The Pharmacology and Toxicology of Alcohol: Body Metabolism

a.

General Principles of the Body's Processing of Alcohol

        How an individual body reacts to the ingestions of alcohol is determined by the persons genetics, and the pharmacology and toxicology of alcohol.  Within pharmacology are subsets of pharmacodynamics and pharmacokinetics that describe the dynamics of drug metabolism and the effects of a drug on the human body. Pharmacokinetics includes the absorption, distribution and elimination of alcohol that can be consumed and is absorbed, distributd to the tissues and metabolized. Pharmacodynamics includes the action of alcohol on the brain, pharmacologic effect and toxicity.  

        Alcohol is a depressant. In order for the brain to be influenced by alcohol it must be absorbed into the body and circulate through the blood stream to the various affected organs through two main circulatory routes in the body: Pulmonary circulation to the lungs.and systemic circulation to the rest of the body. The arteries in the body carry the oxygenated blood to the organs and tissues and returns to the heart via the veins. The exception to this general rule is that the pulmonary artery going to the heart is deoxygenated, and the pulmonary vein, returning back to the heart, is oxygenated. Alcohol follows this route, distributing and circulating in the body until it is finally metabolized or excreted.  

        Once ingested, alcohol is constantly absorbed into, and eliminated from, the body. The factors that influence a persons metabolising alcohol are: The presence or absence of food in the stomach;  alcohol % concentration; rate of consumption; vascularization; emotional state; and ratio of muscle mass to fat.  As long as the amount of alcohol entering the blood is greater than what the persons liver can oxidize, their BAC will rise. This is an important concept in the defense of DUI cases because the driver will generally have a lower BAC during the absorption phase than at the time of the chemical test, which is taken at a later time. If the blood alcohol test is taken when the alcohol level has peaked, or reached its plateau, the BAC level will test as higher than it was earlier in the absorption phase; whereas during the elimination phase the BAC level starts to decline.. At some time after the cessation of drinking, when the amount entering into the body from the small intestine equals the amount the liver can handle, the BA level will peak; then after the peak, the amount entering the body will be much less than the liver can handle, and the liver can both handle what is entering the body, and start eliminating alcohol from the blood stream.

        Ingested alcohol that has not yet been absorbed has no neurological effects and cannot cause driving impairment. Consequently, both the time-frame in which alcohol is absorbed into the bloodstream and the corresponding volume absorbed are significant in determining both impairment and the blood alcohol concentration. Therefore, characteristics of the absorption, distribution and elimination of alcohol are the keystones to the determination of BAC at the time of driving.

b.

The Body's Absorption of Alcohol.

      Alcohol is absorbed through the skin, lungs, or the gastrointestinal tract, what iss the main route of alcohol absorption from mouth to rectum. Because of alcohol's small molecular size, it readily diffuses through membranes of the gastrointestinal tract by passive diffusion, and mostly through the small intestine where the structural presence of microvilli greatly increase the surface area available for absorption. After the consumption of a drink, alcohol travels down the esophagus and enters the stomach where a small portion of the dose (25%) is absorbed via passive diffusion from the stomach into the blood. The remainder of the alcohol is absorbed from the small intestine, notably the duodenum and the jejunum. The absorbed alcohol travels from the stomach and into the intestine through the pyloric valve, which opens approximately three times a minute to allow the passage of food and liquid from the stomach. Alcohol from the stomach and intestine travels through the mesenteric veins, into the portal vein, to the liver, where the major site of oxidation takes place.  There are also other methods of absorption, including directly from the mouth and predominantly through the mucosa into the blood, and circulating in the veins in the buccal tissue; mostly within the first 15 minutes after a drink.

      Absorption is affected by many factors, including genetic and environmental factors such as gender, body composition, food consumption, liver volume, genetic polymorphisms, and ethnicity, time of day, drinking pattern, dosage form, concentration of alcohol in the beverage, and the existence of food in the stomach.  Alcohol consumed on an empty stomach is absorbed by most people within 15 minutes to 2.5 hours. If alcohol is consumed with a moderate amount of food, the range typically increases to 30 minutes to 3.0 hours; but on a full stomach it can  range from 3 to 6 hours.  This is because food delays the gastric emptying time of alcohol, and decreases the availability of alcohol in the blood stream due to the slow gastric emptying, and peak BAC is lower with food in the stomach than without food. Thus, consumption of alcohol with food can increase alcohol clearance by 1-2 hours, and increase the rate of alcohol metabolism by between 36% and 50%, as compared to consumption on an empty stomach.   

