06 alcohol
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Discusses Pharmacology and toxicology of alcohol
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06 alcohol
- 2. Outline • Pharmacology and toxicology of alcohol • Absorption, distribution and elimination in the body • Stages of alcohol intoxication • Tolerance • Alcohol in breath, blood, and urine • Alcohol and driving impairment • Effects of alcohol on memory • Toxicology, • Uses 02/07/19 patki 2
- 3. Types of Alcohol • Ethanol (ethyl alcohol, grain alcohol) • Methanol (methyl alcohol, wood alcohol) • Isopropanol (isopropyl alcohol, rubbing alcohol) • Ethylene glycol • Absolute alcohol- • Proof alcohol- 50% 02/07/19 patki 3
- 4. Routes of Administration • Topical • Inhalation • Intravenous injection • Oral ingestion 02/07/19 patki 4
- 5. Absorption • Absorption of ethanol is by simple diffusion • 25% of an ingested dose of ethanol is absorbed from the stomach • 75% of an ingested dose of ethanol is absorbed from the small intestine 02/07/19 patki 5
- 6. Factors affecting absorption Alcohol concentration of the ingested beverage • Optimal absorption occurs for beverages with alcohol concentrations between 10% alc. v/v and 30% alc. v/v • Beverages <10 % alc. v/v do not present as large a concentration gradient- Beer • Beverages >30% alc. v/v will irritate the gastric mucosa and increase mucous production-Whisky etc02/07/19 patki 6
- 7. Factors affecting absorption Presence of food in the stomach • Food in the stomach will prolong gastric emptying time, resulting in a lower, delayed peak blood alcohol concentration 02/07/19 patki 7
- 8. Effect of food on absorption 120 0 20 40 60 80 100 0 20 50 60 100 120 140 200 220 250 300 Time BloodAlcoholConcentration Empty stomach With food in stomach 02/07/19 patki 8
- 9. Distribution • Alcohol is hydrophilic and will distribute into fluids and tissues according to water content • Total body water (TBW) is dependent upon • Age • Sex • Body weight 02/07/19 patki 9
- 10. • 5-10% of ingested ethanol is excreted • Biotransformation occurs in the liver • Commences as soon as EtOH is absorbed • Alcohol dehydrogenase is primary enzyme Alcohol Metabolism 02/07/19 patki 10
- 11. Ethanol Acetaldehyde Acetic Acid CO2 + H2O Alcohol dehydrogenase Aldehyde dehydrogenase 02/07/19 patki 11
- 12. Elimination • Elimination of alcohol from the blood: • Follows zero-order kinetics-Constant amount is metabolised. • Ranges from 10-20 mg/100 mL/hour • Average rate of elimination is 15 mg/100 mL/hour • Is fixed and unaffected by:• coffee • sleep • exercise • eating • showering • fresh air 02/07/19 patki 12
- 13. Fructose • There is scientific agreement that fructose can increase the elimination rate of alcohol • However – the required intake of fructose is so high that vomiting and abdominal pains result from the ingestion 02/07/19 patki 13
- 14. GABA Receptors • Ethanol is a GABA agonist, binds to a subunit of the GABAA receptor • It increases Cl- ions thus hyperpolarizing the cell • Low doses of alcohol can reduce panic and anxiety 02/07/19 patki 14
- 15. Effects of Alcohol on the Body • Vasodilatation • Creates a feeling of warmth when alcoholic beverages are consumed • Contributes to paradoxical undressing in hypothermia deaths • Disinhibition • Responsible for the “stimulant” effects of alcohol • Euphoria, ↑ talkativeness, ↑ sociability 02/07/19 patki 15
- 16. Effects of Alcohol on the Body • Central nervous system depressant • Non-selective depression of brain and spinal cord • Effects occur on a continuum - with increased BAC, increased effects occur • Sedated → Sleepy → Stuporous → Unconscious • Effects are additive with other CNS depressants 02/07/19 patki 16
- 17. Stages of Alcohol Intoxication See also: Table 2, Chapter 10. Levine, 1999. p. 177 10–50 mg/100 mL • Slight intoxication • May be no observable signs of intoxication • Laboratory testing may reveal some effects 30-120 mg/100 mL • Mild euphoria, ↑ sociability, talkativeness • Increased self confidence, ↓ inhibitions • Sensory perception ↓ (e.g. hearing) • Loss of fine motor skills • Slowed information processing 02/07/19 patki 17
