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    Health & Fitness

    The Poison Lab

    Dive into the captivating world of poisons with The Poison Lab! Hosted by Clinical Toxicologist Ryan Feldman (@EMPoisonPharmD), who has over a decade of managing poisoning and drug overdose via poison centers and in the emergency department. Also occasional co-hosted by his robo cohost Toxo! (@LabPoison). This show unpacks the fascinating history, cutting-edge science, and life-saving medical management of toxins from around the globe. From stories of those impacted to expert insights from pioneers in poisoning treatment, each episode brings you closer to understanding the poisons that lurk in plain sight. Explore episodes, med videos, games, and more at thepoisonlab.com—every poison has a story to tell!

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    Copyright: © thepoisonlab

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    Latest Episodes:
    Toxicologists vs the Internet (#2) With Guest Dr Jillian Theobald MD, PHD Feb 03, 2021
    Show notes

    In this second rendition of toxicologist vs the internet Ryan Is joined by special guest Dr. Jillian Theobald, MD, PHD an emergency medicine physician and medical toxicologist. They take turns answering questions from reddit.com/r/askdrugs (the internet, really, really needs a toxicologist) and challenge each others toxic sleuthing by presenting cases of poisoning and allowing the other to determine the toxin responsible. Listen in to hear about the clinical effects of benzodiazepine on TV watching, the patient side of ketamine, cocaine chest pain, heavy metals, flower petals and much much more!

    Things from the Show!

    Ketamine for Depression

    • Patient Experience Blog:
    • "30 Years of Depression Gone"
    • https://humanparts.medium.com/30-years-of-depression-gone-3dffafabc7cf?fbclid=IwAR1gh08Kn3uSczlKbvMH54yjkWILzyA_6O3Y82q4hVqcAr3shozxwegCnmg

    Fasoracetam

    • Study on Cognitive Enhancers:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5770454/#CR14

    Kava

    1. Hepatic Injury Risk:https://pubmed.ncbi.nlm.nih.gov/15114493/
    2. Anti-Anxiety Effects:https://pubmed.ncbi.nlm.nih.gov/33207379/

    Cocaine Chest Pain

    1. Propranolol Effects on Coronary Constriction:https://pubmed.ncbi.nlm.nih.gov/1971166/
    2. Labetalol Effects on Coronary Constriction:https://pubmed.ncbi.nlm.nih.gov/8506886/

    Management of Amphetamine Compound Toxicity

    • Clinical guidance for toxicity management:
    • https://pubmed.ncbi.nlm.nih.gov/25724076/

    Heavy Metals in Cakes

    • https://pubmed.ncbi.nlm.nih.gov/18802411/

    A Morel Dilemma

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    The GOTTA PICCEM Poisonous Mushroom Game!

    The Poisonus Fungus Amongus Children's Book!

    • Full book reading (6 minutes!)

    Tox trinkets (Rep the show at home!)

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    • Email: Toxtalk1@gmail.com

    More Show Resources

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    Mini Episode: Managing Crashing Hydroxychloroquine/Chloroquine OD Dec 16, 2020
    Show notes

    Quick Review: Chloroquine and Hydroxychloroquine Toxicity

    Toxic Dose

    • Chloroquine: >5 g is associated with severe toxicity (though toxicity can occur at lower doses).
    • Hydroxychloroquine (HCQ): Toxic dose is less well-defined.

    Clinical Effects

    • Seizures: Due to sodium channel blockade.
    • Arrhythmias: Resulting from sodium channel blockade.
    • Hypotension: Caused by alpha-adrenergic blockade.
    • Hypokalemia: Often a notable feature.

    Management

    1. Decontamination:

    • Administer activated charcoal if the patient is awake, alert, and has no risk of emesis.

    1. Supportive Care:

    • High-dose epinephrine:
    • Recommended dose: 0.25 mcg/kg/min.
    • Based on retrospective case-control series: https://www.nejm.org/doi/full/10.1056/NEJM198801073180101
    • Diazepam:
    • Administer 1–2 mg/kg over 30 minutes, followed by 1–2 mg/kg over 24 hours.
    • Prevents seizures and may provide cardioprotective effects.

