Poisonous Panacea
Want to know what’s called the disease of kings? What toxic plant is used to treat it? What prehistoric animal also suffered from this disease? 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 patients survive this podcast? It’s up to you and the choices you make. Our episode today is called the Painful Panacea.
Want to know what’s called the disease of kings? What toxic plant is used to treat it? What prehistoric animal also suffered from this disease? Then stay tuned!
The nurse asks you to see a 62- year-old-man next because he’s been vomiting continuously and she’d like to give him some nausea medicine. The patient says he’s been having vomiting and diarrhea for the past four hours. He denies other complaints including fever and abdominal pain.
He’s clutching a vomit bag, and his affect seems flat, meaning emotionless or withdrawn when you talk to him. His vital signs are temperature 98.5, pulse 99 beats per minute, blood pressure 160/72, respiratory rate eighteen, and oxygen saturation is 100% on room air. Like his vital signs, his exam is otherwise unremarkable.
You order routine lab work, IV fluids and nausea medicine, then move on to see a critical patient. In the meantime, the nurse asks you for several more doses of antinausea medicine. His labs come back, completely normal.
His wife arrives and is very concerned. She reports he’s been depressed recently and though he hasn’t expressed suicidal thoughts, she’s concerned he may have taken an overdose. When you asked the patient about this, he doesn’t answer. And he’s still vomiting.
Could this be a stomach virus, diverticulitis, or some other gastrointestinal problem? Of course. But this is a toxicology podcast so let’s get right to it. How do we know this is an overdose? We don’t. In real life we would be investigating the common causes of nausea and vomiting.
There are some red flags in this case. A flat affect goes along with depression. Just because the patient hasn’t expressed suicidal ideation, doesn’t mean he hasn’t taken an overdose or attempted to harm himself. Another red flag is this vomiting. While continued vomiting after several doses of nausea medicine isn’t intractable vomiting, the medicine should’ve relived his symptoms for most things, like a stomach virus. He’s not the first patient whose taken an overdose and refused to admit it or refused to tell us what he took. So how do we get to the bottom of problem like this?
It’s extremely difficult, in truth, and I’d be lying if I said we could always figure it out. But often, we can get to the bottom of it. What’s the best approach? To think about potential exposures in an organized fashion and match them with his symptoms.
The first one is obvious, ask the patient. We’ve tried this. Next is EMS, sometimes they bring empty bottles from the house, or give additional info. A differential diagnosis list based on the patient’s symptoms is always important like we’ve done in prior episodes. Nausea and vomiting? Good luck, you’ll be working on that list until next year. If you’ve ever taken medicine for anything, you know any drug can cause nausea and vomiting. The list of medicines and toxins on this list would be literally almost everything. Diarrhea, not much better.
Family members can provide useful information. The wife doesn’t know what he took, but she should know or be able to tell us what medicines and potential toxins are in the house. She reports she doesn’t take any medicine herself. In the medicine cabinet they have Tylenol and cough syrup, in addition to the patient’s meds. It’s an apartment, so no garage toxins like pesticides or engine coolant as far as she knows.
This brings us to the patient’s med list. Certainly, you’ve heard of suicidal patients with complicated plans, like mixing chemicals or ordering things online. That approach isn’t common, most patients take what’s readily available to them. What’s available to our patient certainly includes his own prescriptions. His past medical history shows he has hypertension, diabetes, hyperlipidemia or high cholesterol, depression, and gout.
A fairly common problem list. Let’s go through his medicines to see if anything fits. An extra dose or two of any drug can cause nausea and vomiting, but I wouldn’t expect it to persist after some nausea medicine. Antihypertensives cause low blood pressure, obviously and some cause low heart rates, neither of which he has. Antidiabetics can cause low blood sugar, but we’ve already checked his labs and his blood sugar was normal. Last week we discussed anion gap metabolic acidosis including an old anti-diabetes medicine called phenformin. This has been replaced in the US by a very commonly used drug called metformin. Metformin causes lactic acidosis which can certainly lead to nausea and vomiting, but again the patient’s labs were normal. Medicines to treat high cholesterol can cause muscle pain and damage, doesn’t really fit here.
