ALCOHOL

ethanol, methanol and ethylene glycol

By Ghaida al Daoud
Contents
• Definition
• Dangers of Drunkenness
• Drinking & Driving
• pharmacokinetics
• Measuring Alcohol
• Effects of Alcohol
• Acute & chronic alcoholism
**********
• Ethanol
• Methanol
• Ethylene glycol
• ‫القانون األردني‬
Definition
Alcohols are organic chemicals that have
hydroxyl groups.
There are an extremely large number of such
compounds based on the simplicity of this
definition. However , only a small number of
the low molecular weight alcohols are
encountered clinically , they include :
Ethanol , Methanol, Ethylene glycol
isopropanol, and very rarely, n-propanol or butanol.
How Manufactured ?
1. Fermentation 12%-15%
– Sugar to Alcohol and Carbon
dioxide
C6H12O6→ 2(CH3-CH2-OH) + 2CO2
(Yeasts +sugar + water = CO2 + ethanol)

• Yeasts are living micro-organisms that contain special enzymes

responsible for this rxn , which die in concentrations of alcohol
greater than 10 to 15%.

Starch Convertase Maltose

• Commercially - obtained from Mollases
2.Distillation: 40-60%

since yeast cannot survive in high levels of alcohol , then we

need another way which is distillation. Fermented drinks
are distilled to create vodka , rum and other spirits.

Distillation relies on ethanol having a lower boiling point

than water. When the fermented drink is heated the
ethanol vaporises at 78.5 degree and the water is left
behind (water vap at 100 degree) , then the ethanol gas is
caught and cooled so it condenses into a stronger
concentration of ethanol liquid.
 Alcohol and forensic medicine
• Alcohol assumes an importance in clinical forensic
medicine because of its link with criminal
activity.

• Traffic accidents, suicide, and rape are correlated

with the concurrent use of alcohol.

• Child physical and sexual abuse, spouse abuse ,

and elder abuse are also associated with alcohol use.

*1 Spousal abuse : is a form of abuse in which someone targets his or her spouse, with
the goal of creating and demonstrating control.
While many people think of physical violence when they hear the words “spousal
abuse,” this type of abuse is not necessarily physical in nature, and in fact it
includes a very complex emotional component.
Dangers of Drunkenness
• Respiratory paralysis.
• Accidents: RTA, pedestrian(‫(مشاة‬victims,
falling down.
• Burning, drowning.
• Vomiting: stimulates vagal nerve or simple
mechanical obstruction.
• Police, acute poisoning.
• Liver disease: fatty change fibrosis cirrhosis
 splenomegally, portal hypertension,
varices, GI bleeding.
Drinking & Driving
• Deterioration of driving skills occurs at BAC of 30
mg/dl.
• British Isles have a BAC limit of 80 mg/100 mL in
blood, 35 mg/100mL in breath or 107 mg/100 mL in
urine.
• Over half the drivers charged with excess alcohol
have more than twice the legal limit in their breath
or blood.

• Statutory limit?
If no  clinical testing
If yes blood (doctor) +
breath/urine(police officers)
Scheme of examination for
impairment of ability to drive
• Not to see if drunken, but to see if he can control
a vehicle.
• Not sufficient alone, you need samples.
• Informed consent, if not obtained depend on
your observations.
• The patient has the right to choose his doctor.
• Don’t delay the test for more than ½ hour.
Scheme of examination for
impairment of ability to drive
• History: mainly past medical history
& drug history.
• Orientation, demeanor
• Recent drink: amount, type, timing
• Long term drinking
• Write, draw
• Pick up an object from the floor better than
walking a chalk-line
Scheme of examination for
impairment of ability to drive
• Watch the patient undressing
• Routine exam
• Focus on: scalp,eyes,skin,vitals&smell
• Blood sample: Antecubital fossa ,
no alcoholic antiseptic 5 ml, tube containing
NaF, with or without potassium oxalate
(anti-coagulant) .
Send the sample directly to the lab or put in the
refrigerator at 5 degrees Celsius - 3 samples .
Alcohol pharmacokinetics

Absorption Distribution

Metabolism Elimination
Alcohol Absorption
• Most absorption of alcohol takes place in the
stomach ,duodenum and first part of the
jejunum (the last two part are the most effective).

• A single bolus of alcohol taken into an empty

stomach will be completely absorbed into the portal
bloodstream within 30–90 minutes.

• As soon as alcohol enters the bloodstream, the liver

and kidneys will begin to eliminate it, so the peak
blood-alcohol concentration (BAC) achieved
will be governed by  the relative rates of
absorption and elimination.
 Factors
increasing
absorption
1. Empty stomach, as fluid
passes through the pylorus
with almost no delay.
2. Gastrectomy (alcohol go
faster to the small intestine
where higher absorption
happens).
3. 10-20% concentration
of alcohol. Optimum for
rapid absorption.
Factors
decreasing
absorption
1. Food in the stomach
(especially fatty food which
delay the emptying of the
stomach and dilutes alcohol
concentration).
2. High concentration of
alcohol (higher
concentration than 20% will
irritate the stomach and
increase mucous secretion).
Alcohol effect on Male / female
It has been shown that the sexes differ in the amounts of
metabolizing enzymes they possess within the stomach
wall.

