Toxic Alcohols

1
Toxic Alcohols

• John Kashani D.O.
• Attending, St. Josephs Emergency Department
• Staff Toxicologist, New Jersey Poison Center

2
Case

• An 18 year old male is brought into the ED by his
  mother when he was difficult to awaken in the AM
• He was partying the night before, he is not able
  to provide a history
• He becomes progressively more obtunded while in
  the ED

3
Case

• A 22 year old frustrated medical student drinks a
  bottle of formaldehyde he stole from gross
  anatomy lab
• He complains of throat and esophageal irritation
  and has had multiple episodes of emesis

4
Case

• A 65 year old man is found comatosed
• His wife states that he has been depressed
  recently and has been drinking heavily
• An empty bottle of antifreeze was found in his
  kitchen garbage can

5
Case

• A 17 year old female ingests a bottle of rubbing
  alcohol
• She appears drunk, has multiple episodes of
  emesis and complains of abdominal pain

6
Case

• A 25 year old man presents to the ED with blurry
  vision
• For the past few days he has been feeling
  cruddy
• He admits to the ingestion of homemade everclear
  3 days prior

7
Objectives

• Outline the toxic alcohols and potentially
  toxic alcohols
• Discuss the pharmacology, kinetics and
  pathophysiology of the toxic alcohols
• Discuss the clinical manifestations, diagnosis
  and management of patients poisoned by these
  agents

8
Introduction

• Alcohols are hydrocarbons that contain a hydroxyl
  group
• A compound with two hydroxyl groups is called a
  diol or a glycol
• Toxic alcohols commonly refer to methanol,
  ethylene glycol and isopropyl alcohol

9
Introduction

• Less common but potentially toxic alcohols
  include diethylene glycol, benzyl alcohol and the
  glycol ethers

10
(No Transcript)
11
Ethylene Glycol

• Coolant mixtures
• Antifreeze
• Air craft de-icing solutions
• Solvent (inks, pesticides and adhesives)
• Brake fluid
• Heat exchangers and condensers
• Glycerin substitute

12
Propylene glycol

• Commonly used as a diluent for parental
  preparations
• Environmentally safe alternative to ethylene
  glycol antifreeze

13
Benzyl alcohol

14
Methanol

• Antifreeze (window washer fluid)
• Anti icing agent
• Octane booster
• Ethanol denaturant
• Extraction agent
• Solvent
• Fuel source

15
Methanol

• Varnish and paint removers
• Industrial solvent
• Manufacture of acetic acid, formaldehyde and
  inorganic acids

16
Isopropanol

• Synthesis of acetone, glycerin
• Solvent for oils, gums and resins
• Deicing agent
• Rubbing alcohol
• Hair care products, skin lotion and aerosols

17
Diethylene glycol

• Solvent
• Sprinkler antifreeze
• Paints, cosmetics

HEAA

18
Glycol ethers

• Solvents
• Semiconductor industry
• Fingernail polishes and removers
• Dyes, ink, cleaners, degreasers
• Brake fluid, car wax, injector cleaner
• Various household cleaning products

19
Pharmacology and Kinetics

• Exposure may occur dermally, pulmonary and GI
• Pulmonary absorption depends on vapor pressure
• Rapidly absorbed by the gastrointestinal route

20
Pharmacology and Kinetics

• Time to peak concentration
• Ethylene glycol 1 - 4 hrs
• Methanol, isopropyl alcohol 30 - 60 minutes
• VD is 0.6L/kg

21
Pharmacology and Kinetics

• Ethylene glycol and methanol are metabolized by
  alcohol dehyrogenase and aldehyde dehydrogenase
• Isopropanol is metabolized by alcohol
  dehydrogenase
• Binding affinities for
• ethanolgtmethanolgtethylene glycol

22
Pharmacology and Kinetics

• Methanol metabolism may be delayed (up to 72
  hours)
• The volatility of methanol contributes to its
  pulmonary excretion (10-20)
• Ethylene glycol is metabolized over 3 8 hours
• Undergoes multiple oxidations

23
Pharmacology and Kinetics

• Ethylene glycol is not appreciably excreted by
  the lungs
• Isopropanol is rapidly metabolized to acetone via
  alcohol dehyrogenase
• 20 is excreted unchanged
• Acetone is predominantly renally excreted

24
(CH2OH)2
Ethylene glycol
ADH
CH2OHCHO
Glycoaldehyde
ADH
CH2OHCOOH
Glycolic Acid
ADH
Glyoxylic Acid
CHOCOOH
thiamine
B6
Oxalic Acid
Mg
Glycine Benzoic Acid
Alpha-hydroxy-beta-ketoadipic acid
Hippuric Acid
25
CH3OH
Methanol
ADH
Formaldehyde
CH2O
ADH
CHOOH
Formic Acid
Folate
CO2 H2O
26
Isopropyl alcohol
CH3CHOHCH3
ADH
CH3COCH3
Acetone
27
The Usual Suspects
28
Formic acid

