? How could he have an alcohol use disorder? While I’d love to agree this makes withdrawal impossible, sadly I can’t. It’s associated with a muscle finding, tremors, which he doesn’t have. Not impossible, but this category seems unlikely, too.
The last two categories have similar symptoms. Let’s discuss the similarities, then how we differentiate them. Sympathomimetic use, cocaine or meth for example, can cause fever and delirium. This is due to activation and overstimulation of the sympathetic nervous system, the flight or fight response. Anticholinergic toxicity looks very similar, because its suppression of the parasympathetic, rest and digest, system. It’s not hard to imagine activating fight or flight is similar to suppressing rest and digest. Either way the body’s checks and balances are out of order. Both result in hypertension—high blood pressure, tachycardia—fast heart rate, and hyperthermia.
How do we tell these categories apart? There is a distinguishing feature on physical exam. Make sure your gloves are on, we need to check his armpits.
What’s the difference?
Wet vs. dry. If the patient is hot and sweaty, or wet, this is a sign of sympathomimetic toxicity. Hot and dry points to anticholinergic toxicity. Our patient? You try not to wrinkle your nose as you slide your gloved fingers around his armpits.
Dry. This is an anticholinergic toxidrome.
The patient continues to reach for, and pick at things, that are not there. Imagine someone trying to grab dust motes from the air. This unusual behavior will lead an experienced toxicologist right to the diagnosis, for some reason it’s very typical of anticholinergic toxicity.
Mom tells you he can’t urinate to give us the urine specimen. Urinary retention is another feature of anticholinergic toxicity. There’s no test to confirm our diagnosis, but the symptoms all add up, so we can be pretty confident we’re on the right track.
The patient shouts something incomprehensible then gets up from the bed. He starts moving toward the door, ripping off the cardiac monitor as he goes. I say moved, because he’s not exactly walking, he’s stumbling and lurching around like a drunk person. Should we respect his wishes and let him walk out? No way. First, he’s too confused to have rational decision-making capacity. Second, regardless of his ability to reason, he’s about to fall and injure himself. You and mom gently push him back into bed. He goes returns to mumbling and picking at things.
What is anticholinergic toxicity? It’s the opposite of the toxins we discussed in prior episodes The New Guy and Three Little Steps. Medical students use the following pneumonic to remember it. Mad as a hatter, hot as a hare, dry as a bone, blind as a bat, full as a flask.
Mad, as in delirious, hot = fever. Blind, not literally, but enlarged pupils, like having your eyes dilated at the eye doctor’s. Full as a flask, refers to the inability to urinate. Listen to the next episode to find out why we have the expression mad as a hatter in English.
The patients gets out of bed again. I didn’t mention earlier, he’s a strapping two-hundred pound 16-year-old. This time when you try to put him back into bed, he starts bellowing, yanks out his IV and overturns a metal surgical tray with a loud crash.
As is often the case in toxicology and emergency medicine, we’d better treat first and figure out what happened later. There is an antidote for anticholinergic toxicity. What is it?
A. Fentanyl
B. Naloxone (Narcan)
C. Physostigmine
D. Atropine
Answer: Physostigmine brand name (Antlirium) a play on anti delirium.
It’s a cholinergic agent, so it works to reverse the anticholinergic poison. It’s found in the Calabar bean from West Africa. The history of the Calabar bean is fascinating, it was used as a trial bean.
What’s a trial bean? Something used in a “trial”, for example witchcraft, to determine guilt vs. innocence. How does this work? Obviously, it doesn’t. An accused person, on trial, ate the bean. The theory in the old days was the innocent would be fine, while the guilty died. Similar to trial by water. Women accused of witchcraft proved their innocence by sinking, while the guilty floated. If you swallow a bean whole, you’re not likely to develop toxicity. If you bite it, physostigmine is released causing cholinergic toxicity. If you remember, other cholinergic toxins include chemical weapons like VX and rodenticides like aldicarb and pesticides.
Some suggest the innocent didn’t hesitate to swallow the bean and were fine. The guilty were afraid to swallow, bit the bean and died. I seriously doubt there was much, if any, rational thinking involved in these proceedings. Anyway, I could go on with more fascinating facts, but I won’t. European missionaries brought the Calabar bean back and eventually scientists discovered the active ingredient and its medical utility.
You order a dose. The pharmacist calls. There’s no physostigmine.
Physio was a great antidote. Why was? We no longer have it. Why not? You’ve probably heard about drug shortages. Welcome to modern medicine. In recent years we’ve had shortages of drugs from essentials like morphine to basics like normal saline for IV fluid. The single manufacturer of physostigmine went out of business.
