Dasgupta Ph. D / Dasgupta Alcohol and Its Biomarkers

Clinical Aspects and Laboratory Determination
1. Auflage 2015
ISBN: 978-0-12-800409-8
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, 312 Seiten

Reihe: Clinical Aspects and Laboratory Determination

Alcohol and Its Biomarkers: Clinical Aspects and Laboratory Determination is a concise guide to all currently known alcohol biomarkers, their clinical application, and the laboratory methods used to detect them. Pathologists can use this resource to understand the limitations and cost factors associated with each method for determining certain alcohol biomarkers. In addition, interferences in these determinations are discussed, so that clinicians can understand the causes of falsely elevated biomarkers and pathologists and laboratory scientists can potentially eliminate them. The book focuses on the analytical methods used to detect alcohol in blood and urine, the limitations of alcohol determination using enzymatic methods, and the differences between clinical and forensic alcohol measurement. Chapters also cover cutting-edge alcohol biomarkers for potential use. - Focuses on the analytical methods used for detecting alcohol in blood and urine along with the pitfalls and limitations of alcohol determination using enzymatic methods - Explains the difference between clinical and forensic alcohol measurement - Includes a brief overview of the benefits of consuming alcohol in moderation and the hazards of heavy drinking

Amitava Dasgupta received his Ph. D in chemistry from Stanford University and completed his fellowship training in Clinical Chemistry from the Department of Laboratory Medicine at the University of Washington School of Medicine at Seattle. He is board certified in both Toxicology and Clinical Chemistry by the American Board of Clinical Chemistry. Currently, he is a tenured Full Professor of Pathology and Laboratory Medicine at the University of Kansas Medical Center and Director of Clinical Laboratories at the University of Kansas Hospital. Prior to this appointment he was a tenured Professor of Pathology and Laboratory Medicine at the University of Texas McGovern medical School from February 1998 to April 2022. He has 252 papers to his credit. He is in the editorial board of four journals including Therapeutic Drug Monitoring, Clinica Chimica Acta, Archives of Pathology and Laboratory Medicine, and Journal of Clinical Laboratory Analysis.

Autoren/Hrsg.

