NR546 WEEK 6: COMPREHENSIVE PSYCHOPHARMACOLOGY SELF-ASSESSMENT (2025) | 96 EVIDENCE-BASED PRACTICE QUESTIONS WITH DETAILED RATIONALES | ESSENTIAL PREPARATION FOR FINAL EXAMS AND CLINICAL ROTATIONS

Addiction is often driven by the client's attempts to:

self-medicate an underlying mental health disorder

adverse effects associated with the acute use of opioids:

-Itching

-Constipation

-Respiratory depression

-Urinary retention

-Sedation

Opioid medication: Morphine

-Prototype opioid agonist

-indicated for acute pain

-binds to opioid receptors in the CNS, inhibiting ascending pain pathways, altering the perception & response to pain

-also produces CNS depression and potentially respiratory depression

*may be life-threatening, especially if utilized with benzodiazepines, CNS depressants, or alcohol

onset of action:

-immediate release formulation is patient-dependent, with variable absorption.

-IV is 5-10 minutes, with a duration 3-5 hours.

-Also available in controlled release formulation (MS Contin) and extended-release morphine (Avinza).

Opioid medication: Fentanyl

-has an almost immediate onset of action when given IV, with a duration of 0.5-1 hour

-More potent than morphine, but short duration of action

-the preferred opioid for those unable to tolerate morphine or hydromorphone and in those with severe hepatic and renal disease

-same indications as morphine and is also used frequently in procedural sedation and general anesthesia

-Conversion between fentanyl products is NOT mcg for mcg

Opioid medication: Hydromorphone

-Similar opioid agonist as morphine but more potent

-Oral and parenteral doses are not equivalent (parenteral doses up to 5 times more potent)

Opioid medication: Meperidine

-No longer recommended as an analgesic, and not widely available.

-Has numerous concerning adverse effects such as seizures and delirium.

Opioid medication: Methadone

-Utilized in detoxification and maintenance treatment of opioid addiction and heroin addiction, with high variability among patients

-long acting opioid that binds to and occupies mu-opioid receptors, reducing craving for opioids and prevents withdrawal symptoms for 24 hours

-potential for abuse, only licensed opioid treatment programs or licensed inpatient hospital units permitted to order and dispense this medication

-potential for life threatening respiratory depression and QT prolongation

-Equianalgesic conversion ratios between methadone and other opioids are individually variable, with deaths occurring during conversion from chronic high dose opiate history or opioid abuse to methadone

-Discontinuation requires a wean to avoid withdrawal

-pregnant, a risk benefit ratio is necessary as fetal outcomes are improved as compared to illicit drug use, however can have decreased birth weight, length, head circumference and fetal growth

Opioid medication: Ketamine

-Medication useful in general anesthesia and procedural sedation

-off label usage as infusions for acute pain, as both a stand-alone treatment, as an adjunctive option with opioids, as well as an intranasal formulation.

Opioid medication: Tramadol

-Opioid agonist, with similar indications and side effect profile as other opioids, but that also blocks reuptake of serotonin and norepinephrine.

-Indicated for acute pain management, with added benefit for patients with neuropathic pain and nociceptive pain.

-Has a lower risk of constipation and dependence than other opioids, but does have risk of serotonin syndrome.

Opioid medication: Naloxone

-pure antagonist, with clinical indication for treatment of acute opioid overdose.

-IV naloxone can dramatically reverse opioids, even in comatose states

-recent widespread community availability of intramuscular and intranasal administration options available given the prescription and recreational opiate crisis, and related deaths. -Given the short duration of action, patients can relapse into coma or previous overdose state, and may need continued monitoring and potentially further doses or constant infusion.

Opioid medication: Clonidine

-antihypertensive agent, and Alpha2-Adrenergic Agonist

-off-label adjunctive treatment for medically supervised opioid withdrawal.

-Initial treatment is 0.1mg-0.2mg, with ability to repeat up to 4 doses until symptoms resolve, while assuring stability of blood pressure and heart rate.

-Maintenance would be determined by severity of symptoms, with treatment every 6-8 hours.

-Thought to produce analgesia at presynaptic and post junction alpha-2 adrenoceptors in the spinal cord, with pain transmission to the brain prevented.

