ETHANOL
and METHANOL
ETHANOL and METHANOL
Outline
Effects of ethanol on various physiological
systems
Mechanisms of ethanol’s effects in the CNS as
the basis for understanding the rewards,
disease processes, and treatments for ethanol-
related conditions
ETHANOL
The two-carbon ethanol (CH3CH2OH) or
beverage alcohol is one of the most versatile
drugs known to man, with multiple direct
effects on a diverse range of neurochemical
systems
ETHANOL CONSUMPTION
Large amounts of alcohol are required for
physiological effects, resulting in
consumption more as a food than a drug
ETHANOL CONSUMPTION
Alcohol content of beverages typically
ranges from 4-6% (volume/volume) for
beer, 10-15% for wine and 40% and higher
for distilled spirits (the “proof” of an
alcoholic beverage is 2x its percentage of
alcohol; i.e. 40% alcohol is 80 proof)
ETHANOL CONSUMPTION
Blood ethanol levels (BELs) in humans can be
estimated readily by the measurement of
alcohol levels in expired air
The partition coefficient for ethanol between
and alveolar air is approximately 2000
• Because of the causal relationship between excessive alcohol
consumption and vehicular accidents, there has been a near-
universal adoption of laws attempting to limit the operation of
vehicles while under the influence of alcohol.
• Legally allowed BELs typically are set at or below 80 mg% (80 mg
ethanol per 100 mL blood; 0.08% w/v), which is equivalent to a
concentration of 17 nM ethanol in blood. A 12-oz “shot” of 40%
liquor each contains approximately 14g ethanol, and the
consumption of one of these beverages by a 70-kg person would
produce a BEL of approximately 30 mg%.
• It is important to note that this is approximate because the BEL is
determined by a number of factors, including the rate of drinking,
sex, body weight and water percentage and the rates of metabolism
and stomach emptying.
ETHANOL
Pharmacological Properties
Absorbed rapidly after oral administration into
the bloodstream and distributes into total-
body water (0.5-0.7L/kg)
Peak blood levels occur 30 minutes after
ingestion when stomach is empty
ETHANOL
Pharmacological Properties
Delays in gastric emptying (i.e. presence of
food) slows down ethanol absorption
First pass metabolism by gastric and liver
alcohol dehydrogenase (ADH), oral ingestion
of ethanol leads to lower BELs than
intravenous administration
ETHANOL
Pharmacological Properties
Gastric metabolism of ethanol is lower in
women than in men, which may contribute to
the greater susceptibility of women to
ethanol
Aspirin increases ethanol bioavailability by
inhibiting gastric ADH
ETHANOL
Pharmacological Properties
Effects of heavy ethanol ingestion on various
organs:
Damage to tissues very likely reflects the poor
nutritional status of alcoholics (malabsorption and
lack of vitamins A and D and thiamine)
Suppression of immune function by ethanol, and a
variety of other generalized effects
METHANOL
One carbon alcohol (CH3OH) also known as
methyl and wood alcohol.
Important industrial reagent and solvent
(paint removers, shellac, antifreeze)
Added to industrial-use ethanol to mark it
unsafe for human consumption
METHANOL
Rapidly absorbed orally, through inhalation or
through skin
Feelings of intoxication from methanol, while
similar in many ways to those with ethanol,
are less intense, and often delayed by 8 or
more hours from ingestion, progressing even
more slowly if taken along with ethanol
METHANOL
As little as 15 mL of methanol can produce
toxicity including blindness, with doses in
excess of 70 mL capable of producing death.
• Methanol poisoning consists f headache GI distress, and pain
(partially related to pancreatic injury), difficulty breathing,
restlessness and blurred vision associated with hyperemic optic disks.
Severe metabolic acidosis can develop due to the accumulation of
formic acid and the respiratory depression can be severe, especially
in the context of coma.
EFFECTS OF ETHANOL ON
PHYSIOLOGICAL SYSTEMS
CNS depressant – ingestion of moderate
amounts of ethanol, like that of other
depressants such as barbiturates and
benzodizapines, can have anti-anxiety actions
and produce behavioral disinhibition
With more severe intoxication, CNS function
generally is impaired, and a condition of general
anesthesia ultimately prevails
• William Shakespeare described the acute pharmacological effects of
imbibing ethanol in the Porter scene (Act 2, Scene 3) of Macbeth.
