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The Poison Lab

Updated 26 days ago

Education
Science
Natural Sciences
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A show about poisoning from those who treat poisoning. Join your hosts, Clinical Toxicologist Ryan (@EMPoisonPharmD) and Robo-Toxicologist Toxo (@LabPoison) as they discuss the history, science, and medical management of the infinite poisons the world has to offer! Episodes, med videos, games and more at thepoisonlab.com

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A show about poisoning from those who treat poisoning. Join your hosts, Clinical Toxicologist Ryan (@EMPoisonPharmD) and Robo-Toxicologist Toxo (@LabPoison) as they discuss the history, science, and medical management of the infinite poisons the world has to offer! Episodes, med videos, games and more at thepoisonlab.com

iTunes Ratings

5 Ratings
Average Ratings
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Great listen! Highly Recommend!

By Megsies21 - May 27 2020
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Super informative and keeps you engaged all the way through. Also, I love Toxo.. she’s makes the show.

iTunes Ratings

5 Ratings
Average Ratings
5
0
0
0
0

Great listen! Highly Recommend!

By Megsies21 - May 27 2020
Read more
Super informative and keeps you engaged all the way through. Also, I love Toxo.. she’s makes the show.

Best weekly hand curated episodes for learning

Cover image of The Poison Lab

The Poison Lab

Latest release on Dec 16, 2020

Best weekly hand curated episodes for learning

The Best Episodes Ranked Using User Listens

Updated by OwlTail 26 days ago

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This means that the episode rankings aren't working properly. Please revisit us at a later time to get the best episodes of this podcast!

Rank #1: Mini Episode 3.5 Managing Crashing Hydroxychloroquine/Chloroquine OD

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Quick review

  • Toxic dose
    • Chloroquine  >5g  severe toxicity is expected (toxicity may develop below this)
    • HCQ less well defind
  • Clinical effects
    • Seizures (sodium channel blockade)
    • Arrhythmia (sodium channel blockade)
    • Hypotension  (Alpha blockade)
    • Hypokalemia
  • Management
    • Activated Charcoal if awake and alert and no risk of emesis
    • Early invasive supportive care based on the following retrospective case control series  https://www.nejm.org/doi/full/10.1056/NEJM198801073180101
      • High dose epinephrine (0.25 mcg/kg/min) 
      • Diazepam 1-2 mg/kg over 30 minutes followed by 1-2 mg/kg over 24 hours (seizure prevention)
        • Evidence supports this may be cardio protective as well
      • Early intubation 
    • Consultation with poison center recommended 1-800-222-1222

Dec 16 2020

9mins

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Rank #2: Episode 6- Barking Up the Wrong Tree

