http://evolve.elsevier.com/McCuistion/pharmacology
Although most drugs are used safely and within prescribed guidelines, it is possible for all drugs to be misused. It has been reported that over 40 million Americans ages 12 and over use tobacco, alcohol, or illicit drugs. Drug use is a serious and complex social and health issue with negative consequences for both the individual and society that include family dysfunction, loss of employment, failure in school, domestic violence, and child abuse. The economic cost of drug use is staggering: $600 billion annually in costs related to lost productivity, health-related issues, and crime.
Substance Use Disorder
Context
Since 1975, the Monitoring the Future project has been tracking drug use in adolescents and young adults. Current data from the survey indicate that 26.4% of children have tried illicit drugs by the eighth grade, 40% by the tenth grade, and 51.8% by the twelfth grade. Tenth graders had tried alcohol (49.8%), Cannabis (28.8%), amphetamines (6.6%), and prescription and over-the-counter (OTC) drugs such as oxycodone or cough medicine (2.6% to 5.9%). Between 15% and 39% used more than one drug, known as polydrug use.
Many factors play into the decision to use drugs and whether an individual develops substance use disorder. Cognitive development at the time drugs are introduced plays a major role; adolescents are in a period of brain development where they are especially vulnerable to stress and risk-seeking behaviors. Other risk factors are also related to substance use disorder:
• Social risk factors: Deviant peer relationships (i.e., the adolescent associates with abusers and uses drugs to feel accepted), peer pressure, popularity, and bullying have all been correlated to drug use. Gang affiliation is associated with higher drug use and delinquent behavior.
• Individual risk factors: Individuals with attention-deficit/hyperactivity disorder (ADHD) are three times as likely as the general population to use drugs such as nicotine, alcohol, and drugs other than Cannabis; depression is associated with alcohol use, particularly among young men.
It should be noted that positive family relationships are a protective factor that has been related to a decrease in drug use among adolescents.
Definition
According to the Diagnostic and Statistical Manual of Mental Disorders (5th edition [DSM-5]), substance use disorder occurs “when the recurrent use of alcohol and/or drugs causes clinically and functionally significant impairment, such as health problems, disability, and failure to meet major responsibilities at work, school, or home.” Substance use disorder is categorized along a continuum from mild to severe, based on the number of diagnostic criteria met (Table 7.1). The terms abuse and dependence are no longer used due to the violence and stigma associated with the term abuse and the ambiguity associated with the term dependence; gambling is the only condition in the category of behavioral addiction (continued involvement in an activity despite the substantial harm it causes; Table 7.2). Excessive caffeine use is not considered a substance use disorder, even though there appears to be a withdrawal syndrome with cessation of use.
Neurobiology
Drugs that are misused typically increase the availability of dopamine and other neurotransmitters in the limbic system of the brain. This area contains the brain’s reward circuit, a structure that regulates our ability to feel pleasure and other emotions, both positive and negative. The drugs interfere with the way neurons in the brain normally send, receive, and process information by mimicking the brain’s own neurotransmitters; however, drugs do not copy neurotransmitters exactly, which results in faulty transmission or excessive stimulation. Most of the drugs facilitate an increase of dopamine in the system, leading to mood elevation or euphoria—factors that provide strong motivation to repeat the experience. Some drugs increase the availability of other neurotransmitters, such as serotonin and gamma-aminobutyric acid (GABA), but dopamine’s effect on the reward system appears to be pivotal to substance use disorder.
Repeated use of drugs remodels the neural circuitry of the brain cells and reduces the responsiveness of receptors. This decreased responsiveness leads to tolerance, the need for a larger dose of a drug to obtain the original euphoria. Drug use results in levels of dopamine that do not naturally occur; tolerance also reduces the sense of pleasure from experiences that previously resulted in positive feelings, such as food, sex, or relationships. Without the drug, the individual may experience depression, anxiety, and/or irritability (Table 7.3; see also Table 7.2).
Current research is focused on epigenetics, the study of environmental influences on genetics. How a person responds to their social and cultural environment affects drug use. Altering environmental factors that increase the risk for drug use can discourage drug-seeking behavior. Studies have shown that drug use alters DNA proteins, those that affect both gene expression and function, and this influences drug-seeking behavior. Understanding these processes may lead to new treatments for substance use disorders.