Men have higher quantities of alcohol-oxidizing enzyme

so that the alcohol, while passing through the stomach into
the blood, is converted to metabolites (which are not CNS
depressant ).

Women have lesser amounts of these enzymes so more of

the alcohol reaches the blood as un-metabolized alcohol.
This phenomenon also explains why women are affected
by alcohol not only more extensively than men but sooner
after drinking .
Alcohol Distribution
After absorption, alcohol is distributed uniformly throughout the body
into the various organs in proportion to the water content of each.
This also is related to the high water miscibility of alcohol.

Alcohol distributes partly into the alveoli of the lungs. Alcohol

also crosses the blood–brain barrier readily. Alcohol readily
crosses the placenta in a pregnant woman, a phenomenon that
may cause a potentially serious disorder known as fetal alcohol
syndrome.

*1 Fetal alcohol syndrome (FAS) is a pattern of mental and physical defects that can
develop in a fetus in association with high levels of alcohol consumption during pregnancy,
The main effect of FAS is permanent CNS damage.

• Distributed through portal blood stream to all tissues.

• Equilibrium between the blood and tissues is reached 1-2

hours after ingestion .
Factors that affect blood alcohol
concentration (BAC):
• Absorption ?

• Body fat content.

The higher the fat content, the higher the BAC. (Smaller
volume of body water , so less dilution and more BAC).

• Duration of drinking. If the volume of alcohol is consumed

over a prolonged period, it may be eliminated almost as
quickly as it is absorbed, giving rise to a much lower peak
alcohol concentration.
*1 unit of alcohol will elevate BAC within the 1st hour by
15mg/100ml in men and 20mg/100ml in women.
How fast you drink. The quicker you drink, the higher your peak BAC will be.=
duration
• Body weight: more blood and water >> dilute the
alcohol.

• Temperature of the drink: Warm alcohol is absorbed

quicker than cold alcohol.

• Women reach higher BAC’s faster because they have

less water in their bodies and more adipose tissue (fat), which
is not easily penetrated by alcohol.

• Type of mixer used : Water and fruit juices mixed with

alcohol slow the absorption process, while
carbonated beverages will speed it up. Carbon dioxide
speeds the alcohol through the stomach and intestine
into the bloodstream, creating a rapid rise in BAC.
Metabolism of alcohol

The fates of alcohol include excretion into the

urine unchanged, exhalation from the
lungs unchanged, and excretion without
metabolism through the skin.
However, the major part of an alcohol load, at
least 90%, is metabolized by the liver. That
alcohol provides high energy to the body large
amounts of energy-rich adenosine triphosphate
( ATP ) that arise from alcohol.
When alcohol is consumed, it
passes from the stomach and
intestines into the blood, a
process referred to as
absorption.
Alcohol is then metabolized by
enzymes, which are body
chemicals that break down
other chemicals.
In the liver, an enzyme called
alcohol dehydrogenase (ADH)
mediates the conversion of
alcohol to acetaldehyde.
Acetaldehyde is rapidly
converted to acetate by other
enzymes and is eventually
metabolized to CO2+H2O.
Alcohol also is metabolized in
the liver by the enzyme
cytochrome P450IIE1 (CYP2E1),
which may be increased after
chronic drinking .Most of the
alcohol consumed is
metabolized in the liver, but the
small quantity that remains
unmetabolized permits alcohol
concentration to be measured in
breath and urine.
The liver can metabolize
only a certain amount of
alcohol per hour,
regardless of the amount
that has been consumed.
* The liver gets rid of alcohol at the
average rate of one drink per hour (12 oz.
beer, 5 oz. wine, 1shot of distilled liquor).
In general, after the consumption of
one standard drink, the amount of
alcohol in the drinker's blood (blood
alcoholism
alcohol concentration, or BAC) peaks
within 30 to 45 minutes. Liver Gluconeogenesis
Glycogen substrate
(A standard drink is defined as 12 depletion
depletion
ounces of beer, 5 ounces of wine, or
1.5 ounces of 80-proof distilled
spirits, all of which contain the same
amount of alcohol). hypoglycemia
Alcohol is metabolized more slowly
than it is absorbed. Since the
metabolism of alcohol is slow,
consumption needs to be controlled coma
to prevent accumulation in the body
and intoxication.
Elimination of alcohol
Alcohol is eliminated by liver metabolism at a
constant rate until a relatively low level is
reached beyond which the elimination continues but
at a rate which depends on the concentration.

Some alcohol is eliminated into the urine unchanged.

Tests for urinary alcohol are sometimes conducted to
determine whether the subject has been drinking
recently.

only 2-10% being excreted unchanged by

kidneys, lungs, sweat, salivary and mammary
glands.
 The rate of elimination from the bloodstream
varies in different people:

chronic alcoholics, particularly who have

induced liver cytochrome P450 enzymes (until their
livers fail) can metabolize alcohol at an
abnormally high rate.

