Alcohol:
Pharmacology, Toxicology
and Medico-legal aspects
Teri Martin
teri.martin@jus.gov.on.ca
October 14, 2003
Outline
• Pharmacology and toxicology of alcohol
• Absorption, distribution and elimination in the body
• Stages of alcohol intoxication
• Tolerance
• Alcohol in breath, blood, and urine
• Alcohol and driving impairment
• Effects of alcohol on memory
Types of Alcohol
• Ethanol (ethyl alcohol, grain alcohol)
• Methanol (methyl alcohol, wood alcohol)
• Isopropanol (isopropyl alcohol, rubbing alcohol)
• Ethylene glycol
Routes of Administration
• Topical
• Inhalation
• Intravenous injection
• Oral ingestion
Absorption
• Absorption of ethanol is by simple diffusion
• 25% of an ingested dose of ethanol is
absorbed from the stomach
• 75% of an ingested dose of ethanol is
absorbed from the small intestine
Factors affecting absorption
Alcohol concentration of the ingested beverage
•
Optimal absorption occurs for beverages with
alcohol concentrations between 10% alc. v/v
and 30% alc. v/v
•
•
Beverages <10 % alc. v/v do not present as large a
concentration gradient
Beverages >30% alc. v/v will irritate the gastric
mucosa and increase mucous production
Factors affecting absorption
Physiology
• Changes in blood supply to the GI tract
• Changes in motility will affect the speed
with which ethanol enters the small
intestine
Factors affecting absorption
Presence of food in the stomach
• Food in the stomach will prolong gastric
emptying time, resulting in a lower, delayed
peak blood alcohol concentration
Effect of food on absorption
120
100
80
With food in stomach
60
40
20
Time
300
250
220
200
140
120
100
60
50
20
0
0
Blood Alcohol Concentration
Empty stomach
Distribution
• Alcohol is hydrophilic and will distribute into
fluids and tissues according to water content
• Total body water (TBW) is dependent upon
• Age
• Sex
• Body weight
Examples
Effect of sex:
Effect of weight:
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•
Man weighing 150 lbs
Woman weighing 150 lbs
Each consume 2 beer
BAC of the man will be
57 mg/100 mL
• BAC of the woman will
be 67 mg/100 mL
Man weighing 150 lbs
Man weighing 200 lbs
Each consume 2 beer
BAC of the lighter man
will be 57 mg/100 mL
• BAC of the heavier man
will be 43 mg/100 mL
Alcohol Metabolism
• 5-10% of ingested ethanol is excreted
• Biotransformation occurs in the liver
• Commences as soon as EtOH is absorbed
• Alcohol dehydrogenase is primary enzyme
Ethanol
Alcohol dehydrogenase
Acetaldehyde
Aldehyde dehydrogenase
Acetic Acid
CO2 + H2O
Elimination
• Elimination of alcohol from the blood:
•
•
•
•
Follows zero-order kinetics
Ranges from 10-20 mg/100 mL/hour
Average rate of elimination is 15 mg/100 mL/hour
Is fixed and unaffected by:
• coffee
• exercise
• showering
• sleep
• eating
• fresh air
Fructose
• There is scientific agreement that fructose
can increase the elimination rate of alcohol
• However – the required intake of fructose is
so high that vomiting and abdominal pains
result from the ingestion
Effects of Alcohol on the Body
“One day I stumbled across a case of
bourbon… and kept stumbling for several
days thereafter.”
