1. Specific Toxins
Part I

2. Acids Examples Severe burning of stomach Absorption, systemic acidemia
Toilet bowl cleaner
Rust remover
Phenol (carbolic acid)
Hydrochloric acid
Severe burning of stomach
Absorption, systemic acidemia

3. Acids Loss of airway = most immediate threat
Secure airway against edema
IV with LR, NS for volume loss
Emesis, gastric lavage contraindicated
Dilution with water, milk NOT recommended

4. Alkalis Examples Severe burning of esophagus, stricture formation
Drain cleaner
Washing soda
Ammonia
Lye (sodium hydroxide)
Bleach (sodium hypochlorite)
Severe burning of esophagus, stricture formation

5. Alkalis Loss of airway = most immediate threat
Secure airway against edema
IV with LR, NS for volume loss
Emesis, gastric lavage contraindicated
Dilution with water, milk NOT recommended

6. Hydrocarbons Examples Kerosene Gasoline Lighter fluid Turpentine
Furniture polish

7. If the patient is coughing, aspiration has occurred
Hydrocarbons
Signs/Symptoms
Choking, coughing, gagging
Vomiting, diarrhea, severe abdominal pain
Chemical pneumonitis, pulmonary edema
If the patient is coughing, aspiration has occurred

8. Hydrocarbons Signs/Symptoms Euphoria, confusion/anxiety, seizures
Increased myocardial irritability, arrhythmias (adrenergic agents may cause V-fib)
Liver damage, hypoglycemia

9. Hydrocarbons Management 100% oxygen with good humidification IV tko
Monitor ECG
Drug therapy
D50W for hypoglycemia
Diazepam for seizures
Antiarrhythmics

10. Hydrocarbons Inducing emesis controversial
Should NOT be induced with low viscosity hydrocarbons

11. Hydrocarbons
If ingestion has occurred recently, emesis probably should be induced with:
Halogenated hydrocarbons (carbon tetrachloride)
Aromatic hydrocarbons (toluene, xylene, benzene)
>1cc/kg gasoline, kerosene, naptha
Petroleum products with toxic additives (lead tetraethyl, pesticides)

12. Seek advice of medical control and poison control center
Hydrocarbons
Seek advice of medical control and poison control center

13. methyl alcohol wood alcohol wood naphtha
Methanol
methyl alcohol
wood alcohol
wood naphtha

14. Methanol Sources Industry Household solvents Paint remover
Fuel, gasoline additives
Canned heat
Windshield washer antifreeze

15. Methanol Toxic dose Fatal oral: 30-240ml Minimum: 100 mg/kg Example
Windshield washer fluid 10% Methanol
10 kg child needs only 10 cc to be toxic

16. Methanol Mechanism of toxicity
Methanol slowly metabolized to formaldehyde
Formaldheyde rapidly metabolized to formic acid
Acidosis
Ocular toxicity

17. Methanol Metabolism H O C C H O H O C O C H Methanol Formaldehyde
Alcohol dehydrogenase C H O
Formaldehyde
Aldehyde dehydrogenase H O C
Formic Acid O C H + _

18. Methanol Overdose Presentation Inebriation Gastritis
Osmolar gap (osmolar gap as little as 10mOsm/L is consistent with methanol poisoning)

19. Methanol Overdose Presentation Latent period of up to 30 hours
Severe anion gap metabolic acidosis
Visual disturbances, blindness (“standing in a snowstorm”)
Seizures
Coma
DEATH

20. Methanol Management High concentration oxygen IV tko ECG monitor
if < 30 minutes lavage or induce emesis (if not done then it is probably useless)

21. Methanol Management Sodium Bicarbonate Folic acid
50mg IV every 4 hours
Helps convert formic acid to CO2, H2O
Give specific antidote

