Other adverse effects can include slowed psychomotor responses and short-term
memory loss. Slowed psychomotor responses have been shown in certain groups of
acutely intoxicated subjects and chronic users. Even medical marijuana users have
shown a steep increase in automobile accidents. Short-term memory loss is a
frequently documented acute, reversible effect of marijuana intoxication as well.
The paranoid ideation and panic reaction of P.H. could certainly be caused by the
high dose and his inexperience with marijuana.
Chronic use of cannabis has been alleged to produce an “amotivational syndrome”
characterized by apathy, lack of long-term goal achievement, inability to manage
stress, and generalized laziness.
75,80,81 Cognitive impairment can occur after heavy
marijuana use, but appears to be reversible with abstinence.
adolescent brain has shown a drop in IQ related to marijuana use that does not
reverse even after 1 year of abstinence.
83 The impairment is more pronounced the
67 Other concurrent drug use may also contribute to cognitive
79,84 Chronic users will have worse periodontal health.
pulmonary complications of chronic heavy marijuana use are potentially significant.
Chronic cough, sputum, wheezing, bronchitis, and cellular changes typical of chronic
tobacco smokers are reported in chronic cannabis smokers.
to be a potent bronchodilator. Both oral and smoked THCs were shown to produce
significant bronchodilation when given to healthy subjects. The bronchodilatory
response in asthmatics given THC has been shown to be less vigorous.
these effects can develop after some weeks, and chronic marijuana smoking results in
increased airway resistance and decreased pulmonary function.
carcinogens in nicotine cigarettes are also found in marijuana smoke and risk of some
cancers is increased compared to nonusers.
75,81 Aspergillus-contaminated marijuana
has been reported to cause pulmonary fungal infections in immunocompromised
patients, who may be using the drug for its medicinal value.
Tolerance to the psychoactive effects of marijuana does develop. Chronic users
may not experience the full range of effects as new users unless they abstain for
several days or weeks to regain initial sensitivity to the cannabis, and chronic users
can tolerate large doses that generally are toxic to novices. Tolerance develops
rapidly to both physiologic and psychological effects of cannabis. Dependence
characterized by a physical withdrawal syndrome occurs after chronic high-dose use
of cannabis. The withdrawal syndrome can involve anxiety, depression, irritability,
restlessness, anorexia, insomnia and vivid or disturbing dreams, sweating, tremor,
nausea, vomiting, and diarrhea.
57,75,83 Dysphoria and malaise similar to that
experienced with influenza can also occur. The cumulative dose of cannabis and
duration of use necessary to produce dependence is unknown. The withdrawal
syndrome is generally mild and self-limiting, and pharmacologic treatments usually
Marijuana has been labeled as a “gateway drug,” meaning that it will lead to the
use of “harder” drugs, such as cocaine or heroin. Marijuana is the most widely used
illicit drug, but use of drugs such as alcohol and tobacco often predates marijuana
use. No studies have conclusively demonstrated a causal link between marijuana use
and subsequent other drug use.
There are clear acute and chronic risks involved with marijuana use. As more
states legalize it for recreational and “medical” purposes, researchers will be able to
define and predict the fullness of these problems.
The introduction of anesthetics (nitrous oxide, chloroform, and ether) to medicine in
the early 1800s also promoted the widespread and popular recreational use of these
inhalants for mind-altering recreational purposes. Today, abused inhalants include a
wide variety of chemicals that are found readily in homes or workplaces, or
purchased at retail establishments. Inhalants are commonly subdivided into three
main categories: the volatile solvents (mostly hydrocarbons); volatile nitrites (amyl,
butyl, isobutyl, cyclohexyl); and nitrous oxide (laughing gas). The fumes or vapors of
these liquids, or paste in the case of glue, are directly inhaled out of their containers
(“sniffing”); poured onto a rag that is held to the nose (“huffing”); poured into a
plastic bag (“bagging”); or merely cupped in the hands and inhaled. Aerosols and
gaseous substances such as nitrous oxide are also used to inflate a balloon and then
inhaled out of the balloon by the user. These products can also be ingested orally or
sprayed directly into the mouth. Volatile solvents include gasoline, toluene, kerosene,
alcohols, airplane glue, lacquer thinner, acetone (nail polish remover), benzene (nail
polish remover, model cement), naphtha (lighter fluid), plastic cement, liquid paper
(i.e., White Out, usually containing 1,1,1-trichloroethane, also trichloroethylene and
perchloroethylene), and many others. The volatile nitrites, once widely available, are
prohibited by the Consumer Product Safety Commission but can still be found, sold
in small bottles, labeled as “video head cleaner” or “room odorizer.” Amyl nitrite is
used medically as a vasodilator for treatment of angina and requires a prescription.