- 18. 90–250 mg/100 mL • Emotional instability (dissatisfaction) • Mental confusion • Memory impairment • Impaired balance and coordination • Sedation, drowsiness 180-300 mg/100 mL • Disoriented to time and place, ↑ confusion • Exaggerated emotional state • Double-vision • Motor incoordination worsens, apathy • Anesthesia Stages of Alcohol Intoxication 02/07/19 patki 18
- 19. 250-400 mg/100 mL • Loss of motor function • Response to stimuli ↓ • Stupor, unconsciousness • Vomiting, incontinence • Hypothermia 350-500 mg/100 mL • Unconsciousness → Coma • Depression of reflexes • Impairment of respiration, circulation • Death Stages of Alcohol Intoxication 02/07/19 patki 19
- 20. Pharmacological Effects • Alcohol effects many different functions of the brain • Alertness, motor functions, and intellectual abilities decrease • Combined with other sedatives (benzodiapines), this increase the sedativeness of alcohol 02/07/19 patki 20
- 21. Pharmacological Effects – Cont. • Alcohol dilates blood vessels, thus releasing more body heat and decreasing blood temp. • Large doses of Alcohol increases the risk of heart failure • Small Doses decrease the risk of coronary disease • Alcohol is a diuretic – it decrease the amount of diuretic hormone thus increasing the excretion of water 02/07/19 patki 21
- 22. Psychological Effects • Low amounts of Alcohol have minimal Change in behavior < .04 BAC • From .04 - .10 BAC, your 4x more likely to get into an accident • .12-.18 Likelihood increases to 25x • .23-.29 your in a stupor • .30 - .33 your in a coma • .39 and greater, your dead 02/07/19 patki 22
- 23. Alcohol and Death • Primary mechanism for death due to acute alcohol intoxication is respiratory depression • Average BAC at which respiratory paralysis occurs is 350 mg/100 mL • Death can occur at much lower BAC where aspiration of vomit occurs 02/07/19 patki 23
- 24. Positional Asphyxia • Alcohol intoxication is the major risk factor for positional asphyxiation. Central nervous system depression causes relaxation of the muscles that keep the airway open during sleep • Average BAC in 23 cases of positional asphyxiation was reported to be 240 mg/100 mL (Bell et al. 1992) 02/07/19 patki 24
- 25. Tolerance • Chronic use of alcohol will result in a decreased susceptibility to the effects of alcohol • Visible signs of intoxication are decreased • Increased survivability even after consumption of large amounts of alcohol • Tolerance to alcohol may be either functional and/or metabolic in nature 02/07/19 patki 25
- 26. Functional Tolerance • Decreased sensitivity to the CNS depressant effects of EtOH • e.g. Integrity of phospholipid bilayer ↑ • e.g. Up-regulation of excitatory receptors • Requires higher BAC and higher doses of EtOH to produce the same effect • “Learning” by the chronic alcohol user 02/07/19 patki 26
- 27. Metabolic Tolerance • Induction of enzymes in chronic, heavy users of alcohol can result in an enhanced metabolic rate • Elimination rate in alcoholics has been measured at 40 mg/100 mL/hour and up • Result is a comparatively lower BAC after equivalent doses of alcohol are ingested 02/07/19 patki 27
- 28. Alcohol in Blood, Breath and Urine 02/07/19 patki 28
- 29. Alcohol in Blood • Plasma and serum are the “watery” components of whole blood • Plasma and serum therefore have a higher alcohol content than whole blood • Plasma:whole blood ratio ranges from approximately 1.0 to 1.3. Average plasma:whole blood ratio is 1.14 02/07/19 patki 29
- 30. Alcohol in Breath • Alcohol is volatile - at physiological temperatures alcohol will diffuse from the blood into the alveolar air of the lung and into the breath • Breath analysis is rapid, non-invasive, and does not require specialized medical personnel for sampling 02/07/19 patki 30
