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ALCOHOLISM Epidemiology United States • Alcohol use is the fourth leading cause of preventable death in the United States (after smoking, high blood pressure, and obesity). According to the CDC, excessive alcohol use led to approximately 88,000 deaths in the United States from 2006 – 2010. • The economic costs of excessive alcohol consumption in 2010 were estimated at $249 billion, or $2.05 a drink. Turkey • In a review of 7249 autopsies in the Morgue Department of Istanbul, in 1994–1996, alcohol was detected in 21.9% of all traffic accident cases, and 56.2% of these cases were drivers. • Of the 30 485 calls reported to the Drug and Poison Information Center in Izmir, Turkey between 1993 and 2002, 996 (3.3%) cases were that of alcohol poisoning. • The rate of alcoholic psychosis incidence per 100 000 population was 0.04 in both 1997 and 1998. • The number of alcohol-related road traffic accidents per 100 000 population was 4.35 in 2000 and 3.59 in 2001. Diagnosis • The diagnosis of an alcohol problem is best made by the history. Laboratory tests have a sensitivity of no better than 50%, and physical examination is helpful only after the consequences of alcoholism are apparent. Early diagnosis based on a careful history can prevent such consequences. Physicians should use terms such as "person with an alcohol problem" rather than "alcoholic" or "addict," which are commonly used but demeaning shorthand terms. Screening - THE AUDIT - THE CAGE - DSM-5 • The AUDIT (alcohol use disorders identification test) is the best test for screening because it detects hazardous drinking and alcohol abuse. Furthermore, it has a greater sensitivity in populations with a lower prevalence of alcoholism. One study suggested that questions 1, 2, 4, 5, and 10 were nearly as effective as the entire questionnaire. If confirmed, AUDIT would be easier to administer. • The AUDIT can be administered as a paper-and-pencil test, but the CAGE questionnaire should be administered face to face. • The CAGE ([need to] cut down [on drinking], annoyance, guilt [about drinking], [need for] eye-opener) questionnaire is the best-known and most-studied short screening test for alcohol problems. • The CAGE questions should be given face-to-face (not as a paper and pencil test) and should be asked before questions on quantity and frequency (the sensitivity of the questions drops if quantity questions precede them). The following 4 questions make up the CAGE questionnaire: • Have you ever felt the need to cut down on your drinking? • Have people annoyed you by criticizing your drinking? • Have you ever felt bad or guilty about your drinking? • Have you ever had a drink first thing in the morning to steady your nerves or get rid of a hangover? Patients who answer affirmatively to 2 questions are 7 times more likely to be alcohol dependent than the general population. DSM-5 criteria are as follows: • A maladaptive pattern of substance use leading to clinically significant impairment or distress, as manifested by 2 or more of the following, occurring at any time in the same 12-month period: • Alcohol is often taken in larger amounts or over a longer period than was intended. • There is a persistent desire or unsuccessful efforts to cut down or control alcohol use. • A great deal of time is spent in activities necessary to obtain alcohol, use alcohol, or recover from its effects. • Craving, or a strong desire or urge to use alcohol. • Recurrent alcohol use resulting in a failure to fulfill major role obligations at work, school, or home. • Continued alcohol use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of alcohol. • Important social, occupational, or recreational activities are given up or reduced because of alcohol use. • Recurrent alcohol use in situations in which it is physically hazardous. • Alcohol use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by alcohol. Tolerance, as defined by either of the following: • A need for markedly increased amounts of alcohol to achieve intoxication or desired effect. • A markedly diminished effect with continued use of the same amount of alcohol. Withdrawal, as manifested by either of the following: • The characteristic withdrawal syndrome for alcohol • Alcohol (or a closely related substance, such as a benzodiazepine) is taken to relieve or avoid withdrawal symptoms. Specify if the Alcohol Use Disorder is: • Mild - Presence of 2–3 symptoms • Moderate - Presence of 4–5 symptoms • Severe - Presence of 6 or more symptoms Specify if the Alcohol Use Disorder is: • In early remission - The individual who had once met criteria for Alcohol Use Disorder has not met criteria for more than 3 months and less than 12 months (does not count the presence of cravings) • In sustained remission - The individual who had once met criteria for Alcohol Use Disorder has not met criteria for more than 12 