Substance use disorder occurs when:

The recurrent use of a substance, such as alcohol or drugs, causes clinically significant impairment, including health problems, disability, or failure to meet responsibilities at home, work, or school.

Dual Diagnosis and Substance Use Disorders

Dual diagnoses are common in addiction medicine

-up to 60% of adolescents in community-based substance use disorder treatment programs may meet the diagnostic criteria for another mental health condition

-Clients may self-medicate to treat distressing symptoms of other conditions

-Common comorbidities include:

• anxiety disorders

• depression

• bipolar disorder

• psychotic illness

• borderline personality disorder

• antisocial personality disorder

neurobiological factors that contribute to substance use disorders: Genetics

-between 40-60% of a client's vulnerability to substance use disorders may be attributed to genetic factors

-Vulnerability involves complex interactions between multiple genes, and between genes and the environment

-Example: specific genetic factors predispose an individual to alcohol dependence and tobacco use

-Genetic involvement may impact an individual's experience of a drug as pleasurable or not or how long a drug remains in the body.

-Epigenetic factors influence whether genes associated with substance use disorder are activated

neurobiological factors that contribute to substance use disorders: Neuroanatomy

-Brain circuits that mediate reward, impulse control, decision-making, learning, and emotions play a role in substance use disorder

-mesolimbic dopamine pathway has been identified as the key pathway that mediates reward

-mesolimbic pathway connects the ventral tegmental area of the midbrain to the ventral striatum of the basal ganglia

• begins in the ventral tegmental area (VTA) and connects to the ventral striatum/nucleus accumbens, amygdala, hippocampus, and prefrontal cortex (PFC)

• VTA is one of the major dopamine-producing areas of the brain

• nucleus accumbens is an area found within the ventral striatum and has a strong association with motivation and reward

• Conditions that involve impulsive or compulsive behaviors, such as substance use disorder, obsessive-compulsive disorder (OCD), and obesity may relate to inefficient processing in the prefrontal cortex/striatal circuitry

neurobiological factors that contribute to substance use disorders: Neural Networks

-The mesolimbic pathway is the pathway most associated with reward

-Drugs and alcohol act directly on brain receptors leading to a release of dopamine

• the neurotransmitter associated with reward

-As substance use increases, brain circuits adapt by reducing sensitivity to dopamine, leading to tolerance

• need to increase the use of a substance to achieve the same high

neurobiological factors that contribute to substance use disorders: Neural Signaling

-Dopamine is the major neurotransmitter of the mesolimbic pathway

• responsible for regulating the brain's motivation, pleasure, and reward center

• released in response to natural pleasurable activities or situation

-Addictive drugs cause a surge of dopamine in the ventral striatum or nucleus accumbens

• Repeated use can lead to changes in brain circuitry, leading to craving, addiction, dependence, and withdrawal

-Medications which treat addiction target dopamine

Tolerance

With repeated ingestion of a drug, the drug shows decreased effect. Increasing doses are required to achieve the effects noted with the original administration.

Dependence

State of adaptation produced with repeated administration of certain drugs so that physical symptoms occur when the drug is discontinued abruptly

Addiction

A change in behavior caused by biochemical changes in the brain after continued substance use characterized by preoccupation with and repeated use of a substance despite negative outcomes.

Withdrawal

Physiological and psychological reactions that occur when the use of a substance is stopped abruptly.

Intoxication

Condition following the ingestion of a substance resulting in changes in level of consciousness, cognition, perception, judgment, and behavior.

When assessing clients for substance use disorder, to determine the most appropriate course of treatment. the PMHNP must ascertain:

what substance the client is using

how much

how often the substance is used

when the substance was last ingested

MAT

medication-assisted therapy (MAT)

-clients use prescription medications as part of a treatment plan for substance use disorders

-substitutes the drug of abuse for a prescribed medication that targets the same receptor as the preferred substance.