The ‘normal’ rate of elimination

from the blood for non-alcoholics lies between about
11 and 25mg/100 mL/h, with an average of
18 mg/100 mL/h :
 this can eliminate approximately 1 unit of
alcohol (8 g) per hour. 1 unit = 1 hour
Measuring Alcohol
• Calculating units of alcohol
-method 1:
1 unit = 1 small glass of wine
= 1 half-pint of beer
= 1 short of spirits
-method 2:
1 unit = 25 ml of 40% alcohol
= 10 ml ethanol
X% proof = X units of alcohol per liter
Examples:
1 liter of 40% proof spirit = 400 ml ethanol or 40 units
750 ml (standard bottle) = 30 units
1 liter of 4% beer = 40 ml ethanol or 4 units
500 ml can contain 2 units of alcohol
Online calculator: https://www.drinkaware.co.uk/understand-your-
drinking/unit-calculator
• Beer is an alcoholic beverage produced by
the saccharification of starch and fermentation of
the resulting sugar. The starch and saccharification
enzymes are often derived from malted cereal
grains, most commonly malted barley and malted
wheat.
• Wine is an alcoholic beverage made
from fermented grapes or other fruits.
• spirit drinks possess particular organoleptic
qualities and have a minimum alcoholic strength of
15 % vol.
• Alcohol proof is a measure of how
much alcohol (ethanol) is contained in an alcoholic
beverage. alcoholic proof is defined as twice the
percentage of ABV.
 Measuring Alcohol
• The concentration of alcohol in both blood
and urine is usually expressed in …
(mg/100 mL)(mg/dl)

• The BAC is the most useful measure, because the

rapid equilibration of alcohol across the blood–
brain barrier means that the BAC reflects the
concentration of alcohol currently affecting the
brain.
Alcohol – Percentage Calculations
• Alcohol content of beverages:
– specific gravity of alcohol is 79
– Therefore, 1 litre alcohol weighs 790g
– Percent may be by weight or by volume

• By volume:
– 1 litre alcohol add 1 litre water = 50% (vol)
• By weight:
– 1 litre alcohol (790g), add 790g water = 50% (weight)

40% alcohol by weight = 50% by volume

 =
+
1litre water 1litre alcohol
2 litres 50% (volume)

+ =
1 kilo water 1 kilo alcohol
2 kilos 50% (weight)

40% alcohol by weight = 50% by volume

Drink % alcohol

Beer, stout, cider 3-6%

Table wine 9-12%

Sherry, port (fortified with brandy) 17-21%

Spirits (whisky, brandy, rum, gin, 35-45%

vodka,…)
• The concentration of alcohol must be written on
the labels of most bottles containing it.

• It is usually written in the form of weight of

alcohol per volume of liquid (w/v), rather than
as volume of alcohol per volume of liquid,
because alcohol has an appreciably lower
specific gravity than water; for example 40% v/v
whisky only has about 32 g per 100 mL.
‘Safe?’ Alcohol Concentration
• Males up to 21 units weekly
• Females up to 14 units weekly
 Measurement of absorbed alcohol
• In blood: it is the most useful measurement, but
depends on several factors like gender, drinking history,
amount and nature of the meal and the timing, so it’s not
very accurate.

• In urine: it is more concentrated than blood. Ratio 4:3,

due to tubular resorption of water.

• In breath: small concentration 1:2300 to that of blood.

At 37 C 1mg/100ml in blood = 0.43 µg/100ml in breath.

* Blood/breath ratio depends on the temperature,

concentration of alcohol and depth of respiration.
Measuring Alcohol levels at Autopsy…
• In both criminal and civil disputes, evidence is often sought as
to the alcoholic state of the deceased at some material time,
based on calculations made from blood or urine alcohol
analyses taken at autopsy.

• Forensic pathologists tend to deal in a whole blood. At

autopsy, one should obtain the blood from either the
femoral or subclavian vessels, with the former
preferred.

• Aside from blood, the best material to analyze for alcohol is

vitreous (The vitreous is a thick, transparent substance that
fills the center of the eye. It is composed mainly of water ) ,
Vitreous, with a high water content, has
proportionally more alcohol than blood when at
equilibrium. Thus, at equilibrium, for every unit of
alcohol in blood, there are 1.2 units of alcohol in
vitreous.
Measuring Alcohol levels at autopsy
• Thus, the vitreous alcohol levels provide a
method for looking back in time. They will tell
what the blood alcohol level was 1–2 h
prior to death .

