Chapter review

Fitzgerald PMHNP board review. ch11. Substance-related Disorders. This is drive 4 of 8. When I say Pause. Answer. wait, then I will give the answer. New section. Core Definitions and Defense Mechanisms. Topic. Denial vs. Anosognosia. Bottom Line Summary. * **Denial** is defined as the cognitive defense mechanism where an individual believes a **substance use disorder** is not causing problems, minimizes negative consequences, or insists that outside treatment is unnecessary [1, 2]. * **Anosognosia** is a neuro-circuitry failure or organic lack of illness awareness seen in neurological conditions or **schizophrenia**, whereas **denial** is a psychological coping strategy used to avoid emotional distress [1, 3]. * **DSM-5-TR** diagnosis of **substance use disorder** requires 2 or more criteria met within a 12 month period using the mnemonic TEMPTED [4-7]. * Severity is coded as **mild** with 2 to 3 symptoms, **moderate** with 4 to 5 symptoms, and **severe** with 6 or more symptoms [8-10]. * **Physical dependence** requires physiological **tolerance** or **withdrawal**, while **substance dependence** can occur without physical symptoms [11-14]. * **Psychological dependence** features intense cravings, a strong desire to use, and taking the drug to avoid low or unpleasant mood states [1, 12, 15-17]. * Objective lab markers of heavy alcohol use include an **AST** greater than **ALT** ratio resolving in 1 to 3 months of sobriety, **macrocytosis** with **MCV** greater than 96 without anemia resolving in 2 to 3 months, and elevated **triglycerides** resolving in 1 to 2 months [18-22]. Core Definitions and Clinical Distinction. Denial in Substance Use Disorders. In psychiatric practice, **denial** serves as an unconscious defense mechanism to shield the patient from painful realities regarding their addiction [1, 2]. The patient distorts reality by downplaying consumption amounts, attributing life disruptions to external causes, or claiming full personal control [1, 2, 23]. For example, a patient facing academic failure or legal charges may insist that alcohol plays no role in their difficulties [2, 23]. Denial versus Anosognosia. **Board trap:** Do not confuse psychological **denial** with **anosognosia** [1, 3]. **Denial** is a psychological defense mechanism where the patient possesses the anatomical capacity for insight but protects the ego by rationalizing or minimizing consequences [1, 2]. Conversely, **anosognosia** is an anatomical neurological deficit, common in **schizophrenia** or right parietal lobe lesions, resulting in a literal biological inability to perceive illness source 3. **Safety alert:** **Denial** leads patients to severely underreport substance amounts, delaying essential care and increasing the risk of unmonitored **withdrawal seizures** or **delirium tremens** [1, 24-26]. Always obtain collateral information from family members, case managers, or objective lab markers like **AST**, **ALT**, and **MCV** to establish clinical accuracy [18-21, 24, 25, 27-29]. **First-line:** The **first-line** intervention for confronting **denial** is **motivational interviewing** [24, 30-34]. Direct confrontation escalates defensiveness and solidifies **denial** source 30. The PMHNP must utilize open ended questions, validate patient feelings, reflect ambivalence, and support self efficacy [24, 30-32]. Sample Test Questions. Question 1. Marcus, a 24-year-old student who is at risk for failing out of law school, is referred by his academic advisor for psychiatric evaluation source 23. He states that he drinks an average of six beers per night, and last year he had a driving under the influence (DUI) arrest source 23. Marcus states, "I don't think my beer drinking has anything to do with my bad grades. I really only have a couple of beers every night, and it helps me to relax" [2, 23]. This statement is an example of: * A. Enabling * B. Projection * C. Psychological dependence * D. Denial Pause. Answer: D source 2. Why It Is Correct. Marcus is demonstrating **denial**, a classic cognitive defense mechanism where an individual minimizes substance use, refuses to connect chemical use to severe social or academic impairments, and insists that outside intervention is unnecessary [1, 2]. Why the Other Choices Are Wrong. * A. **Enabling** is incorrect because enabling refers to behaviors by family members or friends that inadvertently