      The type of food consumed appears to have an effect as well. Aside from a decreased area under the blood alcohol concentration curve, Studies indicate a decreased alcohol metabolism rate after the ingestion of carbohydrates or fats.  A significantly higher BAC results from eating meals with high sodium.  The speed in which alcohol is consumed can play an important part in alcohol peak levels and times. Large amounts of alcohol taken all at once may cause the pyloric sphincter to seize, thus delaying absorption; Conversely, if alcohol is consumed over a long period of time, the liver has a greater opportunity to eliminate what is being absorbed.  Social drinking often results in the consumption of alcohol over an extended period of time. Other substances such as cigarette smoke affect consumption of alcohol as well. Cigarette smoking during or close in time to a meal has been found to slow gastric emptying and increase the time to reach maximum absorption.

      Other factors influencing absorption of alcohol include alcoholic concentration, gender, age, physical changes to the stomach and other drugs.  Higher concentration alcoholic drinks can delay gastric emptying by up to 2-3 hours. Low alcohol doses accelerate gastric emptying, whereas high doses delay emptying and slow bowel motility.  Thus, high doses of alcohol tend to delay and increase the peak BAC.  Drinks high in sugar have a delayed absorption rate in much the same way food delays absorption. For the same type and amount of alcohol, women tend to have higher BAC than men. This is believed to be because of the difference in size, weight and body water of the sexes, but also because of an apparent lower physical activity in women. In general, the older one is the less physically fit they are, and are less able to absorb alcohol Any physical changes to the stomach and intestines due to disease or surgical intervention have the potential for affecting the absorption kinetics of alcohol. Gastritis and gastric ulcers can increase blood flow and motility in the gastrointestinal tract, while cancers and gastric fibrosis can work to delay gastric emptying. Stomach infections have been shown to significantly reduce first-pass metabolism of alcohol.  Surgeries that change the stomach or intestinal configuration also disrupt normal absorption of alcohol. The maximum blood-alcohol concentration is about 15% higher in gastric bypass patients.   

        The understanding of drug-alcohol interactions is important for the full evaluation of the defense of a DUI case because they effect the abosroption of alcohol dramatically. Glycine and alanine suppress the rate of stomach emptying and thus alcohol absorption because stomach emptying is lowered, alcohol has more time to be oxidized in the stomach.  One consideration is the phenomenon of "first-pass metabolism," where  metabolism of alcohol that occurs before alcohol actually reaches the blood stream while still in the stomach and the lining starts to metabolize the alcohol.  The strength of first-pass metabolism is dependent on the strength of the alcohol dose received, the s gender, stomach food content and the persons experience with alcohol. First-pass metabolism is one reason why alcohol, when consumed with food, exhibits a lower alcohol curve in addition to a delayed peak  These drugs showing inhibition of enzyme action in the stomach are the "H2-receptor antagonists" including ranitidine, cimetidine, and ibuprofen. However, aspirin has the effect of inhibiting the gastric enzyme alcohol dehydrogenase (ADH, and thus increases alcohol bio-availability I men but has negligible effect in women. Parasympathetic drugs, such as opiates and nicotine, increase absorption, decrease gastric motility and prolong gastric emptying time.  

        Alcohol enters the blood stream and collects in the portal vein, where it is transported to the liver. It is then distributed and metabolized in the liver where 90% is oxydized, and the remainder is excreted unchanged from the lungs or urine. The alcohol moves with the blood flow through the liver and, via the hepatic vein, into the inferior vena cava. From the inferior vena cava, the blood (and alcohol) travels to the heart. In the heart, the blood moves from the right atrium to the right ventricle, and to the lungs via the pulmonary artery. From the lungs, the blood (now oxygenated) moves via the pulmonary vein to the left ventricle of the heart. The aorta then carries the blood to the organs and tissues in the body. From the aorta, the blood travels to the brain via the carotid arteries to various areas in the brain. The blood is also returned to the liver by the hepatic artery where metabolism again occurs. From the tissues, the veins return the blood to the heart, where the cycle starts again. Alcohol is distributed throughout the entire body water compartments, both in the extra-and intra-cellular fluids in the body, and those tissues with a higher water content will have a higher proportion of alcohol.

