Substance

Abuse Disorders:
Alcohol,Tobacco, Opiates

Gretchen L. Johnson, Pharm.D., BCPS

Substance Abuse Pharm:
Alcohol
 Acute Alcohol Withdrawal
• BZDs are first-line due to cross-tolerance with alcohol
• Symptom triggered BZD treatment is the standard of care to
minimize sx and avoid progression to more severe stages of
withdrawal (seizures, delirium)
– Results in shorter treatment duration and less risk of
oversedation
• All BZDs equally efficacious, but Lorazepam (Ativan) is preferred
due to multiple routes of administration (PO, SL,IV, IM) with
predictable results
– Lorazepam 2mg PO/IM/IV q 1 hour PRN withdrawal sx.
– Sx. assessed via a validated rating scale- Clinical Institute
Withdrawal Alcohol-Revised
• Anticonvulsants are not required to treat alcohol withdrawal sz.
unless progresses to status epilepticus
• Supportive care with IV fluids, thiamine, MVI, electrolytes
– Watch for low K, Mg, PO4
 Chronic Alcohol Abuse
• Pharmacologic Management of Alcohol
Dependence
– Disulfiram (Antabuse)- Deterrent
– Naltrexone (ReVia)- Anticraving
– Naltrexone IM depot (Vivitrol)- Anticraving
– Acamprosate (Campral)- Anticraving
 Disulfiram (Antabuse)
• Deters a pt. from drinking by producing a negative reaction when
alcohol is consumed

• MOA: Inhibits aldehyde dehydrogenase in alcohol metabolism

which results in an accumulation of acetaldehyde. Acetaldehyde
causes disulfiram reaction
– N/V, flushing, throbbing HA, palpitations, CP, weakness,
tachycardia, blurred vision, confusion, hypotension
– Can occur up to 7-14 days after the last dose
– The intensity and duration of symptoms are related to the dose,
the amount of ETOH consumed and individual sensitivity
– Can occur with as little as “ml” of ETOH and last 30 min - 2 hrs.

• Fallen out of favor

– Data is mixed as to effectiveness
– Poorly tolerated
 Disulfiram (Antabuse)
• Contraindications:
– CAD, severe cardiac disease
– hepatic disease, cirrhosis
– seizure disorders
– schizophrenia
– Hypersensitivity to rubber (thiuram) derivatives
– concomitant use of ETOH or ETOH-containing products
– Metronidazole- causes acute psychosis and confusion
• Side Effects (Usually transient/dose-related)
– GI upset, sedation, rash, garlicky or metallic taste, flushing
– Hepatotoxic- monitor LFTs
• Drug Interactions: Inhibitor of CYP3A4
– May increase and prolong effects of :warfarin, phenytoin, isoniazid,
rifampin. Metronidazole, theophylline
• Pt education:
– Pt must be abstinent before starting- at least 12 hours since last
drink
– OTC meds alcohol content, including topicals
– Medical alert identification
 Naltrexone (ReVia)
• MOA: Opiate antagonist that decreases the reinforcing effects
of alcohol
– Decreases cravings and “buzz”
• Efficacy
– More effective than acamprosate in reducing risk of heavy drinking in
nonabstinent pts.
• Pt. must be opiate-free for 7-10 days
– Verify with urine drug screen
• Contraindications: hepatitis/liver failure; lactation; current
opioid use
• Side Effects : nausea (10%), vomiting, cramps, headache
(7%),dizziness, fatigue, constipation, dose-related reversible
hepatotoxicity
• Hepatotoxic- monitor LFTs
• Pregnancy Category C
• Patient Education:
– Medical alert identification
– DC 24-48 hr prior to procedures where opioids are needed
 Naltrexone IM (Vivitrol)
• Once monthly IM naltrexone formulation
• Increases compliance/adherence
• Watch for injection site reactions
– Cellulitis, hematoma, abscess
 Acamprosate (Campral)
• MOA: glutamate modulator at the NMDA receptor
resulting in dec. craving
• Efficacy:
– More effective than naltrexone in maintaining abstinence
– Combination of acamprosate + naltrexone appears to be
more efficacious than acamprosate alone
• ADRs: >10% = diarrhea, flatulence, syncope, dizziness,
edema, insomnia, anxiety, headache, nausea
• Precautions:
– Moderate renal impairment
• Dec. dose in renal impariment; Not rec. if Clcr < 30ml/min
– Depression/suicidality
– Pregnancy- Category C
Other Off-label Anticraving Agents
• Topiramate (Topamax)
• Baclofen (Lioresal)
• Varenicline (Chantix)
 Substance Abuse Pharm:
Tobacco

Slides adapted and used with permission from Erin Adams PharmD .
 What ever happened to Joe Camel?