TABLE 7.2
Terminology Related to Substance Use Disorder
| Term | Definition |
| Abstinence | Refraining from drug use |
| Craving | Strong desire for a drug or for the intoxicating effects of that drug |
| Intoxication | A condition that results in disturbances in the level of consciousness, cognition, perception, judgment, affect or behavior, or other psychophysiological functions and responses |
| Stabilization | Acute treatment for substance use disorder involving supervision, observation, support, intensive education, and counseling that involves multidisciplinary treatment interventions |
| Tolerance | Requiring a significantly increased amount of a drug to achieve the desired effect |
| Withdrawal syndrome | A group of symptoms of varying severity that occur upon cessation or reduction of use of a drug that has been taken repeatedly, usually for a prolonged period and/or in high doses; may be accompanied by signs of physiological disturbance |
| Remission | None of the 11 criteria for substance use disorder for at least three months (early remission, 3 to 12 months; sustained remission, after 12 months) |
| Controlled environment | Environment where access to any drug is restricted (e.g., treatment center or halfway house) |
| Impaired control | Diminished ability of an individual to control his or her use of a drug in terms of onset, level, or termination |
| Social impairment | Recurrent drug use despite problems at work or school, interpersonal problems, or the cessation of social and recreational activities |
| Risky use | Recurrent drug use despite the difficulty it is causing (e.g., driving while intoxicated, liver damage) |
| Recovery | A process of change through which an individual improves health and wellness, lives a self-directed life, and strives to reach full potentials |
| Relapse | A return to drug use after a period of abstinence, often accompanied by reinstatement of substance use disorder |
From Substance Abuse and Mental Health Services Administration. (2015). Substance use disorders. Retrieved May 17, 2016, from www.samhsa.gov/disorders/substance-use; and World Health Organization. (n.d.). Lexicon of alcohol and drug terms published by the World Health Organization. Retrieved May 18, 2016, from http://www.who.int/substance_abuse/terminology/who_lexicon/en/
Types of Substance Use Disorders
Alcohol Use Disorder (AUD)
People drink for many reasons, including socializing, celebrating, and relaxing; people also drink to cope, because of low self-esteem and a need for approval, or because of peer pressure. Alcohol affects everyone differently, depending on the amount consumed, the frequency of consumption, age, health status, and family history. People of all ages drink, and 15% of all alcohol sales in the United States are to teens. Alcohol use is the underlying cause in 88,000 deaths per year. Additionally, the Centers for Disease Control and Prevention report that AUD may shorten a person’s life by up to 30 years!
Alcohol use inhibits the effects of GABA, thereby reducing neurotransmission in the brain. Short-term effects of alcohol use include nausea, vomiting, headaches, slurred speech, impaired judgment, memory loss, hangovers, and blackouts. Box 7.1 discusses alcohol toxicity.
Long-term problems associated with heavy drinking include stomach ailments, heart problems, cancer, brain damage, serious memory loss, immune system compromise, and liver cirrhosis. Persons with AUD increase their chances of dying from automobile accidents, homicide, and suicide. Spouses and children of persons with AUD may face family violence, and children may suffer physical and sexual abuse and neglect and may develop psychological problems. Women who drink during pregnancy run a serious risk of their fetus developing fetal alcohol spectrum disorder. To intervene promptly and avoid long-term problems associated with AUD, nurses should question all patients about their drinking habits with every encounter, using plain language, without bias (Fig. 7.1).
Treatment
AUD can be treated through a variety of options. However, very few people with the disorder seek care. Alcohol treatment centers offer inpatient-type care, where the person undergoes stabilization in a controlled environment that includes group therapy. Persons with AUD are provided the tools they need to become abstinent and go into remission. Outpatient treatment is also available. People with AUD who participate in outpatient therapy are given the tools to become abstinent and go into remission (Table 7.4).
Drug-assisted treatment
Several drugs have been approved by the U.S. Food and Drug Administration (FDA) to treat AUD. Disulfiram, acamprosate, and naltrexone are the most commonly used (Table 7.5). Disulfiram inhibits aldehyde dehydrogenase, the enzyme involved in metabolizing alcohol. It is best used in people who are newly abstinent. Disulfiram is administered in tablet form; dosage ranges from 125 to 500 mg daily. It is contraindicated in persons who are intoxicated and should not be taken within 12 hours of alcohol consumption (including use of mouthwash, cough medicine, or eating desserts that contain alcohol or eating foods cooked in alcohol). Side effects occur within 10 minutes of alcohol consumption and can last for over an hour. These side effects include nausea, headache, vomiting, chest pains, and difficulty breathing. Disulfiram keeps patients from drinking because of the unpleasant side effects that occur if alcohol is consumed while taking the drug. Patients who have recently been treated with metronidazole or paraldehyde should not take disulfiram because these same side effects will occur, as if they had been drinking. Because of the risk for drug toxicity, disulfiram should never be used in combination with eliglustat or ritonavir.
