#87: Toxicology 101: Talking Tox with The Dantastic Mr. Tox & Howard

March 19, 2018 | By Chris Chiu

Want to look cool like a toxicology consultant, sipping coffee on rounds? Ever check a patient for armpit sweat? Learn the secrets of tox from the titans of toxicology podcasting, The Dantastic Mr. Tox & Howard (AKA Dr. Dan Rusyniak and Dr. Howard Greller), as they loquaciously dish on all things tox. Topics include: how to approach the patient with an unknown overdose, are toxidromes clinically useful, clues on physical exam, is GI decontamination still recommended, and why they hate bupropion and tramadol. We recommend cautious ingestion of fluids while listening because this was a seriously funny episode.

Written and produced by: Christopher Chiu, MD; Graphics by: Beth Garbitelli; Edited by: Matthew Watto, MD

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Self Assessment Questions

Toxicology 101 Quiz

 Words of wisdom

“Toxicology is disordered physiology from something external to the body.” –& Howard

“Really good toxicologists start with the idea, ‘it could be this [certain disease]’ and then try to convince themselves it’s not” –The Dantastic Mr Tox

Clinical Pearls:

1. Initial assessment in overdose: vitals, airway, breathing, circulation, rapid glucose assessment, and then move on to the exam. Nowadays most patients are given naloxone en route by EMS or the police.
2. Initial workup in overdose: a basic metabolic panel, salicylate and acetaminophen levels, EKG +/- pregnancy test +/- an arterial blood gas.
3. Physical exam: Look at heart rate variability. Does heart rate change when you wake a sleeping patient? Does it go up to high, or not at all? How is the patient talking? What are they doing? Observe respiratory pattern and rate. Rapid or slow? Deep or shallow? Are they responding appropriately if they are hypoxic?
4. Anticholinergic toxicity: Blockade of muscarinic receptors (NOT nicotinic, muscle receptors). “Everything in the body that makes juice is blocked.” These agents cause confusion, “picking behaviors”, mumbling speech that trails off due to dry mouth, and tachycardia. Patients are often restless and writhing, but skin and armpits remain dry.
5. Pupils: Atropine (anticholinergic/muscarinic) drops will dilate the pupil by “paralyzing the constrictor”. They remain large even when a light is shined. Sympathomimetics “stimulate the dilator” of the pupil, but still respond to light with constriction. Opioids produce miosis (constriction) by activating the pupillary sphincter muscle.
6. History taking: You must be skeptical even if you have information on what the patient took. A pill bottles contents don’t always match the label.
7. GI decontamination: Controversial among toxicologists. & Howard believes there is a potential here to reduce harm. You can make patient vomit. Push things through more quickly to prevent absorption, or give a binding agent. Ask yourself: Is the exposure life threatening? Is the substance still likely in the stomach? Is it adsorbed by charcoal? The Dantastic Mr Tox is more skeptical of GI decontamination and says, “Charcoal in the lungs is worse than nothing in the lungs”.
8. Sodium bicarbonate (NaHCO3) is often used inappropriately. NaHCO3 should be bolused for widened QRS from sodium channel blockade, but not for a widened QTc (see below for in-depth review of physiology)
9. Quetiapine is a decent alpha blocker/sympatholytic (blocks sympathetic system). It also has anticholinergic properties causing sedation, dry mouth, tachycardia. -Dan and Howard
10. TramaDONT aka tramadol is “like venlafaxine that the body then converts to an opioid.” –Dan. Tramadol is the number one abused drug in Egypt, probably due to lack of other available opioids and due to rapid conversion to opioid. It has bad withdrawal and lots of drug-drug interactions because its an SNRI. (see links below)
11. ILLbutrin aka wellbutrin aka bupropion is a “bath salt”. An antidepressant with sympathomimetic properties, which causes seizures and myocardial arrhythmias/ dysfunction. Overdose is very dangerous. It can cause positives for amphetamine on urine drug screens.