22. Methanol ETHANOL The specific antidote for methanol toxicity
10% EtOH solution in D5W
7.5 ml/kg loading dose and 1.5 ml/kg/hr maintenance
100 proof (50%) EtOH
1.5 ml/kg loading dose and 0.3 ml/kg/hr maintenance

23. Ethanol Metabolism H C O C H O H O C Ethanol Acetaldehyde Acetic Acid
Alcohol dehydrogenase C H O
Acetaldehyde
Aldehyde dehydrogenase H O C
Acetic Acid
Krebs Cycle

24. Alcohol dehydrogenase
Methanol X
Ethanol
Methanol
Alcohol dehydrogenase
Acetic Acid
Urine
CO2 + H2O + Energy

25. Methanol Specific antidote Fomepizole (4-methylpyrazole)
Inhibits alcohol dehydrogenase
Produces same end result as ethanol without causing intoxication

26. Ethylene Glycol Antifreeze (95% ethylene glycol) Tastes sweet
Kids, animals like taste/drink large quantities

27. Ethylene Glycol Mechanism of toxicity
Metabolized via alcohol dehydrogenase to glycoaldehyde then to glycolic , glyoxylic, and oxalic acids
Acids lead to anion gap metabolic acidosis
Oxalate binds with calcium
Forms crystals causing tissue injury
Produces hypocalcemia

28. Ethylene Glycol Toxic dose Approximate lethal oral dose: 1.5ml/kg
Example
10 kg child needs 15ml for lethal dose

29. Ethylene Glycol Overdose Presentation (first 3-4 hours)
Patient may appear intoxicated
Gastritis, vomiting
Increase in osmolar gap
No initial acidosis

30. Ethylene Glycol Overdose Presentation (after 4-12 hours)
Anion gap acidosis
Hyperventilation
Seizures, coma
Cardiac conduction disturbances, arrhythmias
Renal failure
Pulmonary, cerebral edema

31. Ethylene Glycol Management Lavage if within 2 hours Sodium bicarbonate
Fomepizole or ethanol
Folic acid, pyridoxine, thiamine (enhance metabolism of glyoxylic acid to nontoxic metabolites)

32. Cyanide

33. But first…
A little review of biochemistry and biophysics

34. Staying alive requires energy...
The natural tendency of the universe is for things to become more disorderly.
This trend toward disorder is called entropy.
Complex systems (including us) don’t tend to last long, unless…
They have a constant supply of energy to combat entropy.

35. Organisms capture and store the energy they need in the form of...
Adenosine Triphosphate (ATP)
The “currency” cells use to pay off the energy debt built up fighting entropy.
Formed by capturing energy released as the cell breaks down large molecules through glycolysis and the Krebs Cycle.

36. Glycolysis In cytoplasm Does not require oxygen
Breaks glucose molecule into two pyruvic acid molecules
Net gain of 2 ATP
If oxygen absent, pyruvate converted to lactate
If oxygen present, pyruvate changed to acetate (acetyl-CoA) and sent to Krebs Cycle

37. The Krebs Cycle In mitochondria Requires oxygen
Strips H+ and electrons off of acetate, leaving CO2
Sends the H+ and electrons to the electron transport chain

38. Electron Transport/Oxidative Phosphorylation
In mitochondria
Electrons pass down a series of carriers--losing energy as they go
It’s like a series of waterfalls
Energy is released and stored as ATP
Electrons and H+ bind to O2, making H2O
36 ATP produces per glucose molecule

39. Oxidative Phosphorylation
NAD
NADH2
ADP + Pi
ATP
FAD
FADH2
Ox. Cyt. b
Red. Cyt. b
ADP + Pi
ATP
Ox. Cyt. c
Red. Cyt. c
Ox. Cyt. a
Red. Cyt. a
ADP + Pi
ATP
Red. Cyt. a3
Ox. Cyt. a3
2H+
H2O
1/2O2

40. Putting It All Together
Cells have to have energy to stay alive.
Cells get energy by breaking down glucose in two phases: glycolysis and the Krebs Cycle.
Glycolysis yields 2 ATP and pyruvate.
Pyruvate is changed to acetate (acetyl-CoA) and sent to the Krebs Cycle.
The Krebs Cycle strips hydrogen and electrons off acetate and feeds them into the electron transport chain.
Movement of electrons down the transport chain releases energy which is trapped as ATP.
At the end of the chain, the electrons combine with hydrogen and oxygen to form water.