1991
 NONPHARMACOLOGIC METHODS
• Cold turkey: Just do
it!
• Unassisted tapering
(fading)
– Reduced frequency of use
– Lower nicotine cigarettes
– Special filters or holders
• Assisted tapering
n Aversion therapy
n Acupuncture
therapy
n Hypnotherapy
n Massage therapy
n Apps
 PHARMACOLOGIC METHODS:
FIRST-LINE THERAPIES

Three general classes of FDA-

approved drugs for smoking cessation:
§ Nicotine replacement therapy (NRT)
§ Nicotine gum, patch, lozenge, nasal spray (Rx),
inhaler (Rx)
§ Psychotropics
§ Sustained-release bupropion (Zyban) (Rx)
§ Partial nicotinic receptor agonist
§ Varenicline (Chantix) (Rx)
 NRT: RATIONALE for USE

nReduces physical withdrawal from

nicotine
nAllows patient to focus on behavioral
and psychological aspects of tobacco
cessation

NRT APPROXIMATELY DOUBLES QUIT RATES.

 NRT: PRECAUTIONS

nPatients with underlying cardiovascular

disease
– Recent myocardial infarction (within past 2 weeks)
– Serious arrhythmias
– Serious or worsening angina
 NICOTINE GUM
Nicorette (GlaxoSmithKline); generics

• Sugar-free chewing gum base

• Contains buffering agents to enhance buccal
absorption of nicotine
• Available: 2 mg, 4 mg; regular, FreshMint,
Fruit Chill, Orange & Cinnamon Surge
 NICOTINE GUM: DOSING
Dosage based on current smoking patterns:

NOTE: dosing difference

 NICOTINE GUM:
CHEWING TECHNIQUE SUMMARY
NICOTINE GUM: ADDITIONAL PATIENT
EDUCATION

nTo improve chances of quitting, use at

least nine pieces of gum daily
nThe effectiveness of nicotine gum may
be reduced by some foods and
beverages:
• Coffee • Juices
• Wine • Soft drinks

Do NOT eat or drink for 15 minutes BEFORE or while

using nicotine gum.
 NICOTINE GUM:
ADD’L PATIENT EDUCATION (cont’d)
nChewing gum too nSide effects of
rapidly can cause nicotine gum include
excessive release of
– Mouth soreness
nicotine, resulting in
– Hiccups
– Lightheadedness
– Dyspepsia
– Nausea/vomiting
– Jaw muscle ache
– Irritation of throat and
mouth nCaution:
– Hiccups nDental work/aids
– Indigestion nTemporomandibular
Joint (TMJ)
 NICOTINE LOZENGE
Commit (GlaxoSmithKline); generics

n Nicotine polacrilex
formulation
– Delivers ~25% more nicotine than
equivalent gum dose
n Sugar-free, mint or cherry
flavor or MINI sized
n Contains buffering agents
to enhance buccal
absorption of nicotine
n Available: 2 mg, 4 mg
– Dissolves
 NICOTINE LOZENGE: DOSING
Dosage is based on the “time to first cigarette”
(TTFC) as an indicator of nicotine addiction
 NICOTINE LOZENGE:
DOSING (CONT’D)
Recommended Usage Schedule for
Commit Lozenge
Weeks 1–6 Weeks 7–9 Weeks 10–12
1 lozenge 1 lozenge 1 lozenge
q 1–2 h q 2–4 h q 4–8 h
DO NOT USE MORE THAN 24/day
Rotate lozenge
NICOTINE LOZENGE: ADDITIONAL PATIENT
EDUCATION

• The effectiveness of the nicotine lozenge

may be reduced by some foods and
beverages:
• Coffee • Juices
•Wine • Soft drinks

Do NOT eat or drink for 15 minutes BEFORE or while

using the nicotine lozenge.
 NICOTINE LOZENGE:
ADD’L PATIENT EDUCATION (cont’d)

nSide effects of the nicotine lozenge

include
– Nausea
– Hiccups
– Cough
– Heartburn
– Headache
– Flatulence
– Insomnia
 TRANSDERMAL NICOTINE PATCH
Nicoderm CQ (GlaxoSmithKline); generic

n Avoids hepatic first-pass metabolism

n Plasma nicotine levels are lower and
fluctuate less than with smoking
 TRANSDERMAL NICOTINE PATCH:
PREPARATION COMPARISON