    1. Airway Management:

    • Consider early intubation to secure the airway in deteriorating cases.

    1. Expert Consultation:

    • Contact a poison center for guidance: 1-800-222-1222.

    A Morel Dilemma

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    Barking Up the Wrong Tree (Cinohonism, Quinine & Quinidine) Dec 16, 2020
    Show notes

    In this episode Ryan and Toxo discuss some potential toxic spices and break down the toxicity and treatment of a once well known medicine

    Cinchona Bark, Quinine, and Associated Toxicities

    Historical Perspective

    • Use of Cinchona Bark Powder for Malaria:
    • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4973170/
    • Evolutionary Pressure of Malaria on Sickle Cell Traits:
    • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3499995/

    Cinchonism

    • Definition: Classic toxicities caused by ingestion of quinoline derivatives from cinchona bark.
    • Brief Review:
    • https://pubmed.ncbi.nlm.nih.gov/32644745/

    Etiology

    • Sources:
    • Powdered cinchona bark: Used in tonic water, to treat restless legs, or as a remedy for certain viruses.
    • Prescription quinoline derivatives:
    • Quinine
    • Quinidine
    • Hydroxychloroquine
    • Chloroquine

    Clinical Effects

    • Symptoms:
    • Dizziness, flushing, headache, tinnitus.
    • Potential for vision loss.
    • Laboratory Abnormalities:
    • Hypoglycemia, hypokalemia, long QRS.

    Treatment

    Supportive Care:

    • Manage airway, breathing, and circulation (ABCs).
    • Early use of epinephrine as a preferred pressor based on animal and chloroquine data.

    Correct Endocrine/Metabolic Abnormalities:

    • Hypertonic Sodium: For wide QRS (use cautiously to avoid worsening hypokalemia).

    Decontamination:

    • Consider multi-dose activated charcoal for significant ingestions.

    Ocular Toxicity

    • Key Findings:
    • Ocular toxicity is often delayed but can become permanent.
    • Quinine levels >15 are associated with increased ocular toxicity.
    • Quinine-induced blindness: https://pubmed.ncbi.nlm.nih.gov/3983356/
    • Hall AP, et al. Quinine-induced blindness. Br J Ophthalmol. 1997. doi:10.1136/bjo.81.12.1029
    • Recovery:
    • Vision may recover centrally first, then peripherally.
    • Hyperbaric oxygen therapy (HBO) is often used but remains debated.

    Ototoxicity

    • Mechanism:
    • Tinnitus caused by microstructural changes in the outer hair cells of the cochlea and organ of Corti.
    • Vasoconstriction and prostaglandin inhibition contribute to decreased hearing.
    • Studies:
    • Jastreboff PJ, et al. Quinine-induced tinnitus in rats. Arch Otolaryngol Head Neck Surg. 1991. doi:10.1001/archotol.1991.01870220110020
    • Roche RJ, et al. Quinine induces reversible high-tone hearing loss. Br J Clin Pharmacol. 1990. doi:10.1111/j.1365-2125.1990.tb03704.x

    More on Toxicity from Studies

    1. Cardiac Arrhythmias in Patients Taking Quinine Alone:Padmaja UK, Adhikari P, Periera P. Experience with quinine in falciparum malaria. Indian J Med Sci. 1999. PMID: 10695226.
    2. Negative Inotropic Effects of Quinidine:Hoffmeister HM, et al. Negative inotropic effect of class-I antiarrhythmic drugs. Eur Heart J. 1987. doi:10.1093/oxfordjournals.eurheartj.a062178.
    3. Tinnitus and Hearing Effects: Jarboe JK, Hallworth R. The effect of quinine on outer hair cell shape, compliance and force. Hear Res. 1999. doi:10.1016/s0378-5955(99)00031-3.