Uh oh. What now?
We can give benzodiazepines, like lorazepam or Ativan. It will work to sedate him and we do use them to treat anticholinergic toxicity. The problem is, it’s easy to overshoot and cause too much sedation. We don’t want to accidently over sedate a 16-year-old causing him to become unconscious and in need of a ventilator.
Good news. You’ve just returned from the North American Clinical Toxicology Conference in Montreal. If you paid attention, instead of just eating poutine, there were some posters with research about a promising new antidote. Rivastigmine, sounds like physostigmine, because it works similarly. Rivastigmine is used to treat Alzheimer’s disease and is often in patch form in the US. The patients in the posters had anticholinergic toxicity and got better with a rivastigmine patch. Genius!
Either option here is reasonable, benzos or rivastigmine. The benzos treat the symptoms, namely agitation, but don’t directly treat the problem. Or you can talk to mom about an experimental, but pharmacologically sound, solution. A true antidote. Side effects of the patch? You guessed it, cholinergic toxicity like the Calabar beans. According to the posters, the symptoms are generally mild and improve once the patch is removed.
I’d give a dose of lorazepam to keep him from trying to leave, then let Mom decide from there. The lorazepam keeps him in bed, but doesn’t do much else. She decides on the patch. It works with surprisingly good success. An hour later, his mental status is almost back to normal, his temperature is down, and his other vital signs have improved.
Perfect. Exciting to use a new antidote in place of one we’ve lost. Now that he’s treated, we still have to figure out what caused this.
In prior episodes, we’ve discussed one of the very first anticholinergic drugs. It’s an antidote for —not surprisingly— cholinergic toxicity. What is it?
A. Naloxone (Narcan)
B. Charcoal
C. Prussian Blue
D. Atropine
Answer: D. Atropine. This kid probably didn’t get into atropine at home, it’s pretty much found only in the hospital or maybe a military stockpile.
So what else causes anticholinergic toxicity? Once again, it’s a huge list. Lots and lots of medicines. One of the most common overdoses we see causing it is diphenhydramine, or Benadryl. The list includes other antihistamines, psychiatric meds, drugs for Parkinson’s disease….
Mom’s phone beeps with a text. A friend’s mother says the teens were in the woods and ate a plant.
Phew.
This gives us something to focus in on. Some very famously poisonous plants cause anticholinergic toxicity. You’ve probably heard of Belladonna, or deadly nightshade and Mandragora, or mandrake. These plants are in the Solanaceae, or deadly nightshade family. Tobacco is in this family. It includes poisons so toxic they’ve instilled fear for centuries, but also includes such nondeadly plants as tomatoes, potatoes, eggplants, peppers.
Short detour, people in the US and Europe believed tomatoes were poisonous in the 1700 and 1800s. The plants were initially cultivated in Europe for their beauty in gardens, not for their delicious taste. There are belladonna alkaloids in tomato plants, but only in the stems and leaves, not in the fruit.
Did our patient eat a tobacco plant? No, this isn’t nicotine toxicity. Maybe his friend tried to kill him with mandrake or belladonna, but probably not. There is a plant that attracts those interested in getting high, often teenagers. Datura stramonium, or jimsonweed. It’s also called thorn apple, moonflower, the devil’s weed, devil’s trumpet. The name most telling, locoweed. I doubt most people get the high they were expecting.
Jimsonweed grows all over the US and all over the world. The plants contain 28 different belladonna alkaloids. The two main alkaloids are atropine and scopolamine. The amount of these alkaloids varies within the plant and also changes with location. Interestingly, the amount of CO2 in the environment changes the amount of toxin in the plant. As CO2 increases, plants increase atropine and scopolamine production. Meaning climate change is making plants more poisonous! Increased CO2 also increase morphine concentration in narcotics! Fascinating.
Most people eat seeds from inside the seed pod. Each pod contains 50-100 seeds. Fifteen to twenty seeds can be fatal. Jimsonweed exposures occur intentionally, as I mentioned, and unintentionally. It’s contaminated things like honey, tea, and stew. Recent outbreaks in 2022 were caused by contaminated spinach in Australia and Italy.
Both atropine and scopolamine are used medicinally in ancient times and still today, along with a third alkaloid in these plants, hyoscyamine. Mandrake use was described 4th century BC in Greece for use in wounds, gout and as a love potion. Since then, use of these plants as antiasthmatics, antispasmodics, narcotics, and anesthetics is described.
