Transcript 142K PPT - University of Washington

Substances of Abuse
Jonathan Buchholz, MD
Mark Duncan, MD
University of Washington
Goals for today
• Practical basics for most common substances
of abuse
• Key concepts to know in any medical practice
• Preparation for the board exams Steps 2-3
Addiction – As a Brain Disorder
• Studies of twins, adoptees
and family cohorts suggest
that genetic factors
contribute to approximately
50-60% of the variability in
the risk for addiction
• Predictable and persistent
structural and functional
brain changes are seen.
• More focus on genetics on
boards each year!
Orbitofrontal Cortex
Addiction as a Complex
Biopsychosocial Disorder
• “It is impossible to understand addiction without
asking what relief the addict finds, or hopes to
find, in the drug or the addictive behavior.”
Gabor Mate, MD
• Higher rates of addiction in patients with chronic
pain, psychiatric disorders, history of trauma, and
raised in homes with substance abuse
Addiction as a Chronic Disease
• How is it similar or different to DMII?
• Chronic disease model
• Course, etiologic factors, pathophysiology,
response to treatment are similar to other chronic
diseases (HTN, DMII, and Asthma)
• Relapse is common
• 40-60% of patients treated for a SUD return to
regular use within a year following treatment
Approach
• Non-judgmental and compassionate
– “Tell me about your alcohol (or drug use)”
– Discussing their past use can make it easier
– Patients are often embarrassed and vulnerable
• 75% of primary care patients who screened
positive for alcohol misuse showed motivation
to change. This increased as the severity went
up.
DSM 5-Substance Use Disorders
Substance use disorder:
A problematic pattern of substance use leading to clinically significant impairment or distress, as
manifested by at least two of the following, occurring within a 12-month period:
• Failure to fulfill obligations at work, school or home
• Use in dangerous situations
• Craving
• Continued use despite social or interpersonal problems due to the substance use (fights with
significant other)
• Tolerance
• Withdrawal
• Using more than intended
• Persistent desire or unsuccessful efforts to cut down or stop use
• Significant time spent getting, using or recovering from substance use
• Decreased social or occupational activities due to substance use
• Continued use despite physical or psychological problems
•
•
•
•
Severity specifier:
2-3: mild
4-5: moderate
6+: severe
Cannabis
Mechanism of Action
• Mouse Party
– (http://learn.genetics.utah.edu/content/addiction/mouse/)
Effects
• Intoxication
– Common
• Amotivation, perceptual disturbance (slowed time),
tachycardia, anxiety, increased appetite, conjunctival
injection, dry mouth
– Severe
• Paranoia, hallucinations, delusions
• Withdrawal
– Sleep disruption, anxiety, irritability, cravings
Totally safe?!?
Increases over Time in the Potency of Tetrahydrocannabinol (THC) in Marijuana and the Number
of Emergency Department Visits Involving Marijuana, Cocaine, or Heroin.
Volkow ND et al. N Engl J Med 2014;370:2219-2227
Use of Marijuana in Relation to Perceived Risk and Daily Use of Tobacco Cigarettes or Marijuana
among U.S. Students in Grade 12, 1975–2013.
Volkow ND et al. N Engl J Med 2014;370:2219-2227
Adverse Effects of Short-Term Use and Long-Term or Heavy Use of Marijuana.
Volkow ND et al. N Engl J Med 2014;370:2219-2227
Level of Confidence in the Evidence for Adverse Effects of Marijuana on Health and Well-Being.
Volkow ND et al. N Engl J Med 2014;370:2219-2227
A 42 y.o. man with schizophrenia presents to the
ED after being found yelling at cars in traffic. On
interview, the patient has AVH, paranoia and
persecutorial delusions. Initial toxicology
screening shows only cannabis in urine. Patient’s
only medication is Risperidone Consta 50mg IM
q2weeks. You call the patient’s case manager to
get a sense of baseline. Case manager states
that current symptoms are clearly worse than
usual. Chose the correct statement regarding
the case above.
A. Cannabis use among patients with schizophrenia is
associated with more hospital stays and longer
episodes of acute care
B. It is unknown what, if any, effect cannabis has on
patients with schizophrenia
C. Cannabis makes everyone who smokes it prone to
transient psychosis
D. Δ-9-tetrahydrohydrocannabinol (THC) is the only
cannabinoid in marijuana that is psychoactive and
it is likely responsible for the acute psychotic
presentation of the patient
Adolescents and Marijuana:
Genetic Links
– Swedish males using marijuana 6x more likely to be
diagnosed with schizophrenia
– Catechol-O-methyltransferase (COMT) -degrades
dopamine, epinephrine and norepinepherine
• COMT Val108 Met allele homozygotes more likely to develop
schizophrenia with THC exposure
• Carriers of the Val/Met allele more sensitive to psychotic
effects of THC
Questions?
Case
• You are on your family medicine rotation in
Spokane, Wa working at an outpatient clinic. A
24 y.o. man with history of PTSD his first
appointment in this clinic after moving from
Alasak for work. Your attending says, “Go in
and get a history, then come back and present
– we’ll see her together after that.”
The patient appears to be in distress saying, “I
really need help, I’ve run out of my xanax and I
need a refill right away. My anxiety is out of
control and I am not sleeping.” As the history
unfolds the patient says that he was seeing a
psychiatrist previously in Alaska but lost his
prescription for xanax during his move. He has
been out three days and has gone to multiple EDs
to attempt getting refills with no avail. “All they do
is give me a dose of clonazepam and offer me
detox. I’m not an addict! I have PTSD and my
doctor prescribes me the medicine!”