shield the patient from the natural consequences of substance use. * B. **Projection** is incorrect because projection involves attributing one's own unacceptable impulses or feelings onto another person. * C. **Psychological dependence** is incorrect because psychological dependence describes intense cravings and taking a substance specifically to alter mood or avoid negative affect, rather than denying consequences [1, 12, 15-17]. Question 2. The PMHNP's response to Marcus that best illustrates **motivational interviewing** would be: * A. "Relaxing is important to you after you've worked hard at school." * B. "Do you see your DUI as an indication that you likely have a problem with alcohol?" * C. "Your advisor obviously thinks that your beer drinking is affecting your grades, and that is why he referred you here." * D. "What else could be causing your low grades then?" Pause. Answer: A source 30. Why It Is Correct. Option A illustrates **motivational interviewing** by using reflective listening, expressing empathy, and validating the patient's personal perspective without judgment or confrontation [30-32]. Why the Other Choices Are Wrong. * B. Option B is incorrect because asking closed, confrontational questions about alcohol problems forces the patient onto the defensive and increases resistance source 30. * C. Option C is incorrect because citing the advisor's authority creates an external power struggle rather than fostering internal motivation to change source 30. * D. Option D is incorrect because challenging the patient directly or sarcastically damages the therapeutic alliance and reinforces **denial** source 30. ‡ Want to review another leaf in this chapter, such as MAT protocols for alcohol use disorder or CIWA/COWS withdrawal scoring? Next. Topic. Tolerance and Withdrawal. Fitzgerald Chapter 11: Tolerance and Withdrawal (Core Definitions and Defense Mechanisms). Bottom Line Summary. - **Physical dependence** is defined by two cardinal physiological features: **tolerance** (requiring increased doses for the same effect) and **withdrawal** (substance-specific physical or psychological symptoms upon cessation). - **Substance dependence** can occur with or without **physical dependence**, as psychological cravings and loss of control drive compulsive use independently. - **DSM-5-TR criteria** require 2 or more of 11 criteria within a 12-month period to diagnose **substance use disorder** (severity: **mild** = 2 to 3 symptoms, **moderate** = 4 to 5 symptoms, **severe** = 6 or more symptoms). - **Denial** is the primary cognitive defense mechanism in addiction, where the individual minimizes consequences, disavows impairment, or rejects the need for outside treatment. - **Alcohol withdrawal** carries high mortality due to autonomic hyperarousal, **delirium tremens**, and **seizures**; **first-line** pharmacological management utilizes **benzodiazepines** (such as **lorazepam**, **chlordiazepoxide**, or **diazepam**). - **Opioid withdrawal** presents with severe multi-system autonomic hyperarousal (**COWS** scale), managed with **clonidine** for sympathetic surges, **buprenorphine** or **methadone** for substitution, and symptom-specific adjuncts. - **Thiamin** (100 mg IV or IM) must ALWAYS be administered BEFORE glucose in acute alcohol withdrawal to prevent irreversible **Wernicke-Korsakoff syndrome** (**Wernicke encephalopathy** triad: **delirium**, **ataxia**, **ophthalmoplegia**). High-Yield Core Definitions and Concepts. Physical Dependence vs Psychological Dependence. Physical dependence represents a neuroadapted state characterized by physiological tolerance and withdrawal symptoms when the substance is stopped or reduced. In contrast, psychological dependence centers on intense emotional cravings, compulsive drug-seeking behavior, and taking the substance to avoid dysphoria or unpleasant mood states. An individual can develop physical dependence on prescribed opioids or benzodiazepines without meeting criteria for a substance use disorder. Tolerance Mechanism. Tolerance develops as the brain reward circuit (the **mesolimbic dopamine pathway**) adapts to chronic exaggerated dopamine surges. Neurons downregulate postsynaptic receptors or alter synaptic communication, requiring progressively higher doses of the drug to achieve intoxication or the initial therapeutic effect. Withdrawal Syndrome. Withdrawal is a substance-specific cluster