Substance Use Disorders Chapter First Aid PDF

77 SUBSTANCE-RELATED AND ADDICTIVE DISORDERS Substance Use Disorders Substance use disorders are characterized by a problematic pattern of substance use that leads to some...

77 SUBSTANCE-RELATED AND ADDICTIVE DISORDERS Substance Use Disorders Substance use disorders are characterized by a problematic pattern of substance use that leads to some form of functional impairment or distress. Keep in mind that frequent use of a substance does not necessarily indicate a substance use disorder unless it is causing problems for the patient. DIAGNOSIS AND DSM-5 CRITERIA Substance use disorders are characterized by a problematic pattern of substance use causing impairment or distress, as manifested by at least two of the follow- ing within a 12-month period: Using substance more than originally intended. Persistent desire or unsuccessful efforts to cut down on use. Significant time spent in obtaining, using, or recovering from substance. Craving to use substance. Failure to fulfill obligations at work, school, or home. Continued use despite social or interpersonal problems due to the substance use. Limiting social, occupational, or recreational activities because of substance use. Use in dangerous situations (e.g., driving a car). Continued use despite subsequent physical or psychological problem WARDS TIP (e.g., drinking alcohol despite worsening liver problems). It is possible to have a substance Tolerance (needing higher amounts of the substance to achieve the desired use disorder without having phys- effect or experiencing diminished effects when repeating the same dose). iological dependence (i.e., without Withdrawal (a substance-specific syndrome occurring when a patient stops having withdrawal or tolerance). or reduces heavy/prolonged substance use). Note that these criteria remain the same regardless of what substance(s) the patient is using. The disorder may be classified as mild, moderate, or severe depending on the number of criteria met. EPIDEMIOLOGY WARDS TIP One-year prevalence of any substance use disorder in the United States is Substance-induced mood symp- approximately 8%. toms improve during prolonged More common in men than women. abstinence, whereas primary mood symptoms persist. Alcohol and nicotine are the most commonly used substances. PSYCHIATRIC SYMPTOMS Mood symptoms are common among persons with substance use disorders. Psychotic symptoms may occur with some substances. Personality disorders and psychiatric comorbidities (e.g., major depression, anxiety disorders) are common among persons with substance use disorders. It is often challenging to decide whether psychiatric symptoms are primary or substance-induced. Many patients may use substances to self-medicate for undertreated psychiatric symptoms.  78 SUBSTANCE-RELATED AND ADDICTIVE DISORDERS ACUTE INTOXICATION AND WITHDRAWAL KEY FACT Both the intoxicated and withdrawing patient can present difficulties in diag- nosis and treatment. Since it is common for persons to abuse several s­ ubstances Withdrawal symptoms of a drug at once, the clinical presentation is often confusing, and signs/symptoms may are usually the opposite of its be atypical. Always be on the lookout for use of multiple substances. intoxication effects. For example, alcohol is sedating, but alcohol DETECTION OF SUBSTANCE USE withdrawal can cause brain exci- tation and seizures. See Table 7-1. TREATMENT OF SUBSTANCE USE DISORDERS Behavioral counseling should be part of every substance use disorder treatment. See Table 7-2. Psychosocial treatments are effective and include motivational intervention (MI), cognitive-behavioral therapy (CBT), contingency management, and individual and group therapy. For severe substance use disorders, residential (usually 28-day) “rehab” programs are common; some patients may choose to do partial hospitalization or intensive outpatient programming. TABLE 7-1. Direct Testing for Substance Use Alcohol Stays in system for only a few hours. Breathalyzer test, commonly used by law enforcement. Blood/urine testing more accurate. Urine screening for metabolite (ethyl glucuronide) — not useful for assessing acute intoxication, but can indicate alcohol use over the preceding 2–5 days. Cocaine Urine drug screen positive for 2–4 days (up to 8 days for heavy users). Amphetamines Urine drug screen positive for 1–3 days. Most assays have poor sensitivity and/or specificity. Phencyclidine Urine drug screen positive for 4–7 days. (PCP) OTC cold medications may yield false positive. Creatine kinase (CK) and aspartate aminotransferase (AST) are often elevated. Sedative- In urine and blood for variable amounts of time. hypnotics Barbiturates: Short-acting (pentobarbital): 24 hours Long-acting (phenobarbital): 3 weeks Benzodiazepines: Short-acting (e.g., lorazepam): up to 5 days Long-acting (diazepam): up to 30 days Opioids Urine drug test remains positive for 1–3 days, depending on opioid used. Routine screening tests detect morphine, which is the eventual metabolite of all natural opioids. Buprenorphine, synthetic opioids (methadone, fentanyl, tramadol) and semi-synthetic opioids (oxycodone, hydrocodone) will not be detected on routine screening (order separate assay). Marijuana Urine detection: After a single use, about 3 days. In heavy users, up to 4 weeks (THC is released from adipose stores).  