As you attempt to get more history about his
use one question you ask is “did you call your
doctor in Alaska to ask about a refill?” The
patient gets upset and says, “So you probably
think I’m an addict too! I tried that and he is
out of town.” The patient begins to cry and
says, “are you going to help me or not?” His
vitals are BP 160/85, HR 105, RR 18, Temp
37.4. You say, “I’d really like to help you but
there are just a few more questions I’d like to
ask.
• What do you want to know?
• What is your attending going to want to
know?
• Xanax 1.5 mg TID, no other medications or
medical problems known
• Has never run out of meds in the past, no history
of addiction to other substances, no family
history of addiction
• Employed as an asphalt paver, has been
employed for 5 years consistently
• PTSD stems from assault he suffered after being
beaten severely outside a bar 1.5 years ago
Diagnosis?
• You present the information to your attending.
He says “Great, another straightforward case.”
• What is this patient’s diagnosis? Do we have
enough information to make one?
Physiologic Dependence/Tolerance
• Patient is in benzodiazepine withdrawal
• Patient is physiologically dependent on
benzodiazepines and has developed tolerance to
the medications
• He does NOT meet criteria for a benzodiazepine
use disorder, benzodiazepine abuse,
benzodiazepine dependence in the “addiction”
sense of the term….AS OF YET
Substance use disorder/Addiction
• Pathological use of a substance which results in
repeated adverse social consequences related to the
drug use.
– Failure to meet work, school, family obligations
– Interpersonal conflicts
• Patients with severe substance use disorders often
have features of physiologic dependence and tolerance
• Having dependence and tolerance does NOT in itself
equal substance use disorder – *see subspecifier in
handout
Opioids
• What are the signs and symptoms of opiate
overdose?
• What are the signs and symptoms of opiate
withdrawal?
Opioid Overdose
• Respiratory depression
- airway stabilization!
• Naloxone (IV, IM,
Intranasal)
• Take into account
pharmacokinetics of
drug
Medications for
Opioid Use Disorder
• Antagonist
– Naltrexone
• Agonists
– Methadone
• Partial Agonist
– Buprenorphine
Naltrexone for
Opioid Use Disorder
• Most ideal pharmacologic treatment
• Requires detoxification before initiation or
severe withdrawal will be precipitated
• Requires Naloxone challenge test
• Risk of OD if medication stopped
• In general poor patient compliance (? Better
with long-acting injection) but superb
treatment for selected patients
Injectable Extended Release
Naltrexone for Opioid Dependence
Krupitsky, et al., 2011
Methadone Pharmacokinetics
and Dosing
• Rapidly absorbed
• Peak Levels in 4 hours
• t1/2=24 hours
• Metabolized in liver (p450 3A/4)
• Doses should be individualized but higher
doses generally more effective (≈80-120mg)
Swedish Methadone Study
Experimental Group
(Methadone)
Gunne & Gronbladh, 1981
Before
Control Group
(No Methadone)
Swedish Methadone Study
Experimental Group
(Methadone)
After 2 Years
Control Group
(No Methadone)
a
b
c
d
d
d
Gunne & Gronbladh, 1981
a
b
c
d
Sepsis
Sepsis and Endocarditis
Leg Amputation
In Prison
Methadone Side Effects
•
•
•
•
Minimal sedation once tolerance achieved
Constipation
Increased Appetite/Weight Gain
Lowered Libido; May decrease gonadal
hormone levels
• Prolonged Qtc (screen pts w/cardiac disease!)
• Exhaustively studied in all other organ systems
with no evidence of chronic harm
Buprenorphine Pharmacology
Poor oral bioavailability; given sublingually
(subcutaneous implants: experimental;
patch: for pain)
Slow onset (Peak effects 3-6 hrs.)
Long duration (24 - 48 hours)
Slow offset
Half life > 24 hours
Properties of Buprenorphine,
a µ-Opioid Partial Agonist
Ceiling effect on respiratory depression
High affinity for µ-opioid receptor
Slowly dissociates from µ-opioid receptors
Ameliorates withdrawal once underway
Can precipitate withdrawal if given in
temporal proximity to full agonist opioids
Efficacy: Full (Agonist Methadone), Partial Agonist
(Buprenorphine), Antagonist (Naloxone)
100
Full Agonist
(Methadone)
90
80
70
%
60
Efficacy
50
Partial Agonist
(Buprenorphine)
40
30
20
Antagonist
(Naloxone)
10
0
-10
-9
-8
-7
Log Dose of Opioid
-6
-5
-4
Buprenorphine vs. Placebo for Heroin Dependence
Remaining in treatment (nr)
Kakko, Lancet 2003
20
15
4 Subjects in Control Group Died
10
Detoxification
5
Maintenance
0
0
50
100
150
200
250
Treatment duration (days)
300
350
Question
In terms of mortality, what is the highest risk clinical
situation related to opioid use below?
A. A patient titrated to 90mg of methadone in a
methadone clinic
B. A patient using 1/2gram of heroin on a daily basis for 5
years
C. A patient who relapses onto heroin after 30 day
detox/inpatient treatment episode
D. A patient stabilized on 24 mg of daily suboxone who uses
heroin on top of the suboxone
Take Home
• Life threatening aspect of opioid overdose is
respiratory depression – stabilize airway and
give naloxone (consider t1/2)
• Methadone and buprenorphine replacement
have been shown to decrease morbidity and
mortality while engaging patients in treatment
and improving patient outcomes
• IM naltrexone potentially good option for
some patients
Questions?
