The Poison Lab

Do you think you know the cause of these symptoms? Send your guesses to toxtalk1@gmail.com to take part in the next episode 

A quick update to share some other shows Ryan has been on in the last few weeks! Check the show notes for links to each episode!Ryan on "The Larry Meiller Show" discussing delta cannabanoidsLink to streamLink to downloadRyan on EMS2020 talking prehospital overdoseLink to episode Show homepage

In this episode Ryan interviews Dr. Alex Krotulski PhD from the Center for Forensic Science Research and Education. Together take a look at trends in novel opioids, benzodiazepines, stimulants, hallucinogens, synthetic cannabinoids, and "hemp products" that are showing up in your patients, drug products, and fatal overdoses. The conversation takes places around the Center for Forensic Science Research and Education quarterly report on Novel Psychoactive Substances found in patients and drug products. The episode starts with a discussion of the novel benzodiazepines market, highlighting bromazolam and how long it may remain in the market. Then they discuss the opioids highlighting where we are seeing carfentanil, what is happening with Para Fluorofentanyl, and other super potent opioids emergening (such as  N -pyrrolidino etonitazene). After a quick discussion of synthetic cathinone's and PCP/ketamine derivatives they jump to synthetic cannabinoids, examining the history of brodifacoum contamination and how regulation has led to market changes.  Resourceshttps://www.cfsre.org/Quarterly report  discussed on this episodeMore on Dr. KrotulskiPoster from Dr. Kortulksi on naming conventions for NPS Time stamps to jump to any portion of the episode you want to revisitIntroduction-5:00-32:5006:30-25:16- Discussion CSFRE mission, history of NPS reports, and other available reports25:14- "Miscellaneous drugs: Furanyl UF17, medetomidine"28:15- Difference between GC/MS and LCqTOFNovel Benzodiazepines- 32:50Novel Opioids-43:00Stimulants and hallucinogens- 1:01:43Synthetic cannabinoids- 1:07:40Novel psychedelics markets, hemp products, phenibut, tianeptine, and kratom-1:25:12

Dr. Ann Arens, MD an emergency medicine physician and medical toxicologist with Oschner Medical center in New Orleans, LA joins the show to educate us on some HOT toxins, solve toxic cases, and opine on the philosophical and existential reasons drugs even exist. Tune in for a fantastic discussion with Dr. Arens and to hear the answer to our mystery case. Case report for mystery caseReview paper cited by Dr. ArensInterview with DNP user by Chubby EmuCase 1Some also contain CALCIUM NITRATE and can cause methemoglobinemiaCase 2Case 3

Do you think you know the cause of these symptoms? Send your guesses to toxtalk1@gmail.com to take part in episode 18 

In this episode Ryan is joined by a guest panel (Dr. Grant Comstock MD, Dr. Joshua Trebach MD, Dr. Emily Kiernan DO, and Dr Frank Paloucek PharmD, DABAT) to review nine of the most interesting or clinically impactful research abstracts that were presented at the 2023 North American Congress of Clinical Toxicology (NACCT) in Montreal Canada. If you didn't get a chance to read all 363 research abstracts from some of Toxicology's best and brightest this year, tune in for a high yield review as well as clinical a break down of the studies and their relevance from the expert panel.  Check the show notes for a link to the published abstracts and the list of all studies discussed in the showAbstracts available here10:40- Abstract 1 (PDF #225) Methotrexate toxicity in the setting of therapeutic error, a multicenter retrospective reviewLead author: Andrew Chambers24:12- Abstract #2 (PDF #251) Oleander seeds in candlenut weight loss product strike againLead author: Masha Yemets31:16- Abstract #3 (PDF #2) Efficacy of sodium tetrathionate when administered intramuscularly for the treatment of acute oral cyanide toxicity in a swine model (Sus scrofa)Lead author: Brooke Lajeunesse39:45- Abstract #4 (PDF #10) Is HOUR enough after out-of hospital naloxone for opioid overdose? Prospective preliminary data from real-world implementation of the modified St. Paul’s early discharge ruleLead author: Stephen Douglas49:05- Abstract #5- Poster titles at NACCT 2013–2022: is NACCT experiencing a pun-demic?Lead author: Dayne Laskey52:40- Rivastigmine discussionLead author: none58:40- Abstract #6 (PDF #5)  Randomized controlled trial of ANEB-001 as an antidote for acute cannabinoid intoxication in healthy adultsLead author: Andrew Monte1:08:00- Abstract #7 (PDF#216) Successful use of expired physostigmine to treat anticholinergic delirium in a pediatric patientLead author: Bryan Hayes01:20:00- Abstract #8 (PDF #202) Enough negativity? Clinically significant salicylism with first detectable concentration twelve hours )post-ingestionLead author: Stacey Bangh01:25:24 - Abstract #9 (PDF #267) High sensitivity troponin is frequently elevated after carbon monoxide exposureLead author: Abdullatif Aloumi