In-Depth Show Notes

Approach to unknown overdose – Start with the basics

1. Take a good history, if able.
2. Vitals and Exam – Temp, Circulation (Heart rate and variability), Respiratory (Airway, breathing and patterns/rate), neurological assessment (including alertness, speech patterns/phonation), Eye exam (pupillary reaction to light), Dryness (Gloved hand to the armpit or groin, glove will stick if patient is dry)
3. Labs – Basic Metabolic Panel, Acetaminophen, Aspirin, Pregnancy Test, EKG, Blood Gas
4. Look at the big picture: Toxidromes may be useful, but can be misleading since overdoses can be from multiple substances and may present with a mixed picture. Start with what you think it is, and “try to convince yourself with physical symptoms that it isn’t”. –The Dantastic Mr Tox
5. A couple notes on history – If you have it, very helpful. Exercise caution with getting a list of medications or having the patient’s medication bottles accessible. Firstly, this does not mean these are the medications that the patient actually took. Secondly, the pills inside the bottles may not be what is on the label. Could be helpful to work on identifying the pills separate from the labels. In the end, you still have to correlate clinically with the patient’s symptoms.

Review of Some Toxidromes

1. Anticholinergic – Really we are talking about antimuscarinics and NOT antinicotinic agents, which cause paralysis. Parasympathetics control all glandular secretions. A pure antimuscarinic like atropine will give you the classic textbook symptoms: “Everything in your body that makes juice, is blocked” (Rusyniak 2018). Symptoms include dry mouth armpit. Some body systems like the heart and the eye are dually innervated by the sympathetic and parasympathetic systems. Blocking cholinergic receptors (the parasympathetic system) leaves the sympathetic system without a counterbalance and hence tachycardia and mydriasis (dilated pupils). However, many drugs (like quetiapine) may have sympatholytic effects and cause pupil constriction. From the neurological standpoint, you will also see altered mental status where they are typically awake, but will be picking with mumbled speech, probably attributable to the “severe cottonmouth”.
2. Pupils (anticholinergic vs sympathomimetic) – In the anticholinergic state, the pupillary constrictors are paralyzed, whereas in the sympathomimetic state, the dilators are being stimulated. When looking at the reaction to light, a sympathomimetic pupil will constrict and an anticholinergic pupil will remain dilated.
3. Sweat – A gloved hand run through the axillae or groin should always reveal sweat (diaphoresis) unless the patient is hypovolemic, or has a substance affecting sweat glands. Antimuscarinic agents cause dry axilla, but be careful because sometimes a patient on sympathomimetics can sweat themselves dry.
4. Sedative-Hypnotic Overdose – Patients are sleepy because of increased inhibitory control of the brain. Most overdoses are due to polypharmacy and sedatives are usually the least toxic component. In fact, they may help keep the patient comfortable and just sleep it off. -Dan & Howard
5. The approach to a polypharmacy overdose – Look at the physiology and biochemistry. Treat the physiologic derangements that you see. For example, if you see an acidosis, start working down your acid-base differentials. For sleepy patient with sedative-hypnotic overdose that is otherwise stable, conservative management is reasonable. Pay attention to each physiologic abnormality and manage those as necessary. “You treat the patient and not the poison… Who doesn’t love a drug holiday” (& Howard 2018). You have to also be careful about anchoring all the symptoms to a toxic overdose. It should be a diagnosis of exclusion. Sometimes, “The most important thing a toxicologist can say is that it isn’t tox.” (Dan 2018).

