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3/9/2016
1
Drug Therapy for Treatment
of Addictions
Samantha Themas, PharmD
PGY1 Pharmacy Practice Resident
Memorial Regional Hospital
March 13, 2016
www.fshp.org
Disclosure
• I have nothing to disclose.
2
Objectives for Pharmacists
Pharmacists:
• Define and identify the diagnostic criteria of substance use disorders and
addiction
• Review local patterns of substance abuse
• Identify characteristics associated with an increased risk of addiction
• Mention the physiological effects of various substances of abuse
• Review the recommended pharmacological agents for treatment of acute
intoxication
• Discuss long term (maintenance) therapy options for substance abuse
disorders
Technicians:
• Define substance use disorders and addiction
• Identify various substances of abuse
• Review treatment options for addiction
3
Important Terms
Substance induced disorder
VS.
Substance use disorder
4
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Substance Induced Disorders
Psychotic Bipolar Depression Anxiety
Alcohol I/W I/W I/W I/W
Caffeine I
Cannabis I I
Hallucinogens
Phencyclidine I I I I
Inhalants I I I
Opioids I/W W
Sedatives,
Hypnotics,
Anxiolytics
I/W I/W I/W W
Stimulants I I/W I/W I/W
Tobacco
5American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5. 2013.
Substance Induced Disorders
OCD SleepSexual
DysfunctionDelirium
Alcohol I/W I/W I/W
Caffeine I/W
Cannabis I/W I
Hallucinogens
Phencyclidine I
Inhalants I
Opioids I/W I/W W
Sedatives,
Hypnotics,
Anxiolytics
I/W I/W W
Stimulants I/W I/W I I
Tobacco W
6American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5. 2013.
Substance Use Disorders
7
Cognitive Symptoms Behavioral Symptoms
Physiological Symptoms
Substance Use Disorder Diagnosis
• Impaired Control
• Social Impairment
• Risky Use
• Pharmacological Criteria
8American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5. 2013.
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Impaired Control
• Taking larger amounts or for longer time than
originally intended
• Express a persistent desire to cut down
• Spend great deal of time obtaining, using or
recovering from effects of drug
• Craving
9American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5. 2013.
Social Impairment
• Failure to fulfill major role obligations at work,
school or home
• Use despite recurrent social or interpersonal
problems
• Important social, occupational or recreational
activities may be given up or reduced
10American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5. 2013.
Risky Use
• Use in situations in which it is physically
hazardous
• Use despite knowledge of having physical or
psychological problem caused or exacerbated
by substance
11American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5. 2013.
Pharmacological Criteria
• Tolerance- requiring increased dose to achieve
the desired effects
• Withdrawal- occurs when blood
concentrations decline in an individual who
had maintained prolonged heavy use of the
substance
• These may occur during any course of medical
treatment- do NOT always signify substance
use disorder
12American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5. 2013.
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Drug Addiction and The Brain
13
Drug Addiction and The Brain
14Drugs, brains, and behavior: The science of addiction. National Institute of Drug Abuse. 2014.
Risk and Protective Factors
Risk Factors
• Aggressive behavior in
childhood
• Lack of parental supervision
• Poor Social Skills
• Drug experimentation
• Availability of drugs at
school
• Community poverty
Protective Factors
• Good self-control
• Parental monitoring and
support
• Positive relationships
• Academic compentence
• School anti-drug policies
• Neighborhood pride
15
Drugs, brains, and behavior: The science of addiction. National Institute of Drug Abuse. 2014.
Drug Patterns in Southeast Florida
16
Drugs Seized in Miami Area in 2014
Southeastern FL (Miami Area) SCS Profile, 2015.
(Bath Salts)
(Bath Salts)
(Flakka)
(Xanax)
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Alcohol
• Alcohol use disorder separate from substance use
disorder in DSM-5
• Defined by behavioral and physical symptoms
– Withdrawal, tolerance and craving
• Often associated with other substance use disorders
• Usually associated with periods of remission and
relapse
• Prevalence of alcohol use disorder varies between
age groups and sex
– Highest % in men, ages 18-29
17American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5. 2013.