79 SUBSTANCE-RELATED AND ADDICTIVE DISORDERS TABLE 7-2. Stages of Change Stage Definition Example Precontemplation Patients do not view their addiction as a problem. They A college student who drinks heavily feels that may see substance use as helpful and/or enjoyable. they need alcohol to overcome social anxiety and enjoy parties. They do not identify any negative consequences from their use. Contemplation The patient begins to think about cutting down or The student misses several deadlines due to hangovers stopping altogether. They recognize potential benefits from drinking the night before. They think cutting down of making a change, but may be ambivalent or feel on alcohol might improve their grades, but aren’t sure unable to do so. they want to stop. Preparation The patient plans for the process of change. They collect The student begins researching self-help strategies for information, and may experiment with very small reducing alcohol intake. They look up campus resources changes. for individual and group therapy. Action The patient takes direct steps toward reducing or The student begins attending substance-use-focused stopping substance use. groups on campus, and talks with their primary care doctor about starting naltrexone. Maintenance The patient has successfully made significant behavior The student continues to drink, but limits themself change, and works to avoid relapse. to 1–2 drinks per day, and only consumes alcohol on weekends. Relapse After a successful period of remission, patients resume After graduating, the student is unemployed. substance use (or fall back into unhealthy patterns They begin drinking again to cope with stress and of use). unstructured time, and quickly escalates to near daily use. Community-based groups such as SMART Recovery, Alcoholics Anonymous (AA), and Narcotics Anonymous (NA) should also be encouraged as part of the treatment. Pharmacotherapy is available for some drugs of abuse, and will be discussed later in this chapter as relevant to a particular substance. Alcohol (EtOH) Alcohol activates gamma-aminobutyric acid (GABA), dopamine, and WARDS TIP serotonin receptors in the central nervous system (CNS). It inhibits glutamate receptor activity and voltage-gated calcium channels. GABA Alcohol is the most common receptors are inhibitory, and glutamate receptors are excitatory; thus, alcohol co-ingestant in drug overdoses. is a potent CNS depressant. Lifetime prevalence of alcohol use disorder in the United States is 5% of women and 12% of men. Alcohol is metabolized in the following manner: 1. Alcohol → acetaldehyde (enzyme: alcohol dehydrogenase). KEY FACT 2. Acetaldehyde → acetic acid (enzyme: aldehyde dehydrogenase). Most adults will show some signs These enzymes are upregulated in heavy drinkers. Some populations produce of intoxication with BAL >100 less aldehyde dehydrogenase due to genetic variation, resulting in flushing and and obvious signs with BAL nausea with alcohol use. >150 mg/dL. INTOXICATION Clinical Presentation The absorption and elimination rates of alcohol are variable and depend on many factors, including age, sex, body weight, chronic nature of use,  80 SUBSTANCE-RELATED AND ADDICTIVE DISORDERS  ARDS W TABLE 7-3. Clinical Presentation of Alcohol Intoxication QUESTION Effects Impaired fine motor control BAL 20–50 mg/dL Q: What is the average rate of Impaired judgment and coordination 50–100 mg/dL alcohol metabolism? Ataxic gait and poor balance 100–150 mg/dL A: Between15 and 35 mg/dL Lethargy, difficulty sitting upright, difficulty with memory, 150–250 mg/dL per hour. nausea/vomiting Coma (in the novice drinker) 300 mg/dL Respiratory depression, death possible 400 mg/dL KEY FACT duration of consumption, food in the stomach, and the state of nutrition and Ethanol, along with methanol and liver health. ethylene glycol, can be a cause of In addition to the above factors, the effects of EtOH also depend on the anion gap metabolic acidosis. blood alcohol level (BAL). Serum EtOH level or an expired air breathalyzer can determine the extent of intoxication. As shown in Table 7-3, patients with high tolerance may show diminished effects at a given BAL. Treatment Monitor: Airway, breathing, circulation, glucose, electrolytes, acid–base KEY FACT status. Give parenteral thiamine (to prevent or treat Wernicke’s encephalopathy) Males with substance use disor- and folate. Remember thiamine must be given before glucose, as it’s a ders, especially alcohol, have high- necessary cofactor for glucose metabolism. er rates of perpetrating domestic Naloxone may be necessary to reverse effects of co-ingested opioids. violence. A computed tomography (CT) scan of the head may be necessary to rule out subdural hematoma or other brain injury. The liver will eventually metabolize alcohol without any other interventions. Severely intoxicated patients may require mechanical ventilation with  ARDS W attention to acid–base balance, temperature, and electrolytes while they are QUESTION recovering. Gastrointestinal evacuation (e.g., gastric lavage, induction of emesis, Q: What are the typical features of and charcoal) is not indicated in the treatment of EtOH overdose unless Wernicke’s encephalopathy? a significant amount of EtOH was ingested within the preceding 30–60 A: The classic triad is confusion minutes. (altered mental status), ataxic gait, and oculomotor findings (typically nystagmus or gaze palsies). WITHDRAWAL A 42-year-old man has routine surgery for a knee injury. After 72 hours in the hospital he becomes anxious, flushed, diaphoretic, hypertensive, and tachycardic. What most likely accounts for this patient’s symptoms? Alcohol withdrawal. Treatment? Benzodiazepines (chlordiazepoxide [Librium] or lorazepam [Ativan] are considered the drugs of choice). What are you most concerned about? Seizures, delirium tremens, autonomic instability, and car- diac arrhythmias. Remember that alcohol withdrawal can be fatal. Chronic alcohol use has a depressant effect on the CNS, and cessation of use causes a compensatory hyperactivity with glutamate excitotoxicity. Alcohol withdrawal is potentially lethal!  