TABLE 7.3
Most Commonly Used Illicit Drugs
Information obtained from DrugAbuse.com. (n.d.). http://drugabuse.com/library/drugs-a-z/; www.drugs.com. (2016). Drugs A-Z. Retrieved May 15, 2016, from www.drugs.com; and National Institute on Drug Abuse. (2016). Commonly abused drugs. Retrieved May 15, 2016, from www.drugabuse.gov/drugs-abuse/
Other side effects of disulfiram include rash, drowsiness, impotence, acne, and a metallic aftertaste. Serious reactions include psychosis, hepatotoxicity, peripheral neuropathy, and optic neuritis. Patients taking disulfiram should have baseline liver function studies obtained; liver function studies should be repeated after 2 weeks of therapy. For disulfiram to be effective, persons with AUD also need to participate in behavior modification, psychotherapy, and counseling. Disulfiram was designated pregnancy category C, and whether it will harm the fetus is unknown; however, it is excreted into breast milk. Therefore a decision should be made to either discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother.
TABLE 7.4
Nonpharmacological Therapy for Substance Use Disorders: Individual and Group Counseling
| Therapy | Description |
| Cognitive behavioral therapy (CBT) | CBT teaches people to recognize and stop negative patterns of thinking and behavior and helps enhance self-control. For instance, therapy might help a person become aware of the stressors, situations, and feelings that lead to substance use so that the person can avoid them or act differently when they occur. |
| Contingency management | This approach is based on frequent monitoring of behavior and removal of rewards for drug use and was designed to provide incentives to reinforce positive behavior and help the person remain abstinent from drug use. |
| Motivational enhancement therapy (MET) | MET helps people with substance use disorders develop internally motivated changes and commit to specific plans to engage in treatment and seek recovery. It is often used early in the process to engage people in treatment. |
| Twelve-step facilitation therapy | Seeks to guide and support engagement in 12-step programs such as Alcoholics Anonymous or Narcotics Anonymous. |
From Substance Abuse and Mental Health Services Administration. (2015). Treatments for substance use disorders. Retrieved June 3, 2016, from www.samhsa.gov/treatment/substance-use-disorders
Acamprosate is a GABA analogue thought to work in the brain to restore the balance between neuronal excitation and inhibition via GABA and glutamate. It should only be used in persons who are abstinent; however, acamprosate may be continued through a relapse. Usual dosing is 666 mg orally three times per day. Dosing is adjusted in kidney disease, and a serum creatinine level should be obtained at baseline. Persons with a creatinine clearance of 30 mL/min to 50 mL/min should only take 333 mg three times per day. Acamprosate is contraindicated in people with a creatinine clearance less than 30 mL/min. Common side effects include pain, loss of appetite, nausea, diarrhea, dizziness, anxiety, pruritus, depression, insomnia, xerostomia, and paresthesia. Patients should be assessed for suicide ideology prior to beginning treatment. This drug is used in conjunction with behavior modification and counseling. Naltrexone increases acamprosate levels. No dosage adjustment is needed, but patients should be monitored closely. Acamprosate was designated pregnancy category C; it is not known if it will harm the fetus or if it is excreted into breast milk. Therefore a decision should be made to either discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother.
Naltrexone is a competitive opioid antagonist with a high affinity for mu receptors. Oral forms absorbed through the gastrointestinal (GI) tract undergo up to 40% first-pass metabolism. Onset occurs in 15 to 30 minutes with peak occurring in 1 hour. Naltrexone is used in persons who are abstinent. If there is concern about comorbid opioid use disorder (OUD), a naloxone challenge test may be done prior to initiating treatment, in which a test dose of 25 mg is administered orally, and the patient is observed for an hour. If no withdrawal is observed, dosing may begin the following day at 50 mg per day for 12 weeks or less. Dosing using 380 mg intramuscularly (IM) once every 4 weeks can be used for maintenance therapy. Common side effects include insomnia, nausea, vomiting, anxiety, headache, abdominal pain, myalgia, arthralgia, rash, dizziness, fatigue, constipation, and increased creatine phosphokinase (CPK). Serious reactions include suicidality, depression, hepatotoxicity, and hypersensitivity reaction. Patients should be assessed for suicide ideology prior to beginning treatment. This drug should not be taken in conjunction with any drugs that bind to opioid receptors because withdrawal may be precipitated in persons with OUD. Naltrexone was designated pregnancy category C; it is not known if it will harm the fetus, and it is excreted into breast milk. Therefore a decision should be made to either discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother.
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