months (does not count the presence of cravings) Physical • • • • • • • The following are signs and symptoms of alcohol withdrawal: Nausea and vomiting Diaphoresis Agitation and anxiety Headache Tremor Seizures Visual and auditory hallucinations: Many patients who are not disoriented, and who therefore do not have delirium tremens, have hallucinations. The following are signs of delirium tremens (ie, alcohol withdrawal delirium): • Tachycardia and hypertension • Temperature elevation • Delirium • • • • • • The following are signs of chronic alcoholism: Gynecomastia Spider angiomata Dupuytren contractures (also may be congenital) Testicular atrophy Enlarged or shrunken liver Enlarged spleen Causes Psychological studies • Behavioral models explain alcohol abuse in terms of learning theory. Through operant conditioning, the reinforcing elements of alcohol use become habitual. • Cognitive models explain alcohol abuse in terms of “automatic thoughts,” which precede the person’s more identifiable feelings about alcohol. For example, an automatic thought might be “I deserve a drink because I’ve had a rough day." • Psychoanalytic models explain alcohol abuse in terms of ego defenses and intrapsychic conflicts. The alcohol serves as a way to escape the uncomfortable internal conflict. Differential Diagnoses • • • • • • • Anxiety Disorder Bipolar Affective Disorder Depression Dysthymic Disorder Insomnia Panic Disorder Social Phobia Biomarkers • • • • • Indirect alcohol biomarkers include aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltransferase (GGT), mean corpuscular volume (MCV) carbohydrate-deficient transferrin (CDT) Direct alcohol biomarkers include • alcohol itself • ethyl glucuronide (EtG). Medical Care Treatment of alcoholism involves the following: • Brief physician advice makes a difference. • While a trial period of controlled drinking with careful follow-up might be appropriate for a diagnosis of alcohol abuse, this approach increases a physician's professional liability. Complete abstinence is the only treatment for alcohol dependence. Emphasize that the most common error is underestimating the amount of help that will be needed to stop drinking. The differential diagnosis between alcohol abuse and dependence can be a difficult judgment call. • Hospitalize patients if they have a history of delirium tremens or if they have significant comorbidity. Consider inpatient treatment if the patient has poor social support, significant psychiatric problems, or a history of relapse after treatment. • Strongly recommend AA. • Encourage hospitalized patients to call AA from the hospital. AA will send someone to talk to them if the patient makes the contact. Patients need to attend meetings regularly (daily at first) and for a sufficient length of time (usually 2 y or more) because recovery is a difficult and lengthy process. • In the beginning of treatment, and perhaps ongoing, patients should remove alcohol from their homes and avoid bars and other establishments where strong pressures to drink may influence successful abstinence. • If the patient has an antisocial personality (ie, severe problems with family, peers, school, and police before age 15 y and before the onset of alcohol problems), recovery is less likely. If the patient has primary depression, anxiety disorder, or another potentially contributory disorder (the other disorder must antedate the problems with alcohol or it must be a significant problem during long periods of sobriety), treat this primary problem aggressively. Medication • Glutamate receptor blockers - Acamprosate (Campral) Mechanism of action is unknown, but it enhances GABA transmission and inhibits glutamate transmission. Compared with placebo, reduces drinking frequency and effectively increases abstinence in patients with alcoholism. • Aldehyde dehydrogenase inhibitors - Disulfiram (Antabuse) Disulfiram inhibits aldehyde dehydrogenase, and, as a result, acetaldehyde accumulates. This leads to nausea, hypotension, and flushing if a person drinks alcohol while taking disulfiram. • Opiate antagonists - Naltrexone (ReVia, Vivitrol) Alcohol has been shown to bind to opiate receptors in the brain. Studies show that blocking opiate receptors decreases cravings for alcohol. History • Cannabis, also known as marijuana among several other names, is a preparation of the Cannabis sativa plant intended for use as a psychoactive drug or medicine. The main psychoactive part of cannabis is tetrahydrocannabinol (THC); one of 483 known compounds in the plant, including at least 65 other cannabinoids. Cannabis can be used by smoking, vaporization, within food, or as an extract. • Cannabis is mostly used recreationally or as a medicinal drug. It may also be used for religious or spiritual purposes. In 2013, between 128 and 232 million people used cannabis (2.7% to 4.9% of the global population between the ages of 15 and 65).In 2015, 