• Metabolic acidosis
• Inhibits cytochrome oxidase
• Decreased ATP production
• Increased anaerobic glycolysis lactate

29
NAD
NADH H
R-OH
ADH
30
NADH H
NAD
Lactate
Pyruvate
NAD
CO2
NADH H
NADH
Acetyl-CoA
NAD
31
Clinical Manifestations

• Clinical manifestations may be related to the
  parent compound or metabolites
• There may be an initial asymptomatic period
• Inebriation (unreliable)
• Isopropylgtethylene glycolgtmethanol

32
Clinical Manifestations

• Vasodilation hypotension and reflex tachycardia
• Hypoglycemia
• Anion gap acidosis
• Methanol and ethylene glycol
• Visual disturbances (snow Field)
• Formic acid is a retinal toxin

33
Clinical Manifestations

• ATN may develop secondary to calcium oxalate
  crystalluria
• Cranial nerve deficits have been reported with
  ethylene glycol

34
Clinical Manifestations

• Ispopropanol ingestion usually does not cause
  major toxicity unless a large amount is ingested
• CNS depression, hemorrhagic gastritis and
  tracheobronchitis

35
Diagnosis

• Both ethylene glycol and methanol result in an
  anion gap acidosis
• Isopropyl alcohol usually does not result in an
  anion gap acidosis
• Hypocalcemia may be seen in ethylene glycol
  intoxication
• Chelation of calcium by oxalate calcium oxalate
  crystals

36
Diagnosis

• The absence of crystals is an unreliable finding
• The urine of a patient with ethylene glycol
  ingestion may fluoresce
• Short lived, unreliable

37
Calcium oxalate Crystals
38
The Osmolar Gap

• Measured Serum Osmolarity

Minus
Calculated Serum Osmolarity
2(NA) BUN/2.8 Glucose/18Etoh/4.6
39
At 100 mg/dl
40
(No Transcript)
41
AG
mOsm
mEq/L
OG
0
Time since Ingestion
42
Quantitative testing

• If quantitative levels are readily available they
  can be used to determine proper management
• Best method is gas chromatography with flame
  ionization
• Subject to false positives

43
Management

• ABCs
• /---- NGT aspiration
• AC/ipecac/lavage Bad move
• Thiamine and pyridoxine in the setting of
  ethylene glycol toxicity
• Folic acid in the setting of methanol toxicity

44
Management

• Sodium bicarbonate as needed
• Inhibition of Alcohol dehydrogenase
• Ethanol
• Fomepizole

45
Ethanol vs Fompepizole

• Ethanol
• - Oral or IV
• - CNS depression
• - Difficult titration
• - Frequent levels
• - Hypoglycemia

• Fomepizole
• - IV
• - No CNS depression
• - Easy dosing
• - No levels to monitor
• - More predictable
• pharmacokinetcs
• - No Hypoglycemia
• - Cost

46
Fomepizolebecause shit happens
47
(CH2OH)2
Ethylene glycol
X
ADH
CH2OHCHO
Glycoaldehyde
ADH
Glycolic Acid
CH2OHCOOH
ADH
Glyoxylic Acid
CHOCOOH
Thiamine 100 mg IV/day
B6 100 mg/day
Oxalic Acid
Mg
Glycine Benzoic Acid
Alpha-hydroxy-beta-ketoadipic acid
Hippuric Acid
48
CH3OH
Methanol
X
ADH
Formaldehyde
CH2O
ADH
Formic Acid
CHOOH
Folate
CO2 H2O
49
Case

• An 18 year old male is brought into the ED by his
  mother when he was difficult to wake up in the AM
• Apparently he was partying the night before, he
  is not able to provide a history
• He becomes progressively more obtunded while in
  the ED

50
Case

• A 22 year old frustrated medical student drinks a
  bottle of formaldehyde he stole from gross
  anatomy lab
• He complains of throat and esophageal irritation
  and has had multiple episodes of emesis

51
Case

• A 65 year old man is found comatosed
• His wife states that he has been depressed
  recently and has been drinking heavily
• An empty bottle of antifreeze was found in his
  kitchen garbage can

52
Case

• A 17 year old female ingests a bottle of rubbing
  alcohol
• She appears drunk, has multiple episodes of
  emesis and complain of abdominal pain

53
Case

• A 25 year old man presents to the ED with blurry
  vision
• For the past few days he has been feeling
  cruddy
• He admits to the ingestion of homemade everclear
  3 days prior

54
Toxic alcohol Pearls

• Calcium oxalate crystals, renal failure
  ethylene glycol
• Snow field vision methanol
• Methanol has a slower metabolism and there may be
  a significant lag until the onset of symptoms
• A normal osmolar gap does not rule out the
  diagnosis

55
Toxic alcohol Pearls

• ketosis without acidosis isopropyl alcohol
• Inhibition of alcohol dehydrogenase with
  fomepizole

56
The End