• can reduce cravings, improve relapse rates, reduce mortality from overdoses, and increase the likelihood of abstinence either alone or in combination with psychosocial interventions

-most prescribed for opioid use disorder, may be used for alcohol or tobacco

Goals of MAT to include:

-improved survival

-improved treatment retention

-decreased illegal activity

-increased quality of life

-improved birth outcomes in people who use substances while pregnant

-reduced human immunodeficiency virus (HIV) and Hepatitis B & C infections

Other mental health disorders that share similar neurobiological characteristics with substance use disorders

Disorders with impulsive and compulsive components, such as obsessive-compulsive disorder (OCD) and eating disorders

-have comparable neurobiological involvement, including alterations in reward pathways

Pharmacologic management: Obesity

-phentermine or phentermine/topiramate

-bupropion or pubropion/naltrexone

-lorcaserin

-zonisamide

Pharmacologic management: anorexia nervosa

olanzapine may lead to modest weight gain

Pharmacologic management: bulimia nervosa

high-dose fluoxetine

Pharmacologic management: binge eating disorder

-lisdexamefetamine

-topiramate

-bupropion

why avoid bupropion in individuals with anorexia nervosa and bulimia nervosa

bupropion lowers the seizure threshold in these individuals putting them at significantly increased risk for new-onset seizures

Opioid use disorder

the "chronic use of opioids that causes clinically significant distress or impairment"

-Drugs of abuse: illicit drugs, such as heroin, or prescription medications, including morphine, fentanyl, and oxycodone

-experience overwhelming cravings to use the drugs, dependence, increased tolerance, and withdrawal symptoms when the drug is ceased abruptly

-MAT is first-line therapy, essential part of tx

match the appropriate MAT to the client: Bernita is a 64-year-old who has been using heroin for 6 years. She is currently unemployed and lives with her daughter in the city center. She does not have health insurance.

Methadone

a full μ-receptor agonist with a long half-life, which can prevent withdrawal symptoms for 24 hours and provide steady control of cravings throughout the day. Only administered in methadone federally regulated opioid treatment programs (OTP). Methadone clinics incorporate psychosocial interventions and require daily attendance for the first several months, so this is a good option for a client that has the flexibility to attend daily meetings. The use of methadone in MAT for opioid use disorder helps extend client survival. When clients stop methadone, they have a high likelihood of relapsing, even 10 years after starting treatment.

match the appropriate MAT to the client: Antoine is a 34-year-old who has been abusing prescription oxycodone. He is employed but is on probation at work for increased absenteeism. He desires MAT but is concerned about his roommates stealing his medication to get high.

Buprenorphine plus naloxone (Suboxone)

In combination with naloxone (Suboxone): naloxone is a mu-opioid receptor antagonist and can therefore block the effects of buprenorphine; however, because naloxone has poor sublingual bioavailability, it does not interfere with buprenorphine's effects when used properly. Naloxone does have good parenteral bioavailability; thus, if one tries to administer the buprenorphine/naloxone formulation intravenously, naloxone will prevent any rewarding effects from buprenorphine, making this drug a less desirable street drug. Suboxone is a good option for a client who may not be able to leave work for medication dosing, as it does not need to be taken under direct observation.

match the appropriate MAT to the client: Lisa is a 29-year-old who admits to using "pills, heroin, and booze" regularly. She lives in a rural area and is employed part-time. She has a history of poor compliance with past treatments.

Naltrexone

blocks mu-opioid receptors, preventing exogenous opioids from binding there and thus preventing the pleasurable effects of opioid consumption. This medication also reduces alcohol consumption through the modulation of opioid systems, thereby reducing the reinforcing effects of alcohol. For those clients with alcohol use disorder, who have poor adherence to a regimen, and are unable to maintain abstinence, a long-acting injection of naltrexone (Vivitrol) administered monthly can be efficacious.

match the appropriate MAT to the client: Miranda is a 20-year-old who is 18 weeks pregnant and uses heroin. She wants to get clean "for her baby."

Buprenorphine

a partial opioid agonist which binds with a strong affinity to the mu-opioid receptor, preventing exogenous opioids from binding at the receptor site, and preventing the pleasurable effects of opioid consumption. While either methadone or buprenorphine may be prescribed in pregnancy, buprenorphine does not require daily visits to an opioid treatment program and requires less need for dosage adjustments during pregnancy.