- 31. Henry’s Law • At a given temperature, the ratio of the concentration of a volatile compound in solution and the concentration of the volatile compound in the air above the solution is fixed • At 37° C, the amount of alcohol in the blood will be 2300x greater than the amount of alcohol in the end-expiratory breath 02/07/19 patki 31
- 32. Issues in Breath Testing Quality of the breath sample • End-expiratory breath is the best reflection of the alcohol content of the blood • A “poor quality” breath sample will result in an underestimate of blood alcohol concentration 02/07/19 patki 32
- 33. Issues in Breath Testing Mouth alcohol effect • Residual alcohol, temporarily trapped in the mouth may result in an elevated breath alcohol concentration • Sources of mouth alcohol • Recent ingestion of alcohol • Regurgitation or vomiting • Asthma inhalers • Breath sprays and mouthwashes 02/07/19 patki 33
- 34. Mouth alcohol effect • Since the mouth alcohol effect will dissipate within 15 minutes, observation of a subject for a minimum of 15 minutes will protect against artificially elevated breath alcohol results • Duplicate breath testing is a further safeguard against mouth alcohol effect 02/07/19 patki 34
- 35. Behavioural Effects of Alcohol 02/07/19 patki 35
- 36. Laboratory studies • Test the effect of alcohol on skills that are related to the operation of a motor vehicle • Choice reaction time • Visual tracking • Vigilance • Glare recovery 02/07/19 patki 36
- 37. Closed-course studies • Test the effect of alcohol on subjects driving real cars on closed-driving courses • Parking tasks • Emergency-braking tasks • Pylons on curves • Width judgment 02/07/19 patki 37
- 38. Epidemiological studies • Compare the BAC in drivers who have had accidents with the BAC of drivers who have not had accidents • Grand Rapids study by Robert Borkenstein, inventor of the Breathalyzer, conducted in 1964 02/07/19 patki 38
- 39. Grand Rapids Study • Relative probability of causing an accident increases exponentially with ↑ BAC • 80 mg/100 mL - 4x ↑ • 100 mg/100 mL - 7x ↑ • 150 mg/100 mL - 25x ↑ Borkenstein et al. 1974. Blutalkohol. 11: 7-13 0 5 10 15 20 25 30 35 40 45 50 0 20 40 60 80 100120140160 BAC (mg/100 mL) RelativeProbability 02/07/19 patki 39
- 40. Effects of Alcohol on Driving • At low BAC the faculties required for driving that are impaired are: • Judgment • Ability to divide attention • Choice reaction time 02/07/19 patki 40
- 41. Effects of Alcohol on Driving • With increasing BAC, the nature and the extent of impairment will increase • Impairment of other faculties, including: • Tracking • Vision 02/07/19 patki 41
- 42. Alcohol and Driving • In addition to the BAC, driving impairment will also be affected by: • Skills of the driver • Driving task • Tolerance to alcohol 02/07/19 patki 42
- 43. Alcohol and Memory 1. Memory loss may be characterized by forgotten events, later recoverable, either when brought to the individual’s attention or spontaneously 2. Memory loss may be non-recoverable; characterized by feelings of “lost time”, also known as an alcoholic blackout 02/07/19 patki 43
- 44. Alcohol Blackout • Amnesia for events occurring during any part of a drinking episode • Not associated with a loss of consciousness • May vary in length from hours to days • More common among alcoholics • Typically associated with high BAC • Rapid rise in BAC may contribute 02/07/19 patki 44
- 45. Side effects and Toxicity • Liver damage – 75% of all deaths due to alcoholism are caused by cirrhosis of the liver, the 7th most common cause of death in the US • Other effects are Panreatitis and chronic gastritis causing peptic ulcers “it provokes the desire, but it takes away the performance” “it provokes the desire, but it takes away the performance”02/07/19 patki 45
- 46. Side effects and Toxicity – Cont. • The metabolizing of alcohol produces free radicals, causing cancer in the liver and some hypothesis breast cancer also • Alcohol has immunosuppressive effects thus promoting tumor growth 02/07/19 patki 46