43% of Americans had used cannabis, which increased to 51% in 2016. This makes it the most commonly used illegal drug both in the world and the United States. • Synthetic cannabinoids are a class of chemicals that are different from the cannabinoids found in cannabis but which also bind to cannabinoid receptors. They are often marketed as designer drugs or sold in products with claims that they give the effects of cannabis. When these chemicals are sprayed or otherwise soaked into a plant or other base material the blend is sometimes misleadingly referred to as synthetic marijuana. These synthetic marijuana products are sold for recreational drug use. • There are several psychoactive artificial cannabinoid families (e.g. AM-xxx, HU-xxx, JWH-xxx, CP xx) that are sprayed onto plant matter that is then sold under brand names like K2 and Spice (In Turkey, Bonzai) both of which are now often used as generic terms used for any synthetic cannabis product. • Synthetic cannabinoids are made in the lab and are more powerful than natural ones. There is no upper limit to the psychoactive effects of these compounds, and the potency can vary greatly, which means it’s easier to experience harmful reaction with synthetic cannabinoids. Ingestion of synthetic marijuana can lead to toxic side effects like seizures, hallucinations and convulsions, and can cause extremely severe reactions, including ischemic stroke. • Although there’s no official study on the effects of synthetic cannabinoids on humans, there are reports describing harmful effects such as hypertension, tachycardia, vomiting, agitation, myocardial infarction, panic attacks, blurred vision and psychoses. Cannabis intoxication Defined by DSM-5, as the following: • Recent use of cannabis • Clinically significant problematic behavioral or psychological changes (eg, impaired motor coordination, euphoria, anxiety, sensation of slowed time, impaired judgment, social withdrawal) that developed during, or shortly after, cannabis use • At least 2 of the following signs, developing within 2 hours of cannabis use:Conjunctival injection o Increased appetite o Dry mouth o Tachycardia • Symptoms not due to a general medical condition and not better accounted for by another mental disorder Cannabis use disorder DSM-5 as the following: • A problematic pattern of cannabis use leading to clinically significant impairment or distress, as manifested by at least 2 of the following, occurring within a 12-month period: o Cannabis is often taken in larger amounts or over a longer period than was intended. o There is a persistent desire or unsuccessful efforts to cut down or control cannabis use. o A great deal of time is spent in activities necessary to obtain cannabis, use cannabis, or recover from its effects. o Craving, or a strong desire or urge to use cannabis. o Recurrent cannabis use resulting in a failure to fulfill major role obligations at work, school, or home. o Continued cannabis use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of cannabis. o Important social, occupational, or recreational activities are given up or reduced because of cannabis use. o Recurrent cannabis use in situations in which it is physically hazardous. o Cannabis use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by cannabis. • Tolerance, as defined by either a (1) need for markedly increased cannabis to achieve intoxication or desired effect or (2) markedly diminished effect with continued use of the same amount of the substance. • Withdrawal, as manifested by either (1) the characteristic withdrawal syndrome for cannabis or (2) cannabis is taken to relieve or avoid withdrawal symptoms Clinicians are instructed to specify the following: • In early remission - After full criteria for cannabis use disorder were previously met, none of the criteria for cannabis use disorder has been met for at least 3 months but for less than 12 months (with an exception provided for craving). • In sustained remission - After full criteria for cannabis use disorder were previously met, none of the criteria for cannabis use disorder has been met at any time during a period of 12 months or longer (with an exception provided for craving). Cannabis withdrawal DSM-5 provided criteria for cannabis withdrawal defined as follows: • Cessation of cannabis use that has been heavy and prolonged (ie, usually daily or almost daily use over a period of at least a few months). • Three or more of the following signs and symptoms develop within approximately 1 week after cessation of heavy, prolonged use: o Irritability, anger or aggression o Nervousness or anxiety o Sleep difficulty (ie, insomnia, disturbing dreams) o Decreased appetite or weight loss o Restlessness o Depressed mood o At least one of the following physical symptoms causing significant discomfort: abdominal pain, shakiness/tremors, sweating, fever, chills, or headache Physical and psychological