Opioid Overdose

significant risk with opioid abuse

-Fentanyl and carfentanyl are frequent impurities found in opioids sold on the street

• thousands of times more potent than morphine and account for many overdoses across the country

-Naloxone (Narcan), an opioid antagonist, is the drug of choice for an emergency opioid overdose

• given for a known overdose of opioids or when the ingested substance is unknown

• series of small doses is preferred over 1 large dose to lessen antagonist-precipitated withdrawal symptoms

(Acute withdrawal symptoms present within 3 minutes of injection, peaking in 10-20 minutes, and subsiding in about an hour)

Acute withdrawal symptoms after narcan

nausea/vomiting

diarrhea

runny nose

sweating

tremor

irritability

muscle spasms

Clients at high risk for overdose:

-High-dose, long-term pain management

-Use of rotating opioid medications

-Previous opioid overdose

-Uses extended-release opioids

-Users who have had a period of abstinence

-Recently released from incarceration

-Clients who mix opioids and other drugs/alcohol

signs of opioid overdose:

-inability to wake or respond to voice or touch

-slow or absent breathing

-pinpoint pupils

-blue lips

Special considerations when prescribing MAT for opioid use disorder: Pregnancy

-Buprenorphine is an acceptable treatment during pregnancy

• is an increased risk of a neonatal withdrawal syndrome in newborns.

-Suboxone (buprenorphine/naloxone) cannot be used in pregnancy.

-Naloxone increases risk of neonatal abstinence syndrome

• Pregnant clients must be switched to buprenorphine (Subutex) monotherapy.

-Methadone is approved in pregnancy for heroin-addicted women.

• Dosing requires adjustment.

-Short-term newborn withdrawal effects may be seen and may require neonatal intensive care unit (NICU) admission for treatment.

Special considerations when prescribing MAT for opioid use disorder: Breast Feeding

-Naltrexone and buprenorphine are not recommended for breastfeeding mothers.

-Methadone can be prescribed with special consideration given to feeding intervals

• breastfeed prior to or 2-6 hours after dose

Special considerations when prescribing MAT for opioid use disorder: Older adult

-Buprenorphine use in the elderly may lead to confusion and drowsiness.

-Methadone has a high potential for drug interactions, associated with QT prolongation.

-It is difficult to titrate in the elderly and has a risk for accumulation due to the long half-life.

Alcohol Use Disorder

-may affect cardiovascular health and is associated with an increased risk of several types of cancer (especially, liver and pancreatic)

-Other system morbidities: diabetes, gout, renal dysfunction, hematological complications, osteoporosis, and dementia

-frequently associated with trauma and accidents

MAT for Chronic Alcohol Use Disorder

Medication selections based on clinical presentation, history of alcohol use/abuse with comorbid liver disease or renal impairment, concurrent opioid use disorder, and other unique client characteristics.

Meds:

-naltrexone (Revia, Vivitrol)

-acamprosate (Campral)

-disulfiram (Antabuse)

-topiramate (Topamax)

-chlorpromazine (Librium)

MAT for Chronic Alcohol Use Disorder: naltrexone (Revia, Vivitrol)

Initial treatment for alcohol use disorder

-Started while still drinking

-Can treat concurrent opioid use disorder

-Contraindicated in liver disease

-May be given in monthly long-acting injections (Vivitrol)

MAT for Chronic Alcohol Use Disorder: acamprosate (Campral)

-Modulates glutamine transmission, and resembles gamma-aminobutyric acid (GABA)

-Good option for clients who must take opioids for chronic pain

-Treats withdrawal symptoms

-Abstain prior to beginning treatment

MAT for Chronic Alcohol Use Disorder: disulfiram (Antabuse)

-Blocks oxidation of alcohol

-Creates unpleasant symptoms when the client drinks while taking medication:

• Palpitations

• Headache

• Nausea/vomiting

• Flushing

-Abstain prior to treatment to avoid a reaction

MAT for Chronic Alcohol Use Disorder: topiramate (Topamax)

-An anticonvulsant that blocks sodium channels and enhances GABA-A

-Reduces cravings for alcohol

MAT for Chronic Alcohol Use Disorder: chlorpromazine (Librium)

-Benzodiazepine for acute and chronic alcohol use

-Can cause benzodiazepine (BZO) withdrawal symptoms when stopped abruptly

-Avoid in older adults

Alcohol Withdrawal

Clinical Institute Withdrawal Assessment- Alcohol, shortened version (CIWA-Ar)