• After vitreous, the next-best tissue to analylze for

alcohol is muscle. We prefer muscle from
the thigh . A blood to muscle ratio of 0.94 ±
0.086 when blood alcohol concentration was
greater than 0.10 g/dL; 1.48 ± 0.13 with blood
alcohols less than 0.10 g/dL.
Adverse Effects of Alcohol
• Acute Effects
▫ Nausea, Vomiting, hangover and traffic accidents
▫ CNS Depression
▫ Depression of inhibitory control
▫ Vasodilatation, warm, flushed, reddish skin
▫ Emotional outbursts
▫ Decreased memory & concentration
▫ Poor judgment
▫ Decreased reflexes
▫ Decreased sexual response
Guide to the Likely Effects of Alcohol
on a Normal Adult
Blood-alcohol Effects
concentration
(mg/dL)

30–50 Impairment of driving and similar skills

50–100 Reduced inhibitions, talkativeness, laughter, slight

sensory disturbance

100–150 In coordination, unsteadiness, slurred speech

150–200 Obvious drunkenness, nausea and ataxia

200–300 Vomiting, stupor, possibly coma

300–350 Danger of aspirating vomit, stupor or coma

350–450 Progressive danger of death from respiratory paralysis

Consequences of acute
Alcohol intoxication
- images

Hangover

Vomiting Car accidents Loss of inhibitions

Effects of alcohol consumption (acute)
• Impaired performance, slowing of reflexes and fine
discrimination impaired
• Induces sleep – but not ideal hypnotic
• Analgesic – but no ideal analgesic
• Anticonvulsant – but not ideal anticonvulsant

• Mechanism:

– GABAA receptor mediated synaptic inhibition by chloride

channel opening
– Inhibition of NMDA (N-methyl D-asparticacid) excitatory
amino acid receptor
– Stimulates 5-HT3 receptors
Effects of alcohol consumption (acute)
CNS
***Alcohol depresses the nervous system and any
apparent initial excitant effect is due to suppression
of inhibition by the cerebral cortex.

*** The drug begins to act at the lowest concentrations

upon the higher centres and it affects the lower
centres of the central nervous system only
when the BAC becomes higher.

*** The effects of high levels of alcohol on the lower

centres may jeopardize the function of the
cardiorespiratory centres in the brainstem,
with a consequent danger of death.
 Effects of alcohol consumption - Acute
• CNS:
▫ depressant – dose dependent manner
Plasma concentration Expected effects

30 – 100 mg/dl Anxiolytic, euphoria and excitation

Hesitation, restraint, caution are lost
Impaired coordination – mood and feelings are
altered
100 -150 mg/dl Mental clouding, ataxia, disorganization of thought
and impairment of memory and drowsiness

150 – 200 mg/dl Sloppy, ataxia and drunkenness

- Slurring of speech, loss of judgment and inhibition

200 – 300 mg/dl Stupor and unconsciousness

Effects of alcohol consumption (acute) - contd.
• CVS:
• Small doses – cutaneous vasodilatation, flushing
• Medium dose – tachycardia and mild rise in BP
• Large dose - Vasodilatation due to direct vascular
smooth muscle dilatation and vasomotor centre
depression (clinical implication)
• Respiration:
• Stimulation of Respiration – by irritation of pharyngeal
and buccal mucosa
• Central action – depression
• Blood:
• Moderate drinking increases HDL-cholesterol level
• Decrease in LDL oxidation
 Effects of alcohol consumption (acute)
- contd.
GIT :
Dilute alcohol at low doses -
stimulate GI secretion – flavour,
aroma or direct action on gastrin
secretion
Higher doses inhibit GI secretion
Acute consumption –
pylorospasm, gastritis, vomiting,
reflux etc…
Mallory-Weiss lesion
Effects of alcohol consumption (acute)
– contd.
• Kidney: Diuresis – increased water ingestion and
inhibition of ADH
• Uterus: Relaxation of uterine muscles
• Endocrine:
 Low dose – Adrenaline release and hyperglycemia
 High dose – Hypoglycemia
• Sex – Aphrodisiac ( increase in sexual desire ) .
• Acute Alcohol Intoxication:
▫ Estimated ED 50: 150 mg/100 ml and LD 50 = 500
mg/100ml
▫ Therapeutic index about 3.5
▫ Hypotension, hypoglycemia, respiratory depression
coma and death.
▫ Death due to respiratory depression or inhaled vomit.

▫ Treatment:
 Gastric lavage
 Endotracheal intubations
 Fluid and electrolyte balance
 Glucose infusion
 Thiamine injection 100 mg in 500 ml of glucose IV
 Haemodialysis
Toxic Effects - Chronic Alcoholism
• GIT:
▫ Gastritis and damage to the mucosa – anemia
▫ Intestinal damage: Lack of absorption - Deficiency of
water soluble vitamins and amino acids (protein
deficiency) .
▫ Less or no food intake (enough calorie) - Vitamin and
Protein deficiency

(Q. Is Alcohol a total food ? Answer: No - Lacking in total

food value)
Chronic Alcoholism – contd.
• Liver cirrhosis – scarring
of liver
▫ Usually fatal if drinking is not
stopped
 Fatty infiltration (excess
in NADH)
 Oxidative stress and
cellular necrosis
 Damage to hepatocytes
and inflammation –
aldehyde
 Glutathione depletion
 Microsomal enzyme
induction
 Chronic Alcoholism – contd.
• Neurological: Polyneuritis, pellagra (Pellagra is
a vitamin deficiency disease most commonly caused by a chronic lack of niacin (vitamin B3)),
tremors, seizures, loss of brain mass, Korsakoff`s
psychosis and Warnicke`s encephalopathy