of physical, cognitive, and behavioral symptoms occurring when blood or tissue concentrations of a substance decline in an individual who has maintained heavy, prolonged use. Alternatively, withdrawal is demonstrated when the same or a closely related substance is taken to relieve or avoid withdrawal symptoms. Denial as a Defense Mechanism. Denial is an unconscious defense mechanism where the patient insists that substance use is not causing harm, minimizes interpersonal or legal consequences, or claims that formal treatment is unnecessary. When encountering denial in clinical practice, **first-line** communication utilizes **motivational interviewing** to express empathy, roll with resistance, and explore ambivalence rather than direct confrontation. Signpost Summary. - **Safety alert**: Never administer IV glucose prior to **thiamin** in malnourished or severe alcohol use disorder patients; doing so precipitates acute **Wernicke encephalopathy** (**delirium**, **ataxia**, **ophthalmoplegia**). - **Board trap**: Assuming that physical dependence alone equals addiction. On board exams, tolerance and withdrawal resulting from prescribed medical therapy (such as pain management or supervised anxiety treatment) do not count toward DSM-5-TR substance use disorder criteria unless accompanied by loss of control, social impairment, or risky use. - **First-line**: **Benzodiazepines** are the **first-line** intervention for acute alcohol withdrawal to stabilize GABAergic tone and prevent **seizures** or **delirium tremens**. Spoken Concepts: Diagnostic Frameworks and Criteria. DSM-5-TR Substance Use Disorder Criteria. The DSM-5-TR combined former categories of substance abuse and substance dependence into a single entity termed **substance use disorder**. The diagnostic mnemonic **tempted with cocaine, Scotch and rum** outlines the 11 criteria evaluated over a 12-month period: - **Tolerance**: Needing increased amounts for effect or experiencing diminished effect with the same amount. - **Withdrawal**: Characteristic withdrawal syndrome or taking substances to avoid withdrawal. - **Control loss**: Taking larger amounts over longer periods than intended, persistent desire or unsuccessful efforts to cut down, spending excessive time obtaining, using, or recovering, and intense cravings. - **Social consequences**: Failure to fulfill major role obligations at work, school, or home; continued use despite persistent social or interpersonal problems; giving up important activities. - **Risky use**: Recurrent use in physically hazardous situations (such as driving impaired) and continued use despite knowing it causes or worsens physical or psychological problems. Diagnostic severity is classified strictly by symptom count: 2 to 3 symptoms indicates **mild** severity, 4 to 5 symptoms indicates **moderate** severity, and 6 or more symptoms indicates **severe** severity. Substance-Specific Withdrawal Patterns. - **Alcohol withdrawal**: Onset occurs within 6 to 24 hours after last drink. Symptoms include autonomic hyperarousal (tachycardia, hypertension, diaphoresis), coarse hand tremors, nausea, insomnia, anxiety, transient hallucinations, and **grand mal seizures**. **Delirium tremens** typically emerges 48 to 96 hours post-cessation. - **Opioid withdrawal**: Characterized by multi-system distress including nausea, vomiting, abdominal cramps, diarrhea, rhinorrhea, lacrimation, piloerection (gooseflesh), mydriasis, muscle or joint aches, and intense restlessness. Evaluated using the **Clinical Opioid Withdrawal Scale** (**COWS**). - **Stimulant withdrawal** (amphetamines, cocaine): Characterized by dysphoric mood, profound fatigue, vivid unpleasant dreams, hypersomnia or insomnia, increased appetite, and psychomotor retardation or agitation. - **Sedative/Hypnotic withdrawal** (benzodiazepines, barbiturates): Mirrors alcohol withdrawal with severe autonomic instability, tremors, anxiety, confusion, and life-threatening **seizures**. Fitzgerald Sample Practice Questions. Question 1. Marcus, a 24-year-old student at risk for failing out of law school, is referred by his academic advisor for psychiatric evaluation. He states that he drinks an average of six beers per night, and last year he had a driving under the influence (DUI) arrest. Marcus states, "I don't think my beer drinking has anything to do with my bad grades. I really only have a couple of beers every