• The Porter, awakened from an alcohol-induced sleep by Macduff, explains
three effects of alcohol and then wrestles with a fourth effect that combines
the contradictory aspects of soaring overconfidence with physical
impairment:
• Porter: …and drink, sir, is a great provoker of three things.
• Macduff: What three things does drink especially provoke?
• Porter: Marry, sir, nose painting (cutaneous vasoldilation), sleep (CNS
depression), and urine (a consequence of the inhibition of antiduretic
hormone (vasopressin) secretion, exacerbated by volume loading). Lechery,
sir, it provokes and unprovokes: it provokes the desire but it takes away the
performance. Therefrom much drink may be said to be an equivocator with
lechery; it makes him and it mars him; it sets him off and it takes him off; it
persuades him and disheartens him, makes him stand to and not stand to
(the imagination desires what the corpus cavernosum cannot deliver); in
conclusion, equivocates him in a sleep, and, giving him the lie, leaves him.
EFFECTS OF ETHANOL ON
PHYSIOLOGICAL SYSTEMS
There is little margin between anesthetic
actions and little effects (usually owing to
respiratory depression)
Ethanol affects almost all brain systems.
Alcohol perturbs the balance between
excitatory and inhibitory influences in the
brain, resulting in anxiolysis, ataxia and
sedation
EFFECTS OF ETHANOL ON
PHYSIOLOGICAL SYSTEMS
Dopamine-related systems have central
importance regarding the feelings of reward
and craving associated with all intoxicating
substances
EFFECTS OF ETHANOL ON
PHYSIOLOGICAL SYSTEMS
Impact on dopaminergic pathways is closely linked
to changes in stress-related systems – relates to
reinforcement from beverage alcohol and other
drugs of abuse, as well as withdrawal symptoms
and negative moods
EFFECTS OF ETHANOL ON
PHYSIOLOGICAL SYSTEMS
ETHANOL CONSUMPTION AND CNS FUNCTION
Large doses of ethanol can interfere with encoding
memories, producing anterograde amnesias,
commonly referred to as alcoholic blackouts
Can produce disturbances in sleep architecture
(frequent awakening and restless sleep)
Heavier drinking can be associated with sleep apnea
• Affected individuals are unable to recall all or part of experiences
during the period of heavy intake. At even 2-3 drinks, ethanol
consumption can produce disturbances in sleep architecture, with
frequent awakenings and restless sleep; high doses are associated
with vivid and disturbing dreams late as a consequence of earlier
suppression of night rapid eye movement dream state at higher
blood ethanol levels. Perhaps reflecting the effect of ethanol on
respirations as well as the muscle-relaxant effects of this drug,
heavier drinking can be associated with sleep apnea, especially in
older alcohol-dependent subjects.
EFFECTS OF ETHANOL ON
PHYSIOLOGICAL SYSTEMS
The transient CNS effects of heavy ethanol consumption
that produces a hangover—the “next morning”
syndrome of headache, thirst, nausea, and cognitive
impairment
Chronic heavy drinking reportedly increases the
probability of developing a more permanent cognitive
deficit often referred t as alcoholic dementia
Thiamine depletion contributes to Wernicke-Korsakoff
syndromes
• The ataxia and ophalmoparesis of Wernicke’s and the severe
anterograde and retrogade amnesia of Korsakoff’s are seen in <<1%
of chronic alcohol-dependent individuals. Additional severe
neurological syndromes associated with chronic heavy use of alcohol
include cerebellar degeneration with associated atrophy of the
cerebellar vermis.
• Heavy doses of ethanol over multiple days or weeks are also
associated withseveral temporary but disturbing “alocohol-induced”
psychiatric syndromes.