The volatile nitrites are commonly referred to as “poppers,” because of the sound
made when an ampule of amyl nitrite is broken open. The most commonly used
inhalants are glue, shoe polish, toluene, and gasoline.
89 The use of multiple products
is common. Silver and gold paints are popular because they contain more toluene
Inhalant use is most common among younger individuals (consistently highest
annual prevalence among 8th graders) and tends to decline as youth grow older. The
decline likely reflects that other drugs become available and are substituted. Abuse
of inhalants is believed to be popular among children and adolescents because of
their low cost, easy availability, rapid onset, and low threat of legal intervention.
Additionally, they are easily concealed.
The 2009 Monitoring the Future (MTF) study found that 12.5% of 8th, 10th, and
12th graders have abused inhalants.
91 The MTF and other national surveys of
adolescents have found that after marijuana, inhalants are the second most widely
used class of illicit drugs for 8th graders. Most inhalant users, however, have used
alcohol or cigarettes previously.
92 These surveys, most of which are administered in
schools, likely underestimate the true prevalence, as a small but high-risk group
(incarcerated, homeless, and transient adolescents) are not included in the surveys.
Inhalant abuse includes a broad range of chemicals, and they likely have different
pharmacologic effects. In fact, the mechanisms of action of the volatile inhalants are
poorly understood. Nearly all have CNS depressant effects. Evidence from animal
studies suggests the effects and mechanism of action of volatile solvents are similar
to those of alcohol and sedative-hypnotics.
Gases and vapors are rapidly absorbed when inhaled and, because of their high
lipophilicity, tend to distribute preferentially to lipid-rich organs such as the brain
93 Expired air is the major route of elimination, and most are metabolized to
some extent. Inhalation of these products produces a temporary stimulation and
reduced inhibitions before the depressive CNS effects occur. Acute intoxication is
associated with euphoria, giddiness, dizziness, slurred speech, unsteady gait, and
90 As the CNS becomes more deeply affected, illusions, hallucinations,
and delusions develop. The user experiences a euphoric, dreamy high that culminates
in a short period of sleep. The intoxicated state lasts a few minutes, but users may
continue to inhale repeatedly for several hours. Nitrous oxide is an antagonist of the
NMDA subtype of the glutamate receptor.
Its pharmacologic effects are poorly
understood. It produces euphoria and symptoms of intoxication similar to those
described for the volatile solvents.
The major effect of the volatile nitrites is the relaxation of all smooth muscles in
the body, including the blood vessels. This usually allows a greater volume of blood
to flow to the brain. The onset of effects takes 7 or 8 seconds and the effects last
about 30 seconds. A certain “rush” occurs, which may be followed by a severe
headache, dizziness, and giddiness. The volatile nitrites are frequently used in the
context of sexual activity, because of the effect of increased tumescence and
Acute and Chronic Toxicities Associated with Inhalants
The wide variety of chemicals inhaled causes a tremendous range of toxicities.
Toxicity depends on the chemical, and on the magnitude and duration of exposure.
Complications can result from the effects of the solvents or other toxic ingredients,
such as lead in gasoline. The lipophilicity of the volatiles enhances their toxicity.
Injuries to the brain, liver, kidney, bone marrow, and particularly the lungs can occur,
and they may result from the effect of heavy exposure or hypersensitivity. Inhalant
abusers may develop irritation of the eyes, nose, and mouth, including rhinitis,
93 Methemoglobinemia has been associated with volatile
Deaths from inhalant use are well documented and may occur from overdose or
trauma (falls, drowning, hanging). Death from overdose is often caused by
respiratory problems or suffocation after CNS depression.
asphyxiation, convulsions, coma, and aspiration of gastric contents have occurred.