manifestations A thorough mental status examination is an integral component of every patient assessment. Key mental status findings associated with cannabis use, cannabis-induced, and cannabis-related disorders include the following: o Mood: Acute use may be associated with feelings of euphoria, uncontrollable laughter, increased appetite, and difficulty concentrating. In chronic use or withdrawal, patients may report a depressed mood characterized by apathy, lack of motivation, irritability, loss of interest in typical activities, difficulty concentrating, and possibly isolation. o Affect: Acutely, affect may span the spectrum from euphoric to anxious. In chronic use, affect may be constricted or flat. o Thought process and content: As in any mental status examination, assessing the patient for the presence of suicidality or homicidality and taking appropriate action is critical. Patients may demonstrate flight of ideas, loose associations, and, in some cases, delusions and hallucinations. o Cognition: In both acute and chronic use, difficulty concentrating and memory impairment are common. o o o o Physical signs and symptoms associated with cannabis use are particularly relevant to the diagnosis of cannabis intoxication. Clinicians are advised to identify at least 2 or more of the following physical symptoms, occurring within 2 hours of cannabis use, as defined by DSM-5 criteria: Conjunctival injection Increased appetite Dry mouth Tachycardia • • • • • • • • • • • • • • Other adverse physical and psychological manifestations associated with marijuana abuse are as follows: Sweating Headaches Restlessness Forgetfulness Visual distortions Lack of concentration Paranoia Mood changes Perceptual changes Feeling impersonal Panic disorder Amotivational syndrome Delusions Psychosis Differential Diagnoses • • • • • • • • • • • • • • Alcohol-Related Psychosis Allergic and Environmental Asthma Amphetamine-Related Psychiatric Disorders Anxiety Disorders Atrial Tachycardia Benzodiazepine Toxicity Brief Psychotic Disorder Delirium Depression Hallucinogen Use Panic Disorder Primary Hypersomnia Sedative, Hypnotic, Anxiolytic Use Disorders Substance-Induced Mood Disorder Laboratory Studies Urine testing • Cannabinoids can be detected in the urine for as many as 21 days after use in persons chronically using marijuana, because these lipid-soluble metabolites are slowly released from fat cells into the blood; however, 1-5 days is the normal urinepositive period. Blood testing • Blood samples may be used to measure quantitative levels of cannabinoids. Serial monitoring of tetrahydrocannabinol (THC)–COOH to creatinine ratios can distinguish between recent use and residual excretion. To assess the extent of cannabis use, determination of free and bound THC-COOH can be useful. Hair analysis Saliva testing Treatment Acute intoxication of cannabis usually resolves unremarkably within 4-6 hours and is best managed by the following measures: • Frequent reassurance and maintenance of a nonthreatening environment • Minimal stimuli • Use of a specifically assigned nurse to calm the patient • Judicious use of benzodiazepines when significant anxiety is present Medication • Short-term, low-dose benzodiazepines for treatment of significant anxiety associated with acute intoxication has been used. Clinicians are advised to use caution when administering benzodiazepines for the treatment of cannabisinduced anxiety, as the anxiety will invariable resolve with no medication over a short period. Anxiolytics - Lorazepam (Ativan) • These agents depress all levels of CNS, which, in turn, reduces anxiety symptoms. • Amphetamine (contracted from alpha-methylphenethylamine) is a potent central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. Amphetamine was discovered in 1887 and exists as two enantiomers: levoamphetamine and dextroamphetamine. • Historically, it has been used to treat nasal congestion and depression. Amphetamine is also used as an athletic performance enhancer and cognitive enhancer, and recreationally as an aphrodisiac and euphoriant. It is a prescription drug in many countries, and unauthorized possession and distribution of amphetamine are often tightly controlled due to the significant health risks associated with recreational use. • The substance 3,4-methylenedioxymethamphetamine (MDMA) is a popular recreational stimulant commonly referred to as ecstasy. MDMA has the desired effects of euphoria, high energy, and social disinhibition lasting 3-6 hours. The drug is often consumed in dance clubs, where users dance vigorously for long periods. The drug sometimes causes toxicity and dehydration, as well as severe hyperthermia. History • Amphetamine-related psychiatric disorders can be confused with psychiatric disorders caused by organic, medical, neurologic, and/or psychological etiologies. The causes of amphetamine-related psychiatric disorders usually can be