41. Cyanide Chemical, plastic industries Metallurgy, jewelry making
Blast furnace gases
Fumigants, pesticides
Present in various plants
apples, pears, apricots, peaches, bitter almonds

42. Cyanide Acrylonitrile is metabolized to cyanide
Nitroprusside (Nipride) if given too long is metabolized to cyanide
Acetonitrile in some fingernail glues has caused pediatric deaths
Cyanide is so common that all mammals have an enzyme called rhodonase that detoxifies cyanide by converting it to thiocyanate

43. Cyanide Mechanism of Toxicity Chemical asphyxiant
Inhibits functioning of cytochrome a3
Stops electron transport, oxidative phosphorylation
Blocks aerobic utilization of oxygen

44. Cytochrome A3
Cytochrome a
1/2 O2
2e-
Fe3+
Fe2+
2e-
2H+
H2O

45. Cyanide Toxicity
Cytochrome a
1/2 O2
2e- X
CN-
Fe3+
Fe2+
2e-
2H+
H2O

46. Cyanide Clinical Presentation
Variable onset speed with different forms
Headache, nausea, dyspnea, confusion
Rapid, weak pulse
Bright-red venous blood
Syncope, seizures, coma
Agonal respirations, bradycardia, cardiovascular collapse

47. Cyanide Management Treat all cases as potentially lethal
Support oxygenation, ventilation
ECG
IV tko
Cyanide Antidote Kit

48. Cyanide Antidote Kit Amyl nitrite, Sodium nitrite Sodium thiosulfate
Oxidize iron in hemoglobin from Fe2+ to Fe3+ (methemoglobinemia)
Methemoglobin binds cyanide, removing it from cells
Sodium thiosulfate
Provides rhodonase with sulfide anion
Speeds conversion of cyanide to thiocyanate

49. Cyanide Antidote Kit Cytochrome a Fe2+ NO2 - Fe3+ CN- SCN- 2e- Fe3+
H2O

50. Cyanide Antidote Kit Amyl nitrite, sodium nitrite Sodium thiosulfate
Only be used in serious cyanide poisonings
Can induce life-threatening tissue hypoxia secondary to methemoglobinemia
Sodium thiosulfate
Can be used by itself
Is relatively benign

51. Salicylates

52. Salicylates Examples Uses Aspirin Oil of wintergreen Analgesics
Antipyretics
Anti-inflammatories
Platelet function inhibitors

53. Salicylates Mechanism of Toxicity
Direct stimulation of respiratory center, causing respiratory alkalosis
Irritation of gastrointestinal tract, causing decreased motility, pylorospasm, nausea, vomiting, hemorrhagic gastritis
Decreased prothrombin levels/platelet dysfunction, causing prolonged clotting times
Uncoupling of oxidative phosphorylation

54. Aspirin Toxicity 2H NAD NADH2 Heat ADP + Pi FAD FADH2 Ox. Cyt. b
Red. Cyt. b
Heat
ADP + Pi X
Ox. Cyt. c
Red. Cyt. c
Ox. Cyt. a
Red. Cyt. a
Heat
ADP + Pi X
Red. Cyt. a3
Ox. Cyt. a3
2H+
H2O
1/2O2

55. Results of Oxidative Phosphorylation Uncoupling
ATP production decreases, resulting in CNS and cardiovascular failure.
Cells attempt to compensate by increasing the rate they process glucose anaerobically through glycolysis.
Lactic and pyruvic acids accumulate, leading to metabolic acidosis.
Hypoglycemia results as liver sugar stores are depleted.
In absence of sugar cells begin to metabolize lipids, ketone bodies are produced, acidosis worsens.
Energy normally trapped as ATP is wasted as heat, causing a rise in body temperature.
The rise in body temperature accelerates metabolism, increasing tissue oxygen demand and worsening acidosis.

