11.4 Substance Use Disorders: Alcohol, Tobacco, Opioids & Cannabis in Primary Care

Substance Use Disorders: Alcohol, Tobacco, Opioids & Cannabis in Primary Care

Substance use disorders (SUDs) represent chronic, relapsing brain diseases that intersect with every domain of adult and geriatric primary care. The Adult-Gerontology Primary Care Nurse Practitioner (AGPCNP) plays a pivotal role in routine universal screening, early brief intervention, medical detoxification triage, evidence-based medication-assisted treatment, overdose prevention, and harm reduction.

Mastering substance use disorders requires an in-depth appreciation of mesolimbic reward neurobiology, fluency in DSM-5-TR diagnostic criteria, mastery of withdrawal staging and prophylaxis (including the prevention of Wernicke-Korsakoff syndrome), and disciplined prescribing of medications for alcohol, tobacco, and opioid use disorders.

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1. Neurobiology of Addiction & The SBIRT Framework

The Mesolimbic Dopamine Reward Pathway

All addictive substances share a common final neurobiological mechanism: the supraphysiological surge of dopamine release in the Nucleus Accumbens (NAc) via dopaminergic projections originating from the Ventral Tegmental Area (VTA).

+-----------------------------------------------------------------------------+
|                   THE THREE-STAGE CYCLE OF ADDICTION                        |
|                                                                             |
|   1. BINGE / INTOXICATION (Basal Ganglia & Nucleus Accumbens)               |
|      - Acute dopamine and opioid peptide release -> Euphoria, positive      |
|        reinforcement, and incentive salience ("wanting" vs "liking").       |
|                               |                                             |
|                               v                                             |
|   2. WITHDRAWAL / NEGATIVE AFFECT (Extended Amygdala & Habenula)            |
|      - Chronic downregulation of D2 dopamine receptors (anhedonia).         |
|      - Recruitment of stress neurotransmitters: Corticotropin-Releasing     |
|        Factor (CRF), Dynorphin, and Norepinephrine -> Dysphoria, anxiety,   |
|        irritability, and physical withdrawal (negative reinforcement).      |
|                               |                                             |
|                               v                                             |
|   3. PREOCCUPATION / ANTICIPATION (Prefrontal Cortex & Hippocampus)         |
|      - "Craving Circuit": Glutamatergic projections from Prefrontal Cortex   |
|        and Basolateral Amygdala drive compulsive drug-seeking behavior and  |
|        loss of executive inhibitory self-control ("hypofrontality").        |
+-----------------------------------------------------------------------------+

The SBIRT Protocol in Primary Care

SBIRT (Screening, Brief Intervention, and Referral to Treatment) is an evidence-based public health framework validated for early identification and intervention in primary care settings:

1. Screening (S): Universal screening using standardized, validated questionnaires (e.g., AUDIT-C for alcohol, Single-Question Screening for drugs/tobacco) at annual preventive health visits.
2. Brief Intervention (BI): A 5-to-15-minute structured motivational dialogue using Motivational Interviewing (MI) techniques (OARS: Open-ended questions, Affirmations, Reflective listening, Summaries) to enhance the patient's intrinsic motivation to modify substance use.
3. Referral to Treatment (RT): Facilitating seamless connection to specialty addiction medicine, intensive outpatient programs (IOP), residential rehabilitation, or peer-led recovery networks (AA, NA, SMART Recovery) for patients with moderate-to-severe substance use disorders.