• CVS: Hypertension, cardiomyopathy, CHF

arrhythmias and stroke

• Hormonal: Impotence, gynecomastia and

infertility

• Acute pancreatitis
 Chronic Alcoholism – contd.
• Reproduction
▫ Alcohol is a teratogenic , it causes birth defects.
▫ Fetal Alcohol Syndrome (FAS) or Fetal Alcohol
Effects (FAE), or Alcohol-Related Birth Defects
(ARBD)
▫ Symptoms include : retardation, poor
coordination, loss of muscle tone, low birth
weight, slow growth, malformation of internal
organs and peculiar facial characteristics.
Fetal Alcohol Syndrome (FAS)
Characteristics
Growth retardation
Facial malformations
Small head
Greatly reduce intelligence
 Chronic Alcoholism – features
• Craving: A strong need, or compulsion, to drink

• Loss of control: The inability to limit one’s drinking on any given

occasion

• Tolerance: The need to drink greater amounts of alcohol in order

to “get high” – toxicokinetic or cellular tolerance

• Physical dependence: Withdrawal symptoms (long acting BZDs

like chlordizepoxide and diazepam ,Naltrexone (50 mg) ), such as
nausea, sweating, shakiness, sleep impairment, hallucinations,
delirium tremens and anxiety, occur when alcohol use is stopped
after a period of heavy drinking
 Disulfiram (Antabuse)
• Internationally marketed as antabuse
• ALDH ( aldehyde dehydrogenase ) enzyme inhibitor
• Alcohol + disulfiram rise in concentration of aldehyde in
blood and tissue distressing aldehyde syndrome
▫ Symptoms:
▫ flushing,
▫ burning sensation,
▫ throbbing headache,
▫ perspiration,
▫ dizziness,
▫ vomiting,
▫ visual disturbance,
▫ mental confusion,
▫ fainting and circulatory collapse
• Uses: aversion technique in chronic alcoholics: only
to motivate persons by discouraging drinking.

▫ Technique: abstain alcohol overnight and start with 1

gm on day 1 followed by 0.75 gm next day and 0.50 gm
next day and so on. Effects start within few hrs of 1st
dose and lasts for 2 weeks

▫ Mechanism: irreversible inhibition of ALDH and

synthesis of new enzyme takes time and thus person
resolves not to drink for distressing symptoms

• Available as 250 mg tablets

Alcohol withdrawal
 Sudden discontinuation after chronic high-
level alcohol use … causes headache, anxiety,
palpitations, and insomnia . Brief, generalized
seizures may occur, usually within 6–12 hours.

Sympathetic nervous system overactivity may

progress to delirium tremens, a lifethreatening
syndrome charecterized by tachycardia, diaphoresis,
hyperthermia,and delirium, which usually manifests
48–72 hours after cessation of heavy alcohol use.
Ethyl Alcohol
(Ethanol)
• Besides being found in commercial beer, wine, and
liquors . Ethanol is also found in a variety of perfumes,
after-shaves , mouthwashes and many food flavorings
(eg, vanilla, almond, and lemon extracts)

• pharmaceutical preparations (eg, elixirs)

• Ethanol is the most common co-ingestant with other

drugs in suicide attempts.

• Ethanol may also serve as an antidote in the

emergency treatment of …
methanol & ethylene glycol poisonings.
Mechanism of toxicity of ethanol
1- CNS depression

• the principal effect of acute ethanol intoxication.

• Ethanol has additive effects with other CNS depressants such as
barbiturates, benzodiazepines, opioids, anti-depressant and anti-
psychotic.

2- Hypoglycemia …

• caused by impaired gluconeogenesis in patients with depleted

glycogen stores. particularly small children and poorly
nourished persons.

3- Trauma, injurious effects

• of alcohol on the gastrointestinal tract and nervous system, and a

number of nutritional disorders and metabolic derangements.
 Toxic dose of ethanol
0.7 g/kg pure ethanol (approximately 3–4 drinks)
will produce a blood ethanol concentration of 100 mg/dL,
legally considered intoxicated in many states.

A. level of 100 mg/dL  decreases reaction time and judgment

and may be enough to cause hypoglycemia in children
and patients with liver disease, but by itself is not
enough to cause coma.

B. The level sufficient to cause deep coma or respiratory

depression is highly variable, depending on the
individual’s degree of tolerance to ethanol.
Although levels >300 mg/dL usually cause coma in novice
drinkers (‫ )مبتدئ‬, chronic alcoholics may be awake with levels of
500–600 mg/dL or higher!!!
Clinical presentation of ethanol
Acute intoxication
1. Mild to moderate intoxication…
- Patients exhibit mild in coordination, ataxia, and impaired
judgment and reflexes.
- aggressive behavior.
- Hypoglycemia may occur

2. Deep intoxication…
- coma, respiratory depression, and pulmonary aspiration
may occur.
- In these patients, the pupils are usually small and the
temperature, blood pressure, and pulse rate are often decrease.
- Rhabdomyolysis may result from prolonged immobilization on a
hard floor.
Chronic ethanol abuse
1- Hepatic toxicity …
- fatty liver, alcoholic hepatitis, and cirrhosis.
- Liver scarring leads to portal hypertension, ascites,
and bleeding from esophageal varices and hemorrhoids.
- Production of clotting factors is impaired, leading
to prolonged prothrombin time (PT).