Product Nicoderm CQ/Generic

Nicotine
24 hours
delivery
Availability OTC
Strengths 7-mg patch
14-mg patch
21-mg patch
 TRANSDERMAL NICOTINE PATCH: DOSING

Product Light Smoker Heavy Smoker

Nicoderm CQ £10 cigarettes/day >10 cigarettes/day
Step 2 (14 mg x 6 Step 1 (21 mg x 6
weeks) weeks)
Step 3 (7 mg x 2 Step 2 (14 mg x 2
weeks) weeks)
Step 3 (7 mg x 2 weeks)
Generic £10 cigarettes/day >10 cigarettes/day
(formerly Step 2 (14 mg x 6 Step 1 (21 mg x 4
Habitrol) weeks) weeks)
Step 3 (7 mg x 2 Step 2 (14 mg x 2
weeks) weeks)
Step 3 (7 mg x 2 weeks)
 TRANSDERMAL NICOTINE PATCH:
DIRECTIONS for USE
n Apply adhesive side
– Clean, dry, hairless
and not irritated
– Location
n Rotate
– Press firmly x10 sec
n Wash hands
n Other info:
– OK to shower with patch on
– Do not cut patches
– No more than 24 hours/patch
– Adhesive remaining on skin
– Disposal of used patch
 TRANSDERMAL NICOTINE PATCH:
DIRECTIONS for USE (cont’d)
• Side effects to expect in first hour:
– Mild itching
– Burning
– Tingling
• Additional possible side effects:
– Headache
– Vivid dreams or sleep disturbances
• Avoid use in dermatological issues
 NICOTINE NASAL SPRAY
Nicotrol NS (Pfizer)
n Aqueous solution
of nicotine in a
10-ml spray
bottle
n Each metered
dose actuation
delivers 0.5 mg
nicotine
n ~100 doses/bottle
 NICOTINE NASAL SPRAY:
DOSING & ADMINISTRATION

• Dose: 1 spray in each nostril

• Start with 1–2 doses per hour
– Maximum : 5 doses/hr or 40 mg daily
• For best results, patients should use at
least 8 doses daily for the first 6–8 weeks
• Termination:
– Gradual tapering over an additional 4–6
weeks
 NICOTINE NASAL SPRAY:
DIRECTIONS FOR USE

• Blow nose (if not clear)

• Prime
– If pump is not used for 24 hours, prime the
pump 1–2 times

• Do not sniff or inhale while spraying

– If nose runs

• Wait 5min
 NICOTINE NASAL SPRAY:
PATIENT EDUCATION

nWhat to expect (first week):

— Hot peppery feeling in back of throat or nose
— Sneezing
— Coughing
— Watery eyes
— Runny nose

nCaution
— If side effects do not decrease after a week, contact health care
provider
— Patients with chronic nasal disorders or severe reactive airway
disease should not use the spray
 NICOTINE INHALER
Nicotrol Inhaler (Pfizer)

¢Nicotine inhalation system

consists of
— Mouthpiece
— Cartridge with porous plug
containing 10 mg nicotine
¢Delivers 4 mg nicotine
vapor
¢May satisfy hand-to-
mouth ritual of smoking
 NICOTINE INHALER
Nicotrol Inhaler (Pfizer)

¢Nicotine inhalation system

consists of
— Mouthpiece
— Cartridge with porous plug
containing 10 mg nicotine
¢Delivers 4 mg nicotine
vapor
¢May satisfy hand-to-
mouth ritual of smoking
 NICOTINE INHALER: DOSING

n Start with 6 cartridges/day

n Maximum of 16 cartridges/day

n Use for minimum of 3 weeks, maximum of 12 weeks

n Gradual dosage reduction: if needed over additional 6–12

weeks
NICOTINE INHALER:
 NICOTINE INHALER:
DIRECTIONS FOR USE (CONT’D)
• Inhale into back of throat or puff in
short breaths
– Frequent puffing
• Depletion of plug
– Cartridge does not have to be used all at once
– Open cartridge retains potency for 24 hours
 NICOTINE INHALER:
ADDITIONAL PATIENT EDUCATION
• Side Effects
– Mild irritation
– Unpleasant taste or cough when first using
the inhaler
• Other (less common) side effects include
– Rhinitis
– Dyspepsia
– Hiccups
– Headache
• Precautions
– Underlying bronchospastic conditions
– Storage
 NICOTINE INHALER:
ADD’L PATIENT EDUCATION (cont’d)