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2. DSM-5-TR Diagnostic Criteria for Substance Use Disorder

Under DSM-5-TR, substance abuse and substance dependence are unified into a single diagnosis: Substance Use Disorder (SUD). Diagnosis requires meeting $\ge 2$ of the following 11 criteria over a 12-month period, categorized into 4 functional domains:

+-----------------------------------------------------------------------------+
|                        DSM-5-TR 11 DIAGNOSTIC CRITERIA                      |
|                                                                             |
|   DOMAIN 1: IMPAIRED CONTROL                                                |
|   1. Consuming substance in larger amounts or over longer period than intended|
|   2. Persistent desire or unsuccessful efforts to cut down or control use   |
|   3. Great deal of time spent obtaining, using, or recovering from substance|
|   4. CRAVING: Intense urge or desire to use the substance                   |
|                                                                             |
|   DOMAIN 2: SOCIAL IMPAIRMENT                                               |
|   5. Recurrent use resulting in failure to fulfill major role obligations   |
|      at work, school, or home                                               |
|   6. Continued use despite persistent/recurrent social or interpersonal probs|
|   7. Important social, occupational, or recreational activities given up    |
|                                                                             |
|   DOMAIN 3: RISKY USE                                                       |
|   8. Recurrent use in physically hazardous situations (e.g., driving)       |
|   9. Continued use despite knowledge of physical or psychological problem   |
|      caused or exacerbated by the substance                                 |
|                                                                             |
|   DOMAIN 4: PHARMACOLOGICAL CRITERIA                                        |
|  10. TOLERANCE: Need for markedly increased amounts to achieve intoxication |
|  11. WITHDRAWAL: Characteristic withdrawal syndrome or substance taken to   |
|      relieve/avoid withdrawal symptoms                                      |
|   *(Note: Tolerance and withdrawal do NOT count toward diagnosis when taken |
|     under appropriate medical supervision, e.g., prescribed opioids/benzos!)|
|   -----------------------------------------------------------------------   |
|   SEVERITY STRATIFICATION:                                                  |
|   * MILD: 2 to 3 criteria                                                   |
|   * MODERATE: 4 to 5 criteria                                               |
|   * SEVERE: 6 or more criteria                                              |
+-----------------------------------------------------------------------------+

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3. Alcohol Use Disorder (AUD)

Primary Care Screening Tools

• AUDIT-C (Alcohol Use Disorders Identification Test - Consumption): A validated 3-item questionnaire scored 0–12 evaluating frequency of drinking, quantity consumed, and binge drinking ($\ge 6$ drinks on one occasion). Positive screen: $\ge 4$ in adult men, $\ge 3$ in women and adults aged $\ge 65$.
• CAGE Questionnaire: Scored 0–4 (Score $\ge 2$ indicates high likelihood of clinically significant alcohol misuse):
  • C: Have you ever felt you should Cut down on your drinking?
  • A: Have people Annoyed you by criticizing your drinking?
  • G: Have you ever felt bad or Guilty about your drinking?
  • E: Have you ever had an Eye-opener (a drink first thing in the morning to steady nerves or relieve a hangover)?

Clinical Biomarkers of Chronic Heavy Alcohol Ingestion

• AST to ALT Ratio $\ge 2:1$: Classic hallmark of alcoholic liver disease (mitochondrial AST release combined with hepatic pyridoxal-5-phosphate depletion suppressing ALT synthesis).
• Gamma-Glutamyl Transferase (GGT): Highly sensitive marker of heavy alcohol consumption (inducible enzyme; normalizes over 2–4 weeks of sobriety).
• Macrocytosis (Elevated MCV > 100 fL): Direct toxic effect of ethanol on erythropoiesis in the bone marrow (frequently present without anemia or B12/folate deficiency).
• Carbohydrate-Deficient Transferrin (CDT): Highly specific biomarker of sustained heavy drinking ($>4-5$ drinks/day for $\ge 2$ weeks).
• Urine Ethyl Glucuronide (EtG): Direct non-oxidative metabolite of ethanol detectable in urine for up to 3 to 5 days post-ingestion.