Name the Drug?
What is the primary neurotransmitter
involved in cocaine intoxication and
how is it influenced?
• A. Glutamate, cocaine primarily binds to glutamate
receptors, blocking stimulation
• B. GABA, cocaine primarily binds to GABA receptors,
blocking stimulation
• C. Dopamine, cocaine primarily blocks the
transporter responsible for reuptake of dopamine
making it over stimulate the cell
• D. Dopamine, cocaine stimulates the release of
dopamine and blocks the transporter responsible for
reuptake making it over stimulate the cell
Stimulants – Cocaine and
Methamphetamine
• Mouse party
– (http://learn.genetics.utah.edu/content/addiction/mouse/)
• Mechanism of action with neurotransmitter
dopamine. Be sure to know the difference!
This is a favorite test question of the boards.
Dopamine Reward
Symptoms
• Physical Symptoms
– Anorexia, hyperactivity, dilated pupils, flushing,
tachycardia, hypertension, hyperthermia,
twitching, insomnia, arrhythmias
• Positive Psychiatric Symptoms
– Euphoria, paranoia, persecutorial delusions,
hallucinations, disorganized thinking, aggression,
hypersexuality
Overdose
• Life threatening condition
– Vasoconstriction can result in MI and Stroke
– Cardiac Arrhythmias and seizures also common
conditions seen on boards
• Treatment
– Ensure Cardiac stabilization, Supportive Care,
symptomatic treatment
Cocaine + “?”
• Levamisole
– Antihelminthic adulterant found in
up to 70% of cocaine in the US
– Potentiates cocaine and adds bulk
– Severe vasculitis
Long Term Treatment
• Disulfiram - possibly to help reduce cravings
• Contingency management – most evidence
– Reward positive behavior
Review
• A patient presents to the Emergency
Department in severe distress. Unfortunately,
the man speaks no English aside from
screaming “Help!” Vitals are BP: 184/114; HR:
122, RR: 18, Temp 37.8. On physical exam his
pupils are dilated, he is sweating profusely
and clinching his stomach. What is the next
step in management?
• A. Give Buprenorphine because patient is in opioid
withdrawal
• B. Give Naloxone, patient is intoxicated on opioids
and at risk for respiratory depression
• C. Start oxygen and obtain EKG because patient is
likely intoxicated on cocaine
• D. Give benzodiazepine because patient is likely
intoxicated on cocaine
• E. Give 5mg of Haldol and 2mg of lorazepam because
patient is likely intoxicated on cocaine
Amphetamines
• Similar intoxication syndrome to cocaine but usually
longer
• No vasoconstrictive effect
• Possible neurotoxicity in chronic use: possibly from
glutamate and axonal degeneration
• Can see permanent amphetamine psychosis with
long term use
• Pathogenesis
– Reverses and blocks transport of DA, NE, Serotonin
– Stimulates release of DA
– Inh monamine oxidase activity
Treatment – amphetamines
• Withdrawal can last for >2 weeks and mimic
anxiety and depressive disorders
• CD treatment: including support, education,
skills, CA
– Treatment similar as for cocaine but no known
substances to reduce cravings
• No specific medications have been found
helpful in treatment
• Responsible for 88,000 deaths each year
• 3rd leading preventable cause of death in the US from behavioral factors
• 40% of all traffic fatalities are related to its use in 2000
ALCOHOL
57yo M with a history of GERD presents to your office for a PPD. You have
been seeing him for the past 3 years, for mostly minor medical issues. He has
recently been diagnosed with hypertension.
He presents requesting a TB test to enter court-ordered alcohol treatment
after a recent DUI. He assures you this was a one-time thing, and that he
does not have an alcohol problem.
Doctor: “How many times in the past year have you had 5 or more drinks in
one day.”
Patient: “It is hard to say.”
Doctor: “On average, how many days a week do you have an alcoholic drink?”
Patient: “6 out of 7 days. It helps me take the edge off.”
Doctor: “On a typical drinking day, how many drinks do you have?”
Patient: “5”
Concerns/Thoughts?
57yo M with a history of GERD presents to your office for a PPD. You have
been seeing him for the past 3 years, for mostly small medical issues. He has
recently been diagnosed with hypertension.
He presents requesting a TB test to enter court-ordered alcohol treatment
after a recent DUI. He assures you this was a one-time thing, and that he
does not have an alcohol problem.
Doctor: “How many times in the past year have you had 5 or more drinks in
one day.”
Patient: “It is hard to say.”
Doctor: “On average, how many days a week do you have an alcoholic drink?”
Patient: “6 out of 7 days. It helps me take the edge off.”
Doctor: “On a typical drinking day, how many drinks do you have?”
Patient: “5”
Concerns/Thoughts?
Doctor:
many
pastfor
year
have
you
57yo
M with a“How
history of
GERD times
presentsin
to the
your office
a PPD.
You have
been
seeing
for thedrinks
past 3 years,
for mostly
had
5 orhimmore
in one
day.”small medical issues. He has
recently been diagnosed with hypertension.
Single Item Alcohol Screener
“How many
times in the past
hadenter
five (fourcourt-ordered
in women) or more drinks
in a day?”
He presents
requesting
ayear
TBhave
testyouto
alcohol
treatment
Scoring and Notes
after a recent
He
you this
washowaoften
one-time thing, and that he
PositiveDUI.
response:
any assures
answer >0 or difficulty
identifying

Sensitivity 82% Specificity 79% (2)
does not
have
an alcohol problem.