night, and it helps me to relax." This statement is an example of: A) Enabling B) Projection C) Psychological dependence D) Denial Pause. Answer: D **Why It Is Correct:** Marcus is exhibiting **denial**, a classic defense mechanism in substance use disorders where the patient minimizes alcohol consumption, denies the connection between substance use and life impairment (failing grades, DUI), and insists the behavior is harmless [1-3]. **Why the Other Choices Are Wrong:** - **A:** Enabling refers to behaviors by family, friends, or associates that inadvertently allow or facilitate the patient's continued substance use. - **B:** Projection is an unconscious defense mechanism where an individual attributes their own unacknowledged or unacceptable thoughts and feelings onto another person. - **C:** Psychological dependence involves intense emotional cravings and drug-seeking behavior to avoid unpleasant mood states, whereas Marcus's statement explicitly disavows impairment [2, 3]. Question 2. The PMHNP's response to Marcus that best illustrates motivational interviewing would be: A) "Relaxing is important to you after you have worked hard at school." B) "Do you see your DUI as an indication that you likely have a problem with alcohol?" C) "Your advisor obviously thinks that your beer drinking is affecting your grades, and that is why he referred you here." D) "What else could be causing your low grades then?" Pause. Answer: A **Why It Is Correct:** Motivational interviewing relies on non-confrontational reflective listening and empathy. Statement A validates the patient's perspective, acknowledges their underlying desire (relaxation), and avoids argument, which helps engage the patient in exploring ambivalence [4-6]. **Why the Other Choices Are Wrong:** - **B:** Option B is a direct, closed question that confronts the patient with their legal history, which increases defensiveness and resistance [4, 5]. - **C:** Option C places the locus of concern on an outside authority (the advisor) and uses a confrontational tone, opposing motivational interviewing principles source 5. - **D:** Option D is argumentative and sarcastic, which damages the therapeutic alliance and increases patient resistance [5, 6]. Question 3. Match the substance with the corresponding withdrawal presentation: Statement 1: Depressed mood, severe fatigue, vivid unpleasant dreams, and psychomotor agitation. Statement 2: Muscle cramps, arthralgia, rhinorrhea, lacrimation, and severe diarrhea. Statement 3: Tachycardia, hypertension, diaphoresis, coarse hand tremor, agitation, and perceptual disturbances. A) Statement 1 = Amphetamine/Cocaine; Statement 2 = Opioid; Statement 3 = Alcohol B) Statement 1 = Alcohol; Statement 2 = Amphetamine/Cocaine; Statement 3 = Opioid C) Statement 1 = Opioid; Statement 2 = Alcohol; Statement 3 = Amphetamine/Cocaine D) Statement 1 = Amphetamine/Cocaine; Statement 2 = Alcohol; Statement 3 = Opioid Pause. Answer: A **Why It Is Correct:** Statement 1 describes stimulant withdrawal (amphetamine/cocaine), characterized by a crash involving depression, fatigue, vivid dreams, and psychomotor changes [7, 8]. Statement 2 describes opioid withdrawal, marked by multi-system flu-like autonomic and GI distress [9, 10]. Statement 3 describes CNS depressant/alcohol withdrawal, marked by dangerous autonomic hyperarousal and tremor [10-12]. **Why the Other Choices Are Wrong:** - **B:** Incorrectly assigns alcohol withdrawal to dysphoric fatigue and amphetamine withdrawal to muscle cramps. - **C:** Incorrectly assigns opioid withdrawal to dysphoric crash symptoms and amphetamine withdrawal to autonomic hyperarousal. - **D:** Incorrectly swaps alcohol and opioid withdrawal presentations. Question 4. A 19-year-old man is brought to the emergency department by his friends who are concerned about his behavior. Physical examination reveals muscle weakness, dilated pupils, a heart rate of 140 beats per minute, and blood pressure of 180/115 mmHg. His friends report he "took something orally" two hours ago. Which of the following is the most likely illicit substance? A) Cannabis B) Dextroamphetamine C) Diazepam D) Oxycodone Pause. Answer: B **Why It Is Correct:** **Dextroamphetamine** is a potent central nervous system stimulant that causes marked sympathomimetic hyperarousal, including severe tachycardia (140 bpm), severe hypertension (180/115 mmHg), mydriasis (dilated pupils), and