    A Morel Dilemma

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    Toxicologists vs The Internet (#1) With Guest Dr. Matthew Stanton PharmD, DABAT Nov 04, 2020
    Show notes

    In this episode Ryan Is joined by a special guest Dr. Matthew Stanton PharmD, BCPS, DABAT, an emergency medicine pharmacist and clinical toxicologist. Ryan and Matt take turns answering questions from reddit.com/r/askdrugs (the internet, really, really needs a toxicologist) and finally they challenge each others toxic sleuthing by presenting some cases of poisoning and allowing the other to try to determine the toxin responsible.

    Episode Show Notes

    Articles by the Host and Collaborators

    • Potential Toxicity of Vitamin E Acetate in THC Vape Cartridges
    • Authored by Ryan and Matt:
    • Study 1
    • Study 2
    • Related News:
    • Article covering the arrest of a man selling vape cartridges—incident occurred one floor below our host. Co-author of the above papers is quoted.
    • Read the full article

    False Positives in Drug Testing

    • False Positive for Fentanyl
    • Review Article

    Serotonin Syndrome

    • Comprehensive Review
    • Understanding Serotonin Syndrome
    • LSD and 5-HT2A Partial Agonism
    • Mechanistic Insights
    • Binding Affinity of Psychoactive Compounds
    • Review Article
    • Cases of LSD-Related Deaths
    • Discussion and Review
    • Serotonin Syndrome with Stimulant Compounds
    • Risk Review
    • Methamphetamine-Induced Serotonin Syndrome
    • Case Report

    Toxicity Cases

    • Case 1: Toxicity Review
    • Detailed Analysis
    • Case 2: Methemoglobinemia
    • Comprehensive Review
    • Case 3: Toxicity Insights
    • In-depth Review
    • Case 4: Poisoning Case Report
    • Case Discussion

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    The Rise of Lethal Loperamide Aug 26, 2020
    Show notes

    Ryan and Toxo go in depth on an old substance that has begun to resurface with new toxicity due to users taking massive amounts. Loperamide. Dive into the regulatory history, mechanisms of its toxic cardiac effects, and a brief discussion of treatment in episode 4.

    Buying as much loperamide as you possibly can

    Loperamide History

    1. 1969: Synthesized. (1)
    2. 1976: FDA Approved as Schedule V. (2)

    • "IMODIUM FDA Application No.(NDA) 017694". U.S. Food and Drug Administration (FDA). 1976.
    • https://www.deadiversion.usdoj.gov/schedules/orangebook/orangebook.pdf

    1. 1982: Descheduled. (3)

    • Florey, Klaus (1991). Profiles of Drug Substances, Excipients and Related Methodology, Volume 19. Academic Press. p. 342. ISBN9780080861142.

    1. 2010: Increasing poison center calls, arrhythmia cases, and hospitalizations. (4,5,6)

    • Eggleston W, Marraffa JM, Stork CM, et al. Notes from the Field: Cardiac Dysrhythmias After Loperamide Abuse — New York, 2008–2016. MMWR Morb Mortal Wkly Rep 2016;65:1276–1277.
    • http://dx.doi.org/10.15585/mmwr.mm6545a7

    1. 2016: DEA denies rescheduling request. (7)

    • https://www.chpa.org/PDF/09_05_17_CommentsCitizenPetitionLoperamide.aspx

    1. 2019: FDA works with manufacturers to reduce package size to 48 tablets. (8)

    • https://www.fda.gov/drugs/drug-safety-and-availability/fda-limits-packaging-anti-diarrhea-medicine-loperamide-imodium-encourage-safe-use
    • Pharmacist Knowledge Gap: Awareness of abuse remains low.
    • Feldman R, Everton E. National assessment of pharmacist awareness of loperamide abuse and ability to restrict sale if abuse is suspected. J Am Pharm Assoc (2003). 2020. doi:10.1016/j.japh.2020.05.021
    • https://pubmed.ncbi.nlm.nih.gov/32641253/