In this episode, Ryan dives into cutting-edge research on the treatment of acetaminophen (APAP) overdose, featuring interviews with authors of several key abstracts from the North American Congress of Clinical Toxicology (NACCT) in Montreal Canada (Abstracts and posters available in the show notes). We get first looks insights into research evaluating the impact of fomepizole high risk acetaminophen overdose, as well as who gets fomepizole for acetaminophen overdose and dies. Then we evaluate the effectiveness of standard N-acetylcysteine (NAC) treatment in high risk patients and high dose NAC in high risk patients. Join us for an insightful discussion on these advancements that are reshaping the management of APAP toxicity. Guests include Dr. Masha Yemets PharmD, Dr. Molly Stott PharmD, Dr. Alexandru Ulici PharmD, and Dr. Michael Moss MD.   Link to published abstracts(First guest) Abstract #126 Characterizing fomepizole use in acetaminophen deaths reported to US poison centers- Dr. Yemets(Second guest) Abstract #125 Clinical impact of fomepizole as an adjunct therapy in massive acetaminophen overdose- Dr. Stott(Third guest) Abstract #131 Comparison of low-risk and high risk acetaminophen ingestions using the standard prescott protocol of intravenous N-acetylcysteine- Dr. Ulici(Fourth guest) Abstract #130 High-risk acetaminophen overdose outcomes after treatment with standard dose vs. increased dose N-acetylcysteine- Dr. MossOther studies discussed regarding NAC dosingATOM 2 Angela ChiewOutcomes of massive APAP treated with regular NAC (Virginia group, lead author Dr. Downes)

In this episode, Ryan sits down with Dr. Eric Lavonas MD, a seasoned EM resuscitation guideline writer, emergency medicine physician, medical toxicologist, and lead author of the latest update to the American Heart Association's guidelines for the management of cardiac arrest and life-threatening toxicity due to poisoning. They have an in-depth discussion as they explore the key aspects of the 2023 AHA treatment recommendations and the rationale behind each decision point. A great review to discover how to effectively apply these guidelines in real-world scenarios and find out what knowledge gaps exist in the realm of toxin resuscitation. Be sure to also check out the accompanying mini-episode for a high-yield review of the major treatment recommendations. Link to guidelinesLink to high yield review Cyanide paper mentioned in the showAdult calcium channel blocker toxicity guidelines

In this episode Ryan does a high yield "just the facts" break down of the recently released "2023 American Heart Association Focused Update on the Management of Patients With Cardiac Arrest or Life-Threatening Toxicity Due to Poisoning: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care". Tune in to learn about the most recent treatment recommendations made by AHA via a panel of toxicology experts. This was released alongside a full interview with the lead author Dr. Eric Lavonas MD. Be sure to check out the full interview to hear it straight from the source! (link in show notes).Link to guidelinesLink to full in depth interview

In this enlightening episode, Ryan engages in a deep conversation with Dr. Paul Hutson, PharmD, a renowned researcher in the field of psilocybin and director of the Transdisciplinary Center for Research in Psychoactive Substances at the University of Wisconsin Madison. Dr. Hutson shares his extensive knowledge and insights into the promising role of psilocybin in the treatment of depression and substance use disorder.  Throughout the discussion, they delve into the research that supports the use of psilocybin in medical therapy, shedding light on the rigorous processes involved in conducting such studies. Dr. Hutson elucidates the efficacy and safety findings that have emerged from his and others research, offering listeners a glimpse into the potential future of psilocybin in mainstream medical practices. Listeners will gain a deeper understanding of the meticulous approach to research that ensures both safety and effectiveness. Dr. Hutson shares firsthand experiences and observations, providing a rich and detailed perspective on the current state of psilocybin research. Moreover, the conversation ventures into the practical aspects of integrating psilocybin into contemporary medical practices, discussing the potential frameworks and guidelines that would govern its use. They explore what the future might hold for patients and practitioners alike as they stand on the cusp of a revolutionary shift in mental health treatment.Whether you're a healthcare professional keen on the latest developments in medical research or someone interested in the evolving landscape of mental health treatment, this episode promises to be a rich source of information and insight. Tune in to be informed and to foster a deeper understanding of the promising horizon that psilocybin research is unveiling in the medical community.Biography for Dr. Paul Hutson PharmDTransdisciplinary Center for Research in Psychoactive SubstancesDr Hutson's PublicationsSingle Dose Psilocybin for Major Depression- JAMA 2023Psilocybin and QTc in healthy volunteersMeta-Analysis of research supporting Psilocybin use in anxiety and depressionPharmacokinetics of PsilocybinSubjective effects of high dose PsilocybinOther referenced studiesSingle dose psilocybin for treatment resistant depression Psilocybin for alcohol use disorderPsilocybin for For tobacco cessation