-highly regarded standardized instrument used to assess the severity of withdrawal symptoms

-directs pharmacotherapy: pharmacologic interventions for individuals with moderate to severe symptoms

• benzodiazepines on a symptom-triggered regimen is the preferred approach

Mild

-Anxiety

-Irritability

-Headache

-Insomnia

-Tremors

-Nausea/vomiting

Moderate

-Increased blood pressure (BP)

-Increased heart rate (HR)

-Confusion

-Mild hyperthermia

-Rapid breathing

Severe

-Hallucinations

-Seizures

-Disorientation

-Impaired attention

-Delirium tremens

-Death

symptom-triggered regimen

Administer CIWA-Ar

• every 4-8 hours until score is lower than 8-10 for 24 hours

Symptom-Triggered Regimen

• Administer benzodiazepine when CIWA-Ar score is 8 or above.

• PO lorazepam (Ativan), diazepam (Valium), or chlordiazepoxide (Librium) for symptom-triggered therapy

• Reassess CIWA-Ar every hour.

A 40-year-old male presents to your emergency department (ED) with severe anxiety, generalized tremors, complaints of dizziness, diaphoresis, and agitation. He was incarcerated 2 days ago and is brought to the ED today by the police due to the development of acute symptoms. His social history is significant for heavy alcohol use. A Clinical Institutes Withdrawal Assessment Scale for Alcohol (CIWA) score is 39.

The client tells you he has had withdrawal seizures in the past when he stops drinking. Which medication should you order?

lorazepam (Ativan)

Rationale: Benzodiazepines are the first-line treatment for clients having psychomotor agitation associated with alcohol withdrawal. This client has an increased risk of an alcohol-related withdrawal seizure, especially since he had one in the past. carbamazepine, levetiracetam, and phenytoin are not routinely used for alcohol withdrawal due to the lack of evidence demonstrating increased efficacy. Additionally, these drugs may potentially mask hemodynamic signs of withdrawal.

You are discharging this client from the hospital following admission for alcohol withdrawal syndrome. He has no further withdrawal symptoms and he would like to abstain from alcohol use. He informs you that has abused opioids in the past, but he has not used them in the last several months. He is concerned that he is at risk of abusing opioids again. Which of the following is the best pharmaceutical option for this client?

naltrexone (ReVia)

Rationale: Narcan is the common initial treatment for alcohol use disorder. Can be initiated while the client is still drinking. Can also be utilized in those with opioid use disorder, as the drug can treat both conditions. However, the client should be opioid-free for at least 7-10 days to avoid withdrawal. Acamprosate is used in the treatment of alcohol use disorders but does not have a similar effect to opiates. Disulfiram is utilized for resistant treatment, but this medication should not be administered to clients until they have abstained from alcohol for at least 12 hours, as a disulfiram reaction can occur for up to 14 days after alcohol has been consumed. Diazepam is not indicated at this time, given this client has already gone through acute withdrawal.

Alcohol special considerations of lifespan and lifestyle factors that are foundational to safe prescribing: Pregnancy

-Teratogenic effects of alcohol on the developing fetus are well known; however, there is limited data on the safety of withdrawal medications in pregnancy.

-Naltrexone is commonly used to treat alcohol use disorder in pregnant women, but its effects on the fetus remain largely unknown.

-Acamprosate is not recommended in pregnancy but may be necessary if the mother cannot stop drinking alcohol.

-Disulfiram's safety in pregnancy is not established.

Alcohol special considerations of lifespan and lifestyle factors that are foundational to safe prescribing: Older adult

-Frequent monitoring is necessary when prescribing benzodiazepines for alcohol withdrawal in older adults.

-Acamprosate should be used with caution in older adults.