    Toxic Mechanisms

    1. Inhibition of Sodium and HERG Channels:

    • Kang J, Compton DR, Vaz RJ, Rampe D. Proarrhythmic mechanisms of the common anti-diarrheal medication loperamide. Naunyn Schmiedebergs Arch Pharmacol. 2016. doi:10.1007/s00210-016-1286-7
    • https://pubmed.ncbi.nlm.nih.gov/10837556/
    • IC50 for HERG Ikr ~ 40 nm/l (1908 ng/dl), inhibits as low as 10 nm/l.
    • Klein MG, Haigney MCP, et al. Potent Inhibition of hERG Channels by Loperamide. JACC Clin Electrophysiol. 2016. doi:10.1016/j.jacep.2016.07.008

    1. Reported Fatalities:

    • Marraffa JM, Holland MG, et al. Cardiac conduction disturbance after loperamide abuse. Clin Toxicol (Phila). 2014. doi:10.3109/15563650.2014.969371
    • https://pubmed.ncbi.nlm.nih.gov/29941678/

    Treatment

    • Guidelines:
    • Eggleston W, Palmer R, Dubé PA, et al. Loperamide toxicity: recommendations for patient monitoring and management. Clin Toxicol (Phila). 2020. doi:10.1080/15563650.2019.1681443
    • https://www.sciencedirect.com/science/article/pii/S1880427611800050
    • Supportive Care:
    • Arrhythmia Management:
    • Electrical cardioversion for torsades.
    • Magnesium to prevent early after depolarizations (target Mg >2, K >4).
    • Lidocaine recommended for VT (does not prolong QTc).
    • Overdrive pacing (e.g., isoproterenol) if bradycardia precedes arrhythmia.
    • Beta-blockers for long QT syndrome.
    • Wide QRS Tachycardia: Use hypertonic sodium (1–2 amps of 8.4% Sodium Bicarbonate IV).

    Where Do We Go From Here?

    • Further research is needed to understand the incidence of loperamide-induced toxicity and the impact of FDA packaging changes.
    • Concerned about loperamide regulation? Contact us at toxtalk1@gmail.com.

    References

    1. https://www.deadiversion.usdoj.gov/schedules/orangebook/orangebook.pdf
    2. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS Guidelines for VT and Sudden Cardiac Death. J Am Coll Cardiol. 2018. doi:10.1016/j.jacc.2017.10.054

    A Morel Dilemma

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    The GOTTA PICCEM Poisonous Mushroom Game!

    The Poisonus Fungus Amongus Children's Book!

    • Full book reading (6 minutes!)

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    Mini episode: Early After Depolarizations and Experimental Mechanisms of Torsades Aug 26, 2020
    Show notes

    Great review of potential torsades mechanisms based off experimental data- https://www.sciencedirect.com/science/article/pii/S1880427611800050

    A Morel Dilemma

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    Mini Episode: The Saga of the Cardiac Action Potential Aug 26, 2020
    Show notes
    • Action potential
    • Sodium/Potassium ATPase pumps create more positively charged ions outside the cell than inside the cell, this creates a relative negative charge in the cell
    • Phase 4- Resting (~ -90 mv)
    • Phase 0- Sodium enters the cell (+10 mv)
    • Phase 1- Potassium efflux from cell as now there is no negative charge holding it in (0 mv)
    • Phase 2- Calcium channels open and allow calcium in, calcium triggers the ryandoine receptor and allows for calcium dependent calcium release from the sarcoplasmic reticulum occurs
    • Phase 3- Potassium continues to leave the cell allowing return to -90 mv

    A Morel Dilemma

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    Toddler Time Bombs (Poison Center Triage) Jul 22, 2020
    Show notes

    Ryan and Toxo cover some topics off the "one pill can kill" list, try breaking down the toxic mechanism of opioid induced respiratory depression in a simplistic way (but maybe fail), and walk through the triage and management of poison center case where a child was "potentially" exposed to a lethal toxin at home.