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  • Historical perspective on use of cinchona bark powder for malaria
  • Evolutionarily pressure of malaria on  beta thalassemia (sickle sell) traits
  • Cinchonism
  • Etiology
    • Powdered cinchona bark
      • Used by people to make tonic water, treat restless legs, or viruses
    • Prescription quinoline derivatives may cause cause similar effects
      • Quinine
      • Quinidine
      • Hydroxychloroquine
      • Chloroquine
  • Clinical effects
    • Dizzy
    • Flushed
    • Head ache
    • Tinnitus
    • Potential for vision loss
  • Laboratory assessment
    • Hypoglycemia
    • Hypokalemia
    • Long QRS
  • Treatment
    • Supportive care for ABCs
      • Potential role for epinephrine as preferred pressor from animal data and chloroquine data
    • Correct endocrine/metabolic abnormalities
    • Hypertonic sodium for wide QRS (be careful of worsening hypokalemia)
    • Consider multi dose activated charcoal
  • More on toxicity/studies from the episodes
    • Incidence of caridac arryhmias in patients taking quinine alone
      • Padmaja UK, Adhikari P, Periera P. Experience with quinine in falciparum malaria. Indian J Med Sci. 1999 Apr;53(4):153-7. PMID: 10695226.
    • Negative inotropic effects of quinidine
      • Hoffmeister HM, Hepp A, Seipel L. Negative inotropic effect of class-I-antiarrhythmic drugs: comparison of flecainide with disopyramide and quinidine. Eur Heart J. 1987 Oct;8(10):1126-32. doi: 10.1093/oxfordjournals.eurheartj.a062178. PMID: 3119341
    • Occular toxicity, can be permanent
      • Treatment is debated, not clear what is preferred , HBO used often
      • Vision may recover centrally first, than peripheral
      • Vision loss usually delayed from initial symptoms
      • Quinine >15 associated w/ more ocular tox- https://pubmed.ncbi.nlm.nih.gov/3983356/
        • Hall AP, Williams SC, Rajkumar KN, Galloway NR. Quinine induced blindness. Br J Ophthalmol. 1997;81(12):1029. doi:10.1136/bjo.81.12.1029
        • Dyson EH, Proudfoot AT, Prescott LF, Heyworth R. Death and blindness due to overdose of quinine. BMJ 1985; 291:31–3.
    • Otooxicity -A hall mark toxicity of tinnitus appears to be caused by
      • Additionally, vasoconstriction and local prostaglandin inhibition within the organ of Corti contributes to decreased hearing.
      • Microstructural lengthening of the outer hair cells of the cochlea and organ of Corti occurs.
        • Jastreboff PJ, Brennan JF, Sasaki CT. Quinine-induced tinnitus in rats. Arch Otolaryngol Head Neck Surg. 1991 Oct;117(10):1162-6. doi: 10.1001/archotol.1991.01870220110020. PMID: 1910705
        • Jung TT, Rhee CK, Lee CS, Park YS, Choi DC. Ototoxicity of salicylate, nonsteroidal antiinflammatory drugs, and quinine. Otolaryngol Clin North Am. 1993 Oct;26(5):791-810. PMID: 8233489.
        • Jung TT, Rhee CK, Lee CS, Park YS, Choi DC. Ototoxicity of salicylate, nonsteroidal antiinflammatory drugs, and quinine. Otolaryngol Clin North Am. 1993 Oct;26(5):791-810. PMID: 8233489.
        • Roche RJ, Silamut K, Pukrittayakamee S, et al. Quinine induces reversible high-tone hearing loss. Br J Clin Pharmacol. 1990;29(6):780-782. doi:10.1111/j.1365-2125.1990.tb03704.x
        • Jarboe JK, Hallworth R. The effect of quinine on outer hair cell shape, compliance and force. Hear Res. 1999 Jun;132(1-2):43-50. doi: 10.1016/s0378-5955(99)00031-3. PMID: 10392546.
    •  

Dec 16 2020

1hr 6mins

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Rank #3: Episode 5- Toxicologists vs The Internet

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Nov 04 2020

1hr 7mins

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Rank #4: Mini episode 3- Early After Depolarizations and Experimental Mechanisms of Torsades

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

Aug 26 2020

11mins

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Rank #5: Mini Episode 2- The Saga of the Cardiac Action Potential

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  • 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 

Aug 26 2020

15mins

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Rank #6: Episode 4- The Rise of Lethal Loperamide

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Buying as much loperamide as you possibly can 