81 SUBSTANCE-RELATED AND ADDICTIVE DISORDERS Clinical Presentation Signs and symptoms of alcohol withdrawal syndrome include insomnia, anxiety, hand tremor, irritability, anorexia, nausea, vomiting, autonomic hyperactivity (diaphoresis, tachycardia, hypertension), psychomotor agitation, fever, seizures, hallucinations, and delirium tremens (see Table 7-4). The earliest symptoms of EtOH withdrawal begin between 6 and 24 hours after the patient’s last drink and depend on the duration and quantity of KEY FACT EtOH consumption, liver size, and body mass. Generalized tonic-clonic seizures usually occur between 12 and 48 hours Risk of suicide attempts is higher after cessation of drinking, with a peak around 12–24 hours. among those with psychiatric dis- orders and concurrent substance About a third of persons with seizures develop delirium tremens (DTs). use (especially alcohol). Hypomagnesemia may predispose to seizures; thus, it should be corrected promptly. Seizures are treated with benzodiazepines. Long-term treatment with anticonvulsants is not recommended for alcohol withdrawal seizures. Delirium Tremens KEY FACT The most serious form of EtOH withdrawal. Delirium tremens is a dangerous Usually begins 48–96 hours after the last drink but may occur later. form of alcohol withdrawal involv- While only 5% of patients who experience EtOH withdrawal develop DTs, ing mental status and neurolog- there is a roughly 5% mortality rate (up to 35% if left untreated). ical changes. Symptoms include Physical illness predisposes to the condition. disorientation, agitation, visual Age >30 and prior DTs increase the risk. and tactile hallucinations, and autonomic instability (increase in In addition to delirium, symptoms of DTs may include hallucinations (most commonly visual), agitation, gross tremor, autonomic instability, and respiratory rate, heart rate, and fluctuating levels of psychomotor activity. blood pressure). It carries a 5% mortality rate but occurs in only It is a medical emergency and should be treated with adequate doses of benzodiazepines. 5% of patients that experience EtOH withdrawal. Patients often Treatment require ICU level of care; treatment Benzodiazepines (lorazepam, diazepam, or chlordiazepoxide) should be given includes supportive care and in sufficient doses to keep the patient calm and lightly sedated, then tapered ­benzodiazepines. down slowly. Carbamazepine or valproic acid can be used in mild withdrawal. TABLE 7-4. Timing of Alcohol Withdrawal Symptoms Onset After Syndrome Clinical Findings Last Drink Minor Tremulousness, mild anxiety, headache, diaphoresis, 6 to 36 hours withdrawal palpitations, anorexia, gastrointestinal upset; normal mental status Seizures Single or brief flurry of generalized tonic-clonic seizures, 6 to 48 hours short postictal period, status epilepticus rare Alcoholic Visual, auditory, and/or tactile hallucinations with intact 12 to 48 hours hallucinosis orientation and normal vital signs Delirium Delirium, agitation, tachycardia, hypertension, fever, 48 to 96 hours tremens diaphoresis Source: Used, with permission, from Hoffman RS, Weinhouse GL. Management of moderate and severe alcohol withdrawal syndromes. https://www.uptodate.com/contents/management-of-moderat e-and-severe-alcohol-withdrawal-syndromes. © 2021 UpToDate, Inc. and/or its affiliates. All Rights Reserved.  82 SUBSTANCE-RELATED AND ADDICTIVE DISORDERS Parenteral thiamine, folic acid, and a multivitamin to treat nutritional deficiencies (“banana bag”). Electrolyte and fluid abnormalities must be corrected. Monitor withdrawal signs and symptoms with the Clinical Institute Withdrawal Assessment (CIWA) scale. Providers must pay careful attention to the level of consciousness, and consider the possibility of traumatic injuries. KEY FACT Check for signs of hepatic failure (e.g., ascites, jaundice, caput medusae, coagulopathy). Confabulation—inventing stories Alcoholic Ketoacidosis of events that never occurred—is Frequently seen in the setting of alcohol cessation after an alcohol binge often associated with Korsakoff’s secondary to protracted vomiting and lack of oral intake. “psychosis,” or alcohol-induced Hallmark is ketosis without hyperglycemia and a negative alcohol level. neurocognitive disorder. Patients are unaware that they are “making Laboratory studies reveal a high anion gap metabolic acidosis, ketonemia, things up.” and low levels of potassium, magnesium, and phosphorus. Treatment consists of hydration with D5NS, and replacing electrolytes. Mr. Smith is a 42-year-old divorced man who arrives to the ED requesting treatment for alcohol detoxification. He began drinking at the age of 17. Although he initially drank only on the weekends, his alcohol use gradually progressed to drinking half a pint of whiskey daily by the age of 35. At that time, he arrived to his workplace intoxicated on several occasions and was referred to a 45-day inpatient alcohol addiction program. After completing the program, he was able to maintain sobriety for 7 years. However, 2 years ago he got divorced, was laid off from work, and ultimately relapsed into alcohol use. Mr. Smith is currently living with his older sister and states that his drinking is “out of control.” He had a DUI recently and has a court date in 2 weeks. He has tried to quit alcohol on his own on several occasions. However, when he stops drinking he feels “shaky, sweaty, anxious, and irritable” and thus resumes his alcohol intake. He also reports a history of a seizure 10 years ago, after he abruptly discontinued his alcohol use for a few days. Mr. Smith’s last drink was about 8 hours prior to his arrival at the ED. During the last month he has been feeling sad, with low energy, difficulty falling and staying asleep, low appetite, and difficulty concentrating. He denies suicidal ideation but has significant guilt over not being able to stop drinking. He denies a