      The term used to represent how alcohol distributes is called the volume of distribution, which is a parameter that relates dose to a plasma or whole blood concentration of a drug. The numerical result obtained is a reflection of body composition and the affinity of alcohol with the water fractions in the body. Because women have more adipose tisue than men, women will have a higher alcohol concentration for the same amount of alcohol consumed. During absorption, the alcohol concentration in the arteries is much higher than in the veins, and can be a much as 50 to 100%. Alcohol distributes in the body based on the water content of the tissue. Alcohol can be found in a myriad of matrices including blood, urine, breath, tears, saliva, plasma, serum, cerebral spinal fluid, sweat, breast milk, and vitreous.  The alcohol concentration in urine and saliva is higher than in whole blood, and thus a measured alcohol concentration in urine or saliva must be converted (by division) to the whole blood legal standard.

c)

The Metabolism and Elimination of Alcohol From the Body by Oxidation.

  The elimination of alcohol occurs through the oxidation of alcohol by a variety of enzymes. Alcohol dehydrogenase, aldehyde dehydrogenase, and their isozymes are primarily responsible for the oxidation of alcohol in humans.  Over 90% of the ingested alcohol is oxidized in the liver, and the remainder is excreted unchanged from the lungs or urine. The elimination rate varies for individuals but falls between .015 percent to .020 percent per hour, with an average of .018 percent per hour, bu determining that factor for an individual would be a falwed analysis.

Although the majority of alcohol is eliminated from liver enzymes, oxidation of alcohol can also occur in the blood stream. Alcohol metabolism occurs by oxidation in the presence of body enzymes. The body uses the enzymes to break down the alcohol molecule to facilitate the excretion from the body. Elimination is principally by metabolism in the liver with small amounts excreted in the breath.  The oxidative process begins with the oxidation of alcohol to acetaldehyde. There are three enzyme systems which are involved in this process: Alcohol dehydrogenase; (ADH) , t he microsomal alcohol-oxidizing system; and the catalase system; with the specifics percentages unknown.  the formed acetaldehyde becomes oxidized to acetate. The formed acetate becomes further oxidized to carbon dioxide and water through the Krebs cycle, or tricarboxylic acid cycle.

  ADH is primarily found in the liver, but also can be found in other parts of the body, such as:

the kidney, gastric mucosa, oral mucosa, lung, and esophagus, ADH facilitates the transfer of a hydrogen from the alcohol molecule to the coenzyme nicotinamide-adenine dinucleotide (NAD) to produce acetaldehyde and NADH. This system plays the most predominant role alcohol oxidation, accounting for over 90% of alcohol's total oxidation. ADH enzyme system is divided into three major classes: ADH1, ADH2 and ADH3. ADH1 is the system that plays the major role in alcohol oxidation in the liver, whereas ADH3 is mainly in the stomach.  Microsomal Alcohol-Oxidizing System (MEOS), located in the sub-cellular structure of the liver cells called the smooth endoplasmic reticulum, generally kicks in when the ADH system becomes overwhelmed during excessive alcohol consumption.  The catalase system uses catalase found in the liver celL accounts for 10% of alcohol metabolism.

        There are two hypothesis models for the metabolism of alcohol. The Widmark postulated that alcohol is eliminated in a linear manner where a constant amount of alcohol is eliminated for each hour that passes, The Michaelis-Menten Model postulates that the rate of elimination is dependent on dose and blood alcohol concentration. The factors that affect elimination olf alcohol from the body are: the amount of alcohol ingested; the time-course of alcohol ingestion; the experience of the subject drinking; and the effect of food taken around the time of the drinking. Having food in the stomach slows down the elimination of alcohol, but having fructose accelerates it.  Age and the subsequent loss of lean body mass results n a higher alcoholic concentration. Those who become chronic alcoholics experience permanent changes to their oxidizing enzymes, resulting in faster elimination rates. .