- W.C. Fields
Effects of Alcohol on the Body
• Vasodilatation
• Creates a feeling of warmth when alcoholic
beverages are consumed
• Contributes to paradoxical undressing in
hypothermia deaths
• Disinhibition
• Responsible for the “stimulant” effects of alcohol
• Euphoria,  talkativeness,  sociability
Effects of Alcohol on the Body
• Central nervous system depressant
• Non-selective depression of brain and spinal cord
• Effects occur on a continuum - with increased
BAC, increased effects occur
• Sedated  Sleepy  Stuporous  Unconscious
• Effects are additive with other CNS depressants
Stages of Alcohol Intoxication
See also: Table 2, Chapter 10. Levine, 1999. p. 177
10–50
• Slight intoxication
mg/100 mL • May be no observable signs of intoxication
• Laboratory testing may reveal some effects
30-120 • Mild euphoria,  sociability, talkativeness
mg/100 mL • Increased self confidence,  inhibitions
• Sensory perception  (e.g. hearing)
• Loss of fine motor skills
• Slowed information processing
Stages of Alcohol Intoxication
90–250 • Emotional instability (dissatisfaction)
mg/100 mL • Mental confusion
• Memory impairment
• Impaired balance and coordination
• Sedation, drowsiness
180-300 • Disoriented to time and place,  confusion
mg/100 mL • Exaggerated emotional state
• Double-vision
• Motor incoordination worsens, apathy
• Anesthesia
Stages of Alcohol Intoxication
250-400 • Loss of motor function
mg/100 mL • Response to stimuli 
• Stupor, unconsciousness
• Vomiting, incontinence
• Hypothermia
350-500 • Unconsciousness  Coma
mg/100 mL • Depression of reflexes
• Impairment of respiration, circulation
• Death
Alcohol and Death
• Primary mechanism for death due to acute
alcohol intoxication is respiratory depression
• Average BAC at which respiratory paralysis
occurs is 350 mg/100 mL
• Death can occur at much lower BAC where
aspiration of vomit occurs
Positional Asphyxia
• Alcohol intoxication is the major risk factor for
positional asphyxiation. Central nervous system
depression causes relaxation of the muscles that
keep the airway open during sleep
• Average BAC in 23 cases of positional
asphyxiation was reported to be 240 mg/100 mL
(Bell et al. 1992)
Tolerance
• Chronic use of alcohol will result in a decreased
susceptibility to the effects of alcohol
• Visible signs of intoxication are decreased
• Increased survivability even after consumption of
large amounts of alcohol
• Tolerance to alcohol may be either functional
and/or metabolic in nature
Functional Tolerance
• Decreased sensitivity to the CNS depressant
effects of EtOH
• e.g. Integrity of phospholipid bilayer 
• e.g. Up-regulation of excitatory receptors
• Requires higher BAC and higher doses of EtOH
to produce the same effect
• “Learning” by the chronic alcohol user
Metabolic Tolerance
• Induction of enzymes in chronic, heavy users
of alcohol can result in an enhanced
metabolic rate
• Elimination rate in alcoholics has been
measured at 40 mg/100 mL/hour and up
• Result is a comparatively lower BAC after
equivalent doses of alcohol are ingested
Example: Tolerance
Urso et al. 1981. Life Sciences. 28: 1053-1056.
• Measured range of BAC in 65 patients who had
been deemed “non-intoxicated” by examining
physician
• Ambulatory
• Alert, capable of passing mental status exam
• Responsible for self
• Blood alcohol concentrations ranged from
undetectable to 540 mg/100 mL (average BAC
was 268 mg/100 mL)
Alcohol in Blood, Breath and Urine
Alcohol in Blood
• Plasma and serum are the “watery” components
of whole blood
• Plasma and serum therefore have a higher
alcohol content than whole blood
• Plasma:whole blood ratio ranges from
approximately 1.0 to 1.3. Average plasma:whole
blood ratio is 1.14
Case Example
• An individual suspected of driving while
impaired is brought to the hospital for medical
treatment following a car accident in which his
2 passengers were badly injured
• Blood is drawn at the hospital for medical
purposes and hospital laboratory results reveal a
serum alcohol concentration of 17 mmol/L
• Police would like to know if they can charge
this individual with driving over the legal limit
Over 80?
• 17.5 mmol/L  80 mg/100 mL
• Serum:blood =1.14
• Therefore, a serum alcohol concentration of
80 mg/100 mL indicates a whole blood
alcohol concentration of 70 mg/100 mL
• This individual is not “over 80” at the time
the blood sample is drawn
Alcohol in Urine
• Alcohol will pass from the blood into the
urine as the blood is filtered in the kidneys
• Urine contains approximately 1.3x as much
water as blood, therefore the UAC will be
1.3 times that of the BAC.
Alcohol in Urine
• Urine is stored in the bladder for a period of
time before it is voided.
• The UAC therefore represents the BAC
sometime prior to collection of the urine
sample.