history of depression or anxiety, and has not received any other psychiatric treatment in the past. Upon presentation to ER the patient’s blood alcohol level was 110, he did not have symptoms of intoxication, and his urine drug screen was negative. Vital signs were significant for blood pressure of 150/90 and pulse of 110 bpm. Complete blood count and electrolytes were within normal limits. What is Mr. Smith’s most likely diagnosis? The patient has a diagnosis of alcohol use disorder, with current signs of withdrawal. It is clear that he has exhibited symptoms of tolerance and withdrawal, has been using more alcohol than intended, and has made unsuccessful efforts to cut down. He also describes symptoms suggestive of a depressive disorder. The fact that his depressive symptoms began while abusing alcohol warrants a diagnosis of alcohol-induced depressive disorder. However, major depressive disorder should be ruled out once he remits his alcohol use. If his depressive symptoms are indeed substance-induced, they will improve and resolve with continuing sobriety.  83 SUBSTANCE-RELATED AND ADDICTIVE DISORDERS What would be the next step in management? Given the Mr. Smith’s heavy chronic alcohol use and history of complicated withdrawal (i.e., seizure), he should be admitted to an inpatient unit for close monitoring. Outpatient detoxification is not appropriate in this case. He will likely require a standing and PRN benzodiazepine (the particular benzodiaz- epine sometimes varies depending on hospital’s protocol), as well as close monitoring for signs of withdrawal. WARDS TIP At-risk or heavy drinking for men ALCOHOL USE DISORDER is more than 4 drinks per day or The AUDIT-C (Table 7-5) is used to screen for alcohol use disorder. more than 14 drinks per week. For women, it is more than 3 drinks Biochemical markers are useful in detecting recent prolonged drinking; ongoing monitoring of biomarkers can also help detect a relapse. Most per day or more than 7 drinks commonly used biomarkers are BAL, liver function tests ([LFTs]—aspartate per week. aminotransferase [AST], alanine aminotransferase [ALT]), gamma-glutamyl transpeptidase (GGT), and mean corpuscular volume (MCV). Urine screening for ethyl glucuronide can indicate alcohol use in the 2–5 days prior to testing. Medications for Alcohol Use Disorder KEY FACT See Table 7-6. AST:ALT ratio ≥2:1 and elevated GGT Long-Term Complications of Alcohol Intake suggest excessive long-term alcohol Wernicke’s encephalopathy: use; they take a few weeks to return Caused by thiamine (vitamin B1) deficiency resulting from poor to normal during abstinence. nutrition. TABLE 7-5. AUDIT-C Question #1: How often did you have a drink containing alcohol in the past year? Never (0 points) Monthly or less (1 point) Two to four times a month (2 points) Two to three times per week (3 points) Four or more times a week (4 points) Question #2: How many drinks did you have on a typical day when you were drinking in the past year? 1 or 2 (0 points) 3 or 4 (1 point) 5 or 6 (2 points) 7 to 9 (3 points) 10 or more (4 points) Question #3: How often did you have six or more drinks on one occasion in the past year? Never (0 points) Less than monthly (1 point) Monthly (2 points) Weekly (3 points) Daily or almost daily (4 points) The AUDIT-C is scored on a scale of 0–12 (scores of 0 reflect no alcohol use). In men, a score of 4 or more is considered positive; in women, a score of 3 or more is considered positive.  84 SUBSTANCE-RELATED AND ADDICTIVE DISORDERS TABLE 7-6. Pharmacological Treatment of Alcohol Use Disorder Medication Mechanism Pros Cons Naltrexone Opioid receptor antagonist; reduces First-line treatment. Will precipitate withdrawal in patients cravings and the “high” associated Available as an oral tablet (can be with physical opioid dependence. with alcohol intoxication. taken daily, or as-needed on drinking Can interfere with anesthesia (e.g., for days), or monthly injection. Can allow acute injury or planned surgeries). some patients to engage in moderate Risk of LFT elevation. alcohol use without escalating to binge drinking. Acamprosate Likely modulates glutamate First-line treatment. Contraindicated in severe renal transmission. Can be used for patients with liver disease. disease. Typically used for relapse prevention in patients who have already stopped drinking. Disulfiram Blocks aldehyde dehydrogenase, Second-line. Can be effective for Medication adherence can be an causing buildup of acetaldehyde highly motivated patients. issue. Contraindicated in severe and aversive symptoms (flushing, cardiac disease, pregnancy, psychosis. headache, nausea/vomiting, Must monitor LFTs. palpitations, shortness of breath). Topiramate Anticonvulsant; potentiates GABA Second-line treatment. Reduces Common adverse effects: impaired and inhibits glutamate receptors. cravings for alcohol, and decreases cognition (“DOPE-a-max”), nausea / alcohol use. weight loss, metabolic acidosis. Acute and can be reversed with thiamine therapy.  ARDS W Features: Ataxia (broad-based), confusion, ocular abnormalities QUESTION (nystagmus, gaze palsies). Q: What is the treatment for Wer- If left untreated, Wernicke’s encephalopathy may progress to Korsakoff nicke’s encephalopathy? syndrome: A: High dose parenteral (IV or IM) Chronic amnestic syndrome. thiamine should be given for 2–7 Reversible in only about 20% of patients. days, followed by daily oral thiamine. Features: Impaired recent memory, anterograde amnesia, compensatory confabulation (unconsciously making up answers when memory has failed). WARDS TIP Cocaine Give all patients with altered men- Cocaine blocks the reuptake of dopamine, epinephrine, and norepinephrine tal status thiamine before glucose, from the synaptic cleft, causing a stimulant effect. Dopamine plays a role in the to avoid precipitating Wernicke– behavioral reinforcement (“reward”) system of the brain. Korsakoff syndrome. Thiamine is a coenzyme used in carbohydrate metabolism. INTOXICATION General: Euphoria, heightened self-esteem, increase or decrease in blood pressure, tachycardia or bradycardia, nausea, dilated pupils, weight loss, psychomotor agitation or depression, chills, and sweating. Dangerous: Seizures, cardiac arrhythmias, hyperthermia, paranoia, and hallucinations (especially tactile). Since cocaine is an indirect sympathomimetic, intoxication mimics the fight-or-flight response. Deadly: Cocaine’s vasoconstrictive effect may result in myocardial infarction (MI), intracranial hemorrhage, or stroke.  