Acute cardiotoxicity resulting in cardiac arrest may cause sudden death. Referred to
as “sudden sniffing death,” it is likely caused by sensitization of the myocardium to
catecholamines, exacerbated by physical exercise, resulting in fatal ventricular
Many of the inhalants produce neurotoxicity, which can range from mild
impairment to severe dementia. Neurologic deficits include cognitive impairment,
ataxia, optic neuropathy, deafness, and disorders of equilibrium. Loss of white
matter, brain atrophy, and damage to specific neural pathways can result from
chronic exposure to some inhalants. Some damage to the nervous system and other
organs may be at least partially reversible when inhalant use is discontinued.
Compulsive use has been documented with inhalants, although inhalant abuse and
dependence is a neglected area of research. Animal studies have shown some of the
abused inhalants to have reinforcing properties.
withdrawal syndrome occurs with chronic use of inhalants. Inhalant use is typically
episodic in nature, and thus users may not be exposed to levels with sufficient
frequency necessary to develop physical dependence or tolerance.
Alcohol Content and Definitions
Beverages containing alcohol (ethanol) have a wide range of ethanol content.
Alcoholic proof is a measure of how much ethanol is in an alcoholic beverage, and is
twice the percentage of alcohol by volume (ABV), the unit that is commonly used as
percent. This system dates to the 18th century, and perhaps earlier, when spirits were
graded along with gunpowder. A solution of water and alcohol “proved” itself when
it could be poured on a pinch of gunpowder and the wet powder could still be
ignited. If the gunpowder did not ignite, the solution had too much water in it and the
proof was considered insufficient. A “proven” solution was defined as 100 degrees
In the United States, the proof is twice the percentage of alcohol
content measured by volume at a temperature of 60°F. Therefore “80 proof” is 40%
ABV, and pure alcohol (100%) is “200 proof.” One hundred percent ethanol does not
stay 100% because it is hygroscopic and absorbs water from the atmosphere.
Legally, in the United States, beers containing up to 0.5% ABV can be called
nonalcoholic. Light beers range from 2% to about 4% ABV; beers range from 4% to
6% ABV; ales, stouts, and specialty brews can be as high as 10% ABV. Wines are
produced at about 14% to 16% (28–32 proof), because that is the point in the
fermentation process at which the alcohol concentration denatures the yeast. Stronger
liquors are distilled after fermentation is complete to separate the alcoholic liquid
from the remains of the source of sugar (e.g., grain, fruit). Distilled liquor cannot be
stronger than 95% (190 proof). A standard drink in the United States is considered to
be 0.5 ounces or contain 15 g (0.5 fl oz of absolute alcohol) of alcohol. This is equal
to 12 ounces (355 mL) of 5% beer, 5 ounces (148 mL) of 12% wine, or 1.5 ounces
Slightly more than half (52.7%) of Americans age 12 or older reported being current
drinkers (at least one drink in the past 30 days) of alcohol in the 2014 National
Survey on Drug Use and Health survey.
4 This translates to an estimated 137 million
people, which is similar to the 2005 estimate of 126 million people (51.8%). In
2014, heavy drinking (five or more drinks on the same occasion on each of 5 or more
days in the past 30 days) was reported by 6.2% of the population age 12 or older.
Approximately 10% of Americans will be affected by alcohol use disorder
97,98 Treatment of alcohol dependence consists mainly of
psychological, social, and pharmacotherapy interventions aimed at reducing alcoholrelated problems.
99 Treatment usually consists of two phases: detoxification and
The rationale for pharmacotherapy is based on several considerations. Advances
in neurobiology have identified neurotransmitter systems that initiate and sustain
alcohol drinking; pharmacologic modification of these neurotransmitters or their
receptors may alter dependence.
100 Promising genetic research confirms that
alcoholics are a heterogeneous population and that several gene variations can
predispose some to increased alcohol use whereas other gene variations can confer
100 Animal models have identified pharmacologic agents that reduce
alcohol consumption in animals, suggesting similar agents could reduce alcohol
Risks and Benefits of Alcohol Consumption
The role of alcohol in the development of medical problems such as cardiovascular
disease, hepatic cirrhosis, and fetal abnormalities is well documented. Alcohol use
and abuse contribute to thousands of injuries, auto collisions, and violence.
Alcohol can dramatically affect worker productivity and absenteeism, family
interactions, and school performance.
102 Some studies suggest, however, that
individuals who abstain from using alcohol may also be at greater risk for a variety
of conditions, particularly coronary heart disease (CHD), than people who consume
small to moderate amounts of alcohol.
