objectives for pharmacists · doering pl, li r. in: dipiro jt. pharmacotherapy: a pathophysiologic...

3/9/2016

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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.

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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

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Important Terms

Substance induced disorder

VS.

Substance use disorder

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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


Substance Use Disorders

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Cognitive Symptoms Behavioral Symptoms

Physiological Symptoms

Substance Use Disorder Diagnosis

• Impaired Control

• Social Impairment

• Risky Use

• Pharmacological Criteria


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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


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


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


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


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Drug Addiction and The Brain

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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

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Drugs, brains, and behavior: The science of addiction. National Institute of Drug Abuse. 2014.

Drug Patterns in Southeast Florida

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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


Alcohol Use Disorder Risk Factors

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• 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)


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


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

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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.”

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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


• 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

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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


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• 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

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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.


• 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.


• 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


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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


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


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• 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


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


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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