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Alcohols

Lahorra, Angelo S.
Solidum, Diore M.
(MD4Y1-6)

BCM 413
Introduction
The toxic effects of alcohol are both general and
specific.

Exposure to alcohol:
Disorientation
confusion
euphoria, which can progress to unconsciousness,
Paralysis with high-level exposure
Death
Introduction

Recovery from CNS effects is rapid and complete
after cessation of exposure.

Distinct from the general CNS effects are the specific
toxicities of each type of alcohol.
biotransformation of alcohols to toxic products.

There are several pathways by which short-chain
aliphatic alcohols can be metabolized.
Introduction
SEVERAL PATHWAYS:

Hepatic conversion to an aldehyde, by alcohol
dehydrogenase (ADH):



Ethanol
Most common exposure.

Leading cause of economic, social, and medical
problems throughout the world.

One of the top 10 causes of hospital admissions.
About 20% of all hospital admissions.

An estimated 80,000 Americans die each year, either
directly or indirectly, as a result of abusive alcohol
consumption.

Ethanol
Ethanol consumption during pregnancy
lead to fetal alcohol syndrome or fetal alcohol
effects.
delayed motor and mental development in
children.

80 mg/dL of blood alcohol level has been
established as the statutory limit for operation
of a motor vehicle in most states.
Ethanol
Ethanol abuse are associated with chronic consumption
over a long period.
Average adult: 50 g of ethanol per day for about 10
years.
Consumption to this degree:
compromised function in: various organ, tissue, and cell
types.
Liver is the most sensitive organ.
accumulation of lipids in hepatocytes.
may progress to alcoholic hepatitis. About 20% of
individuals with long-term, high intake.
May progress to cirrhosis.
Ethanol
Ethanol |
Several mechanisms have been proposed to
mediate the pathologic effects of long-term
ethanol consumption.

Of these, adduct formation with acetaldehyde
appears to play a key role.
Ethanol |
Hepatic metabolism of ethanol is a two step
enzymatic reaction.
The final product is acetic acid.


Methanol
Common solvent.

It may be ingested accidentally.

Initially metabolized by hepatic ADH to the intermediate
formaldehyde.
Formaldehyde is rapidly converted to formic acid by
hepatic ALDH.
Formation of formic acid causes:
severe acidosis, which may lead to death.

Responsible for an optic neuropathy that may lead to
blindness.
Isopropanol
AKA: rubbing alcohol
commonly available.

Metabolized by hepatic ADH to acetone.

Both isopropanol and acetone have CNS depressant effects
similar to ethanol.
acetone has a long half-life.

Intoxication with isopropanol:
may result in severe acute-phase ethanol-like symptom
Ethylene glycol (1,2-ethanediol)
common component of hydraulic fluid and antifreeze.

Commonly ingested by children because of its sweet taste.

Immediate effects of ingestion are similar to those of
ethanol.


Ethylene glycol (1,2-ethanediol)
Metabolism by hepatic ADH and ALDH will form toxic
species including :
oxalic acid
glycolic acid,
which results in severe metabolic acidosis.

Rapid formation and deposition of calcium oxalate
crystals in renal tubules.
Result to renal tubular damage.

Determination of Alcohols
Determination of blood ethanol concentration must be
accurate and precise.

Serum, plasma, and whole blood are acceptable specimens.

Correlations have been established between ethanol
concentration in these specimens and impairment of
psychomotor function.

Ethanol uniformly distributes in total body water:
Serum = water content than whole blood
Serum = conc. Per unit volume than whole blood
Specimen Collection
For ethanol determination:
the venipuncture site - cleaned with an alcohol-free
disinfectant.

Specimens must be capped at all times to avoid
evaporation.
volatile properties

Sealed specimens:
refrigerated or stored at RT for up to 14 days without
loss of ethanol.

Specimen Collection
Nonsterile specimens or those intended to be stored for
long periods:
preserved with sodium fluoride
to avoid increases in ethanol content that result from
contaminating bacterial fermentation.

Analytic Methods of Determination
Determination of ethanol in serum.
Most Commonly used:
enzymatic
GC
osmometry

When osmolarity is measured by freezing point
depression,
in serum osmolarity correlate well with in
serum ethanol conc.
Analytic Methods of Determination
The degree of in osmolality due to ethanol is
expressed as:
Osmolar gap = measured osmolarity - calculated osmolarity

the difference is called the osmolar gap.

Serum osmolality by about 10 mOsm/kg for each
60-mg/dL in serum ethanol.

Osmolar Gap lacks specidicity. used as screening
test.

Analytic Methods of Determination
GC Method
the reference method for ethanol determination.
can simultaneously quantitate other alcohols:
eg; methanol and isopropanol

Analysis starts with dilution of serum or blood
samples with saturated solution of NaCl in a closed
container.

Volatile will partate into the air space.
Analytic Methods of Determination
GC Method
Head space provides clean specimens with little or
no matrix effect.

Quantitaion of peaks:
Constructing a standard curve, or;
Ratio to an internal standard (n-propanol)
Analytic Methods of Determination
Enzymatic Method
Common in ethanol
Nonhuman form of ADH enzyme used
oxidizes ethanol to acetaldehyde with reduction of NAD
to NADH.
Analytic Methods of Determination
Enzymatic Method

NADH produced:
monitored directly by at 340 nm or can be coupled
to an indicator reaction.

Relatively specific for ethanol.

Intoxication with methanol or isopropanol:
negative or low result