- 47. Teratogenic Effects • FAS – Fetal Alcohol Syndrome is accountable for 3 to 5 birth defects in 1000 • Causes low intelligence, mental retardation, behavioral abnormalities • There is retard body growth • Facial Abnormailities 02/07/19 patki 47
- 48. Teratogenic Effects – Cont. • Adolescents engage in anti-social behavior • These people are slow learners • Congenital heart defects • The point is – drinking is bad if you are pregnant, do not do it. 02/07/19 patki 48
- 49. Drugs to Help Maintain Abstinence • Alcohol-sensitizing drugs (including: disulfiram & calcium carbimide) : - Used to prevent the patient from drinking by producing an aversive reaction when consuming alcohol - The drug alters the metabolism of alcohol - Naltrexone. - Acamprosate- 02/07/19 patki 49
- 50. Drugs to Help Maintain Abstinence – Cont. - Allows acetaldehyde to accumulate which in turn causes acetaldehyde syndrome (characterized by throbbing headache, nausea, vomiting, chest pain ect.) Metronidazole, Graseofulvin. 02/07/19 patki 50
- 51. Alcohol. • Food value- 7 cal/g. • Contra- Peptic ulcer, Epilepsy. Liver problems. Pregnancy. Unstable . • Safe – 1-2. 02/07/19 patki 51
- 52. uses • Appetizer • Antiseptic • Rubefacient • Trigeminal • Bedsores • Methylalcohol poisoning. • Fainting. 02/07/19 patki 52
- 53. Methyl alcohol poisoning. • Gastric lavage • Sodium bicarbonate • Ethanol. • Hemodialysis. • Fomepizole- 4-Methyl pyrazole. Inhibitor of alcohol dehydrogenase. 02/07/19 patki 53 Comments- drpatki@gmail.com
Editor's Notes
- Pharmacology and toxicology of alcohol How is alcohol absorbed, distributed and eliminated in the human body? What are the effects of alcohol on the body and the various stages of alcohol intoxication? What role does tolerance play on the pharmacology and toxicology of alcohol? Alcohol in breath, blood and urine Since breath, blood and urine are the most important specimens that are analyzed for their alcohol content, we will concentrate on these samples and how they are used to measure alcohol at times of interest (for example the time of an assault or a car accident). Alcohol and driving impairment The most important behavioural effect of alcohol from the point of view of the forensic toxicologist is the effect of alcohol on the ability to drive a car. By far, this is the area of forensic toxicology that we are called upon the most to give expert witness testimony on so we will spend some time discussing how alcohol impairs driving ability. Effects of alcohol on memory and aggression These effects of alcohol are also important, and will come into play in cases other than impaired driving cases, such as homicides and sexual assault cases.
- What is alcohol? There are several different types of alcohol, all of which you are likely familiar with from their various household and industrial uses. The alcohol which we commonly associate with drinking is ethanol, or ethyl alcohol. Other alcohols which are encountered in forensic toxicology are: Methanol – also known sometimes as wood alcohol, methanol is a commonly used solvent and reagent in the chemical industry and is a component of windshield washer antifreeze. Isopropanol – what we commonly know as “rubbing alcohol”, isopropanol is a commonly used antiseptic. For example if you have had blood drawn at your physician’s office or at the hospital, it is likely that they swabbed the skin with isopropanol before insertion of the needle. Isopropanol is less toxic than methanol but actually has a greater central nervous system depression than ethanol does. Ethylene Glycol – the active component of antifreeze. It is very toxic and will be covered in the upcoming lecture on “other poisons”. Although there are several different types of alcohol that are encountered in forensic toxicology, I’m going to focus this lecture on ethanol. I will use ethanol and alcohol interchangeably – unless I specifically state otherwise you can assume that when I say alcohol, I am talking about ethanol.