85 SUBSTANCE-RELATED AND ADDICTIVE DISORDERS Management For mild-to-moderate agitation and anxiety: Reassurance of the patient and benzodiazepines. For severe agitation or psychosis: Antipsychotics (e.g., haloperidol). Symptomatic support (i.e., control hypertension, arrhythmias). Temperature of >102°F should be treated aggressively with an ice bath, cooling blanket, and other supportive measures.  ARDS W QUESTION COCAINE USE DISORDER Q: Why should beta-blockers be avoided for patients who regularly Treatment of cocaine use disorder: use cocaine? There is no Food and Drug Administration (FDA)-approved A: Cocaine has both alpha- pharmacotherapy for cocaine use disorder. and beta-adrenergic effects. Off-label medications are sometimes used (naltrexone, modafinil, If a beta-blocker is given topiramate). ­simultaneously, unopposed Psychological interventions (contingency management, relapse prevention, alpha-adrenergic activity can NA, etc.) are the mainstay of treatment. cause coronary vasoconstriction and induce myocardial infarction. WITHDRAWAL Abrupt abstinence is not life threatening. Produces post-intoxication depression (“crash”): Malaise, fatigue, hypersomnolence, depression, anhedonia, hunger, constricted pupils, vivid KEY FACT dreams, psychomotor agitation, or retardation. Occasionally, these patients can become suicidal. Cocaine or amphetamines can With mild-to-moderate cocaine use, withdrawal symptoms resolve within both cause formication, a tactile 72 hours; with heavy, chronic use, they may last for 1–2 weeks. hallucination of something crawl- Treatment is supportive, but severe psychiatric symptoms may warrant ing on or under the skin. hospitalization. Amphetamines Classic amphetamines: Block reuptake and facilitate release of dopamine and norepinephrine from nerve endings, causing a stimulant effect. Examples: Dextroamphetamine (Dexedrine), methylphenidate (Ritalin), methamphetamine (Desoxyn, “ice,” “speed,” “crystal meth,” “crank”). Methamphetamines are easily manufactured in home laboratories using over-the-counter medications (e.g., pseudoephedrine). Methamphetamines are used medically in the treatment of narcolepsy, attention deficit/hyperactivity disorder (ADHD), binge eating, and occasionally depressive disorders. Substituted (“designer,” “club drugs”) amphetamines: KEY FACT Release dopamine, norepinephrine, and serotonin from nerve endings. Symptoms of amphetamine intox- Examples: MDMA (“ecstasy”), MDEA (“eve”). ication include euphoria, dilated Often used in dance clubs and raves. pupils, increased libido, tachycar- Have both stimulant and hallucinogenic properties. dia, perspiration, grinding teeth, Serotonin syndrome is possible if designer amphetamines are combined and chest pain. with selective serotonin reuptake inhibitors (SSRIs).  86 SUBSTANCE-RELATED AND ADDICTIVE DISORDERS INTOXICATION WARDS TIP Clinical Presentation Amphetamine intoxication causes symptoms similar to those of cocaine (see Chronic amphetamine use leads above). to accelerated tooth decay (“meth MDMA and MDEA may induce sense of closeness to others. mouth”). Overdose can cause hyperthermia, dehydration (especially after a prolonged period of dancing in a club), rhabdomyolysis, and renal failure. Complications of their long half-life can cause ongoing psychosis, even during abstinence. WARDS TIP Amphetamine withdrawal can cause prolonged depression. Treatment Both amphetamine and PCP use Rehydrate, correct electrolyte balance, and treat hyperthermia. can cause rhabdomyolysis. Look for elevated creatine kinase (CK) and monitor closely for acute Phencyclidine (PCP) kidney injury. Treatment is mostly PCP, or “angel dust,” is a dissociative, hallucinogenic drug that antagonizes supportive and emphasizes N-methyl-d-aspartate (NMDA) glutamate receptors and activates dopaminergic ­hydration. ­neurons. It can have stimulant or CNS depressant effects, depending on the dose taken. PCP can be smoked as “wet” (sprinkled on cigarette) or as a “joint” (sprinkled on marijuana). Ketamine is similar to PCP, but is less potent. Ketamine is sometimes used KEY FACT as a “date rape” drug, as it is odorless and tasteless. Ketamine (“special K”) can produce tachycardia, tachypnea, hallucina- INTOXICATION tions, and amnesia. Clinical Presentation Effects include agitation, depersonalization, hallucinations, synesthesia (one sensory stimulation evokes another—e.g., hearing a sound causes one to see a color), impaired judgment, memory impairment, combativeness, KEY FACT nystagmus (rotary, horizontal, or vertical), ataxia, dysarthria, hypertension, tachycardia, muscle rigidity, and high tolerance to pain. PCP intoxication ­symptoms— Overdose can cause seizures, delirium, coma, and even death. RED DANES Treatment Rage Monitor vitals, temperature, and electrolytes, and minimize sensory Erythema (redness of skin) stimulation. Dilated pupils Use benzodiazepines (lorazepam) to treat agitation, anxiety, muscle spasms, Delusions and seizures. Amnesia Use antipsychotics (haloperidol) to control severe agitation or psychotic Nystagmus symptoms. Excitation Skin dryness WITHDRAWAL No withdrawal syndrome, but “flashbacks” (recurrence of intoxication ­symptoms due to release of the drug from body lipid stores) may occur. KEY FACT Nystagmus (especially rotary) is very common in PCP intoxication.  