Atropine was extracted from atropa belladonna in 1831, and is used to treat slow heart rates and as an antidote for chemical weapons and pesticides. I’m willing to bet you’ve experienced the effects of belladonna and mandrake plants yourself. Yep, you heard me right. Atropine is used in ophthalmology along with scopolamine to dilate the pupils, a class of drugs called cycloplegics.
In fact, this is how the plant got the name Belladonna. It was named after it’s use by women in the Renaissance as a beauty aid. Yes, a deadly poison and a cosmetic. (See also lead, arsenic, mercury and thallium). Large pupils were considered attractive and women used juice from Atropa belladonna to get this look, so the plant was named belladonna or beautiful woman. Some say Cleopatra and Roman women did the same. According to modern studies, people still find large pupils attractive. Is it a coincidence that your eyes dilate when you see someone you’re attract to? Probably not. Beauty is one thing, but honestly how could these women see? Have you ever tried to drive or read after leaving the eye doctor’s office?
How did Jimsonweed get its name? Datura is from a Hindi word for the plants. Jimsonweed is from Jamestown, Virginia one of the original European settlements in the US. According to one report in 1705, British soldiers sent to quell Bacon’s rebellion ate Jimsonweed. Apparently, they sat around naked in their own feces, grinning like monkeys. The report can’t be confirmed, but this description sounds about right. However, it also says the effects lasted for 2 weeks, which isn’t true, so who knows.
In reality, symptoms last for a day or two after ingesting jimsonweed. Occasionally longer, because anticholinergics delay stomach emptying, causing delayed absorption. Either way, not longer than a few days.
The plants have a dark history in both ancient and modern times. Belladonna was believed to be part of witches flying potion, along with wolfbane, a plant we’ve discussed previously, maybe due to the sensation of flying some report after exposure. In popular culture, not quite pop culture, some believe belladonna was the poison Shakespeare described in Romeo and Juliet. In history, there are reports the Roman’s used it to poison enemies’ food reserves during warfare. Some have suggested it was the poison used to kill Emperors Claudius and Nero. Others believe it’s part of Haitian zombie powder.
In modern times, there are reports of criminals blowing scopolamine into the faces of victims, leading them to become “zombies,” making them prey to robbery and rape. It’s called Burundanga in South America, meaning Devil’s’breath.
Unlike the fearsome reputation of belladonna and mandrake, fatalities from jimsonweed are rare, but reported. Datura has been used in drug-facilitated sexual assault and robbery. There’s a case report about a 35-year-old man who travelled to Java. He was dead on arrival to a local hospital. His body was returned to France where an autopsy revealed the presence of scopolamine, atropine and hyoscyamine. The man’s tour guide admitted to giving him a poisoned drink to rob him.
Back to our patient. He’s admitted to the hospital for monitoring. The next day, he’s awake, alert and back to normal. With mom out of the room, he admits to ingesting 10 seeds of jimsonweed to get high. The monitor shows his heart rate is low, in the 50s. You remove the rivastigmine patch. His heart rate improves and his mental status remains normal. He’s discharged uneventfully. This is a fictional case, as are all our cases, to protect the innocent. But it is based on real poisonings.
There’s one last cool story I want to share with you, about an ingenious bit of pharmacologic knowledge from ancient Greece. The Greeks knew jimsonweed caused hallucinations. If you remember the Odyssey, the sorceress Circe is said to have turned Odysseus’ crew into pigs.
On his way to rescue them, the god Hermes advises Odysseus to protect himself from Circe with a plant called moly. Some have suggested the crew were not turned into pigs, but given jimsonweed, leading them to hallucinate that they were animals. Moly might’ve been the snowdrop plant. Why the snowdrop? The plant contains a cholinergic compound galantamine, a natural antidote for anticholinergic toxicity. If Circe was poisoning the sailors with jimsonweed, galantamine would’ve protected Odysseus. True? Who knows, but really interesting. We use galantamine today, like rivastigmine, to treat Alzheimer’s.
The last question for today. Which famous artist’s painting of jimsonweed sold for 44.4 million dollars?
A. Monet
B. Georgia O’Keeffe
C. Van Gogh
D. Klimt
Post your answers on our Twitter and Instagram feeds both @pickpoison1. Follow and you’ll see the answer when I post it. Remember, never try anything on this podcast at home or anywhere else.
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While I’m a real doctor this podcast is fictional, meant for entertainment and educational purposes, not medical advice. If you have a medical problem, please see your primary care practitioner. Thank you. Until next time, take care and stay safe.