Substance Abuse Flashcards
What is A chronic disorder characterized by the compulsive use of substance resulting in physical, psychological, or social harm to be user and continued use despite the harm?
Addiction
What is the physiological adaptation to the effect of drugs so as to diminish effects with constant dosages or to maintain the intensity and duration of effects through increased dosage?
Tolerance
What is the development of a substance-specific syndrome due to the cessation use that has been heavy and prolonged?
Substance withdrawal
What is reversible substance-specific syndrome due to a recent ingestion or exposure to a substance?
Substance intoxication
What is substance intoxication?
Clinically significant maladaptive behavior or psychological changed due to the effect of the substance on the CNS
Develops during or shortly after use of the substance
Not due to a general medical condition or another mental disorder.
All abused substance appear to activate what?
The same brain reward pathway.
What are the key components in the pathophysiology of abuse?
DA in mesocorticolimbic system
Nucleus Accumbens (NA) to prefrontal cortex, amygdala and olfactory tubule.
Cocaine and stimulants block DA reuptake
Opioids activate μ receptors resulting in increased release of DA in NA
Nicotine also interacts with the opioid pathway
Marijuana’s active component, tetrahydrocannabinol (THC), binds to cannabinoid-1 (CB1) receptors resulting in activation of DA neurons in mesolimbic system
How does chronic substance use affect DA?
General decrease in DA neurotransmission
What are the 2 explanations for development of substance dependence?
Sensitization– Increased response following repeated intermittent administration of a drug, in contrast to tolerance to drug effects that occur secondary to continuous exposure to a drug
Counteradaptation– Initial positive reward feeling followed by the opposing development of tolerance
What is substance abuse via the DSM-IV?
Any 1 of:
Recurrent use causing failure to fulfill major role obligations at work/home/school
Recurrent use when physically hazardous
Recurrent substance-related legal problems
Continued use despite persistent social/interpersonal problems due to substance use
What is Substance dependence via the DSM-IV?
Any 3 of: Tolerance Withdrawal Uses more or longer than intended Unable to cut down Use consumes a great deal of time Important social/work activities given up Continued use despite physiological or physical problems know to be caused by substance
Alcohol- MOA
CNS depressant Works in a dose dependent fashion Sedative, sleep, unconsciousness, coma, respiratory depression and CV collapse Affects GABA, glutamate and dopamine Affects endogenous opioids (release)
How is current use of alcohol use defined? Binge use? heavy use?
Current use- at least one drink in the past 30 days (includes binge and heavy use)
Binge use- five or more drinks on the same occasion at least once in the past 30 days
Heavy use- five or more drinks on the same occasion on at least 5 different days in the past 30 days.
What is the neurobiology of alcohol involving glutamate?
Major excitatory system in CNS
Four principal receptor subtypes
NMDA receptor
NMDA receptor activation → excitation
Acute ethanol intoxication → inhibition
NMDA R inhibited (↓glutamate activity)
Sedative, incoordinating, amnestic, and anxiolytic effects of alcohol
Chronic ethanol intoxication → hypersensitivity
Up-regulation of NMDA R number and function
Enhancement of NMDA R stimulated intracellular Ca2+ levels
What is the neurobiology of alcohol involving GABA?
Gamma-aminobutyric Acid (GABA)
Major inhibitory system in CNS
Two principal receptor subtypes
GABAA receptor subtypes
GABAA R activation→ inhibition
Acute ethanol intoxication→ activation
Potentiates GABAA inhibition
Sedative, incoordinating, amnestic, and anxiolytic effects of alcohol
Chronic ethanol intoxication→ hyposensitivity
Down-regulation of GABAA R number and function
What is the neurobiology of alcohol involving dopamine (DA)?
Ethanol activates mesolimbic DA systems→
increases DA release in nucleus accumbens (NAc)
Positive reinforcement and pleasurable effects of ethanol
What are the sx and tx of mild-moderate intoxication (BAL 0.08-0.1%)
Lower limits of legal intoxication
Do not require formal treatment
Mood labilty, loud or inappropriate behavior, slurred speech, incoordination, unsteady gait
What are the sx and tx of sever intoxication?
(BAL 0.2-0.3%) confusion, depressed consciousness, vomiting
(BAL 0.3-0.4%) stupor, coma
(BAL > 0.4%) cardiac arrhythmias, respiratory depression, death
If consciousness is impaired then thiamine should be given IV or IM for at least 3 days
What does CAGE stand for and what does it assess?