87 SUBSTANCE-RELATED AND ADDICTIVE DISORDERS Sedative-Hypnotics Agents in the sedative-hypnotics category include benzodiazepines, barbiturates, KEY FACT zolpidem, zaleplon, gamma-hydroxybutyrate (GHB), meprobamate, and others. PCP intoxication is associated These medications, especially benzodiazepines, are highly abused in the United with violence, more so than other States, as they are more readily available than other drugs such as cocaine. drugs. Benzodiazepines (BZDs): Commonly used in the treatment of anxiety disorders. Easily obtained via prescription from physicians’ offices and emergency departments. Potentiate the effects of GABA by modulating the receptor, thereby KEY FACT increasing frequency of chloride channel opening. Barbiturates: Gamma-hydroxybutyrate (GHB) is Used in the treatment of epilepsy and as anesthetics. a CNS depressant that produces Potentiate the effects of GABA by binding to the receptor and increasing confusion, dizziness, drowsiness, duration of chloride channel opening. memory loss, respiratory distress, and coma. It is commonly used as At high doses, barbiturates act as direct GABA agonists, and therefore have a lower margin of safety relative to BZDs. Overdose can be lethal. a date-rape drug. They are synergistic in combination with BZDs (as well as other CNS depressants such as alcohol); respiratory depression can occur. INTOXICATION  ARDS W Clinical Presentation QUESTION Intoxication with sedatives produces drowsiness, confusion, hypotension, Q: Which substances of abuse slurred speech, incoordination, ataxia, mood lability, impaired judgment, have potentially fatal withdrawal nystagmus, respiratory depression, and coma or death in overdose. syndromes? Symptoms are synergistic when combined with EtOH or opioids/narcotics. A: Alcohol, benzodiazepines, and barbiturates. Long-term sedative use may lead to dependence and may cause depressive symptoms. Treatment Maintain airway, breathing, and circulation. Monitor vital signs. Activated charcoal and gastric lavage to prevent further gastrointestinal WARDS TIP absorption (if drug was ingested in the prior 4–6 hours). Flumazenil is a very short-acting For barbiturates only: Alkalinize urine with sodium bicarbonate to promote BZD antagonist used for treating renal excretion. BZD overdose. Use with caution For benzodiazepines only: Flumazenil in overdose. when treating overdose, as it may Supportive care—Improve respiratory status, control hypotension. precipitate seizures. WITHDRAWAL Abrupt abstinence after chronic use can be life threatening. While physiolog- ical dependence is more likely with short-acting agents, longer-acting agents can also cause dependence and withdrawal symptoms. KEY FACT The opioid dextromethorphan is CLINICAL PRESENTATION a common ingredient in cough Signs and symptoms of withdrawal are the same as these of EtOH withdrawal. syrup. Tonic-clonic seizures may occur and can be life threatening.  88 SUBSTANCE-RELATED AND ADDICTIVE DISORDERS Treatment KEY FACT Benzodiazepines (stabilize patient, then taper gradually). Carbamazepine or valproic acid taper not as beneficial. Infection secondary to needle sharing is a common cause of morbidity from street heroin Opioids usage. Opioid medications and drugs of abuse stimulate mu, kappa, and delta opiate receptors (normally stimulated by endogenous opiates), and are involved in analgesia, sedation, and dependence. Examples include heroin, oxycodone, codeine, dextromethorphan, morphine, methadone, and meperidine (Demerol). Opioids also have effects on the dopaminergic system, which mediates their KEY FACT addictive and rewarding properties. Prescription opioids (OxyContin [oxycodone], Vicodin [hydrocodone/ Opioid intoxication: Nausea, vom- acetaminophen], and Percocet [oxycodone/acetaminophen])—not heroin— iting, sedation, decrease in pain are the most commonly used opioids. perception, decrease in gastroin- Behaviors such as losing medication, “doctor shopping,” and running out of testinal motility, pupil constriction, medication early should alert clinicians of possible misuse. and respiratory depression (which Opioids are associated with more deaths (usually due to unintentional can be fatal). overdose) than any other drug. INTOXICATION Clinical Presentation KEY FACT Opioid intoxication causes drowsiness, nausea/vomiting, constipation, slurred speech, constricted pupils, seizures, and respiratory depression, which may progress to coma or death in overdose. Meperidine is the exception to Meperidine and monoamine oxidase inhibitors taken in combination may opioids producing miosis. cause serotonin syndrome: hyperthermia, confusion, hypertension or “Demerol Dilates pupils.” hypotension, and hyperreflexia. Treatment Ensure adequate airway, breathing, and circulation. In overdose, administration of naloxone (an opioid antagonist) will KEY FACT improve respiratory depression but may cause severe withdrawal in an opioid-dependent patient. Naloxone is the treatment of Ventilatory support may be required. choice for opiate overdose. Patients at risk of opioid overdose should be prescribed a naloxone (Narcan) kit to keep at home for emergencies. OPIATE USE DISORDER See Table 7-7 for treatment of opioid use disorder. WARDS TIP WITHDRAWAL Classic triad of opioid over- While not life threatening, abstinence in the opioid-dependent individual dose—Rebels Admire Morphine leads to an unpleasant withdrawal syndrome characterized by dysphoria, Respiratory depression insomnia, lacrimation, rhinorrhea, yawning, weakness, sweating, Altered mental status piloerection, nausea/vomiting, fever, dilated pupils, abdominal cramps, Miosis arthralgia/myalgia, hypertension, tachycardia, and craving.  