        One of the hazards of estimating peak alcohol levels based on a drinking pattern is the over-simplification and unrealistic reliance on the absolute number, as predicting the exact time of peak absorption is very difficult.  Conservative estmates are traditionally more accurate. Thus, when an expert witness is asked to determine the time of peak absorption in a given circumstance, the entire range must be considered. Using a more conservative time frame will most likely make the expert's assumption of peak absorption time true in the unknown Defendant's situation, since the statement statistically will include the largest portion of the population.   

  The movement of alcohol in the body and the systematic excretion and metabolism is a dynamic process. Nonetheless, most States have enacted laws that allow a presumption of the driver being at the same BA level at the time of driving as at the time of the test, provided the test is given within a mandated number of hours after driving. i.e., without a scientific basis. Many experts develop graphs that show the change of alcohol over time to aid the jury in visualizing how alcohol rises for a period of time, peaks, and then decreases over time. alcohol levels change over time. It is this fact that makes extrapolation and prediction of alcohol levels difficult when only the consumption pattern or a test result is known. Further, alcohol levels may remain the same level over a period of time.

        There are three anamolies occuring in BAC that can be shown to affect a true result. During the metabolism process, short-term fluctuation and spiking in the "linear" curve and curve irregularities are common. A "zig-zag" effect can be seen most readily in studies where many blood or breath samples are taken in 2-10 minute intervals; and where the BAC is plotted against time, the BAC curve no longer has a smooth line, but rather a "saw-tooth" pattern. Lastly, an inter- and intra-individual variability of time profiles of alcohol concentration has been studied by several scientists.
 

d)

The Dynamics of Alcohol's Effects on the Body

        Alcohol affects the body in two ways: (1) by altering cell function at the cellular level, and (2) by affecting neurotransmitters systems by acting on specific receptors. Effects and impairment are two separate issues. Effecs are manifestations of the drug action on a cell. these effects have to become so egregious that they affect a particular performance for a subject to be considered "impaired" to perform a target function. In the case of DUI/DWI, this function is driving. All subjects have various degrees of responses to the effects of alcohol consumption, bu primarily the BAC increases, and impairment for cognitive functioning becomes markedly affected at levels over 0.10%.   Alcohol acts at many sites in the body, including the reticular formation, spinal cord, cerebellum and cerebral cortex. Several neurotransmitter systems are also affected. Some of the neurochemical effects of alcohol are: Increased turnover of norepinephrine and dopamine; Decreased transmission in acetylcholine systems; Increased transmission in GABA systems; and increased production of beta-endorphin in the hypothalamus. All of these sites of action contribute to the overall effects of alcohol on the body.

        Alcohol effects are progressive and cumulative. At low BAC levels, effects may include a loss of inhibition or increased loquaciousness, followed by reaction time effects, increased risk-taking, issues with small muscle dexterity, and changes in vision. At higher levels, changes in motor coordination, speech and cognition are evident. Finally, at extremely high levels, stupor, coma, and death are a possibility. At some point in this continuum of effects, the degree and amount of effects reach a point were the individual becomes impaired for driving. Although subjects may demonstrate alcohol-related impairments in depth perception and in visual short-term memory, performance does not correlate with blood alcohol levels (BAL) to any degree of reliability. Total impairment of "blackouts" can be induced by alcohol. The frequency of blackouts correlates with age and the frequency of intoxicating drinking.  