Easy to remember and quick.
AUDIT-C
(Alcohol
Use Disorders
Test-Consumption)
Doctor:
“How
many times
in the pastIdentification
year have you
had 5 or more drinks in
How often do you have a drink containing alcohol?
one1. day.”
a: Never
b: Monthly or less
c: 2-4 times a month
d: 2-3 times a week e: 4 or more times a month
Patient: “It is hard to say.”
1.
How many standard drinks containing alcohol do you have on a typical day?
Doctor:
how many
do
anoralcoholic
drink?”
a: 1 or 2“On average,
b: 3 or 4
c: 5 or 6days a week
d: 7 or
9 you have
e: 10
more
Patient:
“6 often
out of
days.
me
takeonthe
off.”
1.
How
do 7you
have It
sixhelps
or more
drinks
oneedge
occasion?
a: Never
Less than monthly c: Monthly
d: Weekly
e: Daily or almost daily
Doctor:
“On ab:typical
drinking day, how many
drinks do you
have?”
Scoring and Notes
Patient:
“3”a=0, b=1, c=2, d=3, e=4 (3)

Scoring:
o
o
Positive response indicates unhealthy alcohol use
 Men: >4 Sensitivity 85% Specificity 89%
 Women: >3 Sensitivity 73% Specificity 91%. (4)
Scores >7 suggest alcohol dependence (5)
Thoughts? Next Steps?
Healthy Drinking
Limits
Healthy Men <65 years old
 ≤ 4 drinks in a day and
 ≤ 14 drinks in a week
All Healthy Women and
Healthy Men > 65 years old
 ≤ 3 drinks in a day and
 ≤ 7 drinks in a week
Abstinence for selected
populations
 Pregnant
 Medication interactions
 Health conditions with
contraindications
 Under 21yo
Next Steps?
• Make a diagnosis
DSM 5-Substance Use Disorders
Substance use disorder:
A problematic pattern of substance use leading to clinically significant impairment or distress, as
manifested by at least two of the following, occurring within a 12-month period:
• Failure to fulfill obligations at work, school or home
• Use in dangerous situations
• Craving
• Continued use despite social or interpersonal problems due to the substance use (fights with
significant other)
• Tolerance
• Withdrawal
• Using more than intended
• Persistent desire or unsuccessful efforts to cut down or stop use
• Significant time spent getting, using or recovering from substance use
• Decreased social or occupational activities due to substance use
• Continued use despite physical or psychological problems
•
•
•
•
Severity specifier:
2-3: mild
4-5: moderate
6+: severe
• On further discussion the patient admits the
following.
–
–
–
–
–
–
–
His father was a “functional alcoholic”
He has never been in treatment before
This is his first legal issue around drinking
He has called in sick to work because of hangovers
He has thought about drinking at work, but is able to resist
He has never tried to cut back
Denies increasing amounts, but admits to handling his alcohol
much better then when he was younger
– His ex-wife told him he drank too much, and was “toxic” around
his kids, but he feels he is fine. The kids primarily live with their
mother.
– Drinking helps with his anxiety and sleep
Next Steps?
• Make a diagnosis
• Evaluate medical and psychiatric
stability
Medical Associations of Alcohol
•
•
CV: cardiomyopathy, afib, HTN, dysrhythmia, coronary artery spasm, MI, CAD, suden death
Hepatic: steatosis, acute & chronic hepatitis (including infectious), cirrhosis, portal hypertension &
varices, spont bacterial peritonitis
•
Renal: hepatorenal syndrome, rhabdomyolysis, acute renal failure, volume depletion acidosis,
hypokalemia, hypophosphatemia
•
GI: gastritis, esophagitis, pancreatitis, diarrhea, malabsorption, parotid enlargement, malignancy, colitis,
Barrett esophagus, GERD, Mallory-Weiss syndrome, GI bleeding
•
•
Pulmonary: aspiration, sleep apnea, respiratory depression, apnea, chemical or infectious pneumonitis
Neurologic: peripheral and autonomic neuropathy, seizure, hepatic encephalopathy, Korsakoff dementia,
•
Wernicke syndrome, cerebellar dysfunction, Marchiafava-Bignami syndrome, central pontine myelinosis,
myopathy, amblyopia, stroke, withdrawal delirium, hallucinations, toxic leukoencephalopathy, subdural
hematoma, intracranial hemorrhage
Infectious: HCV, pneumonia, TB, HIV, STIs, spontaneous bacterial peritonitis, brain abscess, meningitis
•
•
•
•
Sleep: apnea, periodic limb movements of sleep, insomnia, disrupted sleep, daytime fatigue
Trauma: motor vehicle crash, injuries, abuse
Prenatal/Perinatal: fetal alcohol effects and syndrome
Hematologic: macrocytic anemia, pancytopenia, leukopenia, thrombocytopenia, coagulopathy, iron
deficiency, folate deficienc, spur cell anemia, burr cell anemia
•
Musculoskeletal: rhabdo, compartment syndromes, gout, saturnine gout, osteopenia, osteonecrosis
•
Nutritional: vitamin and mineral def (B1, B6, Riboflavin, Niacin, Vit D, Mag, Ca, Folate, Phosphate, Zinc),
protein
Psychiatric Associations of Alcohol
Suicide-a real risk
Rate increased nearly 10 fold in people with an Alcohol Use disorder
Heavier drinking days found to be associated with a higher risk
Next Steps?