Acute Alcohol Withdrawal Syndrome: Staging & Management

+---------------------------------------------------------------------------------------------------------+
|                              ALCOHOL WITHDRAWAL TIMELINE & STAGING                                      |
|                                                                                                         |
|   WITHDRAWAL STAGE     ONSET POST-LAST DRINK       HALLMARK CLINICAL SIGNS & SYMPTOMS                   |
|   ---------------------------------------------------------------------------------------------------   |
|   Stage 1: Minor       6 to 12 hours               * Fine resting tremor, anxiety, diaphoresis,         |
|   Withdrawal                                         palpitations, insomnia, headache, mild nausea.     |
|                                                    * Intact sensorium and orientation.                  |
|                                                                                                         |
|   Stage 2: Alcoholic   12 to 24 hours              * Visual, auditory, or tactile hallucinations /      |
|   Hallucinosis                                       illusions (e.g., seeing insects, hearing voices).  |
|                                                    * CRITICAL: SENSORIUM IS COMPLETELY CLEAR!           |
|                                                      Patient is alert and oriented (unlike DTs!).       |
|                                                                                                         |
|   Stage 3: Withdrawal  24 to 48 hours              * Generalized tonic-clonic seizures. Single or brief |
|   Seizures ("Rum Fits")                              burst of 2-3 seizures.                             |
|                                                    * ~30% of untreated patients progress to DTs.        |
|                                                                                                         |
|   Stage 4: DELIRIUM    48 to 96 hours              * MEDICAL EMERGENCY (5-15% mortality if untreated!). |
|   TREMENS (DTs)        (can last up to 5-7 days)   * PROFOUND DELIRIUM: Severe fluctuating confusion,   |
|                                                      disorientation, agitation, visual hallucinations.  |
|                                                    * SEVERE AUTONOMIC INSTABILITY: Extreme tachycardia, |
|                                                      hypertension, marked diaphoresis, fever/hyperthermia|
+---------------------------------------------------------------------------------------------------------+

CIWA-Ar Protocol & Pharmacotherapy of Acute Withdrawal:

• CIWA-Ar (Clinical Institute Withdrawal Assessment for Alcohol, Revised): Evaluates 10 clinical parameters (nausea/vomiting, tremor, paroxysmal sweats, anxiety, agitation, tactile/auditory/visual disturbances, headache, orientation) scored 0–67. A score $\ge 8-10$ triggers symptom-triggered benzodiazepine administration.
• Benzodiazepine Selection:
  • Long-Acting (Diazepam, Chlordiazepoxide): Preferred in patients with normal hepatic function due to smoother tapering profile and lower incidence of breakthrough seizures.
  • Short/Intermediate-Acting ("LOT" Agents: Lorazepam, Oxazepam, Temazepam): MANDATORY DRUGS OF CHOICE in patients with hepatic cirrhosis, acute alcoholic hepatitis, or elderly patients because they undergo direct Phase II glucuronidation and do not rely on Phase I hepatic CYP450 oxidation (avoiding drug accumulation and hepatic encephalopathy!).

Mandatory Wernicke-Korsakoff Syndrome Prevention Protocol:

• Wernicke Encephalopathy Triad: (1) Acute encephalopathy / confusion, (2) Oculomotor dysfunction (nystagmus, bilateral lateral rectus / CN VI palsy), and (3) Gait ataxia.
• Pathophysiology: Thiamine (Vitamin $B_1$) deficiency impairs pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase, causing cellular metabolic failure and hemorrhagic necrosis in the mammillary bodies, thalamus, and periaqueductal gray.
• MANDATORY CLINICAL RULE: High-dose parenteral Thiamine (100 to 500 mg IV/IM) must ALWAYS be administered PRIOR TO or CONCURRENTLY WITH any IV glucose/dextrose infusions! Infusing dextrose without thiamine forces remaining thiamine cofactors into the glycolysis cycle, precipitating acute irreversible Wernicke Encephalopathy and progression to Korsakoff Syndrome (irreversible anterograde and retrograde amnesia with prominent confabulation).

