Alcohols

Alcohols
Prepared and Presented by: Majd Al-Qudah, MD.

Alcohols
Ethanol
Isopropanol
Methanol
Ethylene Glycol

Ethanol
Ethanol Alcohol is one of the most widely used drugs in the
world.

Ethanol Alcohol
 The degree to which the brain is affected by this central nervous
system depressant depends on how much, and how fast, a person
drinks.
 Due to the initial positive behavioral effects of alcohol, many people
don’t realize that the substance is a CNS depressant. For example,
when someone first begins to drink, he or she may feel less reserved
and more relaxed because of the chemical changes alcohol causes
within the brain.
 However, the more someone drinks, the more the brain is affected
and the likelihood that a negative emotional response will take over.
https://www.addictioncenter.com/drugs/drug-classifications/central-nervous-system-depressants/

Ethanol Alcohol
 Alcohol can actually increase anxiety and stress rather than reduce it,
and elicit other negative reactions such as anger, aggression, and depression.
 Chronic alcohol use can also lead to dependence, addiction, and withdrawal symptoms when
attempting to stop usage of the drug.
https://www.addictioncenter.com/drugs/drug-classifications/central-nervous-system-depressants/

Ethanol Alcohol
 Alcohol misuse is when you drink in a way that's harmful, or
when you're dependent on alcohol. To keep health risks from
alcohol to a low level, both men and women are advised not to
regularly drink more than 14 units a week.
 A unit of alcohol is 8g or 10ml of pure alcohol, which is about:
 half a pint of lower to normal-strength lager/beer/cider (ABV 3.6%)
 a single small shot measure (25ml) of spirits (25ml, ABV 40%)
 A small glass (125ml, ABV 12%) of wine contains about 1.5 units of alcohol.
https://www.nhs.uk/conditions/alcohol-misuse/

Ethanol Alcohol
Ethanol concentrations in some common alcoholic
beverages are as follows:
Whiskey, 40-60%
Liqueurs, 22-50%
Wine, 8-16%
Beer, 3-7%
Alcohol Toxicity, Updated: Nov 01, 2018 , Author: Michael D Levine, MD; Chief Editor: Jeter (Jay) Pritchard
Taylor, III, MD

Pathophysiology
• Ethanol has a volume of distribution (0.6 L/kg) and is readily distributed throughout the body.
The primary route of absorption is oral, although it can be absorbed by inhalation and even
percutaneously.
• Ethanol exerts its actions through several mechanisms.
o For instance, it binds directly to the gamma-aminobutyric acid (GABA) receptor in the CNS and causes
sedative effects similar to those of benzodiazepines, which bind to the same GABA receptor.
o Furthermore, ethanol is also an N -methyl-D-aspartate (NMDA (excitatory NT)) glutamate antagonist in
the CNS.
o Ethanol also has direct effects on cardiac muscle, thyroid tissue, and hepatic tissue.
Taylor, III, MD

Pathophysiology
Ethyl alcohol (ethanol; CH3 -CH2 -OH) is a low molecular
weight hydrocarbon that is derived from the fermentation
of sugars and cereals. It is widely available both as a
beverage and as an ingredient in food extracts, cough and
cold medications, and mouthwashes.
Alcohol Toxicity, Updated: Nov 01, 2018 , Author: Michael D Levine, MD; Chief Editor: Jeter (Jay) Pritchard Taylor, III, MD

Pathophysiology
Ethanol is rapidly absorbed across both the gastric mucosa and the
small intestines, reaching a peak concentration 20-60 minutes after
ingestion. Once absorbed, it is converted to acetaldehyde. This
conversion involves three discrete enzymes: the microsomal
cytochrome P450 isoenzyme CYP2E1, the cytosol-based enzyme
alcohol dehydrogenase (ADH), and the peroxisome catalase system.
Acetaldehyde is then converted to acetate, which is converted to acetyl
Co A, and ultimately carbon dioxide and water.