  • Loperamide history
    • 1969- Synthesized (1)
    • 1976 FDA Approved as schedule V (2)
    • Jaffe trial of "abuse potential"- https://pubmed.ncbi.nlm.nih.gov/7438696/
    • 1982- Descheduled (3)
    • 2010-Annually Increasing in # of poison center calls, cases of arrhythmia and hospitalization (4,5,6)
    • 2016- Submission to DEA for rescheduling of loperamide denied (7)
    • 2019- FDA works with manufactures to reduce package size to 48 tablets (8)
    • Pharmacist knowledge of abuse remains low https://pubmed.ncbi.nlm.nih.gov/32641253/
  • Toxic Mechanism
    • Fun theories about co evolution of PGP and CYP https://pubmed.ncbi.nlm.nih.gov/10837556/
    • Inhibition of sodium channels, and to a higher affinity, Human Ether a Go-Go Related (HERG) channel leads to prolonged repolarization (9)
      • IC50 for HERG Ikr ~ 40 nm/l (1908 ng/dl), inhibits as low as 10 nm/l (10)
      • Case reports of conduction disturbance with level of 22 ng/ml (14)
      • Levels in fatalities vary but  reported as high as 270 ng/ml in some studies  (15)
    • Prolonged re polarization leads to torsades
      • Early after depolarizations may trigger, which are then propagated torsades via re entrant rhythms (11)
  • Treatment
    • ACMT loperamide guidelines (12)
    • Supportive care
      • Arrhythmia management
        • Torsades (13)
          • Electrical cardioversion (terminates re entrant rhythm)
          • Magnesium (prevents early after depolarization)
          • Target Mg >2 and K >4
          • Lidocaine-> Recommended in 2006 Sudden cardiac death guidlines, not mentioned in 2017, however one of the only VT recommended antiarryhtmics that do not prolong QTc (others, sotalol, amiodarone, and procainamide, do)
          • If preceded by bradycardia, Overdrive pacing with isoproterenol to target HR~ 100
          • Beta blockers are recommended in patients with LQTS
        • Sodium channel blockade induced wide QRS complex tachycardia (12)
          • Hypertonic sodium to over whelm sodium channel blockade (1-2 amps of 8.4% Sodium Bicarbonate given IV)
    • Where do we go in the future?
      • More research will help us understand the true incidence of how often this occurs and what impact the FDA decisions will have
      • Any concerned citizen can submit for rescheduling of loperamide. Interested? Reach out at toxtalk1@gmail.com
  1. Florey, Klaus (1991). Profiles of Drug Substances, Excipients and Related Methodology, Volume 19. Academic Press. p. 342. ISBN9780080861142.
  2. "IMODIUM FDA Application No.(NDA) 017694". U.S. Food and Drug Administration (FDA). 1976.
  3. https://www.deadiversion.usdoj.gov/schedules/orangebook/orangebook.pdf.
  4. Miller H, Panahi L, Tapia D, Tran A, Bowman JD. Loperamide misuse and abuse. J Am Pharm Assoc (2003). 2017;57(2S):S45eS50.
  5. Feldman R, Everton E. National assessment of pharmacist awareness of loperamide abuse and ability to restrict sale if abuse is suspected [published online ahead of print, 2020 Jul 5]. J Am Pharm Assoc (2003). 2020;S1544-3191(20)30264-8. doi:10.1016/j.japh.2020.05.021
  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. DOI: http://dx.doi.org/10.15585/mmwr.mm6545a7
  7. https://www.chpa.org/PDF/09_05_17_CommentsCitizenPetitionLoperamide.aspx
  8. https://www.fda.gov/drugs/drug-safety-and-availability/fda-limits-packaging-anti-diarrhea-medicine-loperamide-imodium-encourage-safe-use
  9. Kang J, Compton DR, Vaz RJ, Rampe D. Proarrhythmic mechanisms of the common anti-diarrheal medication loperamide: revelations from the opioid abuse epidemic. Naunyn Schmiedebergs Arch Pharmacol. 2016;389(10):1133-1137. doi:10.1007/s00210-016-1286-7
  10. Klein MG, Haigney MCP, Mehler PS, Fatima N, Flagg TP, Krantz MJ. Potent Inhibition of hERG Channels by the Over-the-Counter Antidiarrheal Agent Loperamide. JACC Clin Electrophysiol. 2016;2(7):784-789. doi:10.1016/j.jacep.2016.07.008
  11. https://www.sciencedirect.com/science/article/pii/S1880427611800050
  12. Eggleston W, Palmer R, Dubé PA, et al. Loperamide toxicity: recommendations for patient monitoring and management. Clin Toxicol (Phila). 2020;58(5):355-359. doi:10.1080/15563650.2019.1681443
  13. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society [published correction appears in J Am Coll Cardiol. 2018 Oct 2;72(14):1760]. J Am Coll Cardiol. 2018;72(14):e91-e220. doi:10.1016/j.jacc.2017.10.054
  14. Marraffa JM, Holland MG, Sullivan RW, et al. Cardiac conduction disturbance after loperamide abuse. Clin Toxicol (Phila). 2014;52(9):952-957. doi:10.3109/15563650.2014.969371
  15. Miller H, Panahi L, Tapia D, Tran A, Bowman JD. Loperamide misuse and abuse. J Am Pharm Assoc (2003). 2017;57(2S):S45-S50. doi:10.1016/j.japh.2016.12.079

Aug 26 2020

58mins

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Rank #7: Episode 3- Toddler Time Bombs

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Jul 22 2020

1hr 7mins

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Rank #8: Episode 2- The Other Problem With Bullets

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If you have an elevated blood lead level- call your toxicologist or poison center. Thanks for listening!

