1. Medical Student Lecture 2015
Toxicology
Medical Student Lecture
2015

2. History Tox MATTERS M edication A mount/concentration T ime T aken
E mesis?
R eason
S igns/symptoms

3. Physical Exam VITALS! General appearance Pupils
Skin (Wet/dry? Flushed?)
GI (bowel sounds?)
Neuro (clonus? Reflexes?)
MSK tone
Psych (hallucinating? Oriented?)

4. Toxicology Workup

5. Toxicology Workup EKG Labs: BMP (why?), tylenol level If suspected:
ASA, lithium, VPA, toxic alcohols, osmolality, etc

6. Case 1
22 yo M brought in by friends
70, 110/60, 4, 70% RA, 97.8 F

7. What do you need to know?

8. PE General: unresponsive Skin: blue, dry HEENT: pupils 2mm
MSK: decreased tone
Neuro: no clonus, not moving extremities
GI: decreased BS

9. Antidote?

10. Antidote?
Narcan!

11. Antidote?
Narcan!
He wakes up immediately and wants to put his clothes on and go home.
Do you let him?
What questions can you ask to make sure that it is safe for him to leave?
You have to let him if he is now normal. Ask what he took. If he injected heroin, he’s probably fine. If he ingested something like percocet, you have to do a tylenol level. If he took something like methadone he needs to stay in the hospital.

12. Case 2
25 yo F who presents via EMS. She was found outside running around her neighborhood without clothes on.

13. Physical Exam
120, 130/85, 15, 100% RA, 100.5
General: looking around room, not engaged in conversation w/ you.
HEENT: pupils 6mm, equal
Skin: flushed on face and on chest, no sweat in axillae
GI: decreased BS
Neuro: no rigidity, no clonus
Psych: mumbles incoherently, picking at things in the air, not oriented

14. Toxidrome?

15. Anticholinergic Toxicity
Hot as a hare
Mad as a hatter
Red as a beet
Blind as a bat
Dry as a bone
Tachy as a $20 suit
Naked as a jaybird

16. Usual Suspects Antihistamines Antipsychotics Cyclic antidepressants
Benadryl (Tylenol PM), Doxylamine (NyQuil)
Antipsychotics
Seroquel, clozaril, olanzapine
Cyclic antidepressants
Amitriptyline, imipramine, nortriptyline
Plants
Jimsom weed
The list goes on…

17. Treatment?

18. Treatment? Antidote is physostigmine. Inhibits acetylcholinesterase
Can save an intubation

19. Treatment? Physostigmine Available only as an IV preparation
Onset of action is within minutes
Dose can be repeated q min
T1/2 is 16 minutes, but duration of action is usually much longer

20. Physostigmine & TCA OD
Physostigmine was used often in the 1970s to treat undifferentiated delerium
Case report by Pentel in 1980 re: 2 patients who suffered asystole after receiving physostigmine for TCA overdoses
Since then the antidote has greatly fallen out of favor

21. Physostigmine - Indications
Anti-cholinergic manifestations without evidence of QRS or QTc prolongation, such as:
Agitation
Hypertheria
Hallucinations
Delerium
Seizures
coma
The patient to use this in is a known non-TCA anti-cholinergic overdose

22. Physostigmine – Contraindications
Definite contraindications:
Suspicion of TCA ingestion
Widened QRS on ECG

23. Case 3
35 yo M who presents altered. He was found by EMS outside a club. Someone called because he was acting strangely. He is angry and has required multiple doses of benzos in the rig.
Vitals:
140, 160/90, 18, 96% RA, 99.5 F

24. Physical Exam General: angry, shouting at people in the room
HEENT: pupils 6mm, equal
Skin: no flushing. +Diaphoresis
GI: normal BS
Neuro: no rigidity, no clonus
Psych: angry, delusional, but knows where he is.

25. Toxidrome?

26. Toxidrome? Sympathomimetic toxicity Symptoms: Common substances:
anxiety, delusions, diaphoresis, hyperreflexia, mydriasis, paranoia, piloerection, and seizures
hypertension, and tachycardia.
Common substances:
Amphetamines/methamphetamine, cocaine, theophylline
It may appear very similar to the anticholinergic toxidrome, but is distinguished by hyperactive bowel sounds and sweating.