Pathophysiology
Genetic polymorphisms coding for alcohol dehydrogenase,
the amount of alcohol consumed, and the rate at which
ethanol is consumed all affect the speed of metabolism. As
a general rule, ethanol is metabolized at a rate of 20-25
mg/dL in the nonalcoholic but at an increased rate in
chronic alcoholics.

Mortality/Morbidity
Ethanol use is also strongly linked to other risk-
taking behaviors that can lead to minor trauma,
assault, illicit drug use.
alcohol is frequently linked with injuries
secondary to assault and motor vehicle crashes.
The intoxicated individual often engages in
high-risk activities, despite the fact that his or
her reflexes are substantially slowed.
Alcohol Toxicity, Updated: Nov 01, 2018 , Author: Michael D Levine, MD; Chief Editor: Jeter (Jay) Pritchard Taylor, III,
MD

Symptoms
• The symptoms of ethanol intoxication depend on both the serum
concentration as well as the frequency at which an
individual ingests ethanol. Thus, a person who consumes large amounts of
ethanol on a daily basis may appear sober at the same serum ethanol level at which a
novice drinker exhibits cerebellar dysfunction.
• As a general rule:
o levels less than 25 mg/dL are associated with a sense of warmth and well-being.
o Euphoria and decreased judgment occur at levels between 25-50 mg/dL.
o Incoordination, decreased reaction time/reflexes, and ataxia occur at levels of 50-100 mg/dL.
o Cerebellar dysfunction (ie, ataxia, slurred speech, nystagmus) are common at levels of 100-250
mg/dL.
o Coma can occur at levels of greater than 250 mg/dL,
o whereas respiratory depression, loss of protective reflexes, and death occur at levels greater than 400
mg/dL.
Taylor, III, MD

Laboratory Studies
 If ingestion of a toxic alcohol is suspected, a serum ethanol level and
basic electrolytes, including a serum bicarbonate level are vital, as
the latter are needed to calculate an anion gap.
 In addition, a blood sugar level should be obtained on anyone who
appears intoxicated.
Taylor, III, MD

Emergency Department Care
 As with all emergency patients, initial treatment should focus on the
airway, breathing, and circulation.
 Treatment of ethanol intoxication is largely supportive.
 B vitamins (ie, folic acid, pyridoxine, thiamine) may be useful in
selected cases to reduce the toxicity of alcohol metabolites.

Alcohol Dependence
 Disulfiram is used as a second line treatment,
behind acamprosate and naltrexone, for alcohol dependence
 Disulfiram (sold under the trade names Antabuse) is a drug used to support the
treatment of chronic alcoholism by producing an acute sensitivity
to ethanol (drinking alcohol). Disulfiram works
by inhibiting the enzyme acetaldehyde dehydrogenase, causing many of the effects
of a hangover to be felt immediately following alcohol consumption. Disulfiram plus
alcohol, even small amounts, produce flushing, throbbing in head and neck,
throbbing headache, respiratory difficulty, nausea, copious vomiting, sweating,
thirst, chest pain, palpitation, dyspnea, hyperventilation, fast heart rate, low blood
pressure, fainting, marked uneasiness, weakness, vertigo, blurred vision, and
confusion. In severe reactions there may be respiratory depression, cardiovascular
collapse, abnormal heart rhythms, heart attack, acute congestive heart failure,
unconsciousness, convulsions, and death
 Disulfiram does not reduce alcohol cravings, so a major problem associated
with this drug is extremely poor compliance.
Disulfiram From Wikipedia, the free encyclopedia