A number of studies have documented an association between moderate alcohol
consumption and lower risk for CHD and myocardial infarction (MI).
drinking after an MI, however, increases the risk of mortality.
moderate drinking as one drink or less daily for women or people age 65 and older,
and two drinks or less per day for men.
107 An association between moderate drinking
and lower risk of CHD does not mean that alcohol is the cause of the lower risk. A
review of population studies indicates that the higher mortality risk among abstainers
may be attributable to socioeconomic and employment status, mental health, and
overall health, rather than abstinence from alcohol use.
drinking on CHD mortality are offset at higher drinking levels by increased risk of
death because of other types of heart disease, cancer, cirrhosis, and trauma. The risk
of a disease outcome from low to moderate drinking is less than the risk from either
no drinking at all or heavier drinking. This produces a U-shaped curve when
examining the association of alcohol consumption with rates of deaths from all
The exact mechanism by which alcohol use may be protective against morbidity in
those with CHD is not clear. Some evidence indicates that different types of
alcoholic beverages, such as red wines, which are high in tannins, may lower blood
lipids and fats by increasing antioxidants.
106 Specifically, the mechanisms by which
alcohol may reduce the risk of CHD include increasing levels of high-density
lipoprotein cholesterol, decreasing levels of low-density lipoprotein cholesterol,
prevention of clot formation, reduction in platelet aggregation, and lowering of
plasma apolipoprotein(a) concentration, resulting in the attenuation of the formation
of atheroma and decreasing the rate of blood coagulation.
however, that how a person drinks alcoholic beverages matters as well. For
example, wines are ingested more slowly as they are typically consumed in moderate
amounts with food. Binge drinking of any type of beverage, however, increases the
risk of mortality from CHD in particular.
Pharmacokinetics and Pharmacology
When consumed in amounts typical of normal social drinking, the absorption of
ethanol from the stomach, small intestine, and colon is complete; however, the rate is
variable. Peak blood ethanol concentrations after oral doses in fasting subjects
generally are reached in 30 to 75 minutes, but several factors can influence the rate
111 The most rapidly absorbed formulations are carbonated
beverages containing 10% to 30% ethanol. In contrast, high concentrations of alcohol
can produce vasoconstriction in the gastrointestinal (GI) mucosa, which results in
slowed or even incomplete absorption of ethanol. Absorption of ethanol from the
small intestine appears to be more rapid than any other part of the GI tract and does
not depend on the presence or absence of food. Factors that control the rate of gastric
emptying significantly control the rate of absorption by controlling the rate at which
ethanol is delivered to the small intestine.
112,113 For example, food in the stomach
slows the absorption of ethanol, probably by slowing gastric emptying. The level of
intoxication achieved is not solely related to the plasma concentration. For any
particular plasma concentration, greater cognitive impairment is seen during times
when the plasma level is rising compared with when ethanol is primarily being
eliminated. The degree of intoxication also appears to be directly related to the rate
at which pharmacologically active plasma concentrations are attained. Alcohol
negatively affects cognitive performance and has a differential effect on the
descending versus ascending limb of the blood alcohol concentration (BAC) curve.
The latter finding may have important ramifications relating to the detrimental
consequences of alcohol intoxication.
The blood alcohol level (BAL) or BAC is calculated using the weight of ethanol in
milligrams and the volume of blood in deciliters. This yields a BAC expressed as a
proportion (i.e., 100 mg/dL or 1.0 g/L) or as a percentage (i.e., 0.10% alcohol).
Ethanol concentrations are usually converted to equivalent BACs for standardization
purposes when measured in other body fluids.
The alcohol dehydrogenase (ADH) pathway is the major enzyme system
responsible for alcohol metabolism in humans. The main alcohol metabolism occurs
with ADH isoenzymes, in the stomach (ADH6 and ADH7) and in the liver (ADH1,
ADH2, and ADH3). The pathway involves conversion of ethanol to acetaldehyde by
these ADH isoenzymes, resulting in the reduction of nicotinamide adenine
dinucleotide (NAD) to NADH. In the second step, acetaldehyde is converted to
acetate via the enzyme aldehyde dehydrogenase, which also reduces NAD to NADH.