Assesses alcohol dependence
Have you ever felt the need to Cut Down on your drinking?
Have you ever been Annoyed by criticism of your drinking?
Have you ever felt Guilty about your drinking?
Have you ever needed an Eye Opener to get going in the morning?
What are the drugs used to treat alcohol dependence?
Disulfiram – Antabuse®
Naltrexone – Revia®
Acamprosate- Campral®
Disulfiram- Antabuse®- MOA
Acetaldehyde dehydrogenase (ALDH) inhibitor (irreversible)
Disulfiram- Antabuse®- ETOH reaction
Nausea/Vomiting HA Hypotension MI Weakness Tachycardia SOB Sweating Dizziness Blurred vision Confusion
Disulfiram – Antabuse®- treatment recommendations
250mg PO QD
Range from 125-500mg/d
Start when abstinent from ETOH for at least 12 hours
Full “protective” effect in 12-14 hours
2 weeks wash-out before alcohol interaction
What are the predictors of success with disulfiram?
Motivated Compliant High risk situations (e.g. weddings) where behavior is important Contingencies (e.g. loss of license) Supervised administration Stable home life
Naltrexone- Rivia®- indications
Narcotic abuse
Alcohol dependence
Naltrexone- Rivia®- MOA
Competitive mu (µ) opioid receptor antagonist
Naltrexone blocks ß- endorphin which stimulates dopamine release
Naltrexone blocks ethanol- induced DA release in NAC
» May attenuate rewarding effects of alcohol
Naltrexone- Rivia®- effectiveness
Moderate effects at best
More recent study in VA population found naltrexone no different than placebo on time to relapse, % of drinking, or # of drinks per drinking day
Long-term effectiveness???
One study has shown beneficial effects diminish gradually over time
Long-acting injectable: one study has shown effects sustained during 6 months of treatment
Acamprosate- Campral® - Indication
Approved to maintain abstinence after detoxification
Acamprosate- Campral® - MOA
Unknown
“restores balance” between glutamate and GABA
May ↓ glutamate overactivity
Binding to allosteric polyamine site on NMDA R and ↓ polyamine modulation of NMDA activity
Binding postsynaptic metabotropic glutamate receptors (mGluR5) and alter NMDA Receptor number and function
Binding to presynaptic mGluR5 and ↓ glutamate release
May ↓ ability of ethanol to activate mesolimbic dopamine system
Acamprosate- Campral® - effectiveness
Moderate effects at best
Similar decreases in drinking frequency, and similar relapse rates as naltrexone
13 trials, mostly European
Acamprosate- Campral® - Long-term effectiveness
In long-term trials, 16-30% of subjects completely abstinent at 48 and 52 week endpoints
Acamprosate- Campral® - ADRs
Only ADR reported in > 10% patients and at a rate > placebo was transient diarrhea
Asthenia (6%)
Anxiety (6%)
Insomnia (7%)
Acamprosate- Campral®- contraindications
Renally eliminated
Should not be used if CCI < 30 dl/ml
Is pharmacologic management required for patients with no significant withdrawal signs/sx of ETOH?
Nope
What are the signs and sx of ETOH withdrawal with minor withdrawal sx?
Tremor GI (nausea/vomiting) Mild diaphoresis Vital signs increase (mild) Sleep disturbance Hallucinations Seizures (7%)
What is the incidence and time course of ETOH withdrawal with minor withdrawal sx?
Incidence: >/= 1 sign/symptom 95% Time Course: Onset: 8-12 Hours Peak: 24-36 Hours Duration: 60-72 hours(important!)
What are the signs/sx of alcohol withdrawal with major withdrawal sx?
Delirium Delirium Tremems (DT’s) Hallucinations Agitation Tremors Vital signs increased (Marked) Diaphoresis (marked) Sleep disturbance
What is the incidence and time course of alcohol withdrawal with major withdrawal sx?
Incidence: 5% Time Course: Onset: 48-60 hours Peak: 72 hours Duration: 120-168 hours (Important!)
What are the treatment goals of alcohol withdrawal?
Prevent withdrawal symptoms including Seizures Delirium Tremens Medical and psychological complications Encourage long-term abstinence Encourage/refer to outpatient treatment (AA, 12 step programs, etc.)