Alcohol Dependence
 Naltrexone has been shown to decrease the amount and frequency of
drinking.
 Naltrexone is an opioid antagonist and works by blocking the effects
of opioids, both those from inside and outside the body
 Acamprosate is thought to stabilize chemical signaling in the brain
that would otherwise be disrupted by alcohol withdrawal. When used
alone, acamprosate is not an effective therapy for alcoholism in most
individuals; studies have found that acamprosate works best when
used in combination with psychosocial support since it facilitates a
reduction in alcohol consumption as well as full abstinence.
 it is believed to act as an NMDA receptor antagonist and positive allosteric
modulator of GABAA receptors
Disulfiram From Wikipedia, the free encyclopedia

Pathophysiology
• Isopropyl alcohol (isopropanol; CH3 -CHOH-CH3) is a low
molecular weight hydrocarbon. It is commonly found as
both a solvent as well as a disinfectant. It can be found in
many mouthwashes, skin lotions, rubbing alcohol, and
hand sanitizers. Because of its widespread availability,
lack of purchasing restrictions, and profound intoxicating
properties, it is commonly used as an ethanol substitute.

Pathophysiology
Isopropanol is rapidly absorbed across the gastric mucosa
and reaches a peak concentration approximately 30-120
minutes after ingestion. Isopropanol is primarily
metabolized via alcohol dehydrogenase to acetone. A small
portion of isopropanol is excreted unchanged in the urine.
The peak concentration of acetone is not present until
approximately 4 hours after ingestion. The acetone
produces CNS depressant effects and a fruity odor on the
breath.

Exposure and toxicity
 exposures to isopropanol (from sources including rubbing
alcohol, cleaning agents, and hand sanitizers)
 The primary toxicity with isopropanol is CNS depression.
These CNS manifestations can include lethargy, ataxia,
and coma. In addition, isopropanol is irritating to the GI
tract. Therefore, abdominal pain, hemorrhagic gastritis,
and vomiting can be observed. Unlike methanol and
ethylene glycol, isopropanol does not cause a metabolic
acidosis.
 Most isopropanol ingestions occur in children younger
than 6 years.

History
 A history of inebriation with associated slurred speech, ataxia, and
impaired judgment is common in the initial stages of intoxication of
each of these alcohols. Depending on the dose ingested, this may be
followed by progressive levels of CNS depression, coma, and
premorbid multiorgan failure. The history that can be obtained
varies with the timing of presentation.
 Following an isopropanol ingestion, the patient may not complain of
anything specific. Rather, the patient may simply appear intoxicated,
as with ethanol intoxication.
 A history of abdominal pain, nausea, and sometimes hematemesis
may be obtained.

Physical examination
 The patient who consumes isopropanol may appear
inebriated, as with ethanol. Isopropanol concentrations of
50-100 mg/dl typically result in intoxication, which can
progress to include symptoms such as dysarthria and
ataxia, while lethargy or coma can be seen with levels
exceeding 150 mg/dl. Cardiovascular depression can occur
with levels exceeding 450 mg/dL.
 The presence of acetone may induce a fruity odor on the
patient's breath.

Laboratory workup
 If ingestion of a toxic alcohol is suspected, a serum
ethanol level and basic electrolytes, including a serum
bicarbonate level are vital, as the latter are needed to
calculate an anion gap.
 Arterial blood gases and other tests that measure
associated organ dysfunction also become important in
cases of poisoning with toxic alcohols.
 An important point is that laboratory abnormalities vary
dramatically over the course of the patient's presentation
and any laboratory abnormalities must be interpreted
with the time frame of the patient's presentation in mind.

Laboratory workup
 Early in the course of intoxication with a toxic alcohol, a
patient will have neither an anion gap nor an osmolar
gap though their serum toxic alcohol level will be highest
shortly after ingestion. However, as metabolism of the
toxic alcohol occurs, the anion and osmolar gaps develop
as metabolites are formed and the toxic alcohol level
drops.
 Other laboratory abnormalities also develop as end-organ
damage occurs. Coingestion of alcohol delays all the
laboratory value changes as well as the signs and
symptoms of toxic alcohol-induced injury.