2. Gastrointestinal bleeding … from alcohol-induced

gastritis , esophagitis, and duodenitis.
- Other causes of massive bleeding include Mallory-
Weiss tears of the esophagus and esophageal
varices.
- Acute pancreatitis is a common cause of abdominal
pain and vomiting.
3. Cardiac disorders …
- various dysarhythmias and cardiomyopathy, which has
been associated with long-term alcohol use as well as with
ingestion of cobalt … (which was once used to stabilize
beer).

4. Neurologic toxicity …
- cerebral atrophy , cerebellar degeneration; and peripheral
stocking-glove sensory neuropathy.
- Nutritional disorders such as thiamine (Vitamin B-1)
deficiency.

5. Alcoholic ketoacidosis …
- Anion gap metabolic acidosis and elevated levels of
betahydroxybutyrate and, to a lesser extent, acetoacetate.
- The osmolar gap may also be elevated, causing this
condition to be mistaken for methanol or ethylene glycol
poisoning.
• A normal osmol gap is < 10 mOsm/kg
Osmol gap: difference between measured serum osmolality and calculated serum osmolarity.
Calculated osmolality = 2 x [Na mmol/L] + [glucose mmol/L] + [urea mmol/L]
Diagnosis of ethanol
• Often Simple Diagnosis based on…
*** the history of ingestion.
*** the characteristic smell of fresh alcohol or the fetid odor of
acetaldehyde and other metabolic products.
*** the presence of nystagmus, ataxia, and altered mental status.
*** It is imperative to consider other etiologies that may accompany or
mimic intoxication, such as hypoglycemia, head trauma or
intoxication with other drugs or poisons.

 Specific levels.
Serum ethanol levels are easily and rapidly determined by most hospital
laboratories and, depending on the method used, are accurate and
specific.
1. In general, there is only rough correlation between blood levels and
clinical presentation; however, an ethanol level below 300 mg/dL in a
comatose patient should initiate a search for alternative causes.
2. If ethanol levels are not readily available, the ethanol concentration
may be estimated by calculating the osmolar gap
Suggested laboratory studies
include glucose, electrolytes, BUN, creatinine,
liver transaminases, prothrombin time (PT),
magnesium, arterial blood gases or oximetry,
and chest x-ray (if pulmonary aspiration is
suspected).
Consider CT scan of the head if the patient has
focal neurological deficits or altered mental
status inconsistent with the degree of blood
alcohol elevation.
Treatment of ethanol
Emergency and supportive
measures
1. Acute intoxication… Treatment is mainly
supportive.

a. Airway protection … to prevent aspiration and intubate and

assist ventilation if needed .
b. Give glucose and thiamine and treat seizures if they occur.
c. Correct hypothermia with gradual rewarming .

***Most patients will recover within 4–6 hours.

***Observe children until their blood alcohol level is below
50 mg/dL and there is no evidence of hypoglycemia.
2. Alcoholic ketoacidosis… Treat
with volume replacement, thiamine, and
supplemental glucose …Most patients recover
rapidly.

3. Alcohol withdrawal… Treat with

benzodiazepines (eg, diazepam)

Specific drugs and antidotes

 There is no available specific ethanol
receptor antagonist, despite reports of arousal
after administration of naloxone.
Decontamination
1. Prehospital. Do not induce vomiting or
administer activated charcoal.
2. Hospital. Because ethanol is rapidly absorbed,
gastric lavage is usually not indicated unless
other drug ingestion is suspected. Consider
lavage only if the alcohol ingestion was massive
and recent (within 30–45 minutes). Activated
charcoal does not effectively adsorb ethanol but
may be given if other toxins were ingested.
Enhanced elimination
Metabolism of ethanol normally occurs at a fixed
rate of approximately 20–30 mg/dL/h.
Elimination rates are faster in chronic alcoholics
and at serum levels above 300 mg/dL.
Hemodialysis efficiently removes ethanol, but
enhanced removal is rarely needed because
supportive care is usually sufficient.
Hemoperfusion and forced diuresis are not
effective
Methyl Alcohol (Methanol)
*** Methanol (wood alcohol) is a common ingredient
in many solvents, windshield-washing solutions and
paint removers.

*** It is sometimes used as an ethanol substitute by

alcoholics.

*** Methanol metabolic products may cause

metabolic acidosis, blindness, and death after
a characteristic latent period of 6–30 hours.
Methanol
• Methanol is physically similar to ethanol. It is
absorbed rapidly, distribute in bodily tissues
in proportion to their water content.

The lethal dose is : approximately 1g/kg ,

which makes methanol approximately 4
times as toxic as ethanol.
Mechanism of toxicity of methanol
♣ Methanol is slowly metabolized by alcohol
dehydrogenase to formaldehyde and subsequently
by aldehyde dehydrogenase to formic acid (formate).