• Effectiveness of the nicotine inhaler

may be reduced by some foods and
beverages
• Coffee • Juices
• Wine • Soft drinks

Do NOT eat or drink for 15 minutes BEFORE or while

using the nicotine inhaler.
 BUPROPION
Zyban (GlaxoSmithKline); Buproban ER

nNonnicotine
cessation aid
nSustained-release
antidepressant
nWellbutrin?
nOral formulation
 BUPROPION

• MOA: Atypical antidepressant

thought to affect levels of various
brain neurotransmitters
– Dopamine
– Norepinephrine
• Clinical effects
– ¯ craving for cigarettes
– ¯ symptoms of nicotine withdrawal
 BUPROPION:
CONTRAINDICATIONS & WARNINGS
• Contraindications: • Precautions:
– Patients with a seizure
disorder
– Patients taking
• Wellbutrin, Wellbutrin
SR, Wellbutrin XL
• MAO inhibitors in
preceding 14 days
– Anorexia or bulimia
nervosa
– Abrupt d/c of alcohol or
sedatives
– History of seizure/
meds that lower
seizure threshold
(antipsychotics,
antidep, theophylline,
systemic steroids
– Bipolar patients
– History of cranial
trauma
– severe hepatic cirrhosis
 BUPROPION SR: DOSING

Patients should begin therapy 1 to 2 weeks PRIOR

to their quit date to ensure that therapeutic plasma levels of the
drug are achieved.

Initial treatment
n 150 mg po q AM x 3 days

Then…
n 150 mg po bid
n Duration, 7–12 weeks
 BUPROPION:
ADVERSE EFFECTS
Common side effects:
– Insomnia (avoid bedtime dosing)
– Dry mouth
WARNING: neuropsychiatric symptoms

Less common but reported effects:

– Tremor
– Skin rash
– Suicidal Ideations
 VARENICLINE
Chantix (Pfizer)

nNonnicotine
cessation aid
nPartial nicotinic
receptor agonist
nOral
formulation
 VARENICLINE
• MOA: Binds with high affinity and selectivity at a4b2
neuronal nicotinic acetylcholine receptors

– Competitively inhibits binding of nicotine

• Clinical effects

– ¯ symptoms of nicotine withdrawal

– Blocks dopaminergic stimulation responsible for
reinforcement & reward associated with smoking
• T1/2 24 hours
 VARENICLINE: DOSING

Patients should begin therapy 1 week PRIOR to their

quit date. Can also begin therapy and taper cigarettes in first 12
weeks
Treatment Day Dose
0.5 mg
Day 1 to day 3
Initial qd
dose
titration 0.5 mg
Day 4 to day 7
bid
Day 8 to end of treatment* 1 mg bid

* Up to 12 weeks
 VARENICLINE:
ADVERSE EFFECTS
• Common: • Post-marketing
– Nausea – Dizziness/falls/loss
– Sleep disturbances of consciousness
(insomnia, abnormal – Cardiac rhythm
dreams) disturbances
– Constipation – Acute MI
– Flatulence – Severe skin
– Vomiting reactions
• Neuropsychiatric – Seizures
symptoms – Diabetes
– Spasms
• Cardiovascular effects
 PHARMACOLOGIC METHODS:
Second-line and Future Therapies

nClonidine (Catapres transdermal or

oral)
nNortriptyline (Pamelor oral)

nNicVAX Vaccine
 Pharmacotherapy Abstinence Rates

Evidence suggests that rates of smoking abstinence

may increase from
• approximately 10% in control groups (placebo or
no pharmacotherapy) to 17% in persons using
any form of NRT
• approximately 11% in control groups (placebo or
no bupropion SR) to 19% in those using
bupropion SR
• approximately 12% in control groups (placebo) to
28% in those using varenicline
 COMBINATION PHARMACOTHERAPY

nCombination NRT- moderately better than one

NRT product alone
Long-acting formulation (patch)
PLUS
Short-acting formulation (gum, lozenge, inhaler, nasal spray)