Tobacco Use Disorder

-likelihood of dying from a tobacco-related disease such as cancer, cerebrovascular disease, or cardiovascular disease decreases by 90% if the client quits before the age of 40

Treatment Options

Nicotine replacement therapy

bupropion (Zyban)

varenicline (Chantix)

Combination Therapy

Nicotine replacement therapy

-Use for clients who smoke more than 20 cigarettes per day

-(OTC) drugs

• Gum: Nicorette

• Patch: Nicotrol, Nicoderm, Habitrol

• Lozenge: Commit

-Prescription drugs

• Nasal spray: Nicotrol NS

• Inhaler: Nicotrol

Precautions:

-Gum is pregnancy category C

-Transdermal patch is pregnancy category D

Contraindicated:

-Immediately after a myocardial infarction

-Immediately after a stroke

Nicotine Gum

-Buccal absorption

-follow directions or nicotine will release too quickly

• increasing adverse drug reactions (ADRs)

-Dosing:

• smoke within 30 minutes of awakening, 4 mg dose

• wait more than 30 minutes after awakening to smoke, 2 mg dose

• Client weans dose after 2 to 3 months of abstinence

Nicotine Lozenge

-slowly dissolves in mouth

-Advise not to chew lozenge

-Dose:

• 1 lozenge every 1 to 2 hours

• Use 4 mg if client smokes within 30 minutes of waking

-Client should not eat or drink while lozenge is in mouth

-Wean after 6 weeks of abstinence

Nicotine Patch

-Transdermal absorption

-16-hour and 24-hour patches

-Slow onset, steady state once at peak

-Dose of patch is determined by number of cigarettes the client smokes per day

-dose decreased gradually

-cannot smoke while using patch

-ADRs: Monitor for nicotine toxicity

-Advise to dispose of patches safely

Nicotine Nasal Spray

-Intranasal administration

-Rapid onset and peak

-Client education:

• Proper administration

• ADRs

• Abuse potential

Nicotine Inhaler

-Inhaled drug

-Client puffs on inhaler for 20 minutes

-Dose is weaned down gradually over 12 weeks

-ADRs

• Cough

• Mouth irritation

• Dyspepsia

bupropion (Zyban)

-Unknown action but believed to enhance the noradrenergic and dopaminergic release

-Start 1 to 2 weeks before quit date

-Dose: 150 mg daily for 3 days then increase to 150 mg twice daily

-Continue therapy for 7 to 12 weeks, may need longer

-May use with nicotine replacement products

Precautions and Contraindications:

-Seizure disorders, bulimia, and anorexia nervosa

-Neurological disorders

-Reduce dose in renal dysfunction.

-Avoid in pregnancy

-ADRs

• Insomnia (40%)

• Dizziness (10%)

• Dry mouth (10%)

-Important: Wellbutrin SR is the antidepressant version of bupropion and is identical to Zyban. Clients may be prescribed either one but should not be on both!

varenicline (Chantix)

-Highly selective to the alpha-4 beta-2 nicotinic receptor and moderately selective to the 5-HT3 receptor

-Start a week before quit date

-Dosing: 0.5 mg by mouth daily for the first 3 days; then 0.5 mg twice daily on days 4 to 7; increase to 1.0 mg twice daily on day 8

-Continue therapy for 12 weeks

Precautions and Contraindications:

-ADRs

• Nausea

• Sleep disorders (insomnia, vivid dreams)

• Stop medication if rare neuropsychiatric symptoms, such as hostility, depression, and suicidal ideation, occur

-Adult use only (18 years or older)

-Combining with other nicotine replacement products does not improve results

Tobacco use disorder: Combination Therapy

-Long-term (more than 14 weeks) nicotine patch + other nicotine replacement therapy (gum and spray)

-Nicotine patch + nicotine inhaler

-Nicotine patch + bupropion sustained-release

-Nonpharmacological treatment of nicotine addiction

• Individual or group counseling

• Support via a telephone hotline or online support group

*Interventions should include problem-solving, skills training, relapse prevention, and stress management

Tobacco use disorder: Client Variables

Pregnancy

-Nicotine replacement products not recommended

-bupropion (Zyban) not recommended

-varenicline (Chantrix) not recommended

Children

-Not used

Adolescents

-Early identification and support for quitting

-Patch has some evidence for use (prescription needed)

Tobacco use disorder: monitoring and education

Monitoring

-Withdrawal symptoms

-Nicotine toxicity

Education

-Proper dosing

-Removal of patch at appropriate time

-Proper dosing of gum and inhaler

-Advise on OTC products

-Monitor for ADRs

appropriate medication to each client: John is a 56-year-old with a history of seizure disorder who has smoked 1 pack-per-day (PPD) for 30 years. He has tried to quit using nicotine gum without success. He is committed to quitting smoking but feels he would benefit from medication to help

varenicline

Varenicline is an appropriate medication option for clients who want to quit using tobacco products. Bupropion is contraindicated in clients with seizure disorder.