  Determining a magical level of impairment for a particular individual is difficult, if not impossible, but it is clear that, the higher the alcohol level, the greater the risk of accidents and impairment of driving ability. However, there are many factors that affect the level at which a person actually becomes impaired for driving purposes.  Thos include acquired tolerance, acute tolerance, environment, performance enhancement, and food ingestion, Tolerance is a result of modifications in the nervous system and metabolic changes. The two major mechanisms responsible for the development of tolerance are a decreased amount of drug reaching the area when the effect is produced and/or the lowered responsiveness of the tissue to the drug. Regardless of the mechanism responsible for the development of tolerance, tolerance is characterized by two major factors:  The drug effect will lessen with repeated exposure to the same dose; and if the dose is increased, the original effect can be achieved again. Tolerance can be behavioral: learning to mask the outward effects of intoxication by repeatedly practicing physical skills at elevated alcohol levels. Tolerance can also be acute, resulting in less impairment of the descending limb of the alcohol curve than the ascending limb. Acquired tolerance is more common, developing with repeated exposures. Acquired tolerance can be either of the following: dispositional (the alteration of the absorption, distribution and elimination of alcohol) and cellular (the resistance of the cell to alcohol effects).   What is clear on tolerances is drinkers develop a desensitization to the effects of alcohol such that greater doses are required to achieve the same effect as a prior time. In fact, heavy drinkers may experience greater stimulant-like and fewer sedative-like and aversive subjective effects after ethanol than novice drinkers. Alcoholics develop an increased tolerance to alcohol at BACs that are extremely high, including levels generally considered to be potentially fatal. Acute behavioral tolerance occurs when development of tolerance during the rising side of the curve, and this may lessen the degree of impairment during the subsequent falling side of the curve. Differences in the subjective effects of alcohol may be seen depending on whether the subject is on the rising or falling side of the curve.  Environmental factors, such as a reward, play an important part in performance. When a reward is anticipated for a good performance, motivation is increased. Low doses of alcohol appear to increase information processing performance and vigilance. Ingesting food reduces the effects of alcohol on performance.
 
e)

Alcohol's Affects on Driving Impairment.

        The affects of alcohol on driving impairmeent is clear. There are a few undisputable themes:  As alcohol level increases, drivers become more affected by alcohol; The risk of accidents associated with alcohol starts to increase at the 0.08% mark, rises dramatically at the .10% mark, and is extremely high at the .15% mark; some effects of alcohol influence can be seen at very low levels; and higher alcohol levels result in a significant decrease in cognitive functioning.  

        NTSA statistics are an excellent and reliable gauge of the affects of alcohol on driving. Alcohol use increases crash risk and affects driving among many, most or all people above a 0.08%. In 2000, there were 37,409 traffic crashes which resulted in the death of one or more persons. In 31 percent of those crashes, at least one driver (or pedestrian/bicyclist) had a BAC at or above .10%. [NHTSA, Alcohol Involvement in Fatal Crashes 2000, HS 809 419, March 2002.]  Between 49-76% of all fatal crashes have no alcohol involvement, 4-15% percent have "low alcohol" levels (0.01%-0.09%), and 21-43% have levels greater than 0.10%. [NHTSA, Traffic Safety Facts 2000: Alcohol, DOT HS 809 323, p. 7.]

The Increasing Role of Expert Witness on BAC Issues in DUI Defense.

      With the lowering of the BAC required to find Per Se DUI to .08, it has resulted in a greater number of prosecutions.  Increasingly, this has led to the increased use of expert witnesses for both prosecutors and defense attorneys to understand basic scientific principles and concepts so that the direct and cross-examination of an expert can be most effective. Those experts must be aware of the facts and issues of the case, superior knowledge of the science of DUI alcohol and body organ functions to be able to rebut any contrary claims made by the adverse parties own expert witness that have no scientific basis. Those experts must also give unbiased, informed opinions of the case, to supply knowledge and opinions about scientific concepts regarding the case; to relay the information in a manner easily understood by the jury;  unbiased in the review of the case and the application of the science; and provide fair and impartial opinions in court.   

      The qualifications of an expert in DUI cases usually draw from the administrative toxicologists and bench-level chemists that are aware of inaccuracies of the instrument used for the analysis, or the errors that may occur during analysis, have knowledge of all types of BAC testing machinery,  Medical doctors may also be expert witness in DUI cases for pharmacology or toxicology general issues, but may not be qualified on issues they have not specifically explored and researched: drugs of abuse, drug recognition examination, alcohol effects on driving, field sobriety tests, or laboratory instrumentation and interpretation.

      Those wanting to be expert witnesses in DUI cases must keep current on DUI published literature, become a member of technical organizations related to their areas of expertise, and to publish articles and papers in the field.