- Ethanol may be administered through a variety of routes: Topical – dermal absorption of ethanol can occur, however it is a very inefficient means of administering alcohol particularly in adults. Young children, who have less keratin in their skin, are much more susceptible to the receipt of alcohol by this means. Inhalation – inhalation is similarly an ineffective means of administering alcohol. Several experiments have been done to examine this route of administration as it is a commonly used defense in impaired driving trials – that being that an individual “inadvertantly inhaled alcohol through their work or the environment in which they were prior to driving”. However, it has been shown that only small amounts of alcohol can be absorbed by this route and generally the conditions of inhalational exposure must be extreme for it to occur. Intravenous injection – is the most effective means of delivering alcohol to the blood (as with any drug – i.v. injection is ideal in that the drug is delivered directly into the blood, avoiding the necessity of an absorptive phase). Intravenous injection of ethanol does occur in some cases – typically cases of “junkies” who require a needle fix more than anything – however it is rare as there is extreme pain associated with the i.v. injection of alcohol. Given the rarity of i.v. injection of alcohol and the inefficiency of administration of alcohol through topical or inhalational routes, it is no surprise that the most common route of administration of alcohol in humans is via oral ingestion.
- Once ingested, alcohol in the stomach will proceed via the pyloric sphincter into the small intestine. Absorption occurs from the mucosal surfaces of the stomach and small intestine by simple diffusion (movement from a region of high concentration to a region of low concentration). Although a significant amount of ethanol is absorbed in the stomach, the small intestine is the major site of ethanol absorption – this is because the surface area available for contact with the blood is far greater in the small intestine than in the other parts of the GI tract.
- Effect of alcohol content of the ingested beverage on absorption Alcohol is most rapidly absorbed when the concentration of the ingested alcohol is between 10 and 30% v/v. Why? (1) Alcoholic beverages with lower alcohol content by volume (such as beer) do not benefit from as large a concentration gradient across stomach and intestinal wall. (2) Alcoholic beverages with higher alcohol content yield a high concentration gradient, however, more concentrated solutions are actually irritating to the gastric mucosa and pyloric sphincter – this increases mucous production and slows gastric emptying. The type of beverage that is consumed may also play a minor role in affecting absorption. For example, carbonated beverages may enhance absorption while fatty, oily or high volume alcoholic beverages will slow absorption through decreased gastric emptying.
- Presence of food: When food is taken along with alcohol, a lower, delayed BAC will occur. This is due to (1) the reduction in efficiency of absorption of alcohol due to prolonged gastric emptying time, (2) Michaelis-Menten kinetics at low BAC metabolism at proportionately higher rate. Because blood alcohol concentrations rise more slowly, metabolism is occurring at a proportionately higher rate. Secondary mechanisms of metabolism (in the stomah, gastric alcohol dehydrogenase) will also play a role. EXAMPLE GRAPH ON NEXT SLIDE
- Note: Peak blood alcohol concentration when alcohol is consumed on an empty stomach occurs at an earlier point in time than when drinking occurs on a full stomach. The peak blood alcohol concentration where alcohol is consumed on an empty stomach is higher than the peak blood alcohol concentration when consumption occurs on a full stomach.