Laboratory workup
 Serum levels of isopropanol can be obtained but are somewhat of
limited value, as the treatment is largely supportive. However, they
can be useful in confirming the diagnosis.
 Serum ketones will often be positive, although the patient should not
be acidotic. Because ketones will be present in the serum as early as
30 minutes after ingestion, if there is no coexisting ethanol ingestion,
the absence of ketones effectively rules out isopropanol ingestion.
 Depending on the assay used in the laboratory, significant ketosis
can cause interference with the creatinine assay. As such, the serum
creatinine level can be falsely elevated.

Management
• As with all emergency patients, initial treatment should focus
on the airway, breathing, and circulation. Gastric
decontamination is rarely necessary for any of the alcohols. An
exception to this may be a patient who presents immediately
after ingestion of a toxic alcohol in whom one might reasonably
expect to be able to recover a significant amount of the toxin
via aspiration through a nasogastric tube.
• Treatment isopropanol intoxication is largely
supportive. Because of the hemorrhagic gastritis that can
follow isopropanol ingestion, H2 blockade or proton-pump
inhibitors may be helpful. Hemodialysis, while effective, is
rarely indicated, and should only be used in the setting of
profound hemodynamic compromise.

Pathophysiology
Methyl alcohol (methanol; CH3 OH) is widely used as an
industrial and marine solvent and paint remover. It is also
used in photocopying fluid, shellacs, and windshield-
washing fluids. Although toxicity primarily occurs from
ingestion, it can also occur from prolonged inhalation or
skin absorption. Methanol is rapidly absorbed from the
gastric mucosa, and achieves a maximal concentration 30-
90 minutes after ingestion.

Pathophysiology
Methanol is primarily metabolized in the liver via alcohol
dehydrogenase into formaldehyde. Formaldehyde is
subsequently metabolized via aldehyde dehydrogenase into
formic acid, which ultimately is metabolized to folic acid,
folinic acid, carbon dioxide, and water. A small portion is
excreted unchanged by the lungs.

Pathophysiology
Formic acid is responsible for the majority of the toxicity
associated with methanol. Without competition for alcohol
dehydrogenase, methanol undergoes zero-order
metabolism, and is thus is excreted at a rate of 8.5
mg/dL/h to 20 mg/dL/h. Once methanol experiences
competitive inhibition, from either ethanol or fomepizole,
the metabolism changes to first order. In this later
scenario, the excretion half-life ranges from 22-87 hours.

Exposure And Toxicity
 exposures to methanol, including automotive products ( windshield
washer fluid).
 Most cases of methanol toxicity involve single patients. Rarely,
outbreaks may occur in settings where access to ethanol is limited
and methanol is consumed as a substitute.
 The toxicity with methanol occurs from both the ensuing metabolic
acidosis, as well as the formate anion (formic acid) itself. Although
the eye is the primary site of organ toxicity, in the later stages of
severe methanol toxicity, specific changes can occur in the basal
ganglia as well. Pancreatitis has been reported following methanol
ingestion. Hyperventilation will occur as a compensatory mechanism
to counteract the acidosis.
 Most methanol ingestions occur in adults older than 19 years.

History
 Following methanol ingestion, a patient is initially inebriated as
with the other alcohols. Other symptoms can be delayed for up to 12-
24 hours.
 The patient may complain of headache, nausea, or anorexia.
Occasionally, the patient may complain of shortness of breath related
to hyperventilation.
 Because one of the primary end-organs involved in methanol is the
eye, the patient may complain of difficulty seeing. Specifically, vision
is often described as a "snow field," though a variety of visual
complaints may be verbalized.

Physical Examination
• Unlike ethanol or isopropanol, methanol does not cause
nearly as much of an inebriated state. If a patient has
coingested ethanol, signs or symptoms specific to
methanol intoxication are delayed.
• The patient may be hyperventilating.
• If vision is impaired, ocular examination may reveal
dilated pupils that are minimally or unreactive to light.
Over several days, the patient may become blind.