• Make a diagnosis
• Evaluate medical and psychiatric
stability
• Evaluate interest in change
PROCHASKA
STAGES OF CHANGE
(the transtheoretical model)
Precontemplation no intention to take action within next 6 months
Contemplation intend to take action within next 6 months
Preparation intend to take action within 30 days and have already taken some
steps to change
Action behavior has changed for < 6 months
Maintenance behavior has changed > 6 months
Termination not tempted to relapse and certain they will not return to their old
behavior
Next Steps?
• Make a diagnosis
• Evaluate medical and psychiatric
stability
• Evaluate interest in change
• Evaluate risk of withdrawal
Uncomplicated alcohol withdrawal
• Usually 6-8 hours after the last drink (or
reduction in heavy drinking)
• Peaks in 24-48 hours
• Subsides within 5-7 days
• Common symptoms: anxiety, tremor, GI upset,
diaphoresis, sleep disturbance, increases in blood
pressure and heart rate
• There is a ‘protracted withdrawal syndrome’
that can continue several months after acute
detox is complete; this includes anxiety, mood
disturbance, and poor sleep.
When to admit for inpatient detox?
• High ciwa score (12), elevated vitals, with a
still elevated Breathalyzer
• History of complicated withdrawal (DT’s)
• Medical issues (heart arrhythmia)
• Unstable psychiatric issues (suicidal)
• Failure of outpatient treatment (not
applicable here)
CIWA Scoring
• Scoring
– Mild: <9
– Moderate: 10-18
– Severe: <18
• Do not score if patient
is intoxicated
• Helpful in assessing
risk.
Alcohol withdrawal complications:
Withdrawal seizures
Tonic clonic
24-48 hours after last drink
If multiplefurther work-up required.
Risk factor: h/o seizures, heavy sustained drinking
Delirium tremens
Autonomic dysregulation, agitation, diaphoresis,
disorientation, hallucinations.
72-96 hours after last drink
Medical Emergencymortality rate 37% if untreated
Risk factor: h/o DTs, heavy sustained drinking, concurrent
illness
Alcoholic hallucinosis
Characterized by vivid and often unpleasant perceptual
disturbances that can be tactile, auditory or visual.
Wernicke’s
encephalopathy
Encephalopathy, paralysis of eye movements, and ataxia
Atrophy of mammalar bodies-highly specific
Replace thiamine 1st!
Next Steps?
• Make a diagnosis
• Evaluate medical and psychiatric
stability
• Evaluate interest in change
• Evaluate risk of withdrawal
• Consider treatment options
Alcohol Pharmacotherapy:
Naltrexone
Opioid receptor blocker; cuts back craving and ‘reward’ of use
Side effects: Nausea, vomiting, decreased appetite, dizziness.
Injection site (if using depot formulation)
Cons: will precipitate withdrawal in those with physiologic
dependence on opioids
-typically 1st line
Acamprosate
-often considered
on opioids
2nd
line if
Disulfiram
-great for patients with
incredible adherence
(methadone Disulfiram
cocktail)
Topiramate
-consider in pts on opioids
or who cannot tolerate
disulfiram
Structurally similar to GABA, may inhibit glutamatergic system
Side effects: Diarrhea, nausea, vomiting
Pros: Can be used in patients with liver disease.
Cons: TID dosing, use caution in renal disease
Blocks aldehyde dehydrogenase, blocks breakdown of alcohol
With alcohol: flushing, headache, nausea/vomiting,
palpitations, shortness of breath
Without alcohol: liver failure, metallic taste, neuropathy
*Must watch LFT’s!
AVOID in: Pregnancy, psychosis, severe heart disease
Potentiates GABA, inhibits glutamate. May reduce cravings
Side effects: sedation, decreased appetite, weight loss,
dizziness, tremor
Caution in renal disease
Psychosocial Treatments
Brief Interventions
Brief 2-4 semi-structured counseling session emphasizing reduction.
Components: feedback on risk, responsibility, advice to change, goal setting
Useful in risky substance use.
Harm Reduction
Combines compassion and pragmatism to reduce harms of substances.
User driven. “An attitude more then a procedure.”
Motivational therapy
Collaborative, evocative, and autonomy supportive interviewing technique
to build motivation to result in change.
Cognitive Behavioral
Identifies cognitive, behavioral, and environmental risk factors for relapse
prevention. Abstinence based.
Mutual help groups
AA , NA, CA-abstinence based peer support. Dose dependent response.
Widely available and free!
Inpatient
Moderate evidence. Not found to be consistently better then other
approaches. May be better for some people.
Outpatient
A variety of approaches and intensities, such as Intensive Outpatient
Programs. Typically involves regular counseling and monitoring.
Summary: Alcohol
• Universal screening is recommended
• Full medical and psychiatric evaluation is
needed if addicted
• Monitor for alcohol withdrawal complications
• Long term follow-up is needed
Nicotine
Leading Preventable Cause of
Premature Death in the US
http://www.cdc.gov/tobacco/data_statistics/tables/health/attrdeaths/index.htm?utm_source=feedburner&utm_medium=feed&utm_campaign=
Feed%3A+cdc%2FGEla+(CDC+-+Smoking+and+Tobacco+Use+-+Main+Feed)
Nicotine
• Effects of smoking: restlessness, insomnia, anxiety
• Withdrawal: craving, dysphoria, anxiety, poor concentration, increased
appetite, irritability, insomnia
• Cancers associated with smoking
– Cause proven
•
•
•
•
•
•
•
•
•
•
•
•
Colorectal
Head and neck
Liver
Lower urinary tract, including renal pelvis, ureter, and bladder
Lung
Mesothelioma
Myeloid leukemia
Nasal cavity and paranasal sinuses
Pancreas
Penis
Stomach
Uterine cervix
Benefits of Stopping
•
•
•
•
•
•
•
•
•
Live longer
Reduce CV risk after MI by > 1/3 over 5 years
Reduce cancer risk
Improve lung function
Reduce risk of infections
Decreased risk for DMII
Reduce risk of hip fractures
Decrease reproductive disorders
Etc.