Dasgupta Ph. D, Dabcc

Dasgupta, Amitava

Inhaltsverzeichnis

1;Front Cover;1
2;Alcohol and Its Biomarkers;4
3;Copyright Page;5
4;Contents;6
5;Preface;12
6;1 Alcohol;14
6.1;1.1 Introduction;14
6.2;1.2 Alcohol Consumption: Historical Perspective;15
6.3;1.3 Alcohol Content of Various Alcoholic Beverages;16
6.4;1.4 Guidelines for Alcohol Consumption;17
6.5;1.5 Benefits of Drinking in Moderation;19
6.5.1;1.5.1 Moderate Alcohol Consumption and Reduced Risk of Cardiovascular Disease;20
6.5.2;1.5.2 Is Red Wine More Effective than other Alcoholic Beverages for Protecting the Heart?;23
6.5.3;1.5.3 Moderate Consumption of Alcohol and Reduced Risk of Stroke;23
6.5.4;1.5.4 Moderate Consumption of Alcohol and Reduced Risk of Developing Metabolic Syndrome and Type 2 Diabetes;24
6.5.5;1.5.5 Moderate Alcohol Consumption and Reduced Risk of Dementia/Alzheimer’s Disease;26
6.5.6;1.5.6 Association between Moderate Alcohol Consumption and Reduced Cancer Risk;26
6.5.7;1.5.7 Can Moderate Alcohol Consumption Prolong Life?;27
6.5.8;1.5.8 Moderate Alcohol Consumption and Reduced Risk of Arthritis;28
6.5.9;1.5.9 Moderate Alcohol Consumption and Reduced Chance of Getting the Common Cold;28
6.6;1.6 Adverse Heath Effects Related to Alcohol Dependence;29
6.6.1;1.6.1 Liver Diseases and Cirrhosis of the Liver Associated with Alcohol Abuse;29
6.6.2;1.6.2 Alcohol Abuse and Neurological Damage;31
6.6.3;1.6.3 Alcohol Abuse and Increased Risk of Cardiovascular Disease and Stroke;34
6.6.4;1.6.4 Alcohol Abuse and Damage to the Immune System;34
6.6.5;1.6.5 Alcohol Abuse and Damage to the Endocrine System and Bone;35
6.6.6;1.6.6 Alcohol Abuse Increases the Risk of Certain Cancers;35
6.6.7;1.6.7 Fetal Alcohol Syndrome;36
6.6.8;1.6.8 Alcohol Abuse and Reduced Life Span;37
6.6.9;1.6.9 Alcohol Abuse and Violent Behavior/Homicide;38
6.6.10;1.6.10 Alcohol Poisoning;39
6.7;1.7 Blood Alcohol Level;40
6.7.1;1.7.1 Alcohol Odor on Breath and Endogenous Alcohol Production;42
6.8;1.8 Conclusions;43
6.9;References;43
7;2 Genetic Aspects of Alcohol Metabolism and Drinking Behavior;50
7.1;2.1 Introduction;50
7.2;2.2 Alcohol Absorption: Effect of Food;50
7.3;2.3 First-Pass Metabolism of Alcohol;52
7.4;2.4 Alcohol Metabolism;53
7.4.1;2.4.1 Non-Oxidative Pathways of Alcohol Metabolism;55
7.4.2;2.4.2 Factors Affecting Alcohol Metabolism;56
7.5;2.5 Genes Encoding Alcohol Dehydrogenase;58
7.5.1;2.5.1 Polymorphism of Alcohol Dehydrogenase Genes;59
7.6;2.6 Genes Encoding Aldehyde Dehydrogenase;61
7.6.1;2.6.1 Polymorphisms of Alcohol Dehydrogenase and Aldehyde Dehydrogenase Genes that Protect Against the Development of Alcoh...;64
7.6.2;2.6.2 Polymorphism of Alcohol Dehydrogenase and Aldehyde Dehydrogenase Genes that may Increase the Risk of Developing Alcoh...;69
7.7;2.7 Polymorphism of the CYP2E1 Gene;72
7.8;2.8 Conclusions;72
7.9;References;73
8;3 Measurement of Alcohol Levels in Body Fluids and Transdermal Alcohol Sensors;78
8.1;3.1 Introduction;78
8.2;3.2 Breath Alcohol Determination;81
8.2.1;3.2.1 Chemical Principle of Breath Alcohol Analyzers;82
8.2.2;3.2.2 Effect of Breathing Pattern on Breath Alcohol Test Results;84
8.2.3;3.2.3 Interference in Various Breath Alcohol Analyzers;84
8.3;3.3 Blood Alcohol Determination;87
8.3.1;3.3.1 Enzymatic Alcohol Assays and Limitations;88
8.3.2;3.3.2 Gas Chromatography in Blood Alcohol Determination;91
8.3.3;3.3.3 Stability of Alcohol in Blood During Storage;92
8.3.4;3.3.4 Correlation between Blood and Breath Alcohol;93
8.4;3.4 Endogenous Production of Alcohol;94
8.5;3.5 Urine Alcohol Determination;95