determined by assessing the patient's history and the family's genealogy. Psychiatric history • Two issues are emphasized: o Determine whether a psychiatric disorder or symptoms ever occurred when the patient was not exposed to amphetamines. o Determine whether the patient ever had a psychiatric disorder or symptoms similar to the present symptoms in relation to any other drug or medication. Recent history • The patient's history of amphetamine abuse is the most important factor and is determined by asking the following questions: o When did the patient's amphetamine use start? o How often does the patient use amphetamines? o How much does he or she use? o Is the patient currently intoxicated or in withdrawal from amphetamines? o Does the patient frequently attend rave parties? o Has the patient recently increased his or her amphetamine use or started to binge? Substance abuse history • Potentially abused substances include the following: o Alcohol o Marijuana o Cocaine o Lysergic acid diethylamide (LSD) o OTC sympathomimetics o Steroids Family history • A family history of a psychiatric disorder may suggest a primary psychiatric disorder. A diagnosis of amphetamine-related psychiatric disorder might still be possible if the patient has no family history of psychiatric disorder. DSM criteria for intoxication and withdrawal The DSM-5 criteria for stimulant withdrawal are as follows: • A. Cessation of (or reduction in) prolonged amphetamine-type substance, cocaine, or other stimulant use. • B. Dysphoric mood and two (or more) of the following physiologic changes developing within a few hours to several days after Criterion A: o Fatigue o Vivid, unpleasant dreams o Insomnia or hypersomnia o Increased appetite o Psychomotor retardation or agitation • The signs or symptoms are not attributable to another general medical condition, and are not better explained by another mental disorder, including intoxication or withdrawal from another substance. • Delirium is not a condition observed during amphetamine withdrawal. The DSM-5 criteria for stimulant intoxication are as follows: • A. Recent ues of an amphetamine-type substance, cocaine or other stimulant. • B. Clinically significant problematic behavioral or psychological changes (e.g., euphoria or affective blunting; changes in sociability; hypervigilance; interpersonal sensitivity; anxiety, tension, or anger; stereotyped behaviors; impaired judgment) that develop during, or shortly after, use of a stimulant. • C. Two (or more) of the following signs or symptoms, developing during, or shortly after, stimulant use: o Tachycardia or bradycardia o Pupillary dilatation o Elevated or lowered blood pressure o Perspiration or chills o Nausea or vomiting o Evidence of weight loss o Psychomotor agitation or retardation o Muscular weakness, respiratory depression, chest pain, or cardiac arrhythmias o Confusion, seizures, dyskinesias, dystonias, or coma • The signs or symptoms are not attributable to another medical condition, and are not better explained by another mental disorder, including intoxication with another substance. Physical and psychological manifestations • Mental status examination should emphasize delusions, hallucinations, suicide, homicide, orientation, insight and judgment, and affect. The mental status examination can be very different for intoxication and psychosis. A mental status expected for a patient with amphetamine intoxication is as follows: o Appearance and behavior: Unusually friendly, scattered eye contact, buccal oral gyrations, excoriations on extremities and face from picking at skin, overly talkative and verbally intrusive o Speech: Increased rate o Thought process: Tangential, circumstantial over inclusive and disinhibited o Thought content: Paranoid; no suicidal or homicidal thoughts o Mood: Anxious, hypomanic o Affect: Anxious and tense o Insight and judgment: Poor o Orientation: Alert to person, place, and purpose; perspective of time is disorganized A mental status expected for a patient with amphetamine psychosis is as follows: o Appearance and behavior: Disheveled, suspicious, paranoid, difficult to engage, and poor eye contact o Speech: Decreased and rapid o Thought process: Guarded and internally preoccupied o Thought content: Paranoid; possible auditory hallucinations; no suicidal or homicidal thoughts o Mood: Anxious o Affect: Paranoid and fearful o Insight and judgment: Poor o Orientation: Has no concept of purpose, though understands place and person; perspective of time is disorganized. A mental status for a patient withdrawing form amphetamines is as follows: o Appearance and behavior: Disheveled, psychomotor slowing, poor eye contact, pale appearance to skin o Speech: Decreased tone and volume o Thought processes: Decreased content, guarded o Thought content: No auditory, visual hallucinations; suicidal thoughts present, but no homicidal thoughts o Mood: depressed