What about psych meds? Always a possibility, not surprisingly these are common in overdose. In the Loco episode we touched on toxicologic hyperthermia and serotonin syndrome, when serotonin levels in the body are too high. This is caused by many antidepressants, and certainly can cause vomiting before the onset of severe symptoms like a fever and an altered mental status. If you recall, it also causes hyperreflexia, and muscle rigidity. Our patient doesn’t have any of these. Almost all psych meds cause some degree of sedation in overdose. If he’s having this much nausea and vomiting, I’d anticipate some change in his mental status. So while we can’t definitely exclude psych meds, they aren’t at the top of my list.
Lastly, gout.
Question number one. Gout has been called “the disease of kings”. Which monarch famously suffered from gout?
A. Queen Elizabeth
B. Henry VIII
C. King Charles III
D. Louis XIV
Answer B Henry VIII. It’s believed he suffered from gout. He illustrates many of the risk factors for the disease. They include a diet rich in alcohol, sugar, meat and seafood. Obesity is a risk factor. As are hypertension, diabetes, and high cholesterol.
What is gout exactly? It’s arthritis causing severe joint pain. People with gout have high uric acid levels. The uric acid forms crystals that are deposited in the joint space, causing irritation and inflammation. Sharp crystals inside your joints. Sounds painful, doesn’t it? The joint most commonly affected is the base of the big toe.
What medicines are used for gout? Anti-inflammatories like ibuprofen or naproxen are the first line of treatment. Could this be an anti-inflammatory overdose? Yes, definitely. NSAIDs as we call them, cause a lot of nausea and vomiting, the reason you aren’t supposed to take them on an empty stomach. Subacute or chronic use causes acid reflux, stomach ulcers and bleeding. If this is an NSAID overdose he’ll be fine in a few hours once the drug leaves his system.
Steroids are another class of drugs we use. Like NSAIDs, they can cause vomiting. Steroids have tons of side effects, including infection and endocrine system disruption. Again like NSAIDs, the side effects occur with subacute or chronic use, not an acute overdose.
Allopurinol is a drug used to reduce uric acid levels, helping to reduce gout flares. It is toxic, but not acutely. Ongoing exposure causes a severe rash. Febuxostat is another drug to reduce uric acid, it’s so toxic, it has very strict prescribing criteria. I’ve only ever seen one or two patients on it. It has a black box warning about increased risk of cardiovascular events including heart attack and stroke. Neither the patient nor his wife has ever heard of the drug. So, while very toxic, not likely here.
Last, but not least. A drug used to treat gout in various forms for thousands of years. Colchicine. It’s effective, I’ve written many prescriptions myself. The dosing recommendations recently changed for safety reasons. This is how we used to prescribe it. Take 2 tabs, then take 1 tab every two hours until nausea, vomiting, or diarrhea develops. Essentially dose it until you have side effects, then stop.
Could this be a colchicine overdose? Yes. If you’re toxicologist, or anyone who’s ever had a patient with a colchicine overdose you might feel an icy chill of fear. Why? Colchicine in therapeutic doses is a useful drug. In overdose, it’s very dangerous. Reinforcing the prime tenant of toxicology, it’s the dose that determines the poison.
Back to our patient. We order more tests to determine what’s causing his symptoms. Eventually he gets tired of being poked and prodded and admits he took his entire bottle of colchicine because he wanted to kill himself.
First, a reminder that suicide is complex, but preventable. Treatment and support are available if you or someone you know is struggling. Call or text 988 for the American Foundation for Suicide Prevention. Or dial 1-800-273-TALK.
Colchicine. This is not good. You feel your own heart rate and blood pressure shoot up. What now?
We toxicologists love the idea of gastrointestinal decontamination i.e. removing the poison from the stomach before it’s absorbed into the system. Should we do gastric lavage, ie pump his stomach? Tempting but the answer is no. Gastric lavage has never been proven to work, and if done has to be within an hour, while the toxin is still in the stomach. The patient took the pills 4 hours ago. In addition, the vomiting naturally emptied his stomach.