What is the DOC for uncomplicated withdrawal?
Benzodiazepine
What is the criteria for the Mild, moderate, and severe clinical institute withdrawal assessment-alcohol revised (CIWA-Ar)
Mild: less than 8 on CIWA no pharmacological therapy
Moderate: 8-15 Use medication
Severe: 15 Use medication (enough to control symptoms) and monitor closely
When should patients be monitored during withdrawal?
Monitoring patient every 4-8 h
CIWA-Ar until score has been < than 8for 24 h
Use additional assessments as needed
What drugs should be administered when CIWA-Ar is Greater than or equal to 8?
Administer 1 of the following medications every hour when CIWA-Ar is ≥ to 8
Chlordiazepoxide 50-100 mg
Diazepam 10-20 mg
Lorazepam 2-4 mg
Repeat CIWA-Ar 1 after every dose to assess need to further medication
Are short or long acting benzodiazepines preferred for alcohol withdrawal treatment?
Long acting
What are the long acting benzodiazepines used in alcohol withdrawal tx?
Preferred: Long-acting
Chlordiazepoxide (Librium)
Diazepam (Valium)
What are the short acting benzodiazepines used in alcohol withdrawal tx?
Severe liver disease: Short-acting
Lorazepam (Ativan)- used frequently
Oxazepam (Serax)
What should be used to treat complicated alcohol withdrawal?
Complicated withdrawal
Patient NPO/vomiting
Parenteral BZD
Chlordiazepoxide 50mg PO = lorazepam 2-4mg IM
Supplement with lorazepam 2-4mg IM q1h for breakthrough signs/symptoms
What is used to tx seizures from alcohol withdrawal?
Benzodiazepines drug of choice IV diazepam 5-10mg may repeat q 5min till termination seizure IM lorazepam 4mg Correction of Electrolyte Imbalances IV magnesium 1g q hours for 1st day IV thiamine (as in intoxication)
What is used to treat delirium tremens (DTs) in alcohol withdrawal?
IV Benzos ‘till light somnolence is achieved
Haloperidol- given only for severe agitation unresponsive to benzos
IV thiamine
How should benzodiazepines be tapered?
Simple taper 25% dose reduction per week until 50% of original dose is reached Then decrease dose by 1/8 every 4-7 days If therapy > 8 weeks 2-3 week taper is recommended If therapy > 6 months 4-8 week taper should be used If therapy > 1 year Strong consideration should be given to using long-acting agents (Diazepam, Clonazepam)
What can sudden discontinuation of benzodiazepines result in?
Rebound anxiety
Recurrence or relapse of symptoms
Withdrawal symptoms
Onset
Short-acting agents ~ 1-2 days
Longer-acting agents ~ 2-4 days
What are the common sx of benzodiazepine withdrawal?
Anxiety Insomnia Restlessness Muscle tension irritability
What are the rare sx of benzodiazepine withdrawal?
Seizures
Hallucinations
Paranoid delusions
Confusion
Less frequently- nausea, malaise, blurred vision, diaphoresis, nightmares, ataxia, hyperreflexia
When do short acting and long acting benzo agents have withdrawal?
Short-acting agents
~3 days after discontinuation
Longer-lasting agent
~1 week after discontinuation
What are the risk factors for benzodiazepines?
High BDZ doses
Long duration of therapy
Concurrent meds/drugs that lower seizure threshold
What are signs of intoxication of stimulants-cocaine,methamphetamine?
Restlessness/anxiety Euphoria Grandiosity Hypervigilance Tachycardia/elevated blood pressure Mydriasis Sweating and/or chills Nausea, vomiting, diarrhea Psychosis Cardiovascular collapse death
What are the signs of abuse of stimulants-cocaine,methamphetamine?
- Dilated pupils (high dose)
- Dry mouth
- Bad breath
- Frequent lip licking
- Decreased appetite and sleep
- Irritable, argumentative
- Talkative but tangential
- Runny/bloody nose
- Paraphenalia
How do you treat intoxication of stimulant?
Treat and monitor medical problems
Hyperthermia, Hypertension, Cardiac arrhythmias, Stroke
Psychiatric Problems
Benzodiazepines for anxiety
History and drug screen 1st because often used in combo with ethanol, opioids so benzos can increase sedation and respiratory depression
How do you treat intoxication of stimulant?