New Art and New Tox Trinkets. If you want to share your tox joy in the real world, find some trinkets here: https://www.etsy.com/shop/thepoisonlab

This episode is a a high yield "just the facts" break down of the recently released "Management of Acetaminophen Poisoning in the US and Canada Consensus Statement" from the American Academy of Clinical Toxicology, American College of Medical Toxicology, Americans Poisons Centers, and the Canadian Association of Poison Centers. Listen to be informed on the most recent treatment recommendations. This was released alongside a full interview with the consensus statement corresponding author Dr. Richard Dart MD, PhD. Be sure to check out the full interview to hear it straight from the source! (link in show notes).Link to the guidelines:Full interview with consensus statement author Dr. Richard Darthttps://jamanetwork.com/journals/jamanetworkopen/fullarticle/2808062Definitions made by the guidelineAcute ingestion>7.5 g in 24 h per Rummack Matthew initial studies10 g/d or 200 mg/kg/day in <24 h also suggested Repeated Supra Therapeutic Ingestion (RSTI)Repeated dosing totaling10g or 200 mg/kg in 24 hour6g/d or 150 mg/kg/day x 48 h4g/d or 100 mg/kg/day x >48 hHigh risk ingestionReported dose >30 grams OR[APAP] 2 x Rummack-Matthew nomogram treatment lineNAC stopping criteriaAPAP<10INR<2AST/ALT Normal for patient or decreased by 25-50%Patient clinically wellNotable treatment recommendationsRSTIIf patient has history of RSTI (>6 g x 24-48 h, >4 g x >48 hours) AND signs of APAP toxicity (vomiting, RUQ abd pain, AMS)Treat if APAP >20 ug/ml OR AST/ALT elevatedAcuteNon-detectable [APAP] between 2 and 4 hours excludes ingestionGive SDAC w/in 4 hours (something I’ve been a proponent of since ATOM2)Start treatment with NAC if unable to plot on nomogram by 8 hoursNAC dose“Higher dose” NAC (undefined) for high risk ingestionMinimum NAC regimen should include 300 mg/kg orally or within 20-24 hoursCAP NAC dose at 100 kg (this was known with PO, but IV there was always some question since it delivers less overall)Unique scenariosLine crossersAPAP with anticholinergic or opioidIf 1st  concentration below treatment line repeat in 4-6 hoursAPAP Extended releaseIf 1st  concentration below treatment line @ 4-12 hours, repeat in 4-6 hoursDialysis-Dialyze If APAP >900 w/ AMS or acidosis.NAC IV rate during HD 12.5 mg/kg/hr minimum. No dose change for PO (not new but good reminders)Consult liver transplant for rapid AST/ALT inc w/ coagulopathy, AMS, or mulistytem organ failureThe addition of fomepizole to acetylcysteine in the treatment of serious acetaminophen ingestions has been proposed. The panel concluded that the data available did not support a standard recommendation. As for any complicated or serious acetaminophen poisoning, a PC or clinical toxicologist should be consulted.