8.6;3.6 Saliva Alcohol Determination;97
8.7;3.7 Transdermal Alcohol Sensors;98
8.8;3.8 Conclusions;100
8.9;References;100
9;4 Alcohol Biomarkers;104
9.1;4.1 Introduction;104
9.2;4.2 State Versus Trait Alcohol Biomarkers;105
9.3;4.3 Liver Enzymes as Alcohol Biomarkers;107
9.4;4.4 Mean Corpuscular Volume as Alcohol Biomarker;110
9.5;4.5 Carbohydrate-Deficient Transferrin as Alcohol Biomarker;111
9.5.1;4.5.1 Combined CDT–GGT as Alcohol Biomarker;113
9.6;4.6 ß-Hexosaminidase as Alcohol Biomarker;114
9.7;4.7 Ethyl Glucuronide and Ethyl Sulfate as Alcohol Biomarkers;115
9.8;4.8 Fatty Acid Ethyl Ester as Alcohol Biomarker;117
9.9;4.9 Phosphatidylethanol as Alcohol Biomarker;119
9.10;4.10 Total Plasma Sialic Acid as Alcohol Biomarker;121
9.11;4.11 Sialic Acid Index of Apolipoprotein J;122
9.12;4.12 5-HTOL/5-HIAA as Alcohol Biomarker;122
9.13;4.13 Other Alcohol Biomarkers;123
9.14;4.14 Clinical Application of Alcohol Biomarkers;124
9.14.1;4.14.1 Diagnosis Using DSM-IV and DSM-5;124
9.14.2;4.14.2 Self-Assessment of Alcohol Use;124
9.14.3;4.14.3 Alcohol Biomarkers and AUDIT;125
9.14.4;4.14.4 Application of Alcohol Biomarkers;126
9.14.5;4.14.5 Combining Alcohol Biomarkers;127
9.15;4.15 Conclusions;129
9.16;References;129
10;5 Liver Enzymes as Alcohol Biomarkers;134
10.1;5.1 Introduction;134
10.2;5.2 Factors Affecting Liver Function Tests;135
10.3;5.3 Effect of Moderate Alcohol Consumption on Liver Enzymes;138
10.4;5.4 GGT as Alcohol Biomarker;139
10.4.1;5.4.1 Elevated GGT in Various Diseases and as a Risk Factor for Mortality and Certain Illnesses;143
10.4.2;5.4.2 GGT Fraction as Alcohol Biomarker;145
10.5;5.5 Laboratory Determinations of Liver Enzymes;146
10.6;5.6 Conclusions;147
10.7;References;147
11;6 Mean Corpuscular Volume and Carbohydrate-Deficient Transferrin as Alcohol Biomarkers;152
11.1;6.1 Introduction;152
11.2;6.2 Mean Corpuscular Volume as Alcohol Biomarker;152
11.2.1;6.2.1 Mechanism of Increased MCV in Alcoholics;154
11.2.2;6.2.2 Other Causes of Macrocytosis;154
11.3;6.3 Carbohydrate-Deficient Transferrin;155
11.3.1;6.3.1 Mechanism of Formation of CDT;157
11.3.2;6.3.2 Cutoff Values, Sensitivity, and Specificity of CDT;157
11.3.3;6.3.3 CDT and GGT as Combined Alcohol Biomarker;160
11.3.4;6.3.4 Application of CDT;161
11.3.5;6.3.5 Limitations of CDT as Alcohol Biomarker;164
11.4;6.4 Laboratory Determination of CDT;167
11.5;6.5 Conclusions;171
11.6;References;171
12;7 ß-Hexosaminidase, Acetaldehyde–Protein Adducts, and Dolichol as Alcohol Biomarkers;176
12.1;7.1 Introduction;176
12.2;7.2 ß-Hexosaminidase Isoforms;176
12.3;7.3 ß-Hexosaminidase as Alcohol Biomarker;177
12.3.1;7.3.1 Pathophysiological Conditions that Cause Elevated Levels of ß-Hexosaminidase;181
12.4;7.4 Laboratory Methods for Measuring ß-Hexosaminidase;184
12.5;7.5 Acetaldehyde–Protein Adducts as Alcohol Biomarkers;185
12.5.1;7.5.1 Acetaldehyde–Hemoglobin Adducts;186
12.5.2;7.5.2 Acetaldehyde–Erythrocyte Protein Adducts;187
12.5.3;7.5.3 IgA Antibody Against Acetaldehyde-Modified Bovine Serum Albumin;188
12.6;7.6 Dolichol as Alcohol Biomarker;188
12.7;7.7 Conclusions;190
12.8;References;190
13;8 Direct Alcohol Biomarkers Ethyl Glucuronide, Ethyl Sulfate, Fatty Acid Ethyl Esters, and Phosphatidylethanol;194
13.1;8.1 Introduction;194
13.2;8.2 Ethyl Glucuronide and Ethyl Sulfate;195
13.3;8.3 Ethyl Glucuronide and Ethyl Sulfate as Alcohol Biomarkers;199
13.3.1;8.3.1 Ethyl Glucuronide and Ethyl Sulfate Observed Due to Incidental Exposure to Alcohol;201