o Affect: Flat and withdrawn o Insight and judgment: Poor o Orientation: Oriented to person, place, and purpose Differential Diagnoses • • • • • • • • • • • • • • • Cannabis-Related Disorders Cocaine-Related Psychiatric Disorders Delirium Depression Hallucinogen Use Hyperthyroidism Hypothyroidism Inhalant-Related Psychiatric Disorders Insomnia Opioid Abuse Phencyclidine (PCP)-Related Psychiatric Disorders Schizophrenia Toxicity, Heroin Toxicity, Mushroom Wernicke-Korsakoff Syndrome Laboratory Studies • • • • • • • Laboratory evaluation should include the following tests: Finger-stick blood glucose test CBC determination Determination of electrolyte levels, including magnesium, amylase, albumin, total protein, uric acid, BUN, alkaline phosphatase, and bilirubin levels Urinalysis Stat urine or serum toxicology screening to exclude acetaminophen, tricyclic antidepressants, aspirin, and other potential toxins: Individuals who abuse drugs may ingest a substance called Urine Luck, or pyridinium chlorochromate (PCC), to produce invalid results on urine drug screens. PCC alters the results for cannabis and opiates but elevates levels of amphetamines. Blood test for an alcohol level if the patient appears intoxicated HIV and rapid plasma reagin (RPR) tests • • • Other Tests Perform ECG to evaluate for cardiac involvement. Perform EEG if a seizure disorder is considered possible. Use of the brief psychotic rating scale (BPRS), Beck Depression Scale, violence and suicide assessment, and other measures may be helpful. • If persistent psychiatric conditions are noted, neuropsychological testing can be beneficial to assess levels of psychosocial and neurologic function to guide treatment and to assess the need for placement. • Results of projective testing, such as the Rorschach test and the Thematic Apperception Test, can help in clarifying thought disorders. • During amphetamine intoxication, the Mini-Mental State Examination (MMSE) can be helpful in measuring cognitive change. Treatment The excretion of amphetamines can be accelerated by the use of ammonium chloride, given either IV or orally (PO). • Amphetamine intoxication can be treated with ammonium chloride, often found in OTC expectorants, such as ammonium chloride (Quelidrine), baby cough syrup, Romilar, and P-V-Tussin. • The recommended dose to acidify the urine is ammonium chloride 500 mg every 2-3 hours. • The ingredients in OTC cough syrups vary, and the clinician should become familiar with 1 or 2 stock items for use in the emergency department. • Ammonium chloride (Quelidrine), an OTC expectorant, can be used in the absence of liver or kidney failure. • Administer IV fluids to provide adequate hydration. Medication Antipsychotics - Haloperidol (Haldol) • Clinicians should select a high-potency antipsychotic that is available in tablet, liquid, and IM forms for administration in emergency situations. Antipsychotics help control psychotic symptoms and provide rapid tranquilization of the agitated and psychotic patient. Benzodiazepines - Lorazepam (Ativan) • These drugs are primarily used to sedate agitated patients. Availability in PO, IV, and IM forms allowing the drug to be used in emergency situations. Caution must be used in the violent, aggressive patient because benzodiazepines may cause disinhibition. Beta-blockers - Propranolol (Inderal) • Propranolol (Inderal) is useful in patients who are agitated, anxious, and hyperarousable because of amphetamines. They are temporarily used until the amphetamine is eliminated from the patient's system. For some patients, anxiety can be prolonged, and nonaddictive beta-blockers may be helpful. Expectorants - Ammonium chloride (Quelidrine) • Expectorants are used to acidify the urine and increase amphetamine excretion when intoxication from amphetamines has resulted in psychiatric and medical complications. These agents are available in PO form, and the patient must be able to swallow or receive a nasogastric tube. Adsorbents - Activated charcoal suspension (Actidose-aqua, InstAqua, Liquid-Char) • These agents, given through a nasogastric tube into the stomach, absorb intentionally and accidentally ingested substances to prevent their further absorption into the systemic circulation. References • American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Washington, DC: American Psychiatric Association; 2013. DSM-5 • Substance Abuse and Mental Health Services Administration. Results from the 2013 National Survey on Drug Use and Health: Summary of National Findings. • CDC. Alcohol-Related Disease Impact (ARDI). Centers for Disease Control and Prevention. Available at http://nccd.cdc.gov/DPH_ARDI/default/default.aspx. Accessed: March 4, 2016. • World Health Organization. Global status report on alcohol and health. 2014. Available at http://www.who.int/substance_abuse/publications/global_alcohol_ report/msb_gsr_2014_1.pdf?ua=1. TEŞEKKÜRLER… EGEMEN SAV