nBupropion + NRT- may be better than

Bupropion alone
n Monitor BP

nVarenicline + NRT
nVarenicline + Bupropion
 USE in PREGNANCY

nNRT
nCategory D
nBupropion and
varenicline
nCategory C
nAttempt nondrug
treatment first
Substance Abuse Pharm:
Opiates
 Methadone Prescribing Laws
• In the treatment of detoxification or
maintenance, methadone can only be used by
Opiate Treatment Programs (OTP) that are
accredited by Center for Substance Abuse
Treatment.
• Above is waived if patients are admitted for a life
threatening condition that requires methadone
to stabilize their opioid dependence while in the
hospital
– May prescribe to opioid dependent pt up to 72 hr as
bridge to treatment entry
 Office-based opioid treatment
• Evolved after passage of the Drug Addiction Treatment
Act of 2000 (DATA 2000)- Updated with Comprehensive
Addiction and Recovery Act of 2016 (CARA 2016)
• CARA 2016 expanded prescribing for buprenorphine to
PAs and NPs
– Can apply to become waivered to prescribe buprenorphine
for opiate addiction
– Obtain 24 hr training course
– Can treat up to 30 patients in first year with option to
increase to up to 100 patients after 1 year if certain
conditions met
– Defers to state law as to if PA/NP must work with a
physician in a supervisory or collaborative manner
 Buprenorphine Pharmacology
• A mu receptor partial-agonist and an antagonist at kappa
receptor
• High affinity for the mu receptor but low efficacy; thus
producing a dose-related response with a ceiling effect
• High affinity for mu may displace other opioids from the
receptor and cause withdrawal sx
– Start in office AFTER pt shows signs of withdrawal
• Partial agonism:
– Does not activate the mu receptor fully, therefore has a ceiling
effect
– Larger doses do NOT lead to greater agonist effect
– 16mg buprenorphine = 60mg methadone
– Methadone is a full agonist and has no ceiling effect
• Greater margin of safety, less respiratory depression
 Buprenorphine
• Subutex (buprenorphine): CIII
– Use at beginning of tx to dec. risk of withdrawal
– Available as SL tabs
• Suboxone(buprenorpine/naloxone): CIII
– Use in maintenance management
– Naloxone: added to guard against IV abuse of
buprenorphine
– No effect of naloxone orally or SL - poorly absorbed
– Available as SL tabs and SL film
• Dosed once daily
– Do not chew or swallow- dec. absorption
– Dosage adjustment needed in hepatic impairment
 Buprenorphine
• Buprenorphine implant (Probuphine) Schedule III
– New dosage form- 4 subdural rods that are implanted
in the inside of the upper arm every 6 months
• Treatment duration is 12 months
– May address problems with diversion and compliance
– Only for stable patients on <8mg SL buprenorphine
daily
– Prescribers must complete a training course in order
to prescribe and implant
– Expensive
 Buprenorphine
• Drug interactions:
– Benzodiazepines: potentially fatal interaction- resp
depression
• Avoid use
– Increase effects of buprenorphine (3A4 substrate)
• Antiretrovirals, BZD, fluvoxamine, ketoconzaole, ETOH
– Decrease effects of buprenorphine (3A4 substrate)
• CBZ, phenobarbital, rifampin, phenytoin
• Patient education
– Caution with driving care or operating heavy machinery
– Avoid concomitant alcohol
– Store in a secure area out of reach of children and pets
and avoid theft
 Buprenorphine Adverse Effects
• Constipation
• Headache
• N/V
• Sedation
• Hepatotoxicity- get baseline and periodic LFTs
• Precipitate withdrawal

• Pregnancy category C
• Avoid during breastfeeding- passes in to breast
milk
 Induction, Stabilization, Maintenance
• Generally start with Subutex and give a small supply to
pt (usually 2 days)
– If > 1 prescriber with Rx, assume diversion
• Suboxone is preferred for long-term tx
• Determine min amount of buprenorphine required to
prevent withdrawal sx, cravings
• Stabilization lasts 2-3 months at lowest dose
• Length of treatment (maintenance) = at least 6 months
but can last up to 2 yrs.
– Length depends on past instability
– Previous response to tx
 Reversal Agents
• Naloxone (Narcan)
– MOA: Opiate receptor antagonist
– Used to reverse opiate effects/overdose
– CARA 2016 expanded use to law enforcement and other first
responders
– Some states are now allowing prescribing to third parties to
administer in the case of overdose
– Public health emergency declared in VA- Anyone can get naloxone at a
pharmacy for either themselves or someone else of concern through a
standing order from the State Health Commisioner
– Consider for patients at high risk- on large doses of opiates, opiate plus
BZDs, prior h/o overdose
• Flumazenil (Romazicon)
– MOA: BZD receptor antagonist
– Used to reverse BZD effects/overdose