89 SUBSTANCE-RELATED AND ADDICTIVE DISORDERS TABLE 7-7. Pharmacological Treatment of Opioid Use Disorder Medication Mechanism Pros Cons Methadone Full agonist at mu-opioid Administered once daily. Long half life. Restricted to federally licensed substance receptor. abuse treatment programs. Can cause QTc interval prolongation: screening electrocardiogram is indicated, particularly in patients with high risk of cardiac disease. Presenting to the methadone clinic Patients can still use other opioids on top of for regular pickups can be helpful methadone. for patients who benefit from daily structure and access to group therapy or case management. Buprenorphine Partial opioid receptor Sublingual preparation that is safer In the outpatient setting, can only be agonist—can precipitate than methadone, as its effects reach a prescribed by a physician with a special withdrawal if used too plateau and make overdose unlikely. waiver on their controlled substances license. soon after full opioid Combined formulation agonists. (buprenorphine-naloxone, or Suboxone) prevents intoxication from intravenous or intranasal use. Naltrexone Competitive opioid Available as daily oral medication or Adherence is an issue for oral formulation. antagonist, precipitates monthly depot injection. It is a good Risk of LFT elevation. Can interfere with withdrawal if used within 7 choice for highly motivated patients anesthesia (e.g., for acute injuries or surgical days of heroin use such as health care professionals. procedures). Naloxone Competitive opioid Can be life-saving for patients or Does not reduce opioid use or treat antagonist, used in their peers, and should routinely be symptoms of opioid use disorder. treatment of overdose. prescribed for all patients with opioid Very short half-life; patients must be educated use disorder (especially for those who about need to call EMS or present to ED are receiving medication-assisted after it’s administered (even if the overdose treatment). appears to be reversed). Treatment includes: Moderate symptoms: Symptomatic treatment with clonidine (for autonomic signs and symptoms of withdrawal), nonsteroidal KEY FACT anti-inflammatory drugs (NSAIDs) for pain, loperamide for diarrhea, Eating large amounts of poppy dicyclomine for abdominal cramps, promethazine for nausea, etc. seed bagels or muffins can result Severe symptoms: Detox with buprenorphine or methadone. in a urine drug screen that is posi- Monitor degree of withdrawal with COWS (Clinical Opioid Withdrawal tive for opioids. Scale), which uses objective measures (i.e., pulse, pupil size, tremor) to assess withdrawal severity. Hallucinogens Hallucinogenic drugs of abuse include psilocybin (mushrooms), mescaline WARDS TIP (peyote cactus), and lysergic acid diethylamide (LSD). Pharmacological effects vary, but LSD is believed to act on the serotonergic system. Hallucinogens do Rapid recovery of consciousness not cause physical dependence or withdrawal, though users can rarely develop following the administration of in- psychological dependence. travenous (IV) naloxone (a potent opioid antagonist) is consistent INTOXICATION with opioid overdose. Effects include perceptual changes (illusions, hallucinations, body image distortions, synesthesia), labile affect, dilated pupils, tachycardia, hypertension, hyperthermia, tremors, incoordination, sweating, and palpitations.  90 Usually lasts 6–12 hours, but may last for several days. SUBSTANCE-RELATED AND ADDICTIVE DISORDERS KEY FACT May have a “bad trip” that consists of marked anxiety, panic, and psychotic symptoms (paranoia, hallucinations). Remember the withdrawal symp- Treatment: Monitor for dangerous behavior and reassure patient. Use toms of opiates: flu-like symptoms benzodiazepines as first-line for agitation (can use antipsychotics if needed). (body aches, anorexia, rhinorrhea, fever), diarrhea, anxiety, insomnia, WITHDRAWAL and piloerection. These are not life No withdrawal syndrome is produced, but with long-term LSD use, patients threatening. may experience flashbacks later in life. Marijuana Cannabis (“marijuana,” “pot,” “weed,” “grass”) is the most commonly used illicit substance in the world. KEY FACT The main psychoactive component which produces the “high” in cannabis is THC (tetrahydrocannabinol). An LSD flashback is a spontaneous Cannabinoid receptors in the brain inhibit adenylate cyclase. recurrence of symptoms mimick- Marijuana has shown some efficacy in treating nausea and vomiting in ing a prior LSD “trip” that may last chemotherapy patients, increasing appetite in AIDS patients, in chronic pain for minutes to hours. (from cancer), and lowering intraocular pressure in glaucoma. A specific class of compounds found in marijuana, cannabidiols (CBDs), is currently being studied for management of pain, seizures, and anxiety/depression. INTOXICATION Marijuana causes euphoria, anxiety, impaired motor coordination, KEY FACT perceptual disturbances (sensation of slowed time), mild tachycardia, anxiety, conjunctival injection (red eyes), dry mouth, and increased appetite Dronabinol is a pill form of THC (“the munchies”). that is FDA-approved for certain Cannabis-induced psychotic disorders with paranoia, hallucinations, and/or indications. delusions may occur. There is no overdose syndrome for marijuana use. Cannabis use disorder occurs in approximately 10% of those who use (up to 50% of daily users). Chronic use may cause respiratory problems such as asthma and chronic bronchitis, immunosuppression, cancer, and possible effects on reproductive hormones. Treatment: Supportive, psychosocial interventions (e.g., contingency management, groups). WITHDRAWAL Withdrawal symptoms may include irritability, anxiety, restlessness, aggression, strange dreams, depression, headaches, sweating, chills, insomnia, and low appetite. Treatment: Supportive and symptomatic. Inhalants Inhalants include a broad range of drugs that are inhaled and absorbed through the lungs.  