♣ Systemic acidosis is caused by the formic

acid as well as by lactic acid, while blindness
is caused primarily by formate.

♣ Both ethanol and methanol compete for the

enzyme alcohol dehydrogenase; the
preference of this enzyme for metabolizing
ethanol forms the basis for ethanol therapy
in methanol poisoning.
Toxic dose of methanol
*** The fatal oral dose of methanol is estimated to be
30–240 mL (20–150 g).

• The minimum toxic dose is approximately 0.1

g/kg.

• Elevated serum methanol levels have been reported after

extensive dermal exposure and concentrated inhalation.

• The recommended workplace exposure limit for

inhalation is 200 ppm as an 8-hour time-weighted
average.
Clinical presentation of methanol
1. In the first few hours after ingestion methanol-
intoxicated patients present with…

- inebriation and gastritis.

- Acidosis is not usually present because
metabolism to toxic products has not yet
occurred.
- elevation in the osmolar gap.
(an osmolar gap of as little as 10 mOsm/L is consistent
with toxic concentrations of methanol.)
2. After a latent period of up to 30 hours
severe anion gap metabolic acidosis, visual
disturbances, blindness, seizures, coma, and
death may occur.

*** Patients describe the visual disturbance as

haziness or “like standing in a snowfield”.
 Fundoscopic examination may reveal optic
disc hyperemia, venous engorgement, or
papilledema.
 The latent period is longer when ethanol has
been ingested concurrently with methanol.
Q: explain effect of methanol on eye
In severe poisoning vision is affected, with 43% of
patients experiencing blurring of vision and 11%
suffering blindness. This is due to two phenomena:

first, the methanol enters the vitreous humor

extensively because of the extremely aqueous nature
of that medium.
second, retinol dehydrogenase, an enzyme involved
in normal vision, is able to nonspecifically oxidize
methanol to formaldehyde.
Diagnosis of methanol
Based on …
- the history, symptoms, and laboratory
findings .
- Calculation of the osmolar and anion
gaps can be used to estimate the methanol
level and to predict the severity of the
ingestion .
- A large anion gap not accounted for elevated
lactate suggests possible methanol poisoning,
because the anion gap in these cases is
mostly non lactate .
Specific levels
1. Serum methanol levels >20 mg/dL  considered
toxic,
levels >40 mg/dL  considered very serious.

2. Elevated serum formate concentrations may

confirm the diagnosis and are a better measure of
toxicity, but formate levels are not yet widely available.

Other useful laboratory studies

include electrolytes, glucose, BUN, creatinine, serum
osmolality
and osmolar gap, arterial blood gases, ethanol level, and
lactate level.
Treatment of methanol
Emergency and supportive
measures

1. Maintain Airway (assist ventilation if

necessary )
2. Treat coma and seizures if they occur
3. Treat metabolic acidosis with intravenous
sodium bicarbonate .

Correction of acidosis should be guided by

arterial blood gases.
Specific drugs and antidotes
1. Administer fomepizole or ethanol to saturate the
enzyme alcohol dehydrogenase and prevent the formation of
methanol’s toxic metabolites.

 Therapy is indicated in patients with the following:

a. A history of significant methanol ingestion, when methanol
serum levels are not immediately available and the osmolar
gap is > 5 mOsm/L.
b. Metabolic acidosis and an osmolar gap > 5–10 mOsm/L not
accounted for by ethanol.
c. A methanol blood concentration >20 mg/dL.

2. Folic acid may enhance the conversion of formate to

carbon dioxide and water. A reasonable dose is 50 mg IV
every 4 hours.
Decontamination
1. Prehospital. Do not induce vomiting.

2. Hospital. Perform gastric lavage. Activated

charcoal has not been shown to efficiently
adsorb methanol in vivo.
Enhanced elimination
• Hemodialysis rapidly removes both methanol (half-
life reduced to 3–6 hours) and formate.
• The indications for dialysis are suspected methanol
poisoning with significant metabolic acidosis, an
osmolar gap greater than 10 mOsm/L, or a
measured serum methanol concentration greater
than 40 mg/dL.
• Dialysis should be continued until the methanol
concentration is less than 20 mg/dL.
• Note: The ethanol infusion must be increased
during dialysis
Ethylene glycol Alcohol

• The primary ingredient (up to 95%) in

antifreeze. It is sometimes intentionally
consumed as an alcohol substitute by alcoholics
and is tempting to children because of its
sweet taste.
Mechanism of toxicity Ethylene
(Glycol) Alcohol
Ethylene glycol is metabolized by alcohol dehydrogenase
to glycoaldehyde, which is then metabolized to
glycolic, glyoxylic, and oxalic acids.

These acids, along with excess lactic acid, are responsible for
the anion gap metabolic acidosis.

Oxalate readily precipitates with calcium to form insoluble

calcium oxalate crystals.