Laboratory Workup
• If ingestion of a toxic alcohol is suspected, a serum ethanol level and
basic electrolytes, including a serum bicarbonate level are vital, as
the latter are needed to calculate an anion gap.
• Arterial blood gases and other tests that measure associated organ
dysfunction also become important in cases of poisoning with toxic
alcohols.
• An important point is that laboratory abnormalities vary
dramatically over the course of the patient's presentation and any
laboratory abnormalities must be interpreted with the time frame of
the patient's presentation in mind.

Laboratory workup
Serum methanol levels should be obtained when this
diagnosis is suspected. both the osmolar and anion gap
should be obtained.

Management
 The primary antidotal treatment of methanol involves blocking
alcohol dehydrogenase. This enzyme can be inhibited by either
ethanol or fomepizole.
 In addition to blocking alcohol dehydrogenase, significant metabolic
acidosis should be treated with sodium bicarbonate infusions. folinic
acid should be administered If folinic acid is not immediately
available, folic acid can be substituted.
 Because ethanol inhibits gluconeogenesis, hypoglycemia is common
in patients on an ethanol infusion. Thus, serum glucose levels must
be checked frequently.

Pathophysiology
Ethylene glycol (CH2 OH-CH2 OH) is an odorless, colorless,
sweet-tasting liquid, which is used in many manufacturing
processes. Domestically, it is probably most commonly
encountered in antifreeze. It is absorbed somewhat rapidly
from the gastrointestinal tract, and peak concentrations
are observed 1-4 hours after ingestion.

Pathophysiology
 Ethylene glycol itself is nontoxic, but it is metabolized
into toxic compounds. Ethylene glycol is oxidized via
alcohol dehydrogenase into glycoaldehyde, which then
undergoes metabolism via aldehyde dehydrogenase into
glycolic acid.
 The conversion to glycolic acid is somewhat rapid. In
contrast, the conversion of glycolic acid to glyoxylic acid is
slower and is the rate-limiting step in the metabolism of
ethylene glycol.

Pathophysiology
 Glyoxylic acid is subsequently metabolized into several different
products, including oxalic acid (oxalate), glycine, and alpha-hydroxy-
beta-ketoadipate. The conversion to glycine requires pyridoxine as a
cofactor, while the conversion to alpha-hydroxy-beta-ketoadipate
requires thiamine as a cofactor. The oxalic acid combines with
calcium to form calcium oxalate crystals.
 In the presence of normal renal function and no competitive
inhibition for alcohol dehydrogenase, the excretion half-life of
ethylene glycol is approximately 3 hours. However, in the presence of
fomepizole or ethanol, alcohol dehydrogenase undergoes competitive
inhibition, and the resulting excretion half-life increases to
approximately 17-20 hours.

Exposure And Toxicity
 It is mainly used for two purposes, as a raw material in the
manufacture of polyester fibers and for antifreeze formulations.
 ethylene glycol itself is nontoxic. The majority of the metabolic
acidosis occurs from glycolic acid. One form of morbidity occurs when
oxalate combines with calcium to form calcium oxalate crystals,
which accumulate in the proximal renal tubules, thereby inducing
renal failure. Hypocalcemia can ensue, and cause coma, seizures,
and dysrhythmias. Autopsy studies have confirmed that the calcium
oxalate crystals are deposited not only in the kidneys but in many
other organs, including the brain, heart, and lungs.
 Most ethylene glycol ingestions occur in adults older than 19 years.

History
Ethylene glycol toxicity occurs in three stages, as follows:
1. The first stage, called the neurologic phase, can occur in less than 1
hour after ingestion and lasts up to 12 hours. During this stage, the
patient appears inebriated. The patient may not have any other
significant findings during this stage. Occasionally, hypocalcemia
can occur at this point and induce muscle spasms and abnormal
reflexes.