Alcohol Use Disorder Risk Factors
18
• Environmental
– Cultural attitudes toward drinking
– Availability/price of alcohol
– Stress levels
• Epigenetic and physiological
– Rate is 3-4x higher in close relatives of individuals
with alcohol use disorder
– More affective relatives, closer genetic
relationship, severity of disorder = higher risk
• High levels of impulsivity
Physiological Effects
• Increases activity of GABA receptors
• Decreases activity of glutamate receptors
• Increases release of dopamine while blood
alcohol concentration is rising
19Doering PL, Li R. In: DiPiro JT. Pharmacotherapy: A Pathophysiologic Approach, 9e. 2014.
LexiComp, 2015.
Effects on Physical State
Ethanol Dose
(oz/hour)
Blood Ethanol
(mg/100mL)Function Impaired Physical State
1-4 Up to 100
Judgment, fine motor
coordination,
Reaction time
Happy, talkative
boastful
4-12 100-300Motor coordination,
reflexes
Staggering, slurred
speech, nausea,
vomiting
12-16 300-400Voluntary responses
to stimulation
Hypothermia,
hyperthermia,
anesthesia
16-24 400-600
Sensation, movement,
self-protective
reflexes
Comatose
24-30 600-900Breathing, heart
functionDead
20Kuhn C, et al. Norton & Company, Inc.; 2014.
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Treatment of Acute Intoxication
• Important to rule out other causes of altered mental
status
• Treatment is mostly supportive
– Fluids, dextrose, vitamins and minerals (especially
thiamine and folic acid)
• Continuously monitor vitals and airway
• May administer sedatives for agitated patients
• Benzodiazepines- symptom-triggered dosing (CIWA-
Ar) recommended
– Chlordiazepoxide, clonazepam, lorazepam or diazepam
Vonghia L, Leggio L, Ferrulli A, et al. Acute alcohol intoxication. Eur J Intern Med 2008; 19:561. 21
Treatment of Chronic Use
• Counseling and support groups (AA)
• Disulfiram (Antabuse)
– Dose: 125-500mg daily (max 500mg)
– Inhibits aldehyde dehydrogenase � accumulation of
acetaldehyde � headache, N/V, flushing, etc.
– Black box warning: Never administer to intoxicated patient
• Naltrexone (ReVia)
– Dose: 50 mg daily
– Opiate antagonist
– Attenuates reinforcing effects of alcohol � patients feel less
intoxicated and have less craving
– Long acting injection (Vivitrol) available (380mg IM q4w)
22Doering PL, Li R. In: DiPiro JT. Pharmacotherapy: A Pathophysiologic Approach, 9e. 2014.
LexiComp, 2015.
Treatment of Chronic Use
• Acamprosate (Campral)
– Dose: 666 mg three times daily
– GABA agonist and glutamate modulator at NMDA
receptor � decreases alcohol craving
• Off-label medications used for alcohol craving
– Mood stabilizers
• Lithium, topiramate, valproic acid
– Antidepressants
• Bupropion, SSRIs
23Doering PL, Li R. In: DiPiro JT. Pharmacotherapy: A Pathophysiologic Approach, 9e. 2014.
LexiComp, 2015.
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Neurotransmitters and Stimulant
Effects• Norepinephrine
– Increase in blood pressure and heart rate
– Relaxation of bronchioles
– Activation of fat breakdown
– Arousing effects
– Appetite effects
• Serotonin
– Increase in body temperature
– Appetite effects
• Dopamine
– Locomotor activation
– Euphoria: addiction
– Attention
25
Cocaine
“The main use of coca will undoubtedly remain
that which Indians have made of it for centuries:
it is of value in all cases where the primary aim
is to increase the physical capacity of the body
for a given short period of time and to hold
strength in reserve to meet further demands…
Coca is a far more potent and far less harmful
stimulant that alcohol, and its widespread
utilization is hindered at present only by its high
cost.”26
Cocaine
“If I had been in a room full of cocaine, I would have
kept using it until it was all gone, and I still would have
wanted more.”