27. Treatment
Benzos, benzos and…

28. Treatment
Benzos, benzos and…
MORE BENZOS!

29. Case 4
45 yo Mexican migrant worker who presents from his work. He is having a lot of difficulty breathing, per EMS.

30. Physical Exam
50, 120/80, 30, 85% NRB, 98.6 F
General: confused male with obvious difficulty breathing
HEENT: pupils 2mm, tearing, runny nose
CV: brady
Resp: diffuse wheezing, decreased BS throughout
Skin: diaphoretic
Neuro: normal m tone, he is confused, pulling at his lines
GU: urine in pants

31. Toxidrome?

32. Toxidrome?
Cholinergic

33. Toxidrome? Cholinergic Symptoms:
bronchorrhea, confusion, defecation, diaphoresis, diarrhea, emesis, lacrimation, miosis, muscle fasciculations, salivation, seizures, urination, and weakness, bradycardia, hypothermia, and tachypnea.
Substances that may cause this toxidrome include carbamates, mushrooms, and organophosphates.

34. Cholinergic Toxidrome
Common mnemonic:
SLUDGE
Salivation, Lacrimation, Urination, Diarrhea, Gastrointestinal distress, and Emesis
DUMBBELLS
Diarrhea, Urination, Miosis, Bradycardia, Bronchorrhea, Emesis, Lacrimation, Lethargy and Salivation

35. Treatment

36. Treatment 2-PAM (pralidoxime) and atropine
“reactivates” acetylcholinesterase so that it can again break down Ach
Atropine works in conjunction with this (competitive antagonist for M receptor)

37. Case 5
66 yo Farmer who presents obtunded. Found by a family member in the garage. Family was very worried about him because he wasn’t “acting right.” Was slurring his speech initially. Per EMS, became more unresponsive in the rig.

38. PE 110, 100/68, 30, 100% RA, 98.7F General: obtunded
HEENT: pupils midrange, reactive
CV: tachy, no murmurs
Resp: no wheeze/rhonchi
Skin: dry
Neuro: normal m tone, no clonus

39. Workup EKG: sinus tachycardia BMP: Na 162 K 7.2 Cl 119 HCO3 4
BUN/Cr 18/3.04
Glucose 280

40. Workup, cont’d
ABG
6.7/24.8/90/4

41. Workup, cont’d
ABG
6.7/24.8/90/4
Osmolality
391
ETOH
0.0

42. What’s next?!

43. Calculations AG = Na - (Cl +HCO3)
Calculated osmolality = 2 x [Na mmol/L] + [glucose mg/dL /18] + [urea mg/dL /2.8]
Osmolar gap = measured osm - calculated
A normal osmol gap is < 10 mOsm/kg

44. Calculations, cont’d AG = 39 Osmolar gap = 391 - 346 = 45
What’s causing the gap?

45. Ethylene Glycol Toxicity
Found in antifreeze
Tastes sweet (bad for babies and animals)
Metabolites cause high AG acidosis
Ca oxalate crystals form in kidneys causing ARF
Antidote: fomepizole

46. Case 6
20 yo F with hx of depression brought by mother after she said she took “a handful” of OTC Tylenol after getting a text that her boyfriend was breaking up with her.

47. PE 98.8, 86, 20, 98%,120/90 General: Alert, tearful, NAD
HEENT: pupils midrange, reactive
CV: RRR, no m/r/g
Resp: no wheeze/rhonchi
Skin: warm, well perfused
Neuro: normal m tone, no clonus

48. What do you need to know?

49. What do you need to know? 1 hour prior to arrival
Pt texted her friend right after ingestion and friend called pts mother right after

50. What do you want to do now?!

51. Initial Labs BMP: Na 136, K 4.3, Cl 106, HCO3 20, BUN/Cr normal
EKG normal
APAP 250 mcg/ml
Alk phos 87, Tbili 0.3, AST 21, ALT 25

52. Should we start N-Acetylcystine (NAC)?
No. 4 hour APAP level should be drawn if certain of time of ingestion.

53. 4 hour APAP level
APAP 80 mcg/mL

54. Rumack-Matthew Nomogram
Published 1975
Based on a retrospective analysis of previous APAP overdoses and their clinical outcomes
Original line at 200mcg/mL, but moved to 150 at urging of FDA
200 still the treatment threshold in Europe

55. APAP metabolism

56. N-Acetylcystine Provides a substrate for sulfation
Regenerates glutathione (GSH)
GSH reduces NAPQI, allowing it to be cleared via the kidneys

57. Other indications for NAC
Unknown time of ingestion and a serum APAP concentration >10 mcg/mL OR evidence of liver injury (elevated AST/ALT)
Pts with delayed presentation (>24 hours after ingestion) with lab evidence of liver injury and a history of excessive APAP ingestion

58. Other toxidromes Sedative-hypnotics ASA toxicity Benzos, alcohol, GHB
Supportive care
ASA toxicity
Elevated everything (BP, pulse, RR, temp)
Bicarb gtt, dialysis