Long-Term Relapse Prevention Pharmacotherapy for AUD

+---------------------------------------------------------------------------------------------------------+
|                        AUD RELAPSE PREVENTION PHARMACOTHERAPY MATRIX                                    |
|                                                                                                         |
|   MEDICATION           MECHANISM OF ACTION         CLINICAL ADVANTAGES & DOSING CONTRAINDICATIONS & SAFETY|
|   ---------------------------------------------------------------------------------------------------   |
|   Naltrexone           Mu-opioid receptor          * FIRST-LINE for reducing    * ABSOLUTELY CONTRA-    |
|   (Oral & IM Depo)     antagonist. Blocks          cravings and heavy drinking  INDICATED IN PATIENTS   |
|                        endogenous endorphin        days.                        TAKING PRESCRIPTION     |
|                        reward from alcohol.        * Oral: 50 mg PO daily.      OPIOIDS OR WITH ACUTE   |
|                                                    * IM Depo (Vivitrol):        HEPATITIS / LIVER       |
|                                                      380 mg IM monthly (ideal   FAILURE! Check baseline |
|                                                      for poor adherence).       LFTs (hepatotoxicity).  |
|                                                                                                         |
|   Acamprosate          Modulates central           * FIRST-LINE AGENT OF CHOICE * EXCRETED ENTIRELY BY  |
|   (Campral)            glutamatergic (NMDA) and    IN PATIENTS WITH HEPATIC     KIDNEYS!                |
|                        GABAergic neurotransmission;IMPAIRMENT / CIRRHOSIS!      * Dose-reduce in moderate|
|                        restores neurochemical      * Promotes complete          renal impairment.       |
|                        balance disrupted by chronic  abstinence.                * CONTRAINDICATED IN    |
|                        ethanol exposure.           * Dosing: 666 mg PO TID.     SEVERE RENAL FAILURE    |
|                                                                                 (CrCl < 30 mL/min).     |
|                                                                                                         |
|   Disulfiram           Irreversible inhibitor of   * SECOND-LINE AVERSIVE       * Must be fully abstinent|
|   (Antabuse)           ALDEHYDE DEHYDROGENASE.     THERAPY for highly motivated for >= 12-24 hours!     |
|                        Causes rapid accumulation   patients with observed       * Ingestion of ANY      |
|                        of toxic ACETALDEHYDE       dosing.                      alcohol causes severe   |
|                        upon any ethanol ingestion. * Dosing: 250-500 mg PO      flushing, throbbing     |
|                                                      daily.                     headache, vomiting,     |
|                                                                                 hypotension, arrhythmia.|
|                                                                                 * Avoid hidden alcohol  |
|                                                                                 (cough syrups, sauces). |
|                                                                                                         |
|   Topiramate           GABA-A facilitator and      * Off-label second-line;     * Cognitive slowing,    |
|   (Off-Label)          AMPA/kainate antagonist.    reduces heavy drinking.      paresthesias, weight loss|
|                        Reduces dopamine release.   * Dosing: 25-150 mg PO BID.  kidney stones, glaucoma.|
+---------------------------------------------------------------------------------------------------------+

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4. Tobacco & Nicotine Use Disorder

Tobacco use remains the leading cause of preventable disease, disability, and death in the United States.

The 5 A's Evidence-Based Clinical Model

1. Ask: Universally identify and document tobacco use status at every clinical visit.
2. Advise: Strongly urge all tobacco users to quit in a clear, personalized, and non-judgmental manner ("Quitting smoking is the single most important action you can take to protect your heart and lungs").
3. Assess: Determine willingness and readiness to make a quit attempt within the next 30 days.
4. Assist: Provide evidence-based pharmacotherapy and behavioral counseling to support the quit attempt.
5. Arrange: Schedule follow-up contact (in person or via telehealth) within the first week after the established quit date.