Treatment Options

1. Gut/GI Decontamination – Highly controversial. Study interpretation is difficult due to heterogeneity of the patients and exposures. From a philosophical perspective, decontamination may be useful because if we prevent absorption of a drug, we may reduce harm. Unfortunately, the How, When and Who are unclear.
   1. How – Remove the drug by forced emesis (Ipecac), gastric lavage (suck it out), cathartics/whole bowel irrigation (push it out), or activated charcoal (bind it up).
   2. When – In the prehospital setting, a patient will unlikely get anything except activated charcoal. Ipecac is no longer recommended.
   3. Who – Before giving activated charcoal, you should ask yourself…1) Is the overdose is from something life-threatening? 2) Is the pill/substance still likely in the stomach? 3) Is the substance absorbed by charcoal? 4) Is the substance more toxic in the lungs than in the gut (acids, bases, alcohols and hydrocarbons).
2. Charcoal Mechanism of Action: Charcoal is porous and can adsorb many ingested substances. It’s debatable if charcoal is useful after pills have moved past the small bowel, estimated as 1-2 hours after ingestion (Kulig 1985)…BUT, charcoal may work by other mechanisms 1) Charcoal may help to adsorb substances already in the blood (enteroenteric circulation), or 2) break the cycle of enterohepatic circulation i.e. it can adsorb and prevent reabsorption of substances secreted in bile.
3. Empiric Antidotes – Naloxone is now routinely given by EMS or the police during prehospital assessment. Glucose is often used as well. Physostigmine may be used selectively for anticholinergic overdose (but be careful with TCA overdose). Routine use of other antidotes empirically is rare. Sodium bicarbonate (NaHCO3) is often used inappropriately. An amp of NaHCO3 should be bolused for widened QRS (>120 ms) from sodium channel blockade, but NOT for a prolonged QTc (see below for in-depth physiology).
4. EKG and the wide QRS – Don’t mistake a widened QRS (>120 ms) for a prolonged QTc (>470 men, >480 women, source UpToDate). Sodium channel blocking medications like tricyclic antidepressants, Type 1a/1c antiarrhythmics, local anesthetics, propranolol, carbamazepine and quinine can prolong the QRS.
5. Sodium bicarbonate (NaHCO3) should not be given for prolonged QTc because giving NaHCO3 will lower serum potassium further (shifts K+ back into cells), which will prolong QTc. NaHCO3 is appropriate for the patient with hypotension and widened QRS. Widened QRS suggests that sodium channels (fast opening channels in the heart) are blocked. Giving an amp of 8.4% NaHCO3 gives a large load of sodium, which can potentially overcome sodium channel blockade.
6. Sodium concentration of various solutions: Normal saline is 0.9% NaCl (a NaHCO3 drip has a similar sodium concentration). Hypertonic saline is 3% NaCl. An amp of sodium bicarbonate is 8.4% NaHCO3.
7. Tramadol AKA TramaDONT – Toxicologists hate it because it’s basically a serotonin norepinephrine reuptake inhibitor that the body converts to an opioid. It has a high abuse potential with withdrawal and overdose concerns. See links for further discussion below.
8. Bupropion aka Wellbutrin aka ILLbutrin – Has a similar structure to “Bath Salts” and amphetamines. From the toxicologist’s perspective, this is an antidepressant with sympathomimetic properties which causes seizures and myocardial dysfunction. An overdose is very difficult to manage.

Time Stamps

• 00:00 Disclosures
• 00:35 Intro
• 01:19 Guest bios both real and sarcastic
• 04:38 Getting to know our guests
• 06:33 Multiple choice toxicology
• 09:13 Book recommendations
• 11:30 Advice for learners and teachers
• 15:48 Clinical case from Kashlak Memorial Hospital
• 16:27 Initial approach and some thoughts on toxidromes
• 21:59 Physical exam, a toxicologist’s approach
• 27:09 Review of physiology: anticholinergic, cholinergic, sympathomimetic and how to recognize these findings on exam
• 34:18 Different speech patterns seen in toxicology
• 35:30 History taking and how much detective work is truly necessary
• 40:05 The approach to overdose on multiple substances or in setting of polypharmacy
• 45:52 Seinfeld, ipecac, and the controversy about gastrointestinal decontamination
• 63:10 Antidotes and when to give them
• 67:15 EKGs and overdose. Antidote for long QTc versus wide QRS
• 71:25 Tramadol and Egypt
• 73:45 Bupropion and bath salts
• 78:00 Outro

Disclosures: Dr. Rusyniak and Dr. Greller report no relevant financial disclosures. The Curbsiders report no relevant financial disclosures.