Mini episode- High-yield over view of Management of Acetaminophen Poisoning in the US and Canada Consensus Statement In this Ryan sits down with Dr. Richard Dart MD, PhD. He is the lead author of the recently released "Management of Acetaminophen Poisoning in the US and Canada Consensus Statement" from the American Academy of Clinical Toxicology, American College of Medical Toxicology, Americans Poisons Centers, and the Canadian Association of Poison Centers. Listen to be informed on the most recent treatment recommendations.  They dive in to the definitions established by the guideline and notable treatment recommendations, dissecting the ratinonale for each desiscion point and how to apply the guidelines. A mini episode was released along side this episode that is a high yield review of major treatment recommendations and definitions estabilished by the consensus statement.  Links :Mini episode- High-yield over view of Management of Acetaminophen Poisoning in the US and Canada Consensus Statement Guidelines https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2808062Definitions made by the guidelineAcute ingestionAny overdose taken with 24 hours periodOverdose "dose" not defined>7.5 g in 24 h was criteria for Rumack Matthew nomogramConsensus statementAdult overdose at 10g/d or 200 mg/kg/d in <24 hours= potentially toxicPediatric <6 year at 150 mg/kg/d in <24 h = potentially toxicRepeated Supra Therapeutic Ingestion (RSTI)Overdose "dose"Repeated dosing totaling6g/d or 150 mg/kg/day x 24-48 h = potential toxic4g/d or 100 mg/kg/day x >48 h = potential toxic (Recognize this means some people could be toxic at therapeutic dosing, but if they do not have symptoms not likely)High risk ingestionReported dose >30 grams OR[APAP] 2 x Rummack-Matthew nomogram treatment lineNAC stopping criteriaAPAP<10INR<2AST/ALT Normal for patient or decreased by 25-50%Patient clinically wellNotable treatment recommendationsRSTIIf patient has history of RSTI (>6 g x 24-48 h, >4 g x >48 hours) AND signs of APAP toxicity (vomiting, RUQ abd pain, AMS)Treat if APAP >20 ug/ml OR AST/ALT elevatedAcuteNon-detectable [APAP] between 2 and 4 hours excludes ingestionGive SDAC w/in 4 hours (something I’ve been a proponent of since ATOM2)TreatStart treatment with NAC if unable to plot on nomogram by 8 hoursNAC dose“Higher dose” NAC (undefined) for high risk ingestionMinimum NAC regimen should include 300 mg/kg orally or within 20-24 hoursCAP NAC dose at 100 kg (this was known with PO, but IV there was always some question since it delivers less overall)Unique scenariosLine crossersAPAP with anticholinergic or opioidIf 1st  concentration below treatment line repeat in 4-6 hoursAPAP Extended releaseIf 1st  concentration below treatment line @ 4-12 hours, repeat in 4-6 hoursDialysis-Dialyze If APAP >900 w/ AMS or acidosis.NAC IV rate during HD 12.5 mg/kg/hr minimum. No dose change for PO (not new but good reminders)Consult liver transplant for rapid AST/ALT inc w/ coagulopathy, AMS, or mulistytem organ failureThe addition of fomepizole to acetylcysteine in the treatment of serious acetaminophen ingestions has been proposed. The panel concluded that the data available did not support a standard recommendation. As for any complicated or serious acetaminophen poisoning, a PC or clinical toxicologist should be consulted.

Dr. Frank Paloucek, PharmD, DABAT (@itsalltox) joins the show. He was one of the very first emergency medicine pharmacists and one of the original board-certified clinical toxicologists (DABAT). He is now a proudly retired professor emeritus at The Univeristy of Illinois at Chicago. In his tenure there he spent nearly 20 years as the program director for their clinical pharmacy residency, was an integral part of the Toxikon Consortium toxicology fellowship, and coauthored the text book "Poisoning and Toxicology Handbook (Poisoning and Toxicology Handbook (Leiken & Paloucek's)) 4th Edition. Frank and Ryan kick off the show hearing about Frank's fledgling years working in an emergency department without EM attendings. Then they bust some toxicology myths (do you REALLY need BAL before Calcium disodium edetate in severe lead poisoning? Frank thinks no...) before jumping into solving some toxic cases. Finally, the episode ends with Frank and Ryan solving a case of poisoned AI. They ask GPT to take on the role of a poisoned patient and work together to identify the culprit. Enjoy and don't forget to leave a review. IntroductionChisolm lead 1Chisolm lead papers 2Cory-Slechta lead redistribution paperTylenol murders suspect diesFranks bookToxikon fellowshipStump the toxicologistCase 1CDC articleNEJM ArticleCase 2A review paper written by the Frank Paloucek himself on toxin #2Case 3Case reportCase where toxin was found in stomach on autopsy published by colleagues  Dr. Amy Zosel and Dr. Matt Stanton Case 4A very SIMILAR case to case 4