    Case Report

    • Pediatric ingestion case study discussed at the beginning of the episode: https://pediatrics.aappublications.org/content/130/6/e1700

    "One Pill Can Kill" Resources

    1. Missouri Poison Center resource guide:http://missouripoisoncenter.org/wp-content/uploads/2015/02/2011-One-Pill-Can-Kill.pdf
    2. Pediatric poison prevention article:https://pubmed.ncbi.nlm.nih.gov/16419734/
    3. HealthyChildren.org guide on medication safety:https://www.healthychildren.org/English/safety-prevention/at-home/medication-safety/Pages/Poison-Prevention-One-Pill-Can-Kill.aspx

    Respiratory Centers and Drug Effects

    • Detailed overview of the impact of drugs on respiratory centers:
    • https://www.ncbi.nlm.nih.gov/books/NBK482414

    Buprenorphine Studies

    Epidemiology

    1. AAPCC Annual Report on poisoning trends:https://pubmed.ncbi.nlm.nih.gov/31752545/
    2. Trends in pediatric opioid exposures:https://pubmed.ncbi.nlm.nih.gov/32178937/
    3. Trends in ED visits for unsupervised medication exposures:https://pubmed.ncbi.nlm.nih.gov/26347435/

    Exposure Studies

    1. U.S. Poison Center data on buprenorphine: https://pubmed.ncbi.nlm.nih.gov/29941678/
    2. Harvard Emergency Medicine group analysis: https://pubmed.ncbi.nlm.nih.gov/27756148/
    3. Maryland Poison Center/RADARS data:https://pubmed.ncbi.nlm.nih.gov/18381506/
    4. ICU exposures in children:https://pubmed.ncbi.nlm.nih.gov/20921918/

    Triage Considerations for Pediatric Exposures

    • Symptoms: What are the current symptoms and their severity?
    • Causative Agent & Exposure Characteristics: What substance was ingested, and in what quantity? What’s the context of the exposure?
    • History: Includes past medical history, patient weight, and the time elapsed since exposure.
    • Onset: When are symptoms expected to appear?
    • Labs: Perform toxin-specific assessments where applicable.
    • Aggravating/Remitting Factors: What interventions have already been performed, and how have they affected the patient?

    If you have questions about these studies or poisoning scenarios, consult your local poison center or toxicologist. Thank you for tuning in!

    A Morel Dilemma

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    The Other Problem With Bullets (Lead and Lead Poisoning from Bullets) Jun 24, 2020
    Show notes

    Get ready for a HEAVY subject, literally. Ryan and Toxo talk about the toxic mechanisms, signs of poisoning, and treatment of one of the worlds most ubiquitous poisons. This is a long, but interesting one, consider listening in chunks.

    Excellent Review Sources

    • Calello DP, Henretig FM. "Lead." In: Goldfrank's Toxicologic Emergencies, 10th ed, Hoffman RS, Howland MA, Lewin NA, et al (Eds), McGraw Hill Education, New York, 2015. p.1219.
    • Toxic Substances Database for Lead: https://www.atsdr.cdc.gov/toxprofiles/tp.asp?id=96&tid=22

    Clinical Case from Today's Show

    • Severe lead toxicity from retained bullet fragments:
    • Weiss D, Lee D, Feldman R, Smith KE. "Severe lead toxicity attributed to bullet fragments retained in soft tissue." BMJ Case Rep. 2017;2017. doi:10.1136/bcr-2016-217351
    • Full Text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5353372/

    History of Lead

    • Lead’s abundance has increased over time due to radioactive decay: https://iopscience.iop.org/article/10.1086/375492
    • Its use spans currency, cosmetics, aqueducts, and even wine, contributing to societal impacts like the fall of Rome: https://pubmed.ncbi.nlm.nih.gov/14261844
    • Lead in society overview: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6522252/

    Common Sources of Lead Exposure

    1. Lead Paint: Up to 50% lead until 1940; still present in millions of homes.
    2. Soil: Contaminated by tetraethyl leaded gasoline (introduced by Thomas Midgley): https://interestingengineering.com/thomas-midgley-jr-the-man-who-harmed-the-world-the-most
    3. Lead Piping:

    • EPA Lead and Copper Rule: https://www.epa.gov/sites/production/files/2016-10/documents/508_lcr_revisions_white_paper_final_10.26.16.pdf