History
2. The second stage, which occurs between 12 and 24 hours after
ingestion, is referred to as the cardiopulmonary stage. During this
stage, the patient frequently develops mild tachycardia and
hypertension. Acute respiratory distress syndrome (ARDS) can also
occur. These findings are believed to result from calcium oxalate
crystal deposition in the lung parenchyma and myocardium.
Significant hypocalcemia can occur at this stage, with QT
prolongation and associated arrhythmias. Expect hyperventilation
as metabolic acidosis progresses.
3. The third stage, also called the renal stage, typically starts after 24
hours. During this stage, flank pain and acute renal failure can
occur. A premorbid patient with ethylene glycol toxicity typically
presents comatose, hyperventilating, and in multiorgan failure.

Physical Examination
 The physical findings depend on the stage of the presentation. Thus,
the patient may present simply inebriated or progressively more
acidotic as renal failure, cardiovascular dysfunction, and coma
develop.
 Examination findings correlate with the symptoms, as previously
described.
 In patients who survive severe intoxication, calcium oxalate crystal
deposition may occur in the brain parenchyma and can induce
cranial neuropathies. These findings typically occur as the patient is
recovering from the initial intoxication. Cranial nerves II, V, VII,
VIII, IX, X, and XII are most commonly involved.

Laboratory Workup
 A serum ethylene glycol level should be obtained when this diagnosis is suspected.
The osmolar gap and anion gap should also be obtained.
 A baseline creatinine and BUN level should be obtained in all cases of ethylene glycol
intoxication. These values can then be followed to check for the development of renal
failure.
 In addition, the urine can be examined for evidence of fluorescence. In antifreeze,
fluorescein is added to the liquid to permit mechanics to identify the source of a fluid
leaking from a car. However, fluorescein is excreted in the urine faster than ethylene
glycol. Thus, fluorescence can be eliminated before the patient even arrives in the
emergency department. As such, the presence of fluorescence of urine under a Wood's
lamp is not a sensitive test. In addition, because certain containers themselves
fluoresce, the presence of fluorescence is neither sensitive nor specific. Despite this, a
positive test that differentiates urine fluorescence from that of its container may be a
quick bedside clue pointing toward ethylene glycol intoxication.
 Both a serum calcium level and an electrocardiogram should be obtained, since
hypocalcemia may occur as calcium combines with oxalate in the form of calcium
oxalate crystals.

Management of toxicity
 The primary antidotal treatment of methanol or ethylene glycol
involves blocking alcohol dehydrogenase. This enzyme can be
inhibited by either ethanol or fomepizole.
 In addition to blocking alcohol dehydrogenase, significant metabolic
acidosis should be treated with sodium bicarbonate infusions
 If ethylene glycol overdose is suspected, the patient should also
receive intravenous thiamine every 6 hours and pyridoxine every 6
hours. The purpose of the thiamine and pyridoxine is to shunt
metabolism of glyoxylic acid away from oxalate and favor the
formation of less toxic metabolites.

Conclusion
Any Alcohol Can Be Toxic If Ingested In Large Enough Quantities
Acute Intoxication With Any Of The Alcohols Can Result In
Respiratory Depression, Aspiration, Hypotension, And
Cardiovascular Collapse.
Prompt Recognition And Treatment Of Patients Intoxicated With
These Substances Can Reduce The Morbidity And Mortality
Associated With These Alcohols.

References
• Alcohol Toxicity
 Updated: Nov 01, 2018 Author: Michael D Levine, MD; Chief Editor: Jeter (Jay)
Pritchard Taylor, III, MD
• Disulfiram
 From Wikipedia, the free encyclopedia
• https://www.addictioncenter.com/drugs/drug-classifications/central-nervous-
system-depressants/
• https://www.nhs.uk/conditions/alcohol-misuse/

Thank You
Prepared and presented by : Majd Al-Qudah, MD
Supervisor: Prof. Abdelkader Battah
Course title: Chemical Toxins . 2020

Alcohols

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