Download Pain Management and Prevention of Drug Misuse/Abuse

Pain Management and Prevention of
Drug Misuse/Abuse
Andrea Winterswyk, PharmD
Joe Berendse, PharmD
PGY-1 Pharmacy Residents
Boise VA Medical Center
2016 ISHP Spring Meeting
March 6th, 2016
1
Disclosures
• We do not have any vested interest in or
affiliation with any corporate organization
offering financial support or grant monies for
this continuing education activity, nor any
affiliation with an organization whose
philosophy could potentially bias this
presentation.
2
Learning Objectives
1. Describe basic pharmacology and indications for
different classes of analgesics.
2. Identify commonly abused prescription drugs
and in which populations they are most often
misused.
3. Recognize the different routes in which a
prescription drug may be abused and the clinical
presentation of an opioid abuser.
4. Explain key points regarding opioid reversal
agents and opioid dependence treatment
medications.
3
Types of Pain
Pain
Acute
Chronic
Post-surgery, headache, trauma
Nociceptive
Arthritis, soft tissue
injuries (“strains and sprains”)
Nerve
Diabetes, shingles, nerve
injury
Mixed
Lower back pain, cancer,
fibromyalgia
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Adapted from: http://www.denalihealthcaremi.com/tag/classification-of-pain/
Themes in Treating Pain
• Not all pain medications are well-suited to
treat all pain conditions
– e.g. NSAIDs less effective in treating nerve pain
• Severity of pain influences choice of agent
– World Health Organization (WHO) analgesic ladder
– Administer stronger medications in a stepwise
approach
http://www.uptodate.com/contents/overview-of-the-treatment-of-chronic5
pain?source=search_result&search=tramadol&selectedTitle=5%7E127#H45605245
WHO Analgesic Ladder
http://www.uptodate.com/contents/image?imageKey=ONC%2F63298&topicKey=ANEST%2F2785
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&rank=5%7E127&source=see_link&search=tramadol&utdPopup=true
PAIN MEDICATIONS: AN OVERVIEW
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Pain Medication Options
•
•
•
•
•
•
•
Non-opioid agents
Tramadol
Opioids
Antidepressants
Antiepileptic drugs
Muscle relaxants
Topical analgesics
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Non-Opioid Agents
COX
• How they work: inhibit an
enzyme (COX) that produces
pain-signaling substance
Precursor
Substance
Pain-signaling
Substance
• Examples: APAP, ibuprofen, naproxen, celecoxib
(Celebrex)
• Type(s) of pain: first-line for soft tissue injury (strains
and sprains), osteoarthritis (OA), chronic low back
pain
http://www.uptodate.com/contents/overview-of-the-treatment-of-chronic9
pain?source=search_result&search=tramadol&selectedTitle=5%7E127#H45605245
Tramadol
• How it works: blocks receptor (µ-2)
in brain responsible for pain
transmission
Ow!
Pain
Sub.
µ-2
– Also increases “feel-good” substances
• Type(s) of pain: second-line for nerve pain,
moderate-to-severe OA, chronic LBP
• Pearls: Not for use in children <17 years
http://www.uptodate.com/contents/overview-of-the-treatment-of-chronic10
pain?source=search_result&search=tramadol&selectedTitle=5%7E127#H45605245
Opioids
• How they work: blocks opioid receptors
(µ, δ, κ) responsible for pain transmission
and other bodily functions
Pain
Sub.
µ
• Examples: hydrocodone, oxycodone, fentanyl,
morphine, hydromorphone, codeine
• Type(s) of pain: chronic cancer pain, severe acute pain,
second-line for nerve pain
– Controversial: use in other chronic pain (OA, lower back pain)
http://www.uptodate.com/contents/overview-of-the-treatment-of-chronic11
pain?source=search_result&search=tramadol&selectedTitle=5%7E127#H45605245
Risks of Long-term Opioid Use
• Notable side effects
– Constipation, ↓ breathing rate, drowsiness
• Dependence & addiction
• Overdose & death
http://www.uptodate.com/contents/overview-of-the-treatment-of-chronic12
pain?source=search_result&search=tramadol&selectedTitle=5%7E127#H45605245
• How they work: Uncertain, but increase
“feel-good” substances that play a role
in pain
Serotonin,
Norepinephrine
Antidepressants
• Examples: duloxetine (Cymbalta), venlafaxine
(Effexor), amitriptyline (Elavil), nortriptyline
(Pamelor)
• Type(s) of pain: first-line for nerve pain, fibromyalgia
– Duloxetine: FDA-approved for chronic OA/LBP
http://www.uptodate.com/contents/overview-of-the-treatment-of-chronic13
pain?source=search_result&search=tramadol&selectedTitle=5%7E127#H45605245
Antiepileptics
• How they work: prevent release of
pain-signaling substances from nerves
Pain-signaling
Substance
• Examples: gabapentin, pregabalin (Lyrica),
carbamazepine
• Type(s) of pain: first-line for nerve pain
http://www.uptodate.com/contents/overview-of-the-treatment-of-chronic14
pain?source=search_result&search=tramadol&selectedTitle=5%7E127#H45605245
Muscle Relaxants
• How they work: relax muscle tension and pain
• Examples: cyclobenzaprine, baclofen (Lioresal),
carisoprodol (Soma), methocarbamol (Robaxin)
• Type(s) of pain: pain from muscle spasms
– variety of pain conditions feature muscle spasms
http://www.uptodate.com/contents/overview-of-the-treatment-of-chronic15
pain?source=search_result&search=tramadol&selectedTitle=5%7E127#H45605245
Topical Analgesics
• How they work: deliver pain relief
to the site of pain, minimizing side
effects
• Examples: lidocaine, capsaicin, diclofenac (Voltaren
Gel)
• Type(s) of pain: localized pain (including localized
nerve pain)
http://www.uptodate.com/contents/overview-of-the-treatment-of-chronic16
pain?source=search_result&search=tramadol&selectedTitle=5%7E127#H45605245
TRENDS AND STATISTICS
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Commonly Abused Prescription Drugs
• Opioids (for pain)
• Central nervous system depressants (for
anxiety