The nurse reports his vomiting’s finally stopped. I’d probably start multidose activated charcoal, in the hope it would adsorb to colchicine and remove some from his circulation. Again, this isn’t proven, but has some support from animal models. Remember, charcoal is safe in the stomach but toxic to the lungs, so only give once the vomiting is controlled. Certainly, I’d continue nausea medicine and IV fluids to replace losses in the vomit and diarrhea. This doesn’t sound like much for a life-threatening overdose, because it isn’t. But it’s all we have. You call the hospitalist team and get him admitted.
Let’s talk about colchicine, where it comes from and how works because it it’s an interesting drug. Question two. What plant is colchicine derived from?
A. Crocus
B. Foxglove
C. Monkshood
D. Mandrake
Answer A. The Latin name of the autumn crocus Colchicum autumnale. Colchicine is also found in glory lilies. Colchicine containing plants have been used to treat joint pain at least as far back as ancient Egypt. It’s use is recorded in the Ebers papyrus. It’s also noted in the Materia Medica from the first century A.D. Benjamin Franklin is credited with bringing colchicine to the United States In 1820, colchicine was isolated as the active ingredient from the plant.
Unintentional poisonings have occurred in the past, when it’s been mistaken for wild garlic. In a study from German poison centers, 18% of these cases were fatal. If there’s anything I’ve learned as a toxicologist, it’s not to pick and eat wild plants and mushrooms. It’s not worth a fatal mistake.
Colchicine works by inhibiting microtubules inside the cell. What is their purpose? They support the cells structure and shape, help with transport of nutrients and with cell movement. To treat gout, colchicine inhibits the microtubules, ultimately reducing inflammation. Microtubules form the mitotic spindle during chromosome division. The mitotic spindle pulls apart two copies of the chromosome so the cell can split and divide. It’s the disruption of the mitotic spindle which causes colchicine’s deadly toxicity. If cells can’t divide, it results in cellular dysfunction and ultimately death. More on this in a few minutes.
Clinically colchicine toxicity is divided into three phases. Phase 1 is nausea, vomiting, and diarrhea, just like our patient, lasting for 12 to 24 hours. If there’s no vomiting and diarrhea, there’s no colchicine toxicity. A common scenario is a child get’s into grandma’s purse and pills are missing. Did grandma take them, did she lose them, did the child lose them, did the child eat them? Nobody knows. I’d observe the child and if they don’t have any vomiting, they didn’t eat the colchicine pills and they can safely go home.
Phase 2 bone marrow changes, specifically bone suppression. Meaning your body can’t make white blood cells or red blood cells. This is approximately 1 to 7 days. Phase 3 recovery or death, from days 7 to 21.
You check on the patient upstairs in room 427 after your shift ends. He’s fine and has no complaints. He regrets taking the overdose and wants to know if he can go home to see his grandchildren. He can’t, he needs continued monitoring. The next morning, back in the ED for another shift, you open his chart and scroll through. No events overnight, good. Telemetry, heart monitoring, negative. Good. Labs. Uh oh. His white blood cell count is 25, well above normal. In real life, I’d utter an expletive I won’t repeat here.
The overhead speaker crackles with an announcement. Code blue. Code blue room 427. Your heart drops to your feet. This is fiction, so you race upstairs to his room. He’s in cardiac arrest with CPR in progress. After twenty minutes, the patient finally gets a pulse back, though he barely has a blood pressure. The hospitalist calls the ECMO team. Extracorporeal membrane oxygenation. Basically, a heart and lung bypass machine where blood is pumped for a failing heart and oxygenated to bypass failing lungs.
What the hell just happened? Did we do something wrong? He was fine, then suddenly coded. No we didn’t do anything wrong, the mainstay of treatment is supportive care. I’ve taken care of several patients with colchicine overdoses, every case was the same. The patient had vomiting and diarrhea, was asymptomatic on admission to the hospital. The patient was fine, then had sudden cardiovascular collapse and death. Each patient also had a high white blood cell count shortly before this happened. In my personal experience, I consider the elevated white blood cell count a harbinger of death, thus the expletive. It may not always be the case, but it’s a negative prognosticator for sure.