56. Suspect in any child with sudden onset of tachypnea
Salicylates
Clinical Presentation: Acute Toxicity
Coma
Seizures
Hypoglycemia
Hyperthermia
Pulmonary edema
Vomiting
Lethargy
Hyperpnea
Respiratory alkalosis
Metabolic acidosis
Suspect in any child with sudden onset of tachypnea

57. Salicylates Clinical Presentation: Chronic Toxicity
Usually young children, confused elderly
Confusion, dehydration, metabolic acidosis
Higher morbidity, mortality than acute overdose
Cerebral, pulmonary edema more common

58. Salicylates Acute Toxicity Management Oxygen, monitor, IV
GI tract decontamination
Activated charcoal
Replace fluid losses, but do NOT overload
Control hyperthermia

59. Salicylates Acute Toxicity Management
Bicarbonate for metabolic acidosis
D50W for hypoglycemia
Diazepam for seizures

60. Acetaminophen

61. Acetamophen
Examples
Tylenol
Tempra
Datril
Uses
Analgesic
Antipyretic

62. Acetaminophen Mechanism of toxicity
N-acetyl p-benzoquinonimine, normal product of acetaminophen metabolism, is hepatotoxic
Normally is detoxified by glutathione in liver
In overdose, toxic metabolite exceeds glutathione capacity, causes liver damage

63. Acetaminophen Metabolism
Urine
Urine
Urine
2- 4%
28- 52%
45-55%
APAP-sulfate
APAP
APAP-glucuronide
2- 4%
P-450 MFO
2- 4%
N-acetyl-p-benzo-quinonimine
Cysteine Congugates
Urine
Glutathione

64. Acetaminophen Toxicity
Urine
Urine
Urine
APAP-sulfate
APAP
APAP-glucuronide
Hepatocyte Protein Congugates
N-acetyl-p-benzo-quinonimine
Cysteine Congugates
Urine
Glutathione
Cell Death

65. Acetaminophen Minimum toxic dose Adult: 7 grams Child: 140 mg/kg
Onset of symptoms is slow, initially non-specific
Stage Time Symptoms
I 1/2 to 24h Anorexia, NV, malaise, diaphoresis
II 24 to 48h Abdominal pain, liver tenderness, increased liver enzymes, oliguria
III 72 to 96h Peak enzyme abnormality, Increased bilirubin and PT
IV 4d to 2wk Resolution or progressive hepatic failure

66. Acetaminophen Management Induce emesis Do NOT give activated charcoal
Give specific acetaminophen antidote

67. MUCOMYST Acetaminophen
The specific antidote for acetaminophen toxicity.
MUCOMYST

68. Mucomyst N-acetylcysteine Another sulfur-containing amino acid
Substitutes for glutathione.
Allows continued detoxification of NAPBQI.
140mg/kg initially followed by 70mg/kg every 4 hours 17 times.
Tastes, smells like rotten eggs
Mix with chilled fruit juice to decrease odor, taste

69. Can Mucomyst (NAC) Be Given If The Patient’s Gotten Activated Charcoal?
AC and NAC are not given simultaneously
AC is given in the first 4 hours. NAC is given after 4 hours.
The effective dose of NAC is equal to the amount of APAP ingested.
Patients receive a total dose of 1330 mg/kg, so most are over-treated.
The reduction in NAC absorption caused by AC (8 to 39%) applies only to the first dose.
So the potential total decrease in absorption is 4.5%
A patient would have to ingest 1275 mg/kg for this to become a problem.