Smoking reduction vs cessation?
– Maybe helpful for heavy smokers-controversial
– Smokers often compensate-longer puffs, etc.
Smoking Cessation
Varenicline (Chantix)
• A4B2 nicotinic cholinergic receptor (nAChR) partial agonist
• Mimics the action of nicotine & prevents withdrawal symptoms
• Side effects: GI upset, psychiatric changes
Bupropion (zyban)
• Antidepressant that is also a partial agonist at nAChR and inhibitor
of dopamine reuptake
• Helps reduce withdrawal symptoms.
• Tremor, anxiety.
Nicotine Replacement (gum, lozenge, inhaler, patch)
• Replaces nicotine, without additives of tobacco. Often used as a
combination of patch (long acting ‘basal’ nicotine level) and gum or
lozenge for break through cravings.
• Anxiety, restlessness, GI upset, tremor, sleep disturbance
Helping patients QUIT
• The Five A’s Model for facilitating smoking
cessation:
• Ask about tobacco use during each visit
• Advise all patients who smoke to quit
• Assess the patient’s willingness to quit
• Assist the patient in their quit attempt
• Arrange for follow up
• Designed to deliver nicotine without tobacco
Good or Bad?
• Not found to be a gateway to smoking tobacco
• Content
– Propylene glycol, glycerolmostly safe
– Impurities and toxicants in liquidnot safe, but
safer then tobacco
– Nicotine delivered varies
**Long term effects of these
additives are unknown**
• Adverse effects: mouth and throat irritation, increase in blood pressure
– More serious: exploding cartridge, lipoid pneumonia, afib in eldery pt
– CV: increased heart rate
– Resp: increased resistance after 5 min of use, but deemed not
clinically significant
– Nicotine poisoning: 1 report of a child death after drinking e-liquid
• Less calls to poison control then for tobacco exposure
• Effect on smoking behavior
– Reduces urge to smoke
– Preliminary evidence for reduction and cessation
– Method choice in England
Summary: Nicotine
•
•
•
•
Don’t forget to address nicotine use!
Cessation is the goal
Multiple quit attempts likely needed
There are several products that can be helpful
including: patches, gum, bupropion,
Varenicline, and e-cigarettes
QUESTIONS?
THANKS
Summary/Supplement to Substance Use Disorders
Tolerance:
A need for markedly increased amounts of the substance to achieve intoxication or desired effect OR
A markedly diminished effect with continued use of the same amount of the substance.
Withdrawal:
The characteristic withdrawal syndrome for a substance after cessation of heavy and prolonged use of the substance (or reduction in use) OR
The substance, or one very similar (for example, benzodiazepines in someone with alcohol use disorder) is taken to relieve or avoid
withdrawal symptoms.
Wernicke’s encephalopathy:
The “classic triad” of ataxia, nystagmus and mental confusion is a common boards question; however, in clinical practice, all three symptoms
are rarely present. Wernicke’s is missed in 80% of cases! Newer criteria have been proposed:
•Two of the following are required for diagnosis in alcoholics consuming more than 80gm of alcohol daily (more than 5 standard drinks) for
most of their adult life: dietary deficiencies, oculomotor abnormalities, cerebellar dysfunction and either altered mental status or mild
memory impairment. Treatment is thiamine!*
Clinical Management
Clinical Pearls:
Patients who have had alcohol withdrawal seizures or DT’s are considered to have had “complicated alcohol withdrawal.”
When getting the clinical history for a patient in alcohol withdrawal, it is very important to find out:
•
how long the patient has been drinking,
•
how much they’ve been drinking,
•
when their last drink was, and
•
what their prior symptoms have been when in alcohol withdrawal.
This helps you stratify their risk during detox, make decisions regarding management (Outpatient detox? Do they need to be hospitalized?),
and have a timeline for potential complications of withdrawal.
Relapse prevention medications following acute medical stabilization/detox– *see attached chart 1
Clinical Management
Uncomplicated alcohol withdrawal:
•
Begins earlier than the Andreasen textbook suggests; usually 6-8 hours after the last drink (or reduction in heavy drinking)
•
Peaks in 24-48 hours , Subsides within 5-7 days.
•
Common symptoms: anxiety, tremor, GI upset, diaphoresis, sleep disturbance, increases in blood pressure and heart rate
•
There is a ‘protracted withdrawal syndrome’ that can continue several months after acute detox is complete; this includes anxiety,
mood disturbance, and poor sleep.
Alcohol withdrawal seizures:
•
Usually occur when patients have had heavy, sustained alcohol intake
•
Risk peaks 24-48 hours after the last drink (or after significant reduction in alcohol use)
•
Tonic-clonic
•
Usually one seizure, but can be multiple
Alcoholic hallucinosis:
•
As the book notes, this is characterized by vivid and often unpleasant perceptual disturbances that can be tactile, auditory or visual.
•
Usually within 48 hours of alcohol cessation
•
CLEAR SENSORIUM (if there is altered mental status—consider DTs!)