Jun 24 2020

1hr 10mins

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Rank #9: (Mini) Episode 1.5 - Fundamentals: Testings Tests, Addictions vs Dependence, How Do We Alter Drug Absorption, What Do Drugs Do?

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Concepts in this episode

  1. 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
  • (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

Jun 10 2020

27mins

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Rank #10: Episode 1- Cleaning with War Gas and Drinking Javel Water

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  • Key points
    • Bleach mixed with various chemicals can make many toxic substances
    • Chlorine gas  is a high solubility irritant, it dissolves quickly in the mucous membranes and causes severe irritation of upper airway, eyes and nose (moist mucous membranes), effects are noticed quickly
      • Treatment for most chemical inhalation injuries involves removal from ongoing exposure, maintenance of a patent airway, and supportive care
        • Oxygen for hypoxemia
        • Bronchodilators (albuterol)
        • Intubation if needed
      • If the exposure is to chlorine gas there may be a role for nebulized sodium bicarbonate.
      • Due to  initial irritation, exposure may present looking vary severe, but may turn around with good supportive care
    • If you accidentally make chlorine gas, get to fresh air, open windows if you can and call your local poison center or 911
    • Bleach  ingestion are basic and can cause a liquefactive necrosis
      • Some may result in oral irritation
      • Treatment involves assessing the injury to determine risk of stricture  and possible esophageal stenting
  • 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.
      • 1. De Lange DW, Meulenbelt J. Do corticosteroids have a role in preventing or reducing acute toxic lung injury caused by inhalation of chemical agents? Clin Toxicol (Phila) 2011;49:61-71. 
        2. Vagaggini B, Taccola M, Conti I, et al. Budesonide reduces neutrophilic but not functional airway response to ozone in mild asthmatics. Am J Respir Crit Care Med 2001;164:2172–6.
        3. Alexis NE, Lay JC, Haczku A, et a. Fluticasone propionate protects against ozone-induced airway inflammation and modified immune cell activation markers in healthy volunteers. Environ Health Perspect 2008;116:799–805.
        4. Nightingale JA, Rogers DF, Chung KF, et al. No effect of inhaled budesonide on the response to inhaled ozone in normal subjects. Am J Respir Crit Care Med 2000;61:479–86.
  • New story from initial case- https://www.msdsonline.com/2015/02/27/fatal-accident-in-ca-even-small-quantities-of-chlorine-pose-danger/
  • History
  • Data on sodium bicarbonate in CL2 gas
    • Systematic review
      • Huynh Tuong A, Despréaux T, Loeb T, Salomon J, Mégarbane B, Descatha A. Emergency management of chlorine gas exposure - a systematic review. Clin Toxicol (Phila). 2019;57(2):77‐98. doi:10.1080/15563650.2018.1519193
    • Summary of many trials
  • Sodium bicarbonate probably doesn’t help Chloramine gas exposure
    • Pascuzzi TA, Storrow AB. Mass casualties from acute inhalation of chloramine gas. Mil Med. 1998;163(2):102‐104.
  • Chloramine physical properties
  • Reactions of Sodium Hypochlorite wit other compounds to make nasty products -
    • Odabasi M. Halogenated volatile organic compounds from the use of chlorine-bleach-containing household products. Environ Sci Technol. 2008;42(5):1445‐1451. doi:10.1021/es702355u
  • Good review of the basics of caustic ingestions such as bleach
    • Hoffman RS, Burns MM, Gosselin S. Ingestion of Caustic Substances. N Engl J Med. 2020;382(18):1739‐1748. doi:10.1056/NEJMra1810769
    • Pulmonary irritants- Nelson LS, Odujebe OA. Simple asphyxiants and pulmonary irritants. In: Hoffman RS, Howland MA, Lewin NA, Nelson LS, Goldfrank LR, eds.Goldfrank's Toxicologic Emergencies, 11e New York, NY: McGraw-Hill; 2019.
  • Incidence data
    • Gummin DD, Mowry JB, Spyker DA, et al. 2017 Annual report of the American association of poison control centers’ national poison data system (NPDS): 34th annual report. Clin Toxicol (Phila) 2017;55:1072–254.

May 27 2020

32mins

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