- Alcohol is very hydrophilic and therefore present in any body tissue or fluid as a function of the water content of that tissue or fluid. Tissues with high water content (such as blood) will therefore have more alcohol than tissues with a low water content (such as bone or fat). Because the total amount of water in the body is different for different people, 2 people of the same weight, who consume the same amount of alcohol will have different blood alcohol concentrations. For example, age is a factor which affects TBW. TBW decreases with age. A younger person has proportionately more body water than an older person of the same sex and weight. TBW differs between men and women. Women have more fatty tissue than males of equivalent weights. The fatty tissue occurs in the body in place of body water, resulting in proportionately less body water among women as compared to men. For example, the average male is 70% water, whereas the average female is only 60% water. The result of this is that alcohol becomes more diluted when consumed by a male than a female and results in a lower blood alcohol concentration. TBW increases with body mass. The heavier a person is the more water they have, again, this results in a greater pool of water into which the alcohol is distributed and a resulting dilution occurs, producing a lower blood alcohol concentration. Example next slide
- Only between 5-10% of a dose of ingested ethanol is excreted unchanged in the urine, sweat, saliva and breath. The remaining ethanol is metabolized in the liver. Alcohol metabolism commences as soon as ethanol is absorbed and reaches the liver – so even while a person is consuming alcohol and may be experiencing an overall rise in their blood alcohol concentration, alcohol metabolism is occurring. The primary pathway for alcohol metabolism involves an enzyme known as alcohol dehydrogenase.
- Ethanol reacts with the cofactor NAD to form acetaldehyde and NADH. This reaction is facilitated by the cytosolic enzyme alcohol dehydrogenase (ADH). Acetaldehyde is further oxidized to acetic acid by the enzyme aldehyde dehydrogenase. Acetic acid (or acetate) then enters the aerobic respiration process (Krebs cycle or citric acid cycle) and breaks down to the final products – carbon dioxide and water. Although this is not the exclusive route of ethanol metabolism, it is the predominant route by which alcohol in the body is metabolized. Other routes of ethanol metabolism are by the enzyme catalase and by the microsomal ethanol-oxidizing system (MEOS). Catalase and MEOS contribute to less than 10% of the normal metabolism of ethanol. Nicotine adenine dinulcleotide (NAD) is also required in the alcohol dehydrogenase pathway
- At forensically relevant blood alcohol concentrations (for example, BAC greater than 10 mg/100 mL), the elimination of alcohol from the blood follows zero-order kinetics. Zero-order kinetics means that a predictable, constant amount of alcohol is removed from the blood per unit of time. [At lower blood alcohol concentrations &lt;10 mg/100 mL, first-order kinetics takes over and an exponential loss of ethanol occurs per unit time]. Zero-order kinetics = independent of the concentration in the blood and linear with time. For the majority of individuals, this predictable rate of elimination ranges between 10 and 20 milligrams of alcohol per 100 millilitres of blood per hour. A reasonable mean rate of elimination is 15 mg/100 mL/hour although in reality the average rate of elimination is probably slightly higher than this. For a given individual, the rate of elimination of alcohol from the blood is fixed and cannot be changed in the short-term by any of those “quick-fix”, sober-up-quick remedies – such as drinking coffee or taking a cold shower. The only way to remove alcohol from the blood is through the passage of time and none of the factors indicated here will enhance the removal of alcohol from the blood.
- A note on fructose, since the required text p. 175 indicates that the administration of fructose, glycine and alanine may enhance ethanol elimination. The action of fructose in the enhancement of ethanol oxidation has been explained through the production of a metabolite of fructose d-glyceraldehyde which provides increased NAD cofactor for the oxidation of ethanol. [Text also indicates “recent work has suggested that food, as well as affecting the absorption of ethanol might slightly enhance the elimination of ethanol” – this is unreferenced in the text, I would consider this an unfounded claim and until otherwise refuted, food should not be considered a possible means of increasing ethanol elimination in humans].