Since microtubules are in all cells, it’s no surprise colchicine causes multisystem organ failure muscle failure, nerve failure, pancreatitis, liver failure, kidney failure, and DIC failure of the blood clotting system, just to name a few. Those who survive the acute effects, are at risk for infection and sepsis from bone marrow suppression. Survivors often develope alopecia 2 to 3 weeks later, though this is reversible.
I said earlier impairment of cell division was directly related to colchicine’s toxicity. Where are the most rapidly dividing cells in our body? In the G.I. tract which routinely sloughs off and is replaced, in the bone marrow which is constantly making new white and red blood cells, and hair. It’s not a coincidence we first see vomiting and diarrhea as the GI tract is affected, then bone marrow suppression and alopecia.
The toxic dose is debatable and wide ranges are reported. Colchicine concentrations are not well correlated with toxicity and therefore not useful. Mortality is estimated at 14 to 25% in some studies. About 10% of calls to Poison Centers in the US resulted in moderate to major toxicity and death. IV colchicine, given in higher than therapeutic doses, has been associated with twenty-three deaths according to FDA post marketing data.
I want to share the story of one antidote, that’s been used once. I don’t know if it will ever be used again, but it’s a really cool case. In the past we’ve discussed antibodies used as antidotes, basically to bind to the toxin so it can be eliminated from the body. Digibind, dig FAB for digoxin overdose is an example of this. (Episode 1, love hurts for more). Another example are antivenoms for snake bites. Crofab and the newest treatment, Anavip.
In this one case report published in the New England Journal in 1995, French toxicologists administered a colchicine specific FAB fragment to a critically ill patient in shock. The authors had access to the colchicine FAB which was being used at the time in animal studies. They gave it to the 25-year-old woman who survived.
This is one of the remarkable stories that inspired me to subspecialize in toxicity. Wait a minute I hear you saying. Why didn’t we give this to our patient? It might have prevented the cardiac arrest. The colchicine antibody doesn’t exist as an antidote for humans. Despite the toxicity of colchicine overdoses, they aren’t very common. Getting drug approval is a very expensive process. A colchicine antidote would be difficult to study and rarely used. Unfortunately, this is the case with many poisons and toxins. The antidote probably wouldn’t generate enough money for a pharmaceutical company to make a profit.
Back to our patient, he’s on ECMO for several days. Then he develops infection and septic shock, spending another week in the ICU. Eventually, he recovers and gets psychiatric help to treat his depression. This is a fictional case, as are all our cases, to protect the innocent. But it is based on real poisonings.
This old drug is getting attention for a new reason. Recent evidence shows it may reduce the risk of heart attack thanks to its anti-inflammatory effects. Cardiology guidelines in Europe and Canada include colchicine as a potential treatment option for heart disease. If its effect is a promising as it sounds, a lot more patients will be taking it in the future. Meaning an increased risk for overdoses as well.
Colchicine has been investigated as a chemotherapeutic agent. It works, stopping the growth of cancer cells. We don’t use it for chemo, though, because it’s too toxic. I mentioned it’s therapeutic use has been known for thousands of years, likely it’s toxic potential as well. A serial killer nurse in the UK in the 1800s used colchicine to kill several of her victims.
On a lighter note. It isn’t just humans who get gout. Question #3. Evidence of gout has been found in what prehistoric species?
A. Woolly mammoths
B. Sabretooth tigers
C. Tyrannosaurus Rexs
D. Megalodons
Answer is C. T Rex. The bones of the T. Rex named Sue showed signs of bone erosion in the hands consistent with gout. I had no idea there was such a thing as dinosaurian gout until I did the research for this podcast. Sue didn’t just suffer from gout but seems to have had a difficult life, including a broken leg, a dinosaur tooth in her ribs and gashes on her facial bones.
As with so many poisonous plants, colchicine has a role in Greek mythology. Question 4. Which person used colchicine to poison family members?
A. Medea
B. Circe
C. Calypso
D. Medusa
Hint, if you know where she lived, you know the answer.
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.
Finally, thanks for your attention. I hope you enjoyed listening as much as I enjoyed making the podcast. It helps if you subscribe, leave reviews and/or tell your friends.
All the episodes are available on our website pickpoison.com, Apple, Spotify or any other location where podcasts are available. Additional sources like references and photos are available on the website along with transcripts.
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.