These are the rate-limiting steps in ethanol metabolism, and this route becomes
saturated when large amounts of ethanol deplete NAD.
converted to carbon dioxide and water. An additional pathway that is more involved
in alcohol-dependent individuals than those who are not involves the catalase
pathway of peroxisomes and the microsomal ethanol oxidizing system (MEOS), in
the smooth endoplasmic reticulum. The main functional component of the MEOS is
the cytochrome-P450 (CYP) 2E1.
Of a dose of ethanol, 90% to 98% is oxidized in the liver, with the remaining drug
excreted unchanged in the alveolar air and urine. Ethanol metabolism formerly was
described by zero-order kinetics; however, Michaelis–Menten and other nonlinear,
concentration-dependent models are more accurate.
of the absorbed dose of ethanol does not appear to enter the systemic circulation,
suggesting first-pass metabolism. The relative contribution of hepatic versus gastric
ADH to this response continues to be debated, however.
118,119 Using a twocompartment, Michaelis–Menten pharmacokinetic model as well as experimental
data, it appears that gastric metabolism contributes negligibly to first-pass
120–122 They believe that gastric metabolism accounts for sex and ethnic
in first-pass metabolism. Estimates of total gastric ADH suggest that the enzyme
can metabolize 0.9 to 1.8 g/hour of ethanol, depending on the concentration of ethanol
123 The extent of first-pass extraction tends to decrease as the dose of
alcohol increases. This is likely because of saturation of ADH, regardless of the
source. When plasma ethanol levels are greater than 0.2 g/mL, the ADH system
becomes saturated. As hepatic ADH becomes saturated, there is increased unchanged
excretion of alcohol. This results in a more intense odor of alcohol on the breath as
the plasma ethanol concentration increases. The metabolism of alcohol also then
tends to become nonlinear because of stimulation of CYP2E1, which produces
metabolic tolerance to ethanol in chronic users.
Lower first-pass metabolism has been found in alcohol-dependent individuals,
women, the elderly, and Japanese subjects.
120,122 Gastric ADH may also play a role in
the effect of food in reducing ethanol bioavailability. Food, by delaying gastric
emptying, allows for more extensive gastric metabolism.
The accepted average rate of ethanol oxidation is 0.15 g/mL/hour for men and 0.18
124 Although this rate still is widely used for both legal and
medical purposes, other data suggest wide variability in ethanol metabolism. For
example, wide differences in ADH activity have been demonstrated and attributed to
125,126 Chronic heavy drinkers frequently oxidize ethanol at
twice the normal rates, with their metabolic rates returning to baseline after a period
127 The rate of oxidation in chronic heavy drinkers may also increase
with elevated blood ethanol levels.
In contrast, patients with end-stage liver
disease may progress to the point at which they have almost no metabolic capacity.
Chronic alcohol use is associated with characteristic changes in the liver.
Hyperlipidemia and fat deposition in the liver occur because of shunting of the
excess hydrogen into fatty acid synthesis and direct oxidation of ethanol for energy
instead of body fat stores being used for energy. Fatty liver is the first step in a
sequence of events that ultimately leads to alcoholic cirrhosis. Accumulated
acetaldehyde, which interferes with mitochondrial function by shortening and
thickening microtubules, has been implicated as playing a role in the hepatotoxic
process. The damaged microtubules then inhibit the secretory functions of the
hepatocytes, which results in an increase in size and weight of the liver.
deficits and impaired hepatic protein metabolism may contribute as mechanisms of
hepatotoxicity in chronic ethanol consumers.
Acetaldehyde is believed to play a role in most actions of alcohol.
acetaldehyde concentrations during ethanol intoxication cause the commonly seen
sensitivity reactions, including vasodilatation and facial flushing, increased skin
temperature, increased heart and respiration rates, and lowered blood pressure.
Acetaldehyde also contributes to the sensations of dry mouth and throat associated
with bronchoconstriction and allergic-type reactions, as well as nausea and
headache. These adverse effects mediated by acetaldehyde have the potential to
protect drinkers against the excessive ingestion of alcohol, but acetaldehyde also has
the potential to produce euphoric effects that may reinforce alcohol consumption.
Acetaldehyde also contributes to the increased incidence of GI and upper airway
cancers that are seen with increased incidence in heavy consumers of alcohol and
which may also play a role in the pathogenesis of liver cirrhosis.