27
Cocaine
• Stimulant consumed either by ingesting,
snorting, smoking or injecting
• Blocks reuptake of norepinephrine and
dopamine
• Half-life ~ 1 hour � repeated drug use
28Doering PL, Li R.. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 9e. New York, NY: McGraw-Hill; 2014
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Methamphetamine
• Causes stimulant effect by inhibiting breakdown
of NE, DA and 5HT, AND increasing their release
into the synapse � Increase NTs MORE than
cocaine
• Consumed orally, nasally, rectally, IV injection,
and by smoking
29Doering PL, Li R.. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 9e. New York, NY: McGraw-Hill; 2014
Adverse Effects of Stimulants
• Jitteriness
• Paranoia
• Psychosis
• Hostility
• Repetitive aimless activities
• Palpitations
• Headaches
• Hyperthermia
• Arteriosclerosis
• Seizures (more common with cocaine)
• Neurotoxic damage (more common with meth)30
Doering PL, Li R.. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 9e. New York, NY: McGraw-Hill; 2014
Treatment of Acute Intoxication
• Mostly supportive
• Pharmacological therapy warranted if patient
is psychotic and agitated
• Lorazepam 2-4 mg IM every 30 minutes-6
hours PRN
• Haloperidol 2-5 mg IM every 30 minutes-6
hours PRN
• IV lorazepam or diazepam if seizures develop
into status epilepticus31Doering PL, Li R. In: DiPiro JT Pharmacotherapy: A Pathophysiologic Approach, 9e. 2014.
Maintenance Treatment
• Cognitive behavioral therapy
• No FDA approved medications to treat cocaine or
methamphetamine addiction
• Cocaine potential options
– Disulfiram
• Found to be less effective in women
– Bromocriptine
– Propranolol?
– Research on medications that disrupt balance between GABA
and glutamate
32Doering PL, Li R. In: DiPiro JT Pharmacotherapy: A Pathophysiologic Approach, 9e. 2014.
Devito EE, et al. Drug Alcohol Depend.Saladin ME, et al. Psychopharmacology (Berl). 2013.
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Opiates
• Examples: opium, heroin, morphine, codeine,
hydromorphone (Dilaudid), oxycodone
(Percodan, OxyContin), meperidine (Demerol),
hydrocodone (Vicodin), fentanyl (Sublimaze)
• Used medically for analgesic effect
• Enough Rx opiates were prescribed in 2010 to
medicate every American around the clock for
one month
• Which state is the biggest offender?33Doering PL, Li R. In: DiPiro JT Pharmacotherapy: A Pathophysiologic Approach, 9e. 2014.
Opiates
34
Analgesic Effects
Abuse
Opiate Receptors
• Mu
– Analgesia, euphoria, respiratory depression
• Delta
– Cooperates with mu to produce similar effects
• Kappa
– Analgesia, dysphoria (when used alone)
• Act on specific receptor molecules for the
endorphin/enkephalin class of NTs in the brain
35Kuhn C, Swartzwelder S, and Wilson W. Buzzed. New York, NY: W.W. Norton & Company, Inc.; 2014.
Opiate Effects
• Pleasant drowsiness
• Analgesia
• Pinpoint pupils
• Constipation
• Skin flushing
• Nausea/vomiting
• Euphoria
• Impotence
• Decreased respiratory rate
36Kuhn C, Swartzwelder S, and Wilson W. Buzzed. New York, NY: W.W. Norton & Company, Inc.; 2014.
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Treatment of Acute Intoxication
• Naloxone (Narcan, Evzio auto-injector)
– Opiate antagonist- immediately reverse effects of
opiates
– Dose: 0.4-2mg IV (preferred), IM or SQ may repeat
every 2-3 minutes
– Nasal spray: 4mg every 2-3 minutes as needed
until medical assistance available
37
Opiate Withdrawal Symptoms
• Onset and peak of symptoms depend on half-life of drug
– Heroin: peaks in 36-72 hours, lasts 7-10 days
– Methadone: peaks in 72 hours, lasts >2 weeks
• Pupillary dilation
• Lacrimation
• Rhinorrhea
• Goosebumps
• Yawning
• Nausea/vomiting
• Diarrhea
• Sneezing
• Anorexia38Doering PL, Li R. In: DiPiro JT Pharmacotherapy: A Pathophysiologic Approach, 9e. 2014.