muscle weakness/tremor [13, 14]. **Why the Other Choices Are Wrong:** - **A:** Cannabis intoxication causes conjunctival injection, mild tachycardia, and increased appetite, but does not cause severe hypertension or marked pupillary dilation source 15. - **C:** Diazepam is a benzodiazepine CNS depressant that produces sedation, hypoventilation, hypotension, and miosis or normal pupils source 16. - **D:** Oxycodone is an opioid agonist that presents with CNS depression, respiratory depression, hypotension, bradycardia, and marked miosis (pinpoint pupils) source 17. Question 5. When deciding on the appropriate treatment setting to manage acute withdrawal symptoms for a 46-year-old man with a history of severe alcohol use disorder, which factor is most prominent in favoring immediate inpatient hospitalization? A) A CIWA-Ar score of 10 B) A history of alcohol use disorder for two years C) Co-occurring mild generalized anxiety disorder D) A prior history of delirium tremens or withdrawal seizures Pause. Answer: D **Why It Is Correct:** A prior history of **delirium tremens** or **withdrawal seizures** is the strongest clinical predictor of severe, life-threatening alcohol withdrawal, requiring immediate medically monitored inpatient detoxification [18, 19]. **Why the Other Choices Are Wrong:** - **A:** A CIWA-Ar score of 10 represents mild withdrawal (scores under 15 generally do not require inpatient admission or aggressive pharmacotherapy) source 20. - **B:** A two-year history of alcohol use disorder alone without prior withdrawal complications does not mandate inpatient hospitalization if outpatient support is available [18, 21]. - **C:** Co-occurring mild generalized anxiety disorder can be managed safely in an outpatient or intensive outpatient setting source 21. Next. New section. Alcohol Dependence Pharmacotherapy (Table 11-15). Topic. Naltrexone (ReVia, Vivitrol). Bottom Line Summary. * **Naltrexone** (**ReVia**, **Vivitrol**) is a **first-line** FDA-approved medication for moderate to severe **alcohol use disorder** to reduce cravings and heavy drinking. * Mechanism of action: Competitive mu-opioid receptor antagonist that blocks endogenous opioid release triggered by alcohol, preventing the reinforcing euphoria or high. * Formulations: Oral **naltrexone** (**ReVia**) dosed at 50 mg daily, or long-acting injectable **naltrexone** (**Vivitrol**) administered as a 380 mg intramuscular injection every 4 weeks. * **Safety alert**: Strictly contraindicated in patients taking opioids or in acute opioid withdrawal. Patients must be opioid-free for 7 to 10 days prior to initiation to prevent precipitated withdrawal. * **Safety alert**: Strictly contraindicated in acute hepatitis or liver failure. Obtain baseline and periodic liver function tests (**AST**, **ALT**) due to dose-dependent hepatotoxicity. * **Board trap**: Do not confuse **naltrexone** with **naloxone** (**Narcan**). **Naloxone** is a short-acting emergency antagonist for acute opioid overdose, whereas **naltrexone** is a long-acting maintenance therapy. * Clinical selection: **Acamprosate** (**Campral**) is preferred over **naltrexone** in patients with liver disease because **acamprosate** is excreted renally. High-Yield Concept Review: Naltrexone (ReVia, Vivitrol). Mechanism of Action and Clinical Focus. * **First-line** agent recommended by national guidelines for moderate to severe **alcohol use disorder**. * Acts as a competitive antagonist at mu-opioid receptors. * Blocks the pleasure pathway by preventing endogenous opioids from binding after alcohol consumption. * Reduces alcohol cravings and decreases the risk of returning to heavy drinking if a slip occurs. Formulations and Administration. * Oral formulation: **ReVia**, prescribed as 50 mg once daily. * Injectable formulation: **Vivitrol**, administered as a 380 mg intramuscular gluteal injection once every 4 weeks. * Injectable **Vivitrol** improves medication adherence for patients struggling with daily oral dosing. Critical Safety Alerts and Contraindications. * **Safety alert**: Active opioid use. Administering **naltrexone** to a patient taking prescribed opioids or using illicit opioids precipitates acute, severe opioid withdrawal. * Require a negative urine drug screen and an opioid-free window of 7 to 10 days before starting therapy. * **Board trap**: If a patient has upcoming surgery or dental procedures requiring