Ellen is a 35-year-old who has a history of drinking 4-5 alcoholic beverages per day. She was admitted to the hospital for a respiratory infection and was treated with benzodiazepines using the CIWA-Ar scale. She has abstained from alcohol for 8 days and is committed to maintaining abstinence but would like to take a medication to help her stay away from alcohol.

disulfiram

Disulfiram creates unpleasant physical symptoms when taken with alcohol. This mild negative stimulus can help reinforce the client's abstinence from drinking alcohol.

Nori is a 24-year-old who has a history of abusing opioid medications and binge drinking. She is not committed to abstain from using at this time.

naloxone

Since Nori is not committed to abstaining at this time, it is important to provide naloxone along with education to help her remain safe from overdose.

Juan is a 19-year-old who has a history of using oxycodone that he has taken from his grandfather and drinking occasional alcohol. He wants to stop using both substances.

naltrexone

Naltrexone is a good option for clients who use opioids and alcohol and are committed to abstinence.

Impulsivity

predisposition towards rapid, unplanned reactions to internal or external stimuli, with diminished regard for the negative consequences of these reactions

-inability to stop initiating actions

-associated with risk seeking

-action without forethought, lack of reflection on the consequences of one's behavior

compulsivity

performance of repetitive and dysfunctionally impairing behavior that has no adaptive function.

-inability to terminate ongoing actions

-associated with harm avoidance

-action inappropriate to the situation but which nevertheless persists

-characterized by the curious inability to adapt behavior after negative feedback

-Type of compulsion-habits-responses triggered by environmental stimuli

Impulsivity and compulsivity are thought to be mediated by neuroanatomically and neurochemically distinct, but in many ways parallel, components of

cortico-subcortical circuitry

-too much "bottom-up" limbic emotional drive or too little "top-down" cortical inhibition of these drives

Impulsive-compulsive disorder construct

-Impulsivity can be thought of as the inability to stop the initiation of actions and involves a brain circuit centered on the ventral striatum and linked to the thalamus, to the ventromedial prefrontal cortex (VMPFC), and to the anterior cingulate cortex (ACC).

-Compulsivity can be thought of as the inability to terminate ongoing actions and hypothetically involves a brain circuit centered on the dorsal striatum and linked to the thalamus and orbitofrontal cortex (OFC).

Impulsive acts such as drug use, gambling, and over-eating can eventually become compulsive due to neuroplastic changes that engage the dorsal habit system and theoretically cause impulses in the ventral loop to migrate to the dorsal loop.

gambling

natural ways to trigger mesolimbic dopamine neurons to release dopamine (natural high)

brains own:

morphine/heroin (endorphins)

marijuana (anandamide)

nicotine (acetylcholine)

cocaine & amphetamine (dopamine itself)

Dopamine theory of addiction

all drugs of abuse have a final common pathway of causing pleasure by provoking dopamine release in the mesolimbic pathway

"burn-out"

enduring if not irreversible changes in dopamine neurons

-long-lasting depletions of dopamine levels and axonal degeneration

"bath salts"

atypical stimulants

-not for bathing, synthetic stimulants that commonly include the active ingredient methylenedioxypyrovalerone (MDPV) and may also contain mephedrone or methylone

-also called "plant food"

-cause agitation, paranoia, hallucinations, suicidality, and chest pain.

other atypical stimulant

inhalants

-direct releasers of dopamine in the nucleus accumbens

-"huffing": toluene found in paint thinner, felt-tip markers, glue, various aerosol sprays, and even freon found in air conditioners

-cause impaired judgment and possibly hallucinations,

-Short term: sudden death due to cardiac arrest, aspiration, or suffocation, Freon in particular can cause these effects and can also freeze the lungs, making it extremely dangerous.

-Long-term can cause depression, weight loss, and brain damage

*Substances that are huffed do not show up on drug tests.