Analytical Considerations
Ethanol losses during storage can occur by three
mechanisms:
1. Diffusion from improperly sealed containers
2. Metabolism of ethanol by microorganisms
3. Oxidation of ethanol  acetaldehyde
Proper storage conditions will minimize the loss
of ethanol
Analytical Considerations
• Neo-formation of ethanol during storage can
occur if there is a source of microbial
contamination and a suitable substrate for
fermentation (e.g. glucose)
• More likely to occur in postmortem cases but can
also occur in samples taken from living subjects
• Sodium fluoride will prevent the neo-formation
of ethanol during storage
Example Case
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Woman, early 20’s
Sexually assaulted
Blood alcohol level = 0 mg/100 mL
Urine alcohol level = 105 mg/100 mL
Blood alcohol sometime prior to collection
of the urine sample was 80 mg/100 mL
Further history…
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Non-drinker, mentally challenged
Lived in a group home, no access to alcohol
Poorly controlled diabetic
Yeast infection
Sugar + Yeast  Ethanol
The woman had not necessarily been drinking; part
or all of the ethanol detected in the urine may have
been formed after collection of the sample.
Alcohol in Breath
• Alcohol is volatile - at physiological
temperatures alcohol will diffuse from the
blood into the alveolar air of the lung and
into the breath
• Breath analysis is rapid, non-invasive, and
does not require specialized medical
personnel for sampling
Henry’s Law
• At a given temperature, the ratio of the
concentration of a volatile compound in solution
and the concentration of the volatile compound
in the air above the solution is fixed
• At 37°C, the amount of alcohol in the blood will
be 2300x greater than the amount of alcohol in
the end-expiratory breath
Issues in Breath Testing
Quality of the breath sample
• End-expiratory breath is the best reflection
of the alcohol content of the blood
• A “poor quality” breath sample will result in
an underestimate of blood alcohol
concentration
Issues in Breath Testing
Mouth alcohol effect
• Residual alcohol, temporarily trapped in the
mouth may result in an elevated breath
alcohol concentration
• Sources of mouth alcohol
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•
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Recent ingestion of alcohol
Regurgitation or vomiting
Asthma inhalers
Breath sprays and mouthwashes
Mouth alcohol effect
• Since the mouth alcohol effect will dissipate
within 15 minutes, observation of a subject
for a minimum of 15 minutes will protect
against artificially elevated breath alcohol
results
• Duplicate breath testing is a further
safeguard against mouth alcohol effect
Behavioural Effects of Alcohol
Alcohol and Driving
• Laboratory studies
• Simulator studies
• Closed-course studies
• Epidemiological studies
Laboratory studies
• Test the effect of alcohol on skills that are
related to the operation of a motor vehicle
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Choice reaction time
Visual tracking
Vigilance
Glare recovery
Closed-course studies
• Test the effect of alcohol on subjects driving
real cars on closed-driving courses
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Parking tasks
Emergency-braking tasks
Pylons on curves
Width judgment
Epidemiological studies
• Compare the BAC in drivers who have had
accidents with the BAC of drivers who have
not had accidents
• Grand Rapids study by Robert Borkenstein,
inventor of the Breathalyzer, conducted in
1964
Grand Rapids Study
Borkenstein et al. 1974. Blutalkohol. 11: 7-13
• 80 mg/100 mL - 4x 
• 100 mg/100 mL - 7x 
• 150 mg/100 mL - 25x 
Relative Probability
• Relative probability of
causing an accident
increases exponentially
with  BAC
50
45
40
35
30
25
20
15
10
5
0
0 20 40 60 80 100 120 140160
BAC (mg/100 mL)
Effects of Alcohol on Driving
• At low BAC the faculties required for
driving that are impaired are:
• Judgment
• Ability to divide attention
• Choice reaction time
Effects of Alcohol on Driving
• With increasing BAC, the nature and the
extent of impairment will increase
• Impairment of other faculties, including:
• Tracking
• Vision
Alcohol and Driving
• In addition to the BAC, driving impairment
will also be affected by:
• Skills of the driver
• Driving task
• Tolerance to alcohol
Alcohol and Memory
1. Memory loss may be characterized by
forgotten events, later recoverable, either
when brought to the individual’s attention
or spontaneously
2. Memory loss may be non-recoverable;
characterized by feelings of “lost time”,
also known as an alcoholic blackout
Alcohol Blackout
• Amnesia for events occurring during any
part of a drinking episode
• Not associated with a loss of consciousness
• May vary in length from hours to days
• More common among alcoholics
• Typically associated with high BAC
• Rapid rise in BAC may contribute
“Reminds me of my safari in Africa...
Somebody forgot the corkscrew and for several
days we had nothing to live on but food and
water.”
- W.C. Fields