    1. Traditional Medicines: Ayurveda: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2538609/
    2. Kohl (cosmetics): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1567936/
    3. Bullets: https://pubmed.ncbi.nlm.nih.gov/30939573/
    4. The "Lead Crime Hypothesis": https://pubmed.ncbi.nlm.nih.gov/27035924/

    Clinical Effects

    • Ben Franklin’s "Dangles and Bellyaches": https://pubmed.ncbi.nlm.nih.gov/22910081
    • Colic/constipation.
    • Neuropathy.
    • Neurocognitive/Behavioral Effects:
    • IQ reduction, visual-spatial impairment, reduced processing speed, and irritability.
    • Impacts in young children: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3909981/
    • Chronic Conditions:
    • Kidney and vascular disease: https://www.atsdr.cdc.gov/toxprofiles/tp13-c2.pdf
    • Hematologic effects (e.g., hemolytic anemia): https://www.atsdr.cdc.gov/toxprofiles/tp13-c2.pdf
    • Burton lines (sulfate deposits): https://www.amjmed.com/article/S0002-9343(12)00286-0/pdf
    • Lead lines (metaphyseal calcification): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1912933/

    Toxic Mechanisms

    • Binds to sulfhydryl groups.
    • Acts as a divalent cation, interfering with numerous enzymatic processes.
    • Comprehensive overviews:
    • Goldfrank’s Toxicologic Emergencies, 10th ed.
    • https://www.atsdr.cdc.gov/csem/csem.asp?csem=34&po=10

    Treatment Overview

    Chelation Therapy:

    • BAL: Painful IM injection; contraindicated in G6PD deficiency.
    • https://www.sciencedirect.com/science/article/pii/S0041008X99987252
    • Ca2NaEDTA: IV; used for levels >70 µg/dL or encephalopathy.
    • https://www.sciencedirect.com/science/article/abs/pii/S0013935184710632
    • Succimer: Oral; ensure lead has passed the small intestine before starting.
    • https://www.sciencedirect.com/science/article/abs/pii/S0013935184710632

    Management Based on Blood Lead Levels:

    • Kids: https://www.cdc.gov/nceh/lead/advisory/acclpp/actions-blls.htm
    • Adults: https://pubmed.ncbi.nlm.nih.gov/17431500/

    If You Encounter Lead Exposure

    • Confirm elevated capillary blood lead with venous testing.
    • Call your toxicologist or poison center for guidance.

    Thanks for listening!

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    Mini Episode: Fundamentals: Testings Tests, Addictions vs Dependence, How Do We Alter Drug Absorption, What Do Drugs Do? Jun 10, 2020
    Show notes

    Concepts in this episode

    Ryan and Toxo introduce their roles while explaining the current state of toxicology and what exactly a poison is.

    testing our tests

    • Sensitivity: Rate of Positive test in those who have the disease
    • Specificity: Rate of negative test in those without the disease
    • Positive predictive value: True positive/ True Positive + False Positive
    • Negative predictive value: True negative/True negative + False negative

    Pharmacokinetics and dynamics

    • (PK) Bioavailablity = Amount of drug available to be used by the body
    • Oral Bioavailablity= Dose- Fraction excreted unchanged- Fraction metabolized in gut- Fraction metabolized by liver
    • How drugs interact with the body (PD)
    • Agonist- stimulates receptor
    • Partial agonist- Activation of receptor with ceiling effect, never achieves maximal activation
    • Antagonist- Prevents receptor activation
    • Inverse agonist- induces an opposite effect as an agonist after binding receptor
    • Addiction vs dependance
    • Addiction- Relationship between user and substance
    • A few definitions but frequently involving consequences in life from use and loss of control over use of substance
    • Dependence- Physiologic changes in body due to chronic use
    • Down regulation of stimulated receptors
    • Physiologic basis for tolerance and withdrawal

    A Morel Dilemma

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    The GOTTA PICCEM Poisonous Mushroom Game!

    The Poisonus Fungus Amongus Children's Book!

    • Full book reading (6 minutes!)

    Tox trinkets (Rep the show at home!)

    Reach the show

    • Email: Toxtalk1@gmail.com

    More Show Resources

    • Ryan's Medical Games and Resources
    • Show Website

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