91 Inhalants generally act as CNS depressants. SUBSTANCE-RELATED AND ADDICTIVE DISORDERS Most commonly used by preadolescents or adolescents; rate of use is similar between boys and girls (but rare in adult females). Examples: Solvents, glue, paint thinners, fuels, isobutyl nitrates (“huffing,” “laughing gas,” “rush,” “bolt”). INTOXICATION Effects: Perceptual disturbances, paranoia, lethargy, dizziness, nausea/vomiting, headache, nystagmus, tremor, muscle weakness, hyporeflexia, ataxia, slurred speech, euphoria, hypoxia, clouding of consciousness, stupor, or coma. Acute intoxication: 15–30 minutes. May be sustained with repeated use. Overdose: May be fatal secondary to respiratory depression or cardiac arrhythmias. Long-term use may cause permanent damage to CNS (e.g., neurocognitive impairment, cerebellar dysfunction, Parkinsonism, seizures), peripheral neuropathy, myopathy, aplastic anemia, malignancy, metabolic acidosis, urinary calculi, glomerulonephritis, myocarditis, MI, and hepatotoxicity. Treatment: Monitor airway, breathing, and circulation; may need oxygen with hypoxic states. Identify solvent because some (e.g., leaded gasoline) may require chelation. WITHDRAWAL A withdrawal syndrome does not usually occur, but symptoms may include irritability, sleep disturbance, anxiety, depression, nausea, vomiting, and craving. Caffeine Caffeine is the most commonly used psychoactive substance in the United States, usually in the form of coffee, tea, or energy drinks. It acts as an adenos- ine antagonist, causing increase in cyclic adenosine monophosphate (cAMP) and stimulating the release of excitatory neurotransmitters. OVERDOSE More than 250 mg (2 cups of coffee): Anxiety, insomnia, muscle twitching, rambling speech, flushed face, diuresis, gastrointestinal disturbance, restlessness, excitement, and tachycardia. More than 1 g: May cause tinnitus, severe agitation, visual light flashes, and cardiac arrhythmias. More than 10 g: Death may occur secondary to seizures and respiratory failure. Treatment: Supportive and symptomatic. WITHDRAWAL Caffeine withdrawal symptoms occur in 50–75% of caffeine users if cessation is abrupt. Withdrawal symptoms include headache, fatigue, irritability, nausea, vomiting, drowsiness, muscle pain, and depression. Usually resolves within 1½ weeks.  92 SUBSTANCE-RELATED AND ADDICTIVE DISORDERS Nicotine Nicotine is derived from the tobacco plant, and stimulates nicotinic receptors in autonomic ganglia of the sympathetic and parasympathetic nervous systems. It is highly addictive through its effects on the dopaminergic system. Nicotine use causes both tolerance and physical dependence (i.e., prominent WARDS TIP craving and withdrawal). Cigarette smoking is the leading cause of preventable morbidity and Cigarette smoking during preg- mortality in the United States, posing many health risks including chronic nancy is associated with low birth obstructive pulmonary disease (COPD), cardiovascular diseases, and weight, SIDS, and a variety of various cancers. postnatal morbidities. Current smoking prevalence is about 15% of U.S. adults. Effects: Restlessness, insomnia, anxiety, and increase in gastrointestinal motility. Withdrawal symptoms: Intense craving, dysphoria, anxiety, poor concentration, increase in appetite, weight gain, irritability, restlessness, and insomnia. TREATMENT OF NICOTINE DEPENDENCE FDA-approved pharmacotherapy: Varenicline (Chantix): a4b2 nicotinic cholinergic receptor (nAChR) partial agonist that mimics the action of nicotine, reducing the rewarding aspects and preventing withdrawal symptoms. Bupropion (Zyban): Antidepressant inhibits reuptake of dopamine and norepinephrine; helps reduce craving and withdrawal symptoms. Nicotine replacement therapy (NRT): Available as transdermal patch, gum, lozenge, nasal spray, and inhaler. Behavioral support/counseling should be part of every treatment. Relapse after abstinence is common. Gambling Disorder DIAGNOSIS AND DSM-5 CRITERIA Persistent and recurrent problematic gambling behavior, as evidenced by four or more of the following in a 12-month period: 1. Preoccupation with gambling. 2. Need to gamble with increasing amount of money to achieve pleasure. 3. Repeated and unsuccessful attempts to cut down on or stop gambling. 4. Restlessness or irritability when attempting to stop gambling. 5. Gambling when feeling distressed (depressed, anxious, etc.). 6. Returning to reclaim losses after gambling (“get even”). 7. Lying to hide level of gambling. 8. Jeopardizing relationships or job because of gambling. 9. Relying on others to financially support gambling.  93 SUBSTANCE-RELATED AND ADDICTIVE DISORDERS EPIDEMIOLOGY/ETIOLOGY Prevalence: 0.4–1.0% of adults in the United States. Men represent most of the cases. More common in young adults and middle-aged, and lower rates in older adults. Similar to substance use disorders, the course is marked by periods of abstinence and relapse. Increased incidence of mood disorders, anxiety disorders, substance use disorders, and personality disorders. Etiology may involve genetic, temperamental, environmental, and neurochemical factors. One-third may achieve recovery without treatment. TREATMENT Participation in Gamblers Anonymous (a 12-step program) is the most common treatment. Cognitive-behavioral therapy has been shown to be effective, particularly when combined with Gamblers Anonymous. Important to treat comorbid mood disorders, anxiety disorders, and substance use disorders where appropriate.