 Tissue injury is caused by widespread deposition of

oxalate crystals and the toxic effects of glycolic and
glyoxylic acids.
Toxic dose of Ethylene
(Glycol) Alcohol

*** The approximate lethal oral dose of

95% ethylene glycol (eg, antifreeze) is 1.5
mL/kg;
 however, survival has been reported after an
ingestion of 2 L in a patient who received
treatment within 1 hour of ingestion.
Clinical presentation of Ethylene
(Glycol) Alcohol
1. During the first 3–4 hours after acute
ingestion…
- the victim may appear intoxicated as if by ethanol.
- The osmolar gap increase.
- Gastritis with vomiting may also occur.

2. After a delay of 4–12 hours…

***evidence of intoxication by metabolic products occurs,

with: anion gap acidosis, hyperventilation, convulsions,
coma, cardiac conduction disturbances, and arrhythmias.

***Renal failure is common but usually reversible.

***Pulmonary edema and cerebral edema may also occur.
***Hypocalcaemia with tetany has been reported.
Diagnosis of Ethylene (Glycol) Alcohol
• Usually based on…
- the history of antifreeze ingestion
- typical symptoms
-  osmolar and anion gaps
- Oxalate crystals may be present in the urine

- Because many antifreeze products contain

fluorescein, the urine may fluoresce under Wood’s
lamp, depending on the amount ingested, the time
since ingestion, and the urine concentration.

* Fluorescein is a synthetic organic compound available as a dark orange/red powder

soluble
 Diagnosis of Ethylene (Glycol) Alcohol
1- Specific levels.

a.Serum levels higher than 50 mg/dL are usually associated with

serious intoxication,
 Calculation of the osmolar gap may be used to estimate the ethylene glycol
level

b.False-positive ethylene glycol levels can be caused by elevated

triglycerides

c.In the absence of a serum ethylene glycol level

if the osmolar and anion gaps are both normal
the patient is asymptomatic

other useful laboratory studies :

Crystalluria
include electrolytes, glucose, BUN, creatinine, serum osmolality and osmolar
gap, and arterial blood gases or oximetry.
 Treatment of Ethylene (Glycol)
***Emergency and supportive
measures

1. Maintain Airway (assist ventilation ,

administer supplemental oxygen if necessary)
2. Treat coma ,convulsions ,cardiac arrhythmias
& metabolic acidosis if they occur.
3. Treat hypocalcemia with intravenous
calcium gluconate or calcium chloride
Specific drugs and antidotes
(1) Administer fomepizole or ethanol to saturate the
enzyme alcohol dehydrogenase and prevent metabolism
of ethylene glycol to its toxic metabolites.

 Indications for therapy include the following:

a. Ethylene glycol level >20 mg/dL.
b. History of ethylene glycol ingestion accompanied by an
osmolar gap >5 mOsm/L not accounted for by ethanol or
other alcohols.
c. Anion gap acidosis accompanied by a history of glycol
ingestion or presence of oxalate crystalluria or positive
Wood’s lamp examination of urine.

(2) Administer pyridoxine ,folate, and thiamine…

cofactors required for the metabolism of ethylene glycol
that may alleviate toxicity by enhancing metabolism of
glyoxylic acid to nontoxic metabolites.
Decontamination
Because isopropyl alcohol is rapidly absorbed after
ingestion, gastric emptying procedures are not likely to
be useful if the ingestion is small (a swallow or two) or
if more than 30 minutes has passed.

• For large ingestions:

1. Prehospital. Administer activated charcoal if
available. Do not induce vomiting because of the risk of
rapidly developing coma.
2. Hospital. Administer activated charcoal. Although
isopropyl alcohol adsorbs poorly to charcoal,
approximately 1 g of charcoal will bind 1 mL of 70%
alcohol. Consider gastric lavage for very large recent
ingestions.
Enhanced elimination

1. Hemodialysis effectively removes isopropyl

alcohol and acetone but is rarely indicated
because the majority of patients can be
managed with supportive care alone.
• Dialysis is indicated when levels are
extremely high (eg, > 500–600 mg/dL) or if
hypotension does not respond to fluids and
vasopressors.

2. Hemoperfusion, repeat-dose charcoal, and

forced diuresis are not effective.
 ‫القانون األردني‬
‫المادة ‪ -25‬ب‪ :‬يعاقب بالحبس مدة ال تقل عن شهر وال تزيد على ثالثة‬
‫أشهر او بغرامة ال تقل عن (‪ )250‬مائتين وخمسين دينارا وال تزيد‬
‫على (‪ )500‬خمسمائة دينار او بكلتا هاتين العقوبتين كل من ارتكب‬
‫أيا من المخالفات التالية‪:‬‬
‫‪ -1‬قيادة المركبة تحت تأثير المشروبات الكحولية بنسبة تزيد على‬
‫الحد المسموح به لتركيز الكحول في الدم وفق التعليمات الصادرة‬
‫لهذه الغاية‪.‬‬
‫‪ -2‬تناول السائق المشروبات الكحولية أثناء القيادة‪.‬‬
‫‪ -3‬تناول مدرب السواقة المشروبات الكحولية أثناء التدريب‪.‬‬
Thank you for your patience