•
Usually resolve within a week, but in some cases, can be chronic
Alcohol - Delirium Tremens:
•
altered mental status and autonomic dysregulation in the context of alcohol withdrawal
•
Rare complication of alcohol withdrawal-5% of hospitalized patients
•
MEDICAL EMERGENCY; mortality rate if untreated is as high as 25%
•
Usually emerges 48-96 hours after the last drink
*patients (and sometimes physicians!) can be very confused about what DT’s truly are. Many patients will tell you they ‘had the DT’s,’ but will
often mean they had tremor or other unpleasant symptoms of uncomplicated alcohol withdrawal. It is important to clarify: Were they
admitted to the ICU? Did a doctor tell them they became very confused or agitated? Were they admitted to a hospital and not remember
their withdrawal?
Drug-Related Disorders:
Genetic factors are estimated to contribute to 40-60% of the variability in the risk for addiction.
*Reward pathways have been identified in the ventral tegmental area (vta) of the forebrain and the nucleus accumbens, mediated largely by
dopamine*.
Underlying mental illness is associated with higher rates of drug use disorder. Diagnosis and treatment of these disorders (bipolar, psychosis,
depression, anxiety, etc) can be difficult with active substance use but are a key feature in good clinical treatment of this population.
Antisocial and borderline personality disorders are the most common personality disorders associated with substance use across the board.
*Table 9.7 Black* Signs of intoxication– high yield for boards – pay particular attention to Eyes, Vital signs, and Gastrointestinal signs. Will be
tested*
Sedatives, Hypnotics, and Anxiolytics (barbiturates, benzodiazepines, Alcohol)
Clinical Pearls:
•
Are all cross-tolerant with one another.
•
All can cause physical dependence.
•
Both intoxication and withdrawal are potentially life threatening.
Neurotransmitter action: potentiates effects of Gamma-aminobutyric acid (GABA), inhibitory neurotransmitter, by increasing frequency of
chloride channel opening
Withdrawal symptoms include:
Early – anxiety, restlessness
Middle – tremors, sweating, tachycardia, hypertension (24-72hours)
Late – seizures may develop (48-96 hours)
Delirium Tremens – disorientation, confusion, hallucinations (visual and tactile), nystagmus
Assessment of withdrawal using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)
Shorter acting substances are associated with more intense withdrawal symptoms
Benzodiazepines should be tapered over time to avoid severe withdrawal symptoms (seizures, DTs).
Treatment of sedative/alcohol withdrawal: (see Black pg 258 key points*)
•
Patients with history of complicated withdrawal (DT’s, seizures) should be monitored closely and treated with benzodiazepines to avoid
complications.
Benzodiazepine overdose (respiratory depression): stabilize airway, supportive care.
*On boards – give flumazenil.* Drug not used much clinically – can precipitate seizures
Opioid Use Disorders: heroin, morphine, hydrocodone, oxycodone, tramadol, meperidine.
Clinical Pearls:
•
High mortality rates associated with overdose (respiratory depression), accidental deaths, suicide and infections (abscess, sepsis,
hepatitis C, HIV)
•
Treatment of acute overdose: IV naloxone, stabilize airway
Neurotransmitters: endogenous opiate receptors (mu, kappa and delta). Secondary effects on dopamine.
Withdrawal symptoms (miserable but not life threatening):
•
Emerge based on half-life of opiate used. If physiologically dependent, heroin withdrawal begins 6-12hrs after last use, peaking 1-3 days
•
Dilated pupils, sweating, yawning, tachycardia, hypertension, rhinorrhea, piloerection, hot/cold flashes, muscle/joint pain, nausea,
vomiting, GI cramps/diarrhea
Clinical management of acute withdrawal:
•
Assessment of withdrawal done with Clinical Opiate Withdrawal Scale (COWS)
•
Symptom management: Clonidine for autonomic dysfunction, NSAIDs for muscle cramps, dicyclomine for GI symptoms.
•
Replace opiate: initiate opiate and taper - methadone, suboxone
Long-term medical treatment of opiate dependence
Methadone maintenance (only approved in DEA approved methadone programs): Methadone is a full opiate agonist with long half life 24-36
hours on average
Decreases cravings for opiates
Better results than opiate detoxification alone
Engages patients in treatment
Improves social and occupational functioning
Decreases substance use across board
Decreases criminal activity and depressive symptoms
Buprenorphine: partial opiate agonist (ceiling effect reduces chances for overdose)
Higher binding affinity to opiate receptors than other opiates
Suboxone: buprenorphine plus naloxone – oral dissolvable tab. Naloxone not orally bioavailable so no precipitated withdrawal.
However, if injected naloxone can then precipitate withdrawal. Compound prevents misuse of substance.
Because buprenorphine is a partial opiate agonist with high binding affinity, it can precipitate withdrawal in a patient with full opiate
agonist on board. Must wait to administer until patient in partial opiate withdrawal
Naltrexone: full opioid receptor antagonist
Stimulant use disorders: Cocaine, Methamphetamine, methylphenidate, dextroamphetamine
*Psychological euphoria mediated largely by dopamine*:
cocaine: prevents the reuptake of dopamine
methamphetamine: stimulates the release and prevents the reuptake of dopamine
Intoxication – euphoria, dilated pupils, agitation, anxiety, possible psychosis, vitals signs vary
- Treatment of intoxication – supportive care
Overdose (can be life threatening) – acute myocardial infarction and/or anoxic brain injury (stroke) secondary to vasoconstriction,
arrhythmias, hyperthermia.