- Ethanol causes vasodilatation of the cutaneous vessels which creates a feeling of warmth (flush) often associated with the consumption of alcoholic beverages, also results in a decrease in body temperature (loss of heat at the skin surface). This vasodilatation does not occur uniformly over the vasculature. In fact, moderate doses of ethanol can cause vasoconstriction in the heart and the brain. Disinhibition – at low doses, alcohol induces behavioural excitement. The excitement is caused by a depression of inhibitory neurons within the brain that leaves a person in a state of disinhibition. Because alcohol often induces euphoria, it is commonly thought of as a stimulant rather than a depressant. However, behavioural excitation is due not to stmulation but by the depression of inhibition (taking your foot off the brake of a car will cause the car to speed up). “Loss of restraint”
- Ethanol is a non-selective central nervous system depressant; capable of inducing varying degrees of behavioural depression secondary to a non-selective depression of the Sedation – diminished environmental awareness, spontaneity and physical activity Drowsiness -
- Positional asphyxiation (also known as postural asphyxiation) – occurs when a person’s bodily position results in partial or complete airway obstruction. Death may then occur from asphyxiation. Positional asphyxiation criteria: The person is found in a position that does not allow adequate breathing; may involve a restrictive or confining position or a simple flexion of the head onto the chest. Partial or complete external airway obstruction or neck compression may also be apparent. The person could not extricate himself or herself from the fatal position through chemical intoxication or dementia. Other causes of death, either natural or unnatural, excluded as possibility. Bell et al. 1992. Am. J. For. Med. Path. 13(2): 101-107. Positional asphyxiation in adults: a series of 30 cases form the Dad and Broward County Florida Medical Examiner Offices from 1982 to 1990. Alcohol was identified as a risk factor in 22 of 30 cases of positional asphyxiation and the average BAC was 240 mg/100 mL. “Acute alcohol intoxication is the major risk factor for positional asphyxiation. Its central nervous system depression causes relaxation of the muscles that keep the airway open during sleep, in particular the…muscle which draws the tongue forward during inspiration and prevents its lapse into the pharynx”. Alcohol is also a cause of unconsciousness and prevents a victim from being alerted to the position which eventually leads to a lethal outcome.
- Review: definition of tolerance – a decreased response to repeated doses of a drug. Tolerance occurs when, as a result of chronic use of alcohol, there is an adaptation to the effects of alcohol and a decrease in the visible signs of intoxication.
- Functional tolerance is defined as a decrease in the sensitivity of the central nervous system to the depressant effects of ethanol. This occurs through a variety of mechanisms, each of which will compensate for the effects of alcohol. For example, one of the ways in which alcohol exerts its effects is through its entry and dissolution into the internal structure of cell membranes. Exapansion and fluidization of the cell membrane then produces the central nervous system depressant effects and anesthesia. Functional tolerance to alcohol can occur through an adaptation of the cell membrane to the presence of alcohol, thereby decreasing the amount of expansion and fluidization that occurs when alcohol is present. A second example is through the up-regulation of excitatory receptors. Alcohol inhibits excitatory receptors in the central nervous system and prevents the binding and activity of excitatory neurotransmitters (glutamate). By up-regulating or increasing the number of active excitatory receptors on any given neuron, an increased amount of alcohol is required to produce the same effect as was previously required. Another example of tolerance which may be included in this category is “learning” that occurs by the chronic alcohol user. Individuals who use alcohol chronically may develop habits and traits which prevent the visible signs of alcohol intoxication from being as noticeable (for example, they may learn to stand in a different position to avoid swaying).
- Definition of plasma – Plasma is the liquid component of a whole blood sample. Centrifugation of a whole blood sample to remove the red and white blood cells will leave plasma – a clear yellow fluid. Definition of serum – Serum is very similar to plasma, however in addition to the removal of red and white blood cells, the various factors required for clotting of the blood are also removed in a serum sample. Although serum and plasma are not the same thing scientifically speaking, they can be considered to be equivalent for the purposes of determining blood alcohol concentrations. Plasma:Blood Clinical laboratories, such as those in hospitals tend to perform alcohol analyses in serum or plasma and tend to report the results of those analyses in the units of mmol/L which are units that medical personnel are more accustomed to seeing. Therefore it is important to understand the relationship between blood alcohol and serum or plasma alcohol concentrations. Charlebois, Corbett and Wigmore, 1996. Paired serum and whole blood samples for n=235 samples. Found the serum/blood ratio ranged from 1.04:1 to 1.26:1, average serum:blood ratio was 1.14:1. The serum to blood ratio is independent of BAC. This average serum to blood ratio corroborates the theoretical plasma to blood ratio: Water content of plasma = 98% Water content of blood = 86%
- Unlike most drugs – alcohol is a volatile compound, and it will easily vapourize. Breath analysis is rapid, non-invasive, and does not require specialized medical personnel for sampling. This makes it an ideal specimen for testing possible drinking drivers at roadside (for example during RIDE checks) and in police stations.