Goal: Listeners will develop a systematic approach to the diagnosis and management of the patient with the unknown overdose, review the physiology of common toxidromes, and learn the pharmacology of common toxic ingestions.

Learning objectives:
After listening to this episode listeners will…

1. Initiate the workup of an unknown overdose
2. Differentiate between the different types of toxidromes
3. Learn what diagnostic tests are useful in a toxicologic workup
4. Recognize key exam findings from toxic ingestion and overdose
5. Learn what initial treatments should be considered

Links from the show:

1. The Dantastic Mr. Tox & Howard Show – https://itunes.apple.com/us/podcast/the-dantastic-mr-tox-howard/id1247074688
2. Seinfeld Episode: The Burning – http://www.seinfeldscripts.com/TheBurning.html
3. Family Guy: Ipecac Drinking Contest – https://www.youtube.com/watch?v=_SKdN1xQBjk
4. An American Sickness: How Healthcare Became Big Business and How You Can Take It Back – http://a.co/4bA4y84
5. The Power of Habit: Why We Do What We Do in Life and Business by Charles Duhigg – http://a.co/cMlWLEM
6. Smarter Faster Better: The Transformative Power of Real Productivity by Charles Duhigg – http://a.co/hXOG97a
7. Kulig K, Bar-or D, Cantrill SV, Rosen P, Rumack BH. Management of acutely poisoned patients without gastric emptying. Ann Emerg Med. 1985;14(6):562-7. – https://www.ncbi.nlm.nih.gov/pubmed/2859819/
8. Albertson TE, Owen KP, Sutter ME, Chan AL. Gastrointestinal decontamination in the acutely poisoned patient. International Journal of Emergency Medicine. 2011;4:65. – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3207879
9. Slow gastric motility in overdose. 2 studies
   – Adams, Bruce K. et al. Prolonged gastric emptying half-time and gastric hypomotility after drug overdose. Am J Emerg Med. 2004; 22(7), 548-554. – https://doi.org/10.1016/j.ajem.2004.08.017
   – Miyauchi M, Hayashida M, Yokota H. Evaluation of Residual Toxic Substances in the Stomach Using Upper Gastrointestinal Endoscopy for Management of Patients With Oral Drug Overdose on Admission: A Prospective, Observational Study. Bortolin. M, ed. Medicine. 2015;94(4):e463. – https://www.ncbi.nlm.nih.gov/pubmed/25634188
10. IV aminophylline and activated charcoal
    – Berlinger, W. G., Spector, R., Goldberg, M. J., Johnson, G. F., Quee, C. K. and Berg, M. J. (1983), Enhancement of theophylline clearance by oral activated charcoal. Clinical Pharmacology & Therapeutics, 33: 351–354. – http://onlinelibrary.wiley.com/doi/10.1038/clpt.1983.44/abstract
11. 2015 Guidelines for the management of paracetamol poisoning in Australia and New Zealand – https://www.mja.com.au/sites/default/files/issues/203_05/Guidelines_paracetamol_Aus_NZ_2015.pdf
12. Don’t use Tramadol references – –http://empharmd.blogspot.com/2015/05/three-reasons-not-to-prescribe-tramadol.html#!/2015/05/three-reasons-not-to-prescribe-tramadol.html–https://www.aliem.com/2014/01/tramadol-when-to-avoid-it/
13. Check out The Dantastic Mr. Tox & Howard episode “Primum, Non Nocere” with Dr. David Juurlink on the ongoing opioid epidemic – https://itunes.apple.com/us/podcast/the-dantastic-mr-tox-howard/id1247074688
14. Erickson, Timothy B., Trevonne M. Thompson, and Jenny J. Lu. “The approach to the patient with an unknown overdose.” Emergency Medicine Clinics 25.2 (2007): 249-281. – https://doi.org/10.1016/j.emc.2007.02.004