EFFECTS OF ETHANOL
CARDIOVASCULAR SYSTEM
•Elevates the risk for heart attacks and bleeding-
related strokes
•6-fold increased risk for coronary artery diseases
•Heightened risk for cardiac arrythmias
•Elevated rate of congestive heart failure
EFFECTS OF ETHANOL
CARDIOVASCULAR SYSTEM
•HYPERTENSION
Heavy alcohol use can raise diastolic and systolic
blood pressure
Consumption above 30 g alcohol per fday (more
than 2 standard drinks) is associated with a 1.5-2.3
mm Hg rise in diastolic and systemic blood pressure.
• The prevalence of hypertension attributable to excess alcohol
consumption is not known, but studies suggest a range of 5-11%. The
prevalence probably is higher fr men than for women because of
higher alcohol consumption by men. A reduction in or cessation of
alcohol use in heavy drinkers may reduce the need for
antihypertensive medication or reduce the blood pressure to the
normal range. A safe amount of alcohol consumption for
hypertensive pateints who are light drinkers (1-2 drinks per occasion
and less than 14 drinks per week has not been determined. Factors
to consider are a personal history of ischemic heart disease, a history
of binge drinking, or a family history of alcoholism or of
cerebrovascular accident. Hypertensive patients with any of these
risk factors should abstain from alcohol use.
EFFECTS OF ETHANOL
CARDIOVASCULAR SYSTEM
•CARDIAC ARRHYTHMIAS
Pharmacological effects on cardiac conduction
include prolongation of the QT interval, prolongation
of ventricular repolarization, and sympathetic
stimulation
Atrial arrythmias associated with chronic alcohol use
include supraventricular tachycardia, atrial
fibrillation, and atrial flutter.
EFFECTS OF ETHANOL
CARDIOVASCULAR SYSTEM
•CARDIOMYOPATHY
Dose-related toxic effects on both skeletal and
cardiac muscle
Women are at greater risk of alcohol-induced
cardiomyopathy
40-50% of persons with alcohol-induced
cardiomyopathy who continue to drink die within 3-
5 years
EFFECTS OF ETHANOL
SKELETAL SYSTEM
•Chronic, heavy, daily alcohol consumption is
associated with decreased muscle strength
•Can cause irreversible damage to muscle, reflected
by a marked increase in the activity of creatine
kinase in plasma
•Type II fiber atrophy
•Skeletal myopathy
OTHER EFFECTS OF ETHANOL
•BODY TEMPERATURE – Feeling of warmth because
alcohol enhances cutaneous and gastric blood flow,
increased sweating
•DIURESIS – Inhibits the release of vasopressin
(antidiuretic hormone) from the posterior pituitary
gland
• Alcoholics have less urine output than do control subjects in
response to a challenge dose with ethanol suggestng that tolerance
develops to he diuretic effects of ethanol. Alcoholics withdrawing
from alcohol exhibit increased vasopressin releaase and a
consequent retention of water, as well as dilutional hyponatremia.s
OTHER EFFECTS OF ETHANOL
•GASTROINTESTINAL SYSTEM
Esophagus –Esophageal dysfunction, esophageal
reflux, Barrett’s esphagus, traumatic rupture of the
esophagus, Mallory-Weiss tears, and esophageal
cancer
Stomach –Disruption of gastric mucosal barrier and
cause acute and chronic gastritis
Intestines – Chronic diarrhea due to malabsorption
in the small intestine
OTHER EFFECTS OF ETHANOL
•Pancreas – Acute and chronic pancreatitis
(Hemorrhagic pancreatitis can develop and lead to
shock, renal failure, respiratory failure, and death)
•Liver – Fatty infiltration of the liver, hepatitis and
cirrhosis
Fibrosis, resulting from tissue necrosis and chronic
inflammation, is the underlying cause of alcoholic
cirrhosis
• Because of its intrinsic toxicity, alcohol can injure the liver in the
absence of dietary deficiencies (Lieber, 2000). The accumulation of
fat in the liver is an early event and can occur in normal individuals
after the ingestion of relatively small amounts of ethanol.
OTHER EFFECTS OF ETHANOL
•Vitamins and Minerals Deficiency – Lack of protein,
vitamins and most other nutrients in alcoholic
beverages predisposes those who consume large
quantities of alcohol to nutritional deficiencies
-Korakoff’s psychosis
-Wernicke’s encephalopathy
-Osteoporosis
OTHER EFFECTS OF ETHANOL
•SEXUAL FUNCTION IN MEN
Acute and chronic alcohol use can lead to impotence
in men. Increased blood alcohol concentrations lead
to decreased sexual arousal, increased ejaculatory
latency, and decreased orgasmic pleasure.