In this episode Ryan explores the concept of brain death and the implications of drug overdoses causing false positive diagnosis of brain death. He is joined by an author of the ACMT Position statement on brain death in overdose (Dr. Andrew Stolbach MD) as well as authors of two case reports (neuro critical care physician Dr. Ranier Reyes and emergency physician Dr. Doug Stranges) involving bupropion where patients had absent brain stem reflexes after overdose but made a full neurologic recovery. We delve into the criteria used to determine brain death and the challenges faced by families and healthcare professionals when dealing with this sensitive topic. 00:00-19:00 Introduction to brain death guidelines19:00-28:00 Introduction to limitations in guidelines regarding overdose28:30-38:00 Interview with ACMT Position statement author39:00- End- Interview with Bupropion brain death mimic authors and summaryLinks references in showAmerican Academy of Neurology Bran death guidanceACMT Position statement on brain death in overdoseBrain death mimics with cerebral edemaCase report of “hypoxic patient with diffuses cerebral edema” who recovered in 48 hourCarbamazepine with diffuse cerebral edema who recoveredCases taking >2 months to recover brain stem reflexeshttps://www.thelancet.com/journals/lancet/article/PIIS0140-6736(02)07577-3/fulltexthttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4543058/Attempts to withdraw care in as little as 48 hours Dr. Stranges case reportDr. Reyes case reportNarrative review of brain death mimicsIntroductory casesCaroline Burns- Patient who woke up on operating tablePaul Maturo- Patient woke up in a morgue

Dr. Adam Blumenberg, MD (@ABlumenbergMD) Join's the show. He is an emergency medicine physician, medical toxicologist, and Assistant Professor at Columbia University Medical Center in New York City. He hosts his own toxicology youtube series (www.ToxicHistory.com) and has developed multiple free medical education software programs in toxicology (www.toxicrunner.net) and medical simulation (www.medsimstudio.com). Most impressively, he has produced his own free base lidocaine crystals on a stove top, if you ask nicely he might just loan you one. He joins the show to sleuth the cause of fatal poisoning cases and tackle internet questions from reddit.com/r/askdrugs Dr. Blumenberg' s projectswww.ToxicHistory.comwww.medsimstudio.com (medical vital/imaging simulator)www.toxrunner.net (toxicology question bank)Things discussed in the introMithradata Ohio vinyl chloride disasterArizona nitric acid spillOhio metal factory explosionCasesCase 1Case 1 triage guidelinesCase 1 video demonstrationCase 2Full textCase 3Review article MechanismCase 4Full textCase 5Not the actual case from the show but close enough QuestionsBHO explosions

Ready for a high-octane dose of knowledge? 🔥🧠 Ryan's got you covered with this electrifying mini-episode on managing a bupropion overdose! 💊💥  Beware - there are plenty of pitfalls you'll want to avoid. Check out the full episode and other mini-episodes for even more tips and tricks! 🎧👀Bupropion is the #1 antidepressant cause of major (life threatening) reported to U.S. Poison CentersIt is difficult to manage due toPotential for delayed seizuresUnique cardiogenic shock in overdosePotential wide complex arrhythmia refractory to Sodium Bicarbonate Potential interference with brain death testingTreatmentDecontaminationAggressive whole bowel irrigation or charcoal may be indicated if large ingestionSupportive careIntubation if airway compromisedBenzodiazepine for agitationBenzodiazepines and GABA-ergic AED's for status epilepticsTachycardia, tremor, and agitation are risk factor for seizuresTachycardia may be masked by alpha 2 agonist co ingestionsSeizures may occur 24 hour outSodium bicarbonate for wide QRS (it may be refractory)Inodilators and vasopressors for cardiogenic shockECMO for refractory shock or arrhythmiaAwareness that severe bupropion toxicity can mimic brain deathsend analytical confirmation of bupropion if possible to rule out confoundingEnhanced eliminationlimited options due to protein binding, not routineFocused antidoteConsider IV fat emulsion if the patient is peri arrestObservation timesTalk to a toxicolleague about observation times, decontamination, and use of invasive therapies to avoid falling into a trap