Evidence-Based Pharmacotherapy for Smoking Cessation

+---------------------------------------------------------------------------------------------------------+
|                        SMOKING CESSATION PHARMACOTHERAPY MATRIX                                         |
|                                                                                                         |
|   TREATMENT MODALITY   MECHANISM & DOSING          CLINICAL ADVANTAGES          ADVERSE EFFECTS & PEARLS|
|   ---------------------------------------------------------------------------------------------------   |
|   Varenicline          Alpha-4 Beta-2 nicotinic    * HIGHEST MONOTHERAPY        * Nausea (take with food|
|   (Chantix)            acetylcholine receptor      EFFICACY among all smoking   and full glass water).  |
|                        PARTIAL AGONIST.            cessation drugs!             * Insomnia and abnormal/|
|                        - Provides moderate dopamine* Start 1 week BEFORE quit   vivid dreams.           |
|                          release to reduce cravings. date (titrate: 0.5 mg daily* Historical black box |
|                        - Blocks nicotine binding.    to 1 mg BID x 12 weeks).   warning for neuro-      |
|                                                                                 psychiatric risk removed|
|                                                                                                         |
|   Combination Nicotine Long-acting Transdermal     * SIGNIFICANTLY SUPERIOR TO  * Patch: Local skin     |
|   Replacement Therapy  PATCH + Short-acting GUM    SINGLE-AGENT NRT!            irritation, vivid dreams|
|   (Combination NRT)    or LOZENGE for cravings.    * Patch Dosing: 21 mg/day    (remove patch at bed).  |
|                        - Delivers clean nicotine     (if >10 cigs/day);         * Gum/Lozenge: Hiccups, |
|                          without toxic combustion    14 mg/day (if <=10 cigs/d).* "Chew and park" gum  |
|                          carcinogens/tar.          * Gum/Lozenge: 2 mg or 4 mg.   technique; avoid acid!|
|                                                                                                         |
|   Bupropion SR         Norepinephrine-Dopamine     * Dual utility in patients   * ABSOLUTELY CONTRA-    |
|   (Zyban / Wellbutrin) Reuptake Inhibitor (NDRI).  with COMORBID DEPRESSION.    INDICATED IN SEIZURE    |
|                        - Reduces cravings and      * Prevents post-cessation    DISORDERS, BULIMIA, or  |
|                          withdrawal discomfort.      weight gain.               ANOREXIA NERVOSA!       |
|                                                    * Start 1-2 weeks before quit* Insomnia, dry mouth,  |
|                                                      (150 mg daily x 3d -> BID).  agitation.            |
+---------------------------------------------------------------------------------------------------------+

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5. Opioid Use Disorder (OUD) & Harm Reduction

Medications for Opioid Use Disorder (MOUD)

MOUD is the gold-standard medical therapy for OUD, proven to reduce illicit opioid use, decrease overdose mortality by $>50%$, reduce transmission of HIV and Hepatitis C, and improve treatment retention.

+---------------------------------------------------------------------------------------------------------+
|                        MEDICATIONS FOR OPIOID USE DISORDER (MOUD)                                       |
|                                                                                                         |
|   MEDICATION           PHARMACOLOGICAL CLASS       REGULATORY & CLINICAL RULES  ADVERSE EFFECTS & PEARLS|
|   ---------------------------------------------------------------------------------------------------   |
|   Buprenorphine /      PARTIAL MU-OPIOID AGONIST   * Can be prescribed in any   * HIGH AFFINITY / CEILING|
|   Naloxone (Suboxone)  with high receptor affinity  standard office-based primary EFFECT: Minimal risk   |
|                        + Kappa antagonist.         care setting (X-waiver no    of respiratory depression|
|                        * Co-formulated with        longer required!).           as a single agent.      |
|                          naloxone (4:1 ratio) to   * INDUCTION RULE: Patient    * PRECIPITATED WITHDRAWAL|
|                          prevent IV diversion (nal-  MUST be in OBJECTIVE MILD- If given before full    |
|                          oxone inactive sublingually)TO-MODERATE WITHDRAWAL     agonists leave receptors|
|                                                      (COWS SCORE >= 8 - 12)     (buprenorphine displaces|
|                                                      prior to first dose!       full agonists rapidly!).|
|                                                                                                         |
|   Methadone            FULL MU-OPIOID AGONIST with * Restricted by federal law  * Dose-dependent QTc    |
|   (Oral Liquid)        long elimination half-life  to certified Opioid Treatment prolongation and torsades|
|                        (24 - 36 hours).            Programs (OTPs / daily clinic de pointes risk (ECG). |
|                        - Prevents withdrawal and     dosing).                   * High risk of fatal    |
|                          blocks illicit cravings.  * Excellent for high-tolerance respiratory depression|
|                                                      fentanyl-exposed patients. in overdose/diversion.  |
|                                                                                                         |
|   Extended-Release     LONG-ACTING MU-OPIOID       * Indicated for relapse      * MANDATORY 7 TO 14 DAY |
|   Naltrexone           RECEPTOR ANTAGONIST.        prevention post-detox.       COMPLETE OPIOID-FREE    |
|   (Vivitrol IM)        - Blocks subjective high    * Dosing: 380 mg IM gluteal  WASHOUT (verified by    |
|                          from all opioid agonists.   injection every 4 weeks.   negative UDS and naloxone|
|                                                                                 challenge) prior to inj!|
+---------------------------------------------------------------------------------------------------------+

