Getting Learnt. LEGO! Toxicology Ep. 1

A full year of residency DONE. Large accomplishments and small, they all meant something. I had a strange feeling year to say the least. In my intern year of my program I spent eight of the first nine months in the emergency department. The only non-ED month at the start was Anesthesia. AWESOME attendings who made me read A LOT. No joke. I never have read that much for a 30-day rotation. I have a paper stack in my closet that’s a full ONE+ FOOT high of small-font texts, case studies, UpToDate articles, anesthesia guidelines, you name it! I then ended my year with OB-GYN, EMS, then…. the dreaded… trauma. My uppers said it was rough but man I was in for an emotional rollercoaster. I spent my nights in a shitty college dorm in downtown. I would wake at 3:30 > work at 4am, finish at ~7pm every day of the month but 5 days. Then… the year was over. IT FELT SO WEIRD. I can’t say I’m a “tern” any longer. I can’t have zero expectations, I have residents under me! I’m even getting paid a little more (2k). The strangest part is the attendings look at you different. They REFER to you different in lecture. The questions you’re asked changes. It’s a very weird and (should have been expected) life change.

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Sooo to appropriately reflect this I realized it’s time for a personal change. For me and you the readers. We had A LOT of lectures last year. I learned a LOT. I hesitated to write blogs since I didn’t want to sound dumb, to “waste my time”, to blah blah blah. F-that! I learn best by teaching. If I teach it, I know it. If it sits in my head and it doesn’t come out, I most likely don’t really know it all that well. So here’s what’s gonna happen. We have lectures every week. Unless I work the next 6 days in between or I’m on vacation, I want to summarize my teachings and post them for all-y’all. I want to make them super brief. I’m taking hours of lectures and attempting to make EM bullet points that are rapidly digestible and memorable. My references are “Goldfrank’s Toxicologic Emergencies 10th edition” and “EMRA Medical Toxicology Guide“. If something’s wrong, tell me. If you do something different or have some “pro-tips”, let us know. If you hate this content, I’m all ears to that too. And if you’re gonna be at ACEP 2019 say what’s up! (jk I’m gonna be so incognito that Google Chrome won’t be able to find me). So without further adieu, lecture #1…

Toxicology Episode 1: Physostigmine, Amphetamines, Nicotine

(1) Physostigmine:

  • Reversible cholinesterase inhibitor > prevents acetylcholine metabolism > ACh accumulates >  ^muscarinic symptoms: SLUDGE) > inhibits atropine / scopolamine / diphenhydramine effects
  • Dates back to Efik people of Nigeria. Made from bean. Used in traditional “judicial test“. Innocent people swallow and supposedly quickly vomited and survived. Guilty people hesitated, sublingual absorption > fasciculate > die.
  • Consider using on patient’s presenting with anti-muscarinic manifestations (mad as a hatter…, etc.)
    • (peripheral) – dry mucosa, dry skin, flushed face, mydriasis, hyperthermia, tachycardia, decreased bowel sounds, urinary retention
    • (central) – agitation, delirium, hallucinations, seizures, coma

Kloss-and-Bruce-Anticholinergic

  • CONTRAINDICATIONS: reactive airway disease, peripheral vascular disease, intestinal/bladder obstruction, intraventricular conduction defects/AV blocks (significant QRS or QT prolongations), sulfite allergies
  • Dosing: Have Atropine (reversal agent) bedside!
    • Physostigmine: Adult 1-2mg, Children 0.02mg/kg (max 0.5mg) over 5 minutes, may repeat Q5-10 min PRN x1-2 doses

(2) Amphetamines:

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  • Rant: These drugs suck. They’re cheap. They f*** you up. They’re a PAIN to deal with in the ED: they’re a giant waste of time/human resources/innocent lives. Nothing turns a 30 year old > 70 year old like meth. Lastly, from personal experience, they’re the #1 cause of a 20% EF in an otherwise “healthy” 20yo.
  • Synthesized in 1887 > marketed in 1930’s as decongestant “Benzedrine” and amphetamine tablets for narcolepsy > WWII soldier stimulant > 1970’s Schedule II.
  • Mechanism: ^ release & blocks reuptake of norepinephrine, dopamine, serotonin. Also inhibits monoamine oxidase.
  • Chronic use: depletes dopamine/serotonin > irreversible neuronal destruction > impaired memory/psychomotor functions
  • Toxicity: uncontrolled hyperadrenergic state (~cocaine)
    • (Heart) dysrhythmias, HTN, tachycardia, MI, dissection, cardiomyopathy (CNS) choreoathetoid movements “crack dancing”, euphoria, hyperreflexia, hyperthermia, intracerebral hemorrhage, psychosis, pressured speech, seizure (Other) diaphoresis, mydriasis, tremor, ARDS “crack lung”, ischemic colitis, rigidity, rhabdo, pulmonary HTN (Labs) hyperglycemia, hyponatremia, ^LFT
  • UDS: false positives > Bupropion, Trazodone, Labetalol, Ranitidine, Chlorpromazine
  • Management (besides the obvious pt/lab workup) check core body temp (hyperthermia kills), CAREFUL with restraints! (worsens rhabdo), be wary of concomitant ingestions (less single ingestion patients QD)
    • Agitation: Benzo > Diazepam (Valium) 5-10mg IV q5-10 PRN (peds 0.2-0.5 mg/kg) or Lorazepam (Ativan) 2-4mg IV q10-15 PRN (peds 0.05-0.1 mg/kg)
    • Seizure: Benzo > Phenobarbital (130-260 mg IV q20 min: titrate to effect) > Propofol (infusion 5 mcg/kg/min titrate)
    • HTN: alpha-adrenergic antagonist phentolamine (5mg IM/IV) or vasodilators (nitroprusside, nitroglycerin, nicardipine)
    • Choreoathetosis: Haloperidol (5mg IV/IM PRN 10-30min)
    • AVOID SUX for intubating if: hyperthermic, hyperkalemic and/or rhabdo

(3) Nicotine:

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  • Predates Mayan empire. Ramon Pane, monk with Christopher Columbus, brought tobacco back to Europe
  • Secreted in breast milk
  • Caucasians metabolize faster than AA/Asians, women metabolize faster then men (further accelerated by oral contraceptives/pregnancy)
  • Smoking accelerates metabolism: caffeine, clozapine, olanzapine, tacrine, theophylline, erlotinib
  • Smoking diminishes: opioids, benzos, B-adrenergic antagonists, nifedipine
  • Nicotine patches: 7, 14, 21mg > sleeping difficulty, vivid dreams (nightmares) > applied for only 16 hours (can cause severe toxicity if punctured/bitten/torn)
  • Chantix: smoking cessation aid (nicotine receptor partial agonist) > black box warning: depression/suicidal behavior
  • Mechanism: mimics acetylcholine through nicotinic receptors & releases norepinephrine, acetylcholine, GABA, serotonin, glutamate, dopamine, endorphins
  • Symptoms:
    • Biphasic: central stimulation (HTN/tachy) > depression (hypo/brady)
    • (Naive) tremor, nausea, ^HR/RR/BP, GI motility
    • (Mild) salivation, N/V, diaphoresis, diarrhea, pallor, HTN, tachycardia
    • (Severe) dysrhythmia, seizure, fasciculations
    • (Green tree sickness: farmers) ~seasickness: dizziness, headache, N/V, weakness, diarrhea, abdominal cramps, chills
  • Management:
    • Dermal exposure > decontaminate with copious soap/water
    • Parasympathetic excess > Atropine
    • Seizure > benzo > pheno > propofol (as above)

 

And… That’s all he wrote folks! There’s obviously a million more things I could write. I could dive into the pharmacology, history, meticulous mechanisms of actions, every way these drugs could present and new/experimental and questionable treatments. I attempted to spare you. If you’re interested in learning more, grab the two texts I referenced. They’re great! EMRA is purely bullet points and highlights. Goldfranks has literally everything. It’s a nerds dream! Hope this helps someone (I see you reading this LIZ!). I’ll tweak this in the future. Next up should be basic fracture splinting 😉 PEACE!

Image Credits: [Feature, 1, 2, 3, 4]

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