Maintenance Treatment
• Narcotics Anonymous
• Methadone
– Long-acting opiate
– Initial dose: 20-30mg daily
– Maintenance: Titrate to dose which prevents withdrawal symptoms
for 24 hours (usual 80-120mg/day)
– Black box warnings: QTc prolongation, respiratory depression, when
used for treatment of opioid addiction, may only be dispensed by
certified opioid treatment program, neonatal withdrawal syndrome,
risk for addiction/misuse/abuse, overdose potential
• Naltrexone long acting injection (Vivitrol)
– Dose: 380mg IM every 4 weeks
– Must be opiate free for 7-14 days
– Will often need to pass Naloxone IV challenge test39Doering PL, Li R. In: DiPiro JT Pharmacotherapy: A Pathophysiologic Approach, 9e. 2014.
Maintenance Treatment
• Buprenorphine (Subutex)
– Opioid partial agonist
– Induction dose: 8 mg SL (day 1) 12-16mg (day 2-4)
– Maintenance dose: 12-16mg daily
– Black box warnings: Respiratory depression, neonatal opioid
withdrawal syndrome, abuse/misuse/addiction
• Buprenorphine and Naloxone (Bunavail, Suboxone, Zubsolv)
– Induction only for short-acting opioid addiction
– Preferred for unsupervised therapy
– Sublingual and buccal film, sublingual tablet
• Clonidine
– Alpha 2 agonist
– 0.1-0.3 mg every hour until symptoms resolve
40Doering PL, Li R. In: DiPiro JT Pharmacotherapy: A Pathophysiologic Approach, 9e. 2014.
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Benzodiazepines
• “Magic bullet” for anxiety
• MOA: Bind to benzodiazepine receptors on
postsynaptic GABA neuron � increases
neuronal membrane permeability to chloride
ions � enhances inhibitory effect of GABA
• Multiple drugs in this class
41Doering PL, Li R. In: DiPiro JT Pharmacotherapy: A Pathophysiologic Approach, 9e. 2014.
Comparison of Benzodiazepines
Generic BrandOral peak
(hours)
Half-life
(hours) parent
Metabolite
Activity
Alprazolam Xanax 1-2 6-27 Inactive
Chloridiazepoxide Librium 5-25 mg 5-30 Active
Clonazepam Klonopin 1-2 18-50 Inactive
Diazepam Valium 0.5-1 20-50 Active
Lorazepam Ativan 2-4 10-20 Inactive
Midazolam Versed 1-2 1.5-3 Active
Temazepam Restoril 1-2 3-19 Inactive
Flunitrazepam Rohypnol 1-2 16-35 Active
42Greller H, Gupta A. Benzodiazepine poisoning and withdrawal. In UpToDate. 2015.
Clinical Indications
• Anxiety
• Insomnia
• Agitation
• Seizures
• Premedication for anesthesia
43Greller H, Gupta A. Benzodiazepine poisoning and withdrawal. In UpToDate. 2015.
Clinical Effects
• Drowsiness
• Muscle incoordination
• Problems with learning
• Some cause amnesia
• Lightheadedness
• Vertigo
• Nightmares
• Hypotension
• NOT respiratory depression
44Kuhn C, Swartzwelder S, and Wilson W. Buzzed. New York, NY: W.W. Norton & Company, Inc.; 2014.
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Treatment of Acute Intoxication
• Flumazenzil (Romazicon)
– Benzodiazepine antagonist
– Dose:
• 0.2 mg IV over 30 seconds
• if desired response not obtained 30 seconds after dose,
can give 0.3 mg over 30 seconds
• may repeat 0.5 mg over 30 seconds at 1-minute
intervals
• maximum dose: 3 mg (5 mg RARELY)
– Black box warning: Seizures
45Flumazenil. Lexicomp. 2016
Withdrawal Symptoms
• Anxiety
• Insomnia
• Irritability
• Sensitivity to light and sound
• Muscle spasms
46Doering PL, Li R. In: DiPiro JT Pharmacotherapy: A Pathophysiologic Approach, 9e. 2014.