The Clinical Opiate Withdrawal Scale (COWS)

Assesses 11 objective and subjective parameters (resting pulse rate, sweating, restlessness, pupil size, bone/joint aches, rhinorrhea/lacrimation, GI upset, tremor, yawning, anxiety, piloerection ["gooseflesh"]).

• Score 5–12: Mild withdrawal
• Score 13–24: Moderate withdrawal
• Score 25–36: Moderately severe withdrawal
• Buprenorphine Induction Rule: COWS score must be $\ge 8-12$ before administering the first sublingual buprenorphine dose. Administering buprenorphine when full agonist opioids (e.g., heroin, oxycodone, fentanyl) are still bound to mu-receptors immediately displaces the full agonist due to buprenorphine's higher binding affinity, precipitating severe, agonizing precipitated withdrawal.

Universal Harm Reduction: Naloxone Co-Prescribing

• Naloxone (Narcan Nasal Spray 4 mg): Rapid-acting competitive opioid receptor antagonist that reverses life-threatening opioid-induced respiratory depression within 2 to 3 minutes.
• Co-Prescribing Mandate: Co-prescribe naloxone for any patient receiving chronic opioid therapy with $\text{MME} \ge 50\text{ mg/day}$, concurrent benzodiazepine prescriptions, history of substance use disorder, underlying respiratory disease (COPD/sleep apnea), or known illicit opioid use.

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6. Cannabis & Other Substance Use in Primary Care

Cannabis Hyperemesis Syndrome (CHS)

• Pathophysiology: Chronic, daily, long-term consumption of high-potency tetrahydrocannabinol (THC) paradoxically downregulates enteric and central cannabinoid type 1 ($CB_1$) receptors and impairs hypothalamic thermoregulation, while stimulating cutaneous Transient Receptor Potential Vanilloid 1 (TRPV1) nociceptors.
• Clinical Presentation: Recurrent, cyclical episodes of severe intractable nausea, non-bloody vomiting, and colicky diffuse abdominal pain occurring every few weeks to months in chronic daily cannabis users.
• Pathognomonic Behavioral Clue: Patients engage in compulsive, prolonged hot showering or bathing (often spending hours per day in hot water), which provides rapid, transient relief of nausea by activating cutaneous TRPV1 receptors and restoring core thermal homeostasis.
• Acute & Definitive Management:
  • Acute Symptom Relief: Topical Capsaicin 0.075% cream applied to the periumbilical abdominal wall (activates TRPV1 receptors), IV fluid hydration, and IV Haloperidol or Droperidol (dopamine antagonists that suppress the central chemoreceptor trigger zone). Traditional antiemetics (ondansetron, promethazine) are notoriously ineffective.
  • Definitive Treatment: Complete and permanent cessation of all cannabis and cannabinoid products is the ONLY curative intervention. Symptoms completely resolve within 1 to 3 months of sustained abstinence.

