The Poison Lab

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.

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

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

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

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/

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/

• 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!

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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.

• 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

• 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/

• 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/

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/

• 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/

• 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

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/

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

Thanks for listening!

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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

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In this episode, Ryan and Toxo dive into the history of a commonly used disinfectant, exploring its dangers when misused. From creating chemical weapons to causing severe injuries, they break down its toxic potential and offer critical safety tips. They break down the many ways it can cause harm if not used appropriately, including creating chemical weapons and turning your body into soap. Finally they review treatment recommendations if you accidentally are exposed, or if you are health care provider treating an exposure.

1. Bleach + Acid → Chlorine Gas

• Reaction: Cl₂ + H₂O ⇄ HCl + HClO
• Base neutralizes HCl to drive reaction forward; reversed with acid addition.
• Source

1. Bleach + Ammonia → Chloramine Gas

• Chloramine properties: PubChem Link

1. Bleach + Rubbing Alcohol (Isopropyl) → Chloroform
2. Bleach + Soap → Carbon Tetrachloride

• Mechanism: High solubility irritant, dissolving in mucous membranes, causing severe irritation in the eyes, nose, and upper airway.
• Symptoms: Effects are noticed quickly and may appear severe initially.
• Treatment:
• Remove from exposure, ensure a patent airway, and provide supportive care.
• Oxygen for hypoxemia.
• Bronchodilators (e.g., albuterol) for airway irritation.
• Nebulized Sodium Bicarbonate may have a role in treating chlorine gas inhalation.
• Systematic Review

• If exposed to chlorine gas, move to fresh air, open windows, and call 911 or your local poison center.
• Bleach Ingestion: Can cause liquefactive necrosis. Treatment focuses on assessing injury for risk of stricture or esophageal stenting.

• Research Summary:
• Corticosteroids are not routinely recommended due to limited evidence from controlled trials.
• Case reports suggest potential benefit but lack appropriate comparators.
• References:
• Brief summary of steroid use with irritant gases: Reproduced with permission from : Pape KO, Feldman R. Smoke inhalation and Toxic Exposure. Chapter In: Erstad B, ed. Critical Care Pharmacotherapy. Lenexa: American College of Clinical Pharmacy. January 2020.
• Steroid use in pulmonary irritant induced pneumonitis is not well evaluated in randomized controlled trials. Reviews of animal data suggest no significant benefit for poorly water soluble or high doses of water-soluble irritants. They may also have a negative effect on the recovery phase (deLange 2011).Numerous case reports exist detailing positive outcomes from use of steroids in patients exposed to pulmonary irritants (deLange 2011).However, without an appropriate comparator it is not known if symptom resolution is related to the intervention or the natural progression of the disease. Small human crossover trials evaluating the effects of mild ozone exposure found a reduction in bronchiolar lavage inflammatory markers with inhaled fluticasone or budesonide but no difference in clinical effects (deLange 2011, Nightingale 2000, Alexis 2008, Vagaggini 2001). Due to the absence of well controlled trials, steroids are not routinely recommended for chemical pneumonitis. However, there is also a lack of negative data and institutional protocols or patient specific factors may govern their use.

• Claude Berthollet: Pioneer of chlorine disinfection.
• Biography
• Antoine Labarraque: Innovator in bleach use for sanitation.
• Biography

• Caustic Ingestion Review:
• Hoffman RS, Burns MM, Gosselin S. NEJM 2020
• Pulmonary Irritants Overview:
• Nelson LS, Odujebe OA. Goldfrank's Toxicologic Emergencies, 11e.
• Reactions of Sodium Hypochlorite with Other Compounds:
• Odabasi M. Environ Sci Technol 2008
• Chlorine Gas Exposure Management:
• Huynh Tuong A, et al. Clin Toxicol 2019
• Incidence Data:
• Gummin DD, et al. Clin Toxicol 2017

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

Information about medical and clinical toxicology can be found at

• American Academy of Clinical Toxicology (AACT)- clintox.org
• American College of Medical Toxicology (ACMT)- acmt.net

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• Full book reading (6 minutes!)

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• Full book reading (6 minutes!)

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• Email: [email protected]

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