13.3.2;8.3.2 Ethyl Glucuronide and Ethyl Sulfate Cutoff Concentrations in Urine;204
13.3.3;8.3.3 Ethyl Glucuronide and Ethyl Sulfate Cutoff Concentrations in Hair, Meconium, and other Matrices;205
13.3.4;8.3.4 False-Positive/False-Negative Results with Ethyl Glucuronide;207
13.3.5;8.3.5 Application of Ethyl Glucuronide and Ethyl Sulfate as Alcohol Biomarkers;209
13.3.6;8.3.6 Laboratory Methods for Determination of Ethyl Glucuronide and Ethyl Sulfate;212
13.4;8.4 Fatty Acid Ethyl Esters as Alcohol Biomarkers;214
13.4.1;8.4.1 Fatty Acid Ethyl Esters in Hair;215
13.4.2;8.4.2 Fatty Acid Ethyl Esters in Meconium;217
13.4.3;8.4.3 Laboratory Analysis of Fatty Acid Ethyl Esters;219
13.5;8.5 Phosphatidylethanol as Alcohol Biomarker;220
13.5.1;8.5.1 Cutoff Concentration of Phosphatidylethanol;223
13.5.2;8.5.2 Laboratory Analysis of Phosphatidylethanol;224
13.6;8.6 Sensitivity and Specificity of Direct Alcohol Biomarkers;226
13.7;8.7 Conclusions;228
13.8;References;228
14;9 Less Commonly Used Alcohol Biomarkers and Proteomics in Alcohol Biomarker Discovery;234
14.1;9.1 Introduction;234
14.2;9.2 Total Sialic Acid in Serum as Alcohol Biomarker;234
14.2.1;9.2.1 Other Causes of Elevated Plasma Sialic Acid Concentrations;237
14.2.2;9.2.2 Laboratory Determination of Total Sialic Acid;238
14.3;9.3 Sialic Acid Index of Apolipoprotein J as Alcohol Biomarker;240
14.3.1;9.3.1 Laboratory Methods for the Determination of the Sialic Acid Index of Plasma Apolipoprotein J;242
14.4;9.4 5-Hydroxytryptophol as Alcohol Biomarker;243
14.4.1;9.4.1 Laboratory Methods for Determining 5-HTOL and 5-HIAA;248
14.5;9.5 Other Alcohol Biomarkers;249
14.6;9.6 Proteomics in Alcohol Biomarker Discovery;250
14.6.1;9.6.1 Specific Proteins Identified as Alcohol Biomarkers Using the Proteomics Approach;251
14.7;9.7 Conclusions;254
14.8;References;254
15;10 Genetic Markers of Alcohol Use Disorder;258
15.1;10.1 Introduction;258
15.2;10.2 Heredity, Environment, and Alcohol Use Disorder;259
15.2.1;10.2.1 Effect of Nongenetic Factors on the Development of Alcohol Use Disorder;260
15.3;10.3 Genes and Alcohol Use Disorder: An Overview;261
15.4;10.4 Polymorphisms in Genes Encoding Alcohol Dehydrogenase and Aldehyde Dehydrogenase;263
15.4.1;10.4.1 Polymorphisms that Protect from Alcohol Use Disorder;264
15.4.2;10.4.2 Polymorphisms that may Increase the Risk of Alcohol Use Disorder;266
15.5;10.5 Neurobiological Basis of Alcohol Use Disorder;266
15.6;10.6 Polymorphisms of Genes in Dopamine Pathway and Alcohol Use Disorder;267
15.6.1;10.6.1 Dopamine Receptors;268
15.6.2;10.6.2 Dopamine Transporters and Dopamine-Metabolizing Enzymes;271
15.6.3;10.6.3 Monoamine Oxidase;272
15.6.4;10.6.4 Catechol-O-Methyltransferase;272
15.7;10.7 Polymorphisms of Genes in the Serotonin Pathway and Alcohol Use Disorder;273
15.8;10.8 Polymorphisms of Genes in the Gaba Pathway and Alcohol Use Disorder;277
15.9;10.9 Polymorphisms of Genes Encoding Cholinergic Receptors and Alcohol Use Disorder;280
15.10;10.10 Polymorphisms of Genes in the Glutamate Pathway and Alcohol Use Disorder;282
15.11;10.11 Polymorphisms of Genes Encoding Opioid Receptors and Alcohol Use Disorder;285
15.12;10.12 Polymorphisms of Genes Encoding Cannabinoid Receptors and Alcohol Use Disorder;287
15.13;10.13 Adenylyl Cyclase and Alcohol Use Disorder;288
15.14;10.14 Neuropeptide Y and Alcohol Use Disorder;290
15.15;10.15 Possible Association of Polymorphisms of other Genes With Alcohol Use Disorder;291
15.16;10.16 Epigenetics and Alcohol Use Disorder;291
15.17;10.17 Conclusions;294
15.18;References;294
16;Index;302