opioid analgesia, **naltrexone** is contraindicated because it blocks opioid pain relief. * **Safety alert**: Active liver disease. **Naltrexone** is hepatotoxic at high doses and is contraindicated in acute hepatitis or liver failure. Monitor baseline and follow-up **LFTs**. Pharmacotherapy Comparisons. * **Naltrexone** vs **Acamprosate**: Select **naltrexone** to reduce active cravings in patients with normal liver function. Select **acamprosate** in patients with liver impairment, as **acamprosate** is cleared renally. * **Naltrexone** vs **Disulfiram**: **Disulfiram** (**Antabuse**) is an aversion agent causing a severe physical reaction when alcohol is consumed. It does not reduce daily cravings and is not **first-line** initial therapy. * **Naltrexone** vs **Naloxone**: **Naloxone** is a short-acting antagonist used exclusively for emergency opioid overdose reversal. Sample Board Exam Questions. Question 1. Randy, a 32-year-old single manager of a sporting goods store, is being seen for follow-up after a 30-day inpatient stay for alcohol dependence. He has been sober for 45 days and continues to crave alcohol throughout the day. Which medication can be prescribed for Randy as part of his treatment recovery plan to target alcohol cravings? A) Disulfiram B) Bupropion C) Naltrexone D) Naloxone Pause. Answer: C * **Why it is correct**: **Naltrexone** is a craving-reducing medication that blocks endogenous opioid release, preventing the reinforcing high from alcohol and reducing daily cravings during recovery. * **Why the other choices are wrong**: * A) **Disulfiram** is an aversion therapy that causes a toxic physical reaction when alcohol is consumed rather than directly reducing daily alcohol cravings. * B) **Bupropion** is an NDRI antidepressant indicated for major depressive disorder and smoking cessation, not alcohol craving management. * D) **Naloxone** is a short-acting opioid antagonist used exclusively for emergency reversal of acute opioid overdose. Question 2. Dana, a 44-year-old registered nurse, is preparing to be discharged from a 30-day inpatient treatment facility for alcohol and methamphetamine dependence. She wishes to start a medication to help keep her abstinent from alcohol. She has extensive dental work planned to begin within the next month. Which medication would be contraindicated for use given this information? A) Disulfiram B) Naltrexone C) Acamprosate D) Sertraline Pause. Answer: B * **Why it is correct**: **Naltrexone** blocks mu-opioid receptors and is strictly contraindicated in patients who will require opioid analgesics for planned dental or surgical procedures, as it blocks pain relief and can precipitate acute withdrawal. * **Why the other choices are wrong**: * A) **Disulfiram** does not block opioid receptors or interfere with post-procedure opioid pain management. * C) **Acamprosate** acts on GABA and glutamate pathways, making it safe for patients requiring planned opioid analgesia. * D) **Sertraline** is an SSRI antidepressant that does not block opioid analgesia or interact with post-procedure pain management. Question 3. Gary, a 54-year-old man with moderate liver disease and a 3.5-year history of sobriety, presents for evaluation after recent stressful life events have caused increased urges to drink. To prevent a possible relapse, the PMHNP recommends counseling and treatment with: A) Acamprosate B) Naloxone C) Clonidine D) Lorazepam Pause. Answer: A * **Why it is correct**: **Acamprosate** is excreted renally and is the safe choice for maintaining abstinence in a patient with underlying liver disease, whereas **naltrexone** undergoes hepatic metabolism and is contraindicated in liver impairment. * **Why the other choices are wrong**: * B) **Naloxone** is a short-acting emergency reversal agent for opioid overdose, not a long-term craving or relapse prevention medication. * C) **Clonidine** is an alpha-2 agonist used to manage autonomic hyperactivity during acute withdrawal, not for maintaining long-term sobriety. * D) **Lorazepam** is a benzodiazepine used for acute alcohol detoxification that carries abuse potential and is not indicated for relapse prevention. 