What do bath salts, face eating zombies, and antidepressants have in common? In this episode Ryan has a number of guests (Dr Filip, Dr Olives, Dr Reyes) join to discuss a unique heart breaking poisoning that is now the number one cause of major life threatening effects in antidepressant overdose in the United States. Check out the mini episodes for more!This antidepressant is the #1 cause of major (life threatening) effects in overdose reported to U.S. Poison CentersIt is difficult to manage due toPotential for delays seizuresUnique cardiogenic shock in overdosePotential wide complex arrhythmia refractory to Sodium Bicarbonate Potential interference with brain death testingToxicityIt increases dopamine and norepinephrine, it also blocks the gap junction in the cardiac myocyteRohr 2004- Gap junction blockade can cause a wide QRVink 2004 Connexin 43 is the most important protein for connexon formation and cardiac signal transmissionCallier 2012- Bupropion does not block sodium channels, and does exhibit similar effects on the cardiac action potential as known gap junctionBurnham 2014 Bupropion has an IC50 for connexin 43 >50 uMol, larger than other drugs such as fluoextine and lamotrigineShaikh Quereshi 2014 Bupropion interferes with connexin43 production and localization in chicken cardiac myoctes at concentration >50 uMolEffectsSympathetic toxidromeSeizuresTL;DRYour patient can seize 8-24 hours in, usually they have neurologic symptoms and tachycardia before handTachycardia may be masked by coingestions and symptoms may be very delayedDo not discharge a patient without discussing observation time with a toxicologist or poison centerDo not dismiss tachycardia and anxiety as situational in a bupropion overdoseShepherd 2004- Seizures in primarily sustained release productsMost seizures had prodromal neuropsychiatric symptomsStarr 2009- Seizure in XL products. Tachycardia, tremor, agitation most associated with seizuresSeizure occured as late as 24 hours and 25% occurred after 8 hoursOfferman 2020- Primarily sustained/extended release productsTachycardia duration, and extent (>120) predicted seizure. (Hypotnesion and neuropsych symptoms also predict)Late seizure occurred only in those with symptoms on presentationThose who had cardiac arrest had prehospital seizure= bad signRianprakaisang 2021- ToxIC review of risk factors for seizuresQTc and HR>140 predict seizuresUnique cardiogenic shock in overdosePotential wide complex arrhythmia refractory to Sodium Bicarbonate Potential interference with brain death testingTreatment DecontaminationAggressive whole bowel irrigation or charcoal may be indicated if large ingestionSupportive careIntubation if airway compromisedBenzodiazepine for agitationBenzodiazepines and GABA-ergic AED's for status epilepticsTachycardia, tremor, and agitation are risk factor for seizuresTachycardia may be masked by alpha 2 agonist co ingestionsSeizures may occur 24 hour outSodium bicarbonate for wide QRS (it may be refractory)Inodilators and vasopressors for cardiogenic shockECMO for refractory shock or arrhythmiaAwareness that severe bupropion toxicity can mimic brain deathsend analytical confirmation of bupropion if possible to rule out confoundingEnhanced eliminationlimited options due to protein binding, not routineFocused antidoteConsider IV fat emulsion if the patient is peri arrestObservation timesTalk to a toxicolleague about observation times, decontamination, and use of invasive therapies to avoid falling into a trapNot all ingestions are made the same   

TL;DRYour patient can seize 8-24 hours in, usually they have neurologic symptoms and tachycardia before handTachycardia may be masked by coingestions and symptoms may be very delayedDo not discharge a patient without discussing observation time with a toxicologist or poison centerDo not dismiss tachycardia and anxiety as situational in a bupropion overdoseSpiller 1994- Review of instant release product overdoses Shepherd 2004- Seizures in primarily sustained release productsMost seizures had prodromal neuropsychiatric symptomsStarr 2009- Seizure in XL products. Tachycardia, tremor, agitation most associated with seizuresSeizure occured as late as 24 hours and 25% occurred after 8 hours Offerman 2020- Primarily sustained/extended release productsTachycardia duration, and extent (>120) predicted seizure. (Hypotnesion and neuropsych symptoms also predict)Late seizure occurred only in those with symptoms on presentationThose who had cardiac arrest had prehospital seizure= bad signRianprakaisang 2021- ToxIC review of risk factors for seizuresQTc and HR>140 predict seizures 

Rohr 2004- Gap junction blockade can cause a wide QRS Vink 2004 Connexin 43 is the most important protein for connexon formation and cardiac signal transmissionCallier 2012- Bupropion does not block sodium channels, and does exhibit similar effects on the cardiac action potential as known gap junction  Burnham 2014 Bupropion has an IC50 for connexin 43 >50 uMol, larger than other drugs such as fluoextine and lamotrigineShaikh Quereshi 2014 Bupropion interferes with connexin43 production and localization in chicken cardiac myoctes at concentration >50 uMol