- Treat secondary disorder MI, Stroke, hyperthermia
Withdrawal “crash” (not life threatening)- extreme fatigue, depression, intense dysphoria.
Treatment with supportive care.
Treatment of dependence: contingency management, cognitive behavioral therapy, can try disulfiram for cravings or relapse prevention but
pharmacotherapy options are limited
Hallucinogen use disorders: peyote, mescaline, LSD, MDMA (Ecstasy)
Multiple neurotransmitters: dopamine, serotonin, acetylcholine, GABA
MDMA (ecstasy) – both stimulant and hallucinogen properties - more potent serotonin effects - can cause serotonin syndrome
Intoxication: autonomic hyperarousal, perceptual alterations (heightened sensations, increase intensity of emotions). Tx: Supportive care for
intoxication
Overdose: tachycardia, arrhythmias, stroke, dehydration (MDMA mostly)
Phencyclidine (PCP) use disorders:
Neurotransmitters: Antagonizes N-methyl-D-aspartate (NDMA) glutamate receptors and activates dopaminergic neurons
Intoxication: out of control behavior, violence, ataxia, hypertension, tachycardia, hallucinations, and depersonalization (*Rotatry nystagmus
pathognomonic for PCP intoxication* - high yield boards)
Benzos and antipsychotics for severe agitation or psychotic symptoms
Cannabis use disorders:
Many cannabinoids: delta-9-tetrahydrocannabinol (THC) main psychoactive cannabinoid. Secondary effects on dopamine.
Intoxication (not life threatening): time slowing, ↑ appetite, tachycardia, dry mouth, paranoia, and potential psychotic symptoms. Treat with
supportive care
*Chronic heavy use in teens has been shown to increase prevalence of psychotic disorders into adulthood*
Withdrawal (not life threatening): insomnia, anxiety, and nausea
Inhalants (toluene acetone, benzene found in glue, paint, gas, aerosol cans):
Intoxication: 5-45 minutes; though CNS depressants, they can cause euphoria, disinhibition, excitation
At higher levels can cause respiratory depression, slurred speech, ataxia, delirium
Treatment: stabilize airway, supportive care
High Yield Boards* - can cause heavy metal poisoning: kidney liver and neuromuscular damage
Nicotine (cigarettes, chew, and snuff): Up to 25% of adult Americans use regularly. More common in people with mental illness (up to 90%
in patients with schizophrenia). Leading cause of preventable morbidity and mortality in US.
Stimulates nicotinic receptors in the autonomic ganglia of the sympathetic and parasympathetic nervous system.
Highly addictive via the dopamine system.
Withdrawal: begins hours after last cigarette, peaks in first 24 hours, can continue for weeks, cravings for months. Symptoms include
dysphoria, anxiety, weight gain
Treatment
Varenicline (Chantix)
Bupropion (zyban)
Nicotine Replacement
(gum, lozenge, inhaler,
patch)
MOA
a4B2 nicotinic
cholinergic receptor
(nAChR) partial agonist
Antidepressant that is
also a partial agonist at
nAChR and inhibitor of
dopamine reuptake
Same as nicotine.
Effect
Mimics the action of
nicotine & prevents
withdrawal symptoms
Helps reduce
withdrawal symptoms.
Potential SEs
GI upset, psychiatric
changes
Replaces nicotine,
without additives of
tobacco. Works best
with patch (long acting
‘basal’ nicotine level)
and gum or lozenge for
break through cravings.
Anxiety, restlessness, GI
upset, tremor, sleep
disturbance
Tremor, anxiety.
Prescribing Practices: Medications physicians prescribe such as opiates, benzodiazepines, and stimulants are drugs of potential abuse and
misuse. Physicians should consider this risk with all prescriptions given. See table 9-8 – rationale can be applied to all addictive substances.
Additional tool: Washington Prescription Monitoring Program: tracks prescriptions for all controlled substances in the state.
http://www.doh.wa.gov/ForPublicHealthandHealthcareProviders/HealthcareProfessionsandFacilities/PrescriptionMonitoringProgramPMP.as
px
Chart 1
AUD meds
Disulfiram
Mechanism of action Side effects
Consider
avoid
Blocks aldehyde
dehydrogenase,
blocking breakdown
of alcohol
Highly motivated
patients, those who
can be monitored
Pregnancy, psychosis,
severe heart disease
With alcohol:
flushing, headache,
nausea/vomiting,
palpitations,
shortness of breath
Without alcohol: liver
failure, metallic taste,
neuropathy
Patients on
methadone or other
opioids
*Must watch LFT’s!
Naltrexone
Opioid receptor
blocker; cuts back
craving and ‘reward’
of use
Nausea, vomiting,
decreased appetite,
dizziness. Injection
site (if using depot
formulation)
Acamprosate
Structurally similar to Diarrhea, nausea,
GABA, may inhibit
vomiting
glutamatergic system
May work better for
patients with a family
history of alcohol use
disorder
Opioids won’t work;
will precipitate
withdrawal in those
with physiologic
dependence on
Also has a long acting opioids
injectable
formulation
Can be used in
patients with liver
disease.
Caution in renal
disease
TID dosing can make
med adherence
challenging
Topiramate
Anticonvulsant;
potentiates GABA,
inhibits glutamate.
May reduce cravings
for alcohol
Sedation, decreased Consider in patients
appetite, weight loss, on opioids or who
dizziness, tremor
cannot tolerate
disulfiram
Caution in renal
disease
Can interact with
multiple medications
(metformin,
carbamazepine,
valproate, oral
contraceptives)