💡 **Next Study Step**: Review **Acamprosate** (**Campral**) and **Disulfiram** (**Antabuse**) in Fitzgerald Chapter 11 to master the full comparative matrix of alcohol dependence pharmacotherapy for board exam scenarios. Next. Topic. Disulfiram (Antabuse) Safety. Bottom Line Summary. - **Disulfiram** (**Antabuse**) is an aldehyde dehydrogenase inhibitor used as an aversion therapy, NOT as a **first-line** agent or initial craving-reduction therapy. - **Safety alert**: Combining **disulfiram** with alcohol produces a toxic buildup of acetaldehyde, causing severe flushing, throbbing headache, nausea, vomiting, tachycardia, and hypotension. - **Safety alert**: Absolute contraindications include severe cardiac disease, psychosis, active seizure disorders, pregnancy, and concurrent use of **metronidazole** or alcohol-containing products. - **Board trap**: **Disulfiram** does NOT reduce physiological alcohol cravings. **Naltrexone** and **acamprosate** are **first-line** FDA-approved agents for craving reduction and relapse prevention. - Patients must refrain from all alcohol (including mouthwashes, OTC cough syrups, and hand sanitizers) for at least 12 hours before starting **disulfiram** and for 14 days after discontinuation. - **Acamprosate** (**Campral**) is cleared renally and preferred in liver disease, whereas **naltrexone** (**ReVia**, **Vivitrol**) is metabolized by the liver and contraindicated in acute hepatitis or current opioid use. Clinical Teaching and Pharmacotherapy Analysis. Mechanism of Action and Aversion Physiology. **Disulfiram** works by irreversibly blocking the enzyme aldehyde dehydrogenase. Normally, ingested alcohol is metabolized into acetaldehyde, which is then rapidly broken down by aldehyde dehydrogenase into acetic acid. When **disulfiram** blocks this enzyme, drinking even minimal amounts of alcohol leads to a rapid accumulation of toxic acetaldehyde in the blood. Within 5 to 10 minutes of alcohol exposure, the patient experiences a severe disulfiram-alcohol reaction. Symptoms include intense facial flushing, diaphoresis, neck throbbing, throbbing headache, nausea, persistent vomiting, dyspnea, tachycardia, and hypotension. In severe cases, this reaction can cause cardiac arrhythmias, myocardial infarction, acute heart failure, seizures, or death. Safety Alerts, Contraindications, and Drug Interactions. **Safety alert**: Before prescribing **disulfiram**, the PMHNP must confirm that the patient is fully motivated, cognitively intact, and completely abstinent from alcohol for at least 12 hours. Key contraindications and high-risk conditions: - **Severe cardiac disease**: Coronary artery disease, severe hypertension, or heart failure, because severe hypotension and tachycardia during a reaction can be fatal. - **Severe liver disease**: **Disulfiram** carries a risk of severe hepatotoxicity, requiring baseline and periodic liver function tests. - **Psychotic disorders**: Can precipitate acute psychosis or confusion. - **Seizure disorders**: Lowers the seizure threshold. - **Concurrent metronidazole**: Combining **disulfiram** with **metronidazole** can cause acute confusion and psychosis. - **Hidden alcohol exposure**: Patients must be educated to avoid hidden alcohol in cough syrups, elixirs, vinegar, sauces, aftershaves, cologne, and alcohol-based hand sanitizers. Compare and Distinguish: Alcohol Dependence Pharmacotherapy. To master board questions on alcohol dependence, contrast the three FDA-approved medications based on clinical mechanism, organ clearance, and timing: **Disulfiram** (**Antabuse**) - Primary role: Aversion therapy for highly motivated patients seeking complete abstinence. - Mechanism: Inhibits aldehyde dehydrogenase, creating toxic acetaldehyde buildup upon alcohol ingestion. - **Board trap**: Does not reduce cravings. - Organ considerations: Risk of hepatotoxicity; requires baseline liver function tests. - Key restriction: Must avoid all alcohol for 12 hours before starting and up to 14 days after stopping. **Naltrexone** (**ReVia**, **Vivitrol**) - Primary role: **First-line** agent to decrease alcohol cravings and block the euphoric high of drinking. - Mechanism: Competitive mu-opioid receptor antagonist that blocks endogenous opioid release. - **Safety alert**: Strictly contraindicated in patients taking prescription opioids or with acute hepatitis / liver failure. Must be opioid-free for 7 to 10 days prior to initiation. - Formulations: Oral daily **naltrexone** or monthly long-acting injectable **Vivitrol** (380 mg IM every 4 weeks). **Acamprosate** (**Campral**) - Primary role: **First-line** agent to maintain abstinence in patients