Leseproben

Chapter 2 Genetic Aspects of Alcohol Metabolism and Drinking Behavior
This chapter discusses the various pathways of alcohol metabolism, including alternative pathways in alcoholics that may cause the generation of free radicals and oxidative stress. Gender differences in alcohol metabolism and the effect of food on alcohol absorption are also addressed. Keywords
Alcohol metabolism; alcohol dehydrogenase; aldehyde dehydrogenase; polymorphism Contents 2.1 Introduction 37 2.2 Alcohol Absorption: Effect of Food 37 2.3 First-Pass Metabolism of Alcohol 39 2.4 Alcohol Metabolism 40 2.4.1 Non-Oxidative Pathways of Alcohol Metabolism 42 2.4.2 Factors Affecting Alcohol Metabolism 43 2.5 Genes Encoding Alcohol Dehydrogenase 45 2.5.1 Polymorphism of Alcohol Dehydrogenase Genes 46 2.6 Genes Encoding Aldehyde Dehydrogenase 48 2.6.1 Polymorphisms of Alcohol Dehydrogenase and Aldehyde Dehydrogenase Genes that Protect Against the Development of Alcohol Use Disorder 51 2.6.2 Polymorphism of Alcohol Dehydrogenase and Aldehyde Dehydrogenase Genes that may Increase the Risk of Developing Alcohol Use Disorder 56 2.7 Polymorphism of the CYP2E1 Gene 59 2.8 Conclusions 59 References 60 2.1 Introduction
Ethanol, commonly referred to as “alcohol,” is a small water-soluble polar molecule with a molecular weight of 46. The ethanol molecule contains a hydroxyl (–OH) functional group. Alcohol (ethanol) is a nutrient with a caloric value of approximately 7 kcal/g, whereas protein has a caloric value of 4 kcal/g and fat produces 9 kcal/g. After ingestion, alcohol is readily absorbed, but a small amount also undergoes first-pass metabolism. Absorption of alcohol from the gastrointestinal tract depends on how fast the person is drinking as well as whether or not alcohol is consumed with food. After absorption, alcohol is distributed in various tissues and also undergoes extensive metabolism and finally elimination. Although the majority of alcohol is metabolized via the oxidative pathway mainly involving two enzymes—alcohol dehydrogenase and aldehyde dehydrogenase—a small amount is also oxidized by the liver cytochrome P450 enzyme system, most commonly CYP2E1, especially in the presence of a high blood alcohol level. Other enzymes, such as catalase, may also be capable of metabolizing alcohol, but they represent a minor pathway. Polymorphisms of genes coding both alcohol dehydrogenase and aldehyde dehydrogenase enzymes affect blood alcohol level, and some polymorphisms may protect an individual from alcohol abuse. Minor non-oxidative metabolic pathways for alcohol involve conjugation with glucuronic acid yielding ethyl glucuronide and conjugation with sulfate to produce ethyl sulfate. 2.2 Alcohol Absorption: Effect of Food
Alcohol is absorbed from both the stomach and small intestine. A small amount of alcohol that is not absorbed is found in the breath and is the basis of breath analysis of drivers suspected of driving while intoxicated. In general, it is assumed that approximately 1–5% of alcohol is excreted by the lungs, and 1–3% is excreted via other routes such as urine (0.5–2.0%) and sweat (up to 0.5%). A very small amount of alcohol is also metabolized by non-oxidative pathways, and products of such reactions are often used as alcohol biomarkers, such as ethyl glucuronide and ethyl sulfate. The overall elimination process of alcohol can be described by a capacity-limited model similar to the Michaelis–Menten model of enzyme kinetics [1]. When alcohol is consumed, approximately 20% is absorbed by the stomach and the rest is absorbed by the small intestine by passive diffusion. A peak concentration is usually achieved 30–60 min after consumption. Food substantially slows the absorption of alcohol, and sipping of alcohol instead of drinking also slows the absorption of alcohol from the gastrointestinal tract. The presence of food in the stomach before alcohol consumption delays gastric emptying and reduces the rate of delivery of alcohol in the duodenum, thus reducing the alcohol absorption rate. The effect of food on absorption and metabolism of alcohol has been widely studied and reported in the medical literature. In one study, 10 healthy men took in, via drinking, a moderate dosage of alcohol (0.80 g of alcohol per kilogram of body weight) in the morning after an overnight fast or immediately after breakfast (two cheese sandwiches, one boiled egg, orange juice, and fruit yogurt). Subjects who consumed alcohol on an empty stomach felt more intoxicated than those who consumed the