- Henry’s Law is the basis for breath alcohol testing.
- Measurement of blood alcohol concentration through the use of a breath test is an indirect measure of analysis. The limitation of this Quality of sample – It is well established that the terminal portion of a prolonged breath expiration provides a sample that best reflects the alcohol concentration of arterial blood. Analysis of any portion of the breath sample prior to attaining deep lung air will result in an underestimate of blood alcohol concentration. It is standard breath sampling practice to provide a continuous exhalation and discard at least the first 2/3 of the sample before measurement is taken. Mouth alcohol – Alcohol in the oral cavity arising from recent alcohol ingestion, regurgitation of stomach contents containing alcohol can contaminate a breath sample and cause falsely elevated results.
- Mouth alcohol – Alcohol in the oral cavity arising from recent alcohol ingestion, regurgitation of stomach contents containing alcohol can contaminate a breath sample and cause falsely elevated results.
- The duration of the mouth alcohol effect is determined by the concentration of the alcohol containing substance. For example, a mouth alcohol effect that is caused by beer will be of shorter duration (approximately 5 minutes) than a mouth alcohol effect that is caused by vodka (approximately 10 minutes). However, regardless of the alcohol concentration of the substance responsible for the mouth alcohol effect – it has been shown experimentally that the mouth alcohol effect will dissipate within 15 minutes.
- At BAC of &lt; 50 mg/100 mL – alcohol may impair an individual’s ability to divide their attention between tasks and may affect an individual’s judgment – resulting in an increase in risk-taking behaviour. Judgment – At BAC of less than 50 mg/100 mL, experienced, professional drivers tended to overrate their ability to perform and were willing to attempt to drive their vehicle through narrower (sometimes, impossibly narrow) gaps. (Cohen et al. 1958). Increased hazard latency at BAC of 50 mg/100 mL and greater (West et al. 1993). Overall willingness to take risks increases as a result of impaired judgment. Divided attention – Impairment of divided attention has been measured at BAC as low as 15 mg/100 mL (Moskowitz et al. 1985) and 17 mg/100 mL (Hamilton and Copeman, 1970). Choice reaction time – A review of the literature by Howat et al. (1991) found choice reaction time increased over BAC ranging 44 to 92 mg/100 mL.
- Tracking – Alcohol resulted in significantly more errors being made in a compensatory tracking experiment by Burns and Moskowitz (1980) when BAC was 70 mg/100 mL. Vision – A decrease in peripheral attention, with fewer signal detections in the periphery was noted in individuals with BAC of 50 mg/100 mL and 100 mg/100 mL. Visual acuity (the ability to focus and distinguish between objects) was found to be impaired in 85% of subjects with levels between 101 and 125 mg/100 mL (Newman and Fletcher, 1941). Glare recovery is impeded at BAC ranging from 90 to 150 mg/100 mL.
- Alcohol can affect an individual’s memory for events that have occurred during a drinking period.
- Alcohol-induced blackouts are characterized by amnesia without the loss of consciousness – in other words, the person who is experiencing an alcohol-induced blackout will not be “passed out” during the episode, they will be awake and will appear to be functioning (albeit, possibly functioning in an intoxicated state). Witnesses of people who are in an alcohol-induced blackout will typically report that the individual was walking and talking for the duration of the time period. An alcohol-induced blackout may vary in length from a few hours to as long as a few days; although they are more likely to last for a period of hours than a period of days. Alcohol-induced blackouts are common among alcoholics but they can also occur in non-alcoholics including those drinkers that may be categorized as “social” or light drinkers. The typical scenario for an alcohol induced blackout is one in which an individual has consumed a large amount of alcohol over a short period of time. Consumption of alcohol on an empty stomach may also be a contributing factor as alcohol-induced blackouts are not only typified by high BAC but also typified by a rapid rise in the BAC.