who have already stopped drinking. - Mechanism: Restores balance between GABA and glutamate neurotransmission. - Organ considerations: Cleared renally with zero hepatic metabolism, making it the safest choice for patients with liver disease or elevated AST and ALT. - **Safety alert**: Contraindicated in severe renal impairment (creatinine clearance under 30 mL/min); requires dose reduction for moderate renal impairment (creatinine clearance 30 to 50 mL/min). Sample Board Practice Questions. Sample Question 1. Gary, a 54-year-old man with moderate liver disease, has a history of alcohol use disorder but has been abstinent for the past 3.5 years. At this visit, he reports severe life stressors, including the death of a sibling and loss of employment, and states he is having increased urges to drink again. To prevent a possible relapse in this patient, which medication should the PMHNP prescribe? A) acamprosate B) naloxone C) clonidine D) lorazepam Pause. Answer. Best Answer: A) acamprosate Why It Is Correct: **Acamprosate** is excreted renally and does not undergo hepatic metabolism, making it the safest **first-line** choice for craving management and maintenance of abstinence in patients with co-occurring liver disease. Why the Other Choices Are Wrong: - A. Correct choice. - B. **Naloxone** is an acute opioid reversal agent (Narcan) used for opioid overdose, not for alcohol use disorder. - C. **Clonidine** is an alpha-2 adrenergic agonist used to manage autonomic hyperactivity during acute withdrawal, not for relapse prevention or cravings. - D. **Lorazepam** is a benzodiazepine used for acute alcohol withdrawal detoxification; prescribing it for long-term maintenance in alcohol use disorder carries a high risk of dependence and addiction. Sample Question 2. Randy, a 32-year-old single manager of a sporting goods store, is seen for follow-up after a 30-day inpatient stay for alcohol dependence. He has been sober for 45 days and continues to crave alcohol throughout the day. Which medication should be prescribed for Randy as part of his recovery plan to specifically target alcohol cravings? A) disulfiram B) bupropion C) naltrexone D) naloxone Pause. Answer. Best Answer: C) naltrexone Why It Is Correct: **Naltrexone** is a mu-opioid receptor antagonist that directly targets alcohol cravings and reduces the reinforcing euphoric effects of alcohol. Why the Other Choices Are Wrong: - A. **Disulfiram** is an aversion agent that causes a severe physical reaction if alcohol is consumed, but it does not decrease physiological cravings. - B. **Bupropion** is an NDRI antidepressant approved for major depression and smoking cessation, not for alcohol craving reduction. - C. Correct choice. - D. **Naloxone** is a short-acting emergency antagonist used to reverse acute opioid respiratory depression, not an oral maintenance agent. Sample Question 3. Dana, a 44-year-old registered nurse, is preparing for discharge from a 30-day inpatient treatment facility for alcohol and methamphetamine dependence. She wishes to start a medication to help maintain abstinence from alcohol. She notes that she has extensive oral surgery and dental work scheduled to begin within the next month. Which medication is contraindicated for Dana based on this clinical information? A) disulfiram B) naltrexone C) acamprosate D) sertraline Pause. Answer. Best Answer: B) naltrexone Why It Is Correct: **Safety alert**: **Naltrexone** blocks mu-opioid receptors. Because extensive dental surgery will likely require opioid analgesics for post-operative pain management, **naltrexone** is contraindicated as it would block opioid pain relief or precipitate acute withdrawal if opioids are administered. Why the Other Choices Are Wrong: - A. **Disulfiram** does not block opioid analgesics and is not contraindicated by upcoming dental procedures. - B. Correct choice. - C. **Acamprosate** does not interact with opioid analgesics and is safe for patients undergoing medical or dental procedures. - D. **Sertraline** is an SSRI antidepressant that does not treat alcohol dependence directly, but it is not contraindicated by scheduled dental surgery. 💡 **Next Study Step**: Proceed to **Personality Disorders (Fitzgerald Chapter 12)** to review Cluster A, B, and C diagnostic buzzwords, crisis management, and differentiating borderline personality disorder from bipolar spectrum illness. Next. End of this drive.