Detoxification Therapy
• Similar to alcohol but differs by length of
treatment (dependent upon half-life of
abused benzodiazepine)
• Short to intermediate acting
– Lorazepam 2mg TID-QID; taper over 5-7 days
• Long-acting
– Lorazepam 2 mg TID-QID; taper over an additional
5-7 days
47Doering PL, Li R. In: DiPiro JT Pharmacotherapy: A Pathophysiologic Approach, 9e. 2014.
Consideration For All Substances of
Abuse
• Addicts may be self-medicating for underlying
psychiatric disorder
• Consider psychiatric consult for chronic
substance abuse
• Treating underlying illness will increase
likelihood for abstinence
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Maternal Addiction Treatment
• Pharmacist driven program implemented at Memorial
Regional Hospital
• Treat pregnant women addicted to any illicit substances
• Psychological and physiological treatment approach
• Detoxification and/or maintenance regimens ordered
– Subutex
– Clonidine
– Benzodiazepine taper
• Decreases risks to unborn baby and mom
• Mothers are followed by social work and pharmacy as long as
they allow
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Pharmacists’ Role
• Utilize prescription monitoring programs
where available
• Communicate with health care team if drug
abuse concern arises
• Counsel patients on risk of abuse and offer
support for addiction
• Make patient health, safety and well-being
your number one priority
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References
• American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders:: DSM-5. 2013.
• Volkow ND. Drugs, brains, and behavior: The science of addiction. National Institute of Drug Abuse. Pub number 14-5606. 2014.
• National Drug Early Warning System (NDEWS) Sentinel Community Site Profile 2015: Southeastern Florida (Miami Area). 20 Aug 2015.
Accessed from:
http://ndews.umd.edu/sites/ndews.umd.edu/files/SCS%20Southeastern%20Florida%20(Miami%20Area)%202015%20Final%20Web.pd
f
• Kuhn C, Swartzwelder S, and Wilson W. Buzzed. New York, NY: W.W. Norton & Company, Inc.; 2014.
• Vonghia L, Leggio L, Ferrulli A, et al. Acute alcohol intoxication. Eur J Intern Med 2008; 19:561.
• Doering PL, Li R. Chapter 49. Substance-Related Disorders II: Alcohol, Nicotine, and Caffeine. In: DiPiro JT, Talbert RL, Yee GC, Matzke
GR, Wells BG, Posey L.eds. Pharmacotherapy: A Pathophysiologic Approach, 9e. New York, NY: McGraw-Hill;
2014.http://accesspharmacy.mhmedical.com.ezproxylocal.library.nova.edu/content.aspx?bookid=689&Sectionid=45310500.
• Doering PL, Li R. Chapter 48. Substance-Related Disorders I: Overview and Depressants, Stimulants, and Hallucinogens. In: DiPiro JT,
Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 9e. New York, NY: McGraw-
Hill; 2014.http://accesspharmacy.mhmedical.com.ezproxylocal.library.nova.edu/content.aspx?bookid=689&Sectionid=45310499.
• Devito EE, Babuscio TA, Nich C, BallSAM Carroll KM. Gender differences in clinical outcomes for cocaine dependces: randomized clinical
trials for behavioral therapy and disulifram. Drug Alcohol Depend. 2014.0:156-67.
• Saladin ME, Gray KM, McRae-Clark AL, et al. A double blind, placebo-controlled study of the effects of post-retrieval propranolol on
reconsolidation of memory for craving and cue reactivty in cocaine dependent humans. Psychopharmacology (Berl). 2013;226(4): 721-
737.
• Greller H, Gupta A. Benzodiazepine poisoning and withdrawal. In UpToDate. 2015.
• Sullivan, J.T.; Sykora, K.; Schneiderman, J.; Naranjo, C.A.; and Sellers, E.M. Assessment of alcohol withdrawal: The revised Clinical
Institute Withdrawal Assessment for Alcohol scale (CIWA-Ar). British Journal of Addiction 84:1353-1357, 1989.
• Dent LA, Harris KJ, Noonan CW. Randomized trial assessing the effectiveness of a pharmacist-delivered program for smoking cessation.
Ann of Pharmacotherapy. 2009;43:194-201.
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