Incidence of impotence may be as high as 50% for
patients with chronic alcoholism
OTHER EFFECTS OF ETHANOL
•SEXUAL FUNCTION IN WOMEN
Decreased libido, decreased vaginal lubrication,
menstrual cycle abnormalities
Ovaries often are small and without follicular
development
Fertility rates may also be lower
OTHER EFFECTS OF ETHANOL
•HEMATOLOGICAL and IMMUNOLOGICAL EFFECTS
--Anemia
Microcytic anemia
Normochromic anemia
Alcohol-induced sideroblastic anemia
--Reversible thrombocytopenia
ACUTE ETHANOL INTOXICATION
•SYMPTOMS: Feeling of stimulation, giddiness,
muscle relaxation, and impaired judgment
Higher blood levels associated with slurred speech,
incoordination, unsteady gait, potential impairments
of attention
More intense mood lability, greater cognitive deficits,
aggressiveness and anterograde amnesia
BEL >200mg/dL can produce nystagmus nd unwanted
falling asleep
• Signs of intoxication typical of CNS depression are seen in most
people following 2-3 drinks, with the most prominent effect seen at
the times of peak BEL, 30-60 minutes following consumption on an
empty stomach.
ACUTE ETHANOL INTOXICATION
•SYMPTOMS:
BEL 300mg/dL (-65 nM)
-Can produce failing vital signs, coma and death
Body weight and composition and rate of absorption
from the GI tract determine the concentration of ethanol
in the blood
Concentrations of alcohol in blood higher in women due
to less body water per unit of weight into which ethanol
can distribute, and due to less gastric ADH activity
• An increased reaction time, diminished fine motor control,
impulsivity, and impaired judgment become evident when the
concentration of ethanol in the blood is 20-3- mg/dL. More than 50%
of persons are grossly intoxicated by a concentration of 150mg/dL. In
fatal cases, the average concentration is about 400mg/dL, although
alcohol-tolerant individuals often can withstand comparable BELs.
ACUTE ETHANOL INTOXICATION
•Treatment is based on severity of respiratory and CNS
depression
•Comatose patients may be intubated to protect the
airway and to provide ventilatory assistance
•BEL reduced by -15mg/dL per hour
•Sedatives and antipsychotic agents may be used
•Ethanol can be removed from blood by hemodialysis
• Great care must be taken when using sedatives to treat patients who
have ingested an excessive amount of another CNS depressant (i.e.
ethanol because of synergistic effects.
ETHANOL
TOLERANCE, DEPENDENCE AND CHRONIC ETHANOL USE
•Tolerance is the reduced behavioral or psychological
response to the same dose of ethanol
•Acute tolerance can be demonstrated by measuring
behavioral impairment at the same BELs on the ascending
limb of the absorption phase of the BEL-time curve
(minutes after ingestion) and on the descending limb of
the curve as BELs are lowered by metabolism (1 or more
hours after ingestion)
ETHANOL
TOLERANCE, DEPENDENCE AND CHRONIC ETHANOL USE
•PHYSICAL DEPENDENCE
Demonstrated by craving, drug-seeking behavior
(psychological dependence) and withdrawal syndrome
when consumption is terminated
Withdrawal symptoms include sleep disruption, ANS
(sympathetic) activation, tremors and seizures
May also lead to delirium tremens (hallucinations,
delirium, fever, tachycardia)
ETHANOL
TERATOGENIC EFFECTS: FETAL ALCOHOL SYNDROME
•FAS (fetal alcohol syndrome) – children born to
alcoholic mothers display a common pattern of distinct
dysmorphology
•FAS is based on 3 abnormalities in the newborn:
1. A cluster of craniofacial abnormalities
2. CNS dysfunction
3. Pre-and/or postnatal stunting of growth
Hearing, language and speech disorders also may become evident as the child
ages. Children who do not meet all the criteria for a diagnosis of FAS still may
show physical and mental deficits consistent with a partial phenotype.