same amount of alcohol after eating breakfast. The blood alcohol analysis revealed that the average peak blood alcohol in subjects who consumed alcohol on an empty stomach was 104 mg/dL. In contrast, the average peak blood alcohol in subjects who consumed alcohol after eating breakfast was 67 mg/dL. The time required to metabolize the total amount of alcohol was on average 2 hr shorter in subjects who consumed alcohol after eating breakfast compared to subjects who consumed alcohol on an empty stomach. The authors concluded that food in the stomach before alcohol consumption not only reduces the peak blood alcohol concentration but also increases elimination of alcohol from the body [2]. The effect of the nature of the food, such as high fat versus high protein or high carbohydrate, on the magnitude of the reduction of absorption of alcohol has also been studied. Jones et al. reported that the average peak blood alcohol level was 30.8 mg/dL in volunteers when alcohol was consumed on an empty stomach, but levels were respectively 16.6, 17.77, and 13.3 mg/dL when alcohol was consumed after eating a fatty meal, a meal rich in carbohydrates, or a meal rich in protein. The peak blood concentration was reached between 30 and 60 min after alcohol was consumed on an empty stomach or after eating a meal rich in protein. However, peak alcohol level was reached between 30 and 90 min when alcohol was consumed after eating a meal rich in fat or rich in carbohydrates. As expected, intravenous infusion of alcohol resulted in a higher average blood alcohol level of 54.3 mg/mL, and peak blood alcohol was observed within 30 min. The authors concluded that regardless of the composition of the meal, food in the stomach decreases the systemic availability of alcohol, probably due to slower gastric emptying time. Moreover, with food in the stomach, a portion of alcohol may be trapped by the constituents of the meal [3]. 2.3 First-Pass Metabolism of Alcohol
After alcohol is ingested, a small portion of alcohol enters the hepatic portal system and undergoes first-pass metabolism (FPM) by the liver, but gut alcohol dehydrogenase enzymes also play an important role in FPM of alcohol. Lim et al. commented that FPM of alcohol is predominantly gastric in nature [4]. In relation to alcohol, many factors affect FPM of alcohol, including gastrointestinal motility, nutritional status, liver function, gender, and age, as well as the genetic makeup of the person. After drinking the same amount of alcohol, men have a lower peak blood alcohol level compared to women with the same body weight. This gender difference in the blood alcohol level is partly related to the different body water content in men and women: women have a lower amount of body water (52% body water content is the average in women) compared to men (61% average). Therefore, less body water is available to dissolve the same amount of alcohol, which is water soluble, in women compared to men. However, gender difference in the rate of metabolism of alcohol by the alcohol dehydrogenase enzyme present in gastric mucosa is also responsible for higher blood alcohol in women compared to men with same body weight after consumption of the same amount of alcohol. Ammon et al. reported that total FPM on average accounted for 9.1% of alcohol metabolism in men and 8.4% in women. Dose-corrected values for the area under the blood alcohol concentration–time curves (AUC) over time were on average 28% higher in women than in men [5]. Marshall et al., who studied 9 normal women and 10 normal men, observed that, after oral ethanol administration (0.5 g/kg body weight), women showed higher peak blood alcohol levels than did men (mean: 88 mg/dL in women and 75 mg/dL in men). The mean apparent volume of distribution of alcohol was 0.59 L/kg in females and 0.73 L/kg in men. Both apparent volume of distribution of alcohol and AUC were significantly correlated with total body water (measured by 3H water dilution), suggesting that gender difference in ethanol pharmacokinetics may be related to gender difference relating to body water content [6]. First-pass metabolism of alcohol by gastric alcohol dehydrogenase (ADH) is slightly higher in men than in women, and this may be related to higher ADH activity in men than in women, especially women younger than age 50 years. Commonly used drugs, such as acetaminophen, aspirin, and H2 blockers (ranitidine, cimetidine, etc.), may decrease the activity of gastric ADH, thus reducing FPM of alcohol. As a result, elevated...