Stimulant Use Disorder: Cocaine & Methamphetamine

• Mechanism: Cocaine blocks dopamine, norepinephrine, and serotonin reuptake; methamphetamines promote massive reverse transport/release of catecholamines.
• Acute Toxicity: Severe hypertension, tachyarrhythmias, hyperthermia, acute coronary vasospasm, myocardial infarction, aortic dissection, rhabdomyolysis, and acute stimulant-induced paranoid psychosis.
• Clinical Rule for Acute Stimulant Chest Pain: First-line management is IV Benzodiazepines (Lorazepam) to reduce central sympathomimetic outflow, tachycardia, and coronary vasospasm. Pure beta-blockers (e.g., Propranolol) are contraindicated in acute cocaine toxicity due to theoretical unopposed alpha-1 adrenergic vasoconstriction worsening hypertension and coronary ischemia.

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7. Geriatric Considerations in Substance Use

• The "Invisible Epidemic": Substance misuse in older adults is frequently under-identified because symptoms (falls, cognitive decline, insomnia, malnutrition, self-neglect) are erroneously attributed to normal aging or dementia.
• Altered Pharmacokinetics: Due to age-related reductions in total body water, increased relative body fat, reduced hepatic blood flow/CYP450 clearance, and declining GFR, older adults achieve higher peak blood alcohol and drug concentrations with prolonged elimination half-lives.
• Dangerous Drug Interactions: Alcohol combined with antihypertensives causes severe orthostatic hypotension and syncope; combined with sedatives/hypnotics or opioids causes fatal respiratory depression; combined with acetaminophen causes accelerated hepatotoxicity; and combined with warfarin increases INR and life-threatening gastrointestinal bleeding.

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8. Board-Yield Summary & Clinical Pearls

+-----------------------------------------------------------------------------+
|                       ANCC AGPCNP CLINICAL EXAM PEARLS                      |
|                                                                             |
|   * Alcohol Withdrawal in Cirrhosis / Liver Failure -> USE ONLY "LOT"       |
|     BENZODIAZEPINES (Lorazepam, Oxazepam, Temazepam) because they bypass    |
|     Phase I CYP oxidation. Avoid Diazepam/Chlordiazepoxide!                 |
|                                                                             |
|   * Thiamine BEFORE Glucose -> ALWAYS administer IV Thiamine (100-500 mg)   |
|     BEFORE or CONCURRENTLY with IV Dextrose to prevent precipitating acute  |
|     irreversible Wernicke Encephalopathy / Korsakoff syndrome.              |
|                                                                             |
|   * AUD Relapse Prevention in Cirrhosis / Liver Disease -> ACAMPROSATE is   |
|     the drug of choice (100% renal elimination). Naltrexone is CONTRA-      |
|     INDICATED in liver failure / acute hepatitis or concurrent opioid use.  |
|                                                                             |
|   * Buprenorphine Induction -> Patient MUST be in mild-to-moderate withdrawal|
|     (COWS score >= 8-12) before the first dose to prevent PRECIPITATED       |
|     WITHDRAWAL.                                                             |
|                                                                             |
|   * Cannabis Hyperemesis Syndrome -> Cyclical vomiting relieved by HOT      |
|     SHOWERS in a chronic daily cannabis user. Treat acutely with TOPICAL     |
|     CAPSAICIN cream and Haloperidol; definitive cure is TOTAL CANNABIS STOP.|
|                                                                             |
|   * Smoking Cessation -> VARENICLINE is the most effective single agent.     |
|     COMBINATION NRT (Patch + Gum/Lozenge) is superior to single-agent NRT.  |
|     BUPROPION is contraindicated in seizure disorders and eating disorders. |
+-----------------------------------------------------------------------------+