Treatment of Stimulant Addiction

no approved drug treatments for stimulant addicts

-many dopamine-linked and serotonin-linked therapeutics have failed

nicotine's actions at _________________ directly on dopamine neurons in the ventral tegmental area (VTA) are those that are theoretically linked to addiction

α4β2 nicotinic postsynaptic receptors

μ-opioid antagonists

block the euphoria and "high" of heavy drinking

-Naltrexone and nalmefene (approved outside the US)

-If you drink when you take an opioid antagonist, the opioids released by alcohol do not lead to pleasure

Acamprosate

derivative of the amino acid

taurine and interacts with both the glutamate system to inhibit it, and with the GABA system to enhance it

-"artificial alcohol"

-acamprosate can substitute for alcohol in patients during withdrawal

*mitigate the glutamate hyperactivity and the GABA deficiency

Disulfiram (Antabuse)

classic drug for treating alcoholism

-irreversible inhibitor of the liver enzyme aldehyde dehydrogenase that normally metabolizes alcohol

-alcohol ingested with disulfiram, alcohol's metabolism is inhibited, build-up of toxic levels of acetaldehyde, creates an aversive experience with flushing, nausea, vomiting, and hypotension.

-compliance is a problem

Sedative Hypnotics

barbiturates and related agents such as ethchlorvynol and ethinamate, chloral hydrate and derivatives, and piperidinedione derivatives such as glutethimide and methyprylon.

-Experts often include alcohol, benzodiazepines, and Z-drug hypnotics

Gamma-Hydroxybutyrate (GHB)

treatment for narcolepsy/cataplexy

-sometimes also abused by individuals wanting to get high or by predators to intoxicate their dates

-"date rape" drugs

-agonist at its own GHB receptors and at GABA B receptors

distinction between opioids and opiates

opiate is a drug naturally derived from the flowering opium poppy plant

-examples: heroin, morphine, codeine.

opioid is a broader term that includes opiates and refers to any substance, natural or synthetic, that binds to the brain's opioid receptors (the parts of the brain responsible for controlling pain, reward, and addictive behaviors)

-examples: prescription painkillers, hydrocodone (Vicodin), oxycodone (OxyContin), fentanyl, methadone

Endogenous Opioid Neurotransmitter System

three parallel opioid systems

-Neurons that release β-endorphin - sometimes referred to as the "brain's own morphine" synapse with postsynaptic sites containing μ-opioid receptors

-neurons that release enkephalin synapse with postsynaptic δ-opioid receptors

-neurons that release dynorphin synapse with postsynaptic κ-opioid receptors

the US consumes __% of the world's legal and illegal supply of opioids.

85%

opioid withdrawal syndrome is characterized by:

the patient feeling dysphoria, craving another dose of opioid, being irritable, Pilo-erection ("goose-bumps"), and having signs of autonomic hyperactivity such as tachycardia, tremor, and sweating

Hallucinogens

three classes of agents that act, at least in part, as agonists at 5HT2A receptors:

• tryptamines (such as psilocybin)

• ergolines (such as lysergic acid diethylamide [LSD])

• phenethylamines (such as mescaline)

-not selective for 5HT2A receptors

alone, and their actions at other serotonin receptor subtypes may contribute to their mind-altering states

-5HT2A antagonists, but not D2 dopamine antagonists, can reverse the action of hallucinogens in humans, supporting the predominant mechanism of action of hallucinogens as being agonists at 5HT2A receptors

Empathogens

Empathogens produce an altered state of consciousness described as experiences of emotional communion, oneness, relatedness, emotional openness - that is, empathy or sympathy

Treatment of OCD

First-line:

-SSRI

Secont-line:

-tricyclic antidepressant, SNRI, or MAOI.

-high dose of SSRI.

-augmentation of an SSRI with a serotonin-dopamine blocker.

-augmentation of an SSRI with a benzodiazepine, lithium, or buspirone.

Other treatments:

-exposure therapy

-Repetitive transcranial magnetic stimulation (rTMS)

-experimental: deep brain stimulation, sterotactic ablation of the impulsive-compulsive pathways for resistant cases

Impulsivity circuit

prefrontal ventral striatal reward circuit

compulsivity circuit

prefrontal dorsal motor response inhibition circuit