Dependence
Therapy, groups, etc 12 step program
No proven pharmacotherapy, Disulfiram shows some promise with cocaine
What should be used for severe sx in the first 24 hours of stimulant withdrawal?
For severe symptoms in first 24 hours benzodiazepines or antipsychotics might be helpful for delusions, paranoia, compulsive behavior
What are the life threatening complications associated with stimulant withdrawal?
Seizures
Hyperthermia
Ischemic chest pain
Suicide
What are the signs of opioid intoxication?
Euphoria Dysphoria Apathy Motor retardation Sedation Attention impairment Miosis
What are the signs of opioid withdrawal?
Lacrimation Rhinorrhea Mydriasis Piloerection Diarrhea Yawning Insomnia Muscle aching
What is the treatment for opioid intoxication?
Reverse intoxication with naloxone 0.4-2mg IV q 2-3 min up to 10mg
Secure airway
What is the treatment for opioid dependence?
Opioid agonists
Opioid antagonists
What do opioid inhibit?
Opioids inhibit cyclic AMP system Chronic use discontinuation Leads to cyclic AMP in the adrenergic neurons becomes overactive Noradrenergic brain activity increases Contributes to withdrawal symptoms Adrenergic autoreceptors When stimulated decrease neural activity
What are the Mild (grade I)of opioid sx?
Yawning Lacrimation Rhinorrhea Perspiration Restlessness Insomnia
What are the moderate (Grade II) of opioid withdrawal?
Tremors Dilated Pupils Goosebumps Anorexia Muscle Twitching Myalgia/arthralgia Abdominal pain
What are the marked (grade III) of opioid withdrawal?
Nausea Extreme Restlessness Vital Signs ↑ Tachycardia Hypertension Fever Hot/Cold Flashes
What are the severe (Grade IV) of opioid withdrawal?
Vomiting Diarrhea Weight loss Dehydration Hypotension
When is opioid withdrawal fatal?
With a medical complication (still great discomfort, incapacitating)
Clonidine- MOA
Alpha adrenergic autoreceptors
Clonidine- Indications
Heroin: 10 day treatment
Methadone: 14 day treatment
Clonidine taper in both cases
When should vital signs be checked with methadone tx for opioid withdrawal?
Vital signs before each dose
Titration: ↑ 5-10mg QOD as tolerated
Methadone (Dolophine®)- MOA
Mechanism of action
µ and ō opioid withdrawal agonist
Suppresses opioid withdrawal symptoms
Blocks effect of other opioids
Use for detox limited to a licensed treatment facility
Methadone (Dolophine®)- side effects
Constipation, sweating, urinary retention
Respiratory depression in intolerant individuals
Buprenorphine(Subutex®, Suboxone®)- MOA
µ receptor partial agonist and weak K receptor antagonist
Similar effects as methadone
Opioid antagonist at higher doses
Controls cravings
Still some sense of euphoria
Safer than heroin
Not as addictive, little risk of overdose
Naltrexone (ReVia®)
Should not be initiated until patient is opioid free for 7-10d
Poor compliance and high drop-out rates limit usefulness
What CNS neurotransmitters affected by nicotine?
DA, NE, 5-HT, glutamate, GABA, and endogenous opioid peptides
Activates nicotinic acetylcholine receptors in the brain
What are the nicotine replacement therapies?
Patch Gum Lozenge Nasal Spray Inhaler
What are the smoking cessation pharmacotherapies?
Buproprion
Varenicline
Clonidine
TCA’s
When is combining nicotine replacement therapies more effective?
In refractory smokers
Buproprion (Zyban®, WellbutrinSR®)- MOA
Blocks reuptake of DA and NE
Acts as a noncompetitive antagonist on nAch receptor
Reduces nicotine reinforcement, withdrawal, and craving
Varenicline (Chantix®)- MOA
agonizes and blocks nicotinic acetylcholine receptors
Varenicline (Chantix®)- ADRs
Black Box Warning
Neuropsychiatric Symptoms and Suicidality
Weigh varenicline risks vs. benefits of smoking cessation
What are the 2nd line therapies for smoking cessation?
Clonidine
Modest efficacy in smoking cessation trials
TCA’s Nortriptyline (inhibit reuptake NE and 5-HT) Significant disadvantages Anticholinergic burden Cardiac side effects