Ethanol ingestion can depress the CNS through all the different stages of
anesthesia. Tolerance to this effect occurs after chronic use such that a blood ethanol
level of 0.150 g/mL will not produce apparent behavioral or neurologic dysfunction
in persons who drink a pint or more of 80-proof liquor (or its equivalent) daily for
Neurobiological Basis of Alcohol Dependence
Proteins that are particularly sensitive to alcohol include ion channels,
neurotransmitter receptors, and enzymes involved in signal transduction.
neurotransmitters, hormones, and neuropeptides include adenosine, cannabinoid
receptors, corticotropin-releasing factor (CRF), dopamine (DA), γ-aminobutyric
acid (GABA), ghrelin, glutamate, neurokinin-1 (NK1), neuropeptide Y (NPY),
norepinephrine, opioid peptides, and serotonin (5-HT). The key inhibitory
neurotransmitter in the CNS is GABA, which is associated with a chloride-ion
channel that is affected by low concentrations of alcohol. Normally, when GABA
binds to the GABAA receptor, the chloride channel opens, allowing negatively
charged chloride ions to enter the cell and inhibiting neuronal cell activity. In the
presence of alcohol, GABA release accentuates the anxiolytic effect of both
134 Receptor compensation for continual inhibition by alcohol is to reduce
135 Other sedative medications, such as benzodiazepines,
also bind to the chloride channel at slightly different sites and facilitate GABA
inhibition. The existence of a common receptor mechanism for the actions of alcohol
and sedative-hypnotics accounts for the cross-tolerance between these substances.
Glutamate is the major excitatory neurotransmitter in the CNS. Low doses of
alcohol strongly inhibit NMDA receptors and inhibit neuronal activity.
continual exposure to high doses of alcohol, NMDA receptors upregulate in an
attempt to balance alcohol’s inhibitory action. Thus, the combined effect of alcohol
on GABAA and glutamate is to inhibit excitation and facilitate sedation.
Alcohol also affects several other ion channels and receptors. The 5-HT3
subtype is particularly sensitive to the action of low doses of alcohol, and may result
in activation of 5-HT and DA. Alcohol also modifies the activity of β-adrenergic and
5-HT, DA, endocannabinoid signaling system, and other neurotransmitter receptors
On a neurobiological behavioral level, the mesolimbic dopaminergic pathway
from the ventral tegmental area to the nucleus accumbens is activated by most
dependence-producing drugs, including alcohol, cocaine, opiates, and nicotine.
Putatively, activation of this pathway mediates drug reward and is responsible for the
dependence-producing properties of all drugs of abuse.
sensitizes the system, so that behavioral stimuli associated with alcohol also begin to
release dopamine and to facilitate additional alcohol use.
drugs of abuse are 2- to 10-fold that of natural rewards.
account for the craving and preoccupation with drugs of abuse.
Cessation of chronic alcohol use results in a withdrawal state of nervous system
excitation that is dysphoric and negatively reinforcing. It has been suggested that
abstinence contributes to alcohol craving and the preoccupation with alcohol use, in
that dependent individuals will continue alcohol use to avoid this state.
chronic alcohol use causes GABAA downregulation and NMDA upregulation,
proposed as mediating some of the negative effects of withdrawal. Chronic alcohol
and drug use alters gene expression and increases levels of adenylyl cyclase,
upregulates cyclic adenosine monophosphate (cAMP)-dependent protein kinases, and
activates cAMP-response element binding protein (CREB) and several
phosphoproteins in this brain region mediating tolerance and dependence.
In the medulla, ethanol can depress respirations by inhibiting the passive neuronal
flux of sodium via a mechanism similar to that of general anesthetic agents.
-adenosine triphosphatase (ATPase) is inhibited, cAMP
concentrations are reduced, and GABA synthesis is impaired. Ethanol is a CNS
depressant, and even the uninhibited behavior associated with its use is caused by
preferential suppression of inhibitory neurons. More global neuronal inhibition is
seen at high ethanol concentrations.
Treatment of alcohol intoxication is essentially supportive. In highly intoxicated
patients, however, the prolonged slowing of the respiratory rate can lead to
arrhythmias, cardiac arrest, and death, often accompanied by aspiration of vomitus.
Respiratory depression is responsible for the respiratory acidosis acid–base
abnormality. Even when blood ethanol levels are below those associated with
medullary paralysis, a blunted respiratory response to hypercapnia and hypoxia is
148,149 This makes the assessment of respiratory status a primary concern in
severely intoxicated patients.
Highly intoxicated patients with depressed respiration require immediate
supportive care that may include endotracheal intubation for respiratory support. This
should be sufficient to restore acid–base balance to within normal limits. When
metabolic acidosis is a significant component of the acid–base disturbance, it may be
necessary to administer sodium bicarbonate. This should be done only in conjunction
with appropriate respiratory support to prevent the development of hypercapnia.
Chronic use of alcohol can produce significant tolerance; therefore, the BAL cannot
be used as a sole determinant of physiologic status. By contrast, for the alcohol
naïve, a BAC in the 0.30 mg% range can be fatal, although chronic drinkers can be
awake and alert at even higher levels. The blood ethanol concentration generally
correlates with the clinical presentation of the patient (Table 90-4), but tolerance
varies among individuals. Impairment in motor function may become observable at
levels of 0.05 mg%. Moderate motor impairment usually is seen at 0.08 mg%, which
is the legal definition of intoxication in all states when driving. Respiratory
depression may occur with ethanol concentrations 0.45 mg%.
) for ethanol in humans is a blood concentration of 0.50 mg%,
although fatalities have been reported with ethanol concentrations ranging from 0.295
Factors that may be associated with fatalities at lower ethanol concentrations
include lack of tolerance to alcohol, ingestion of other drugs, heart disease, and
pulmonary aspiration. For example, patients who died of combined ethanol and
barbiturate ingestions had a mean ethanol concentration of only 0.359 mg%, a
mechanism that is applicable to other more commonly used drugs that also depress
respiration such as anxiolytics and opioids.
152,153 Therefore, the clinician should
order a toxicologic urine screen to rule out possible concurrent drug ingestion.
Relationship of Blood Alcohol Concentration to Clinical Status
Blood Ethanol Concentration Clinical Presentation
50 mg/dL (0.05 mg%) Motor function impairment observable
80 mg/dL (0.08 mg%) Moderate impairment; legal definition of intoxication in
450 mg/dL (0.45 mg%) Respiratory depression
aTolerance to alcohol varies among individuals.
In the alert intoxicated patient, general management is supportive and protective.
Volume depletion resulting in hypotension often occurs in ethanol-intoxicated
patients. Hypothermia also is a complication of severe intoxication and can
contribute to hypotension. Hypoglycemia most often occurs in conjunction with
reduced carbohydrate intake. This situation is common in malnourished alcoholics
but also might be particularly pronounced if a patient was dieting. If intravenous (IV)
fluids are given, thiamine administration should precede that of glucose to prevent
Wernicke’s encephalopathy. Administration of a short-acting benzodiazepine, such as
lorazepam, should be considered.
Gastric lavage may be useful if ingestion of other drugs is expected, or when the
large consumption of alcohol is very recent. Activated charcoal absorbs ethanol
poorly but should be administered when coingestion of other drugs is suspected.
Hemodialysis rapidly removes ethanol from the body.
has been suggested that dialysis be initiated immediately when the blood ethanol
concentration is greater than 0.6 mg%.
151 Ventilatory assistance and good supportive
care usually are most important because respiratory depression is the primary cause
of death in ethanol intoxication. With good supportive care, dialysis is generally
unnecessary. Dialysis may be considered if the patient cannot be stabilized or has
other complicating factors, such as coexisting disease states (e.g., renal dysfunction)
or ingestion of other drugs (Table 90-5).
Sodium, 143 mEq/L Albumin, 4.7 g/dL
Potassium, 4.2 mEq/L Cholesterol, 423 mg/dL
, 25.2 mEq/L CK, 1,344 units/L
Chloride, 107 mEq/L Total bilirubin, 2.3 mg/dL
BUN, 18 mg/dL Direct bilirubin, 0.3 mg/dL
Creatinine, 0.8 mg/dL ALP, 74 units/L
Glucose, 101 mg/dL AST, 288 units/L
Calcium, 9.9 mg/dL ALT, 148 units/L
Magnesium, 0.9 mg/dL GGT, 992 units/L
Acute Alcohol Intoxication: Symptoms and Treatment
Respiratory acidosis Alcohol-induced respiratory depression;
blunted response to hypercapnia and
Endotracheal intubation for respiratory
Coma Alcohol-induced CNS depression; ingestion
Gastric lavage, naloxone (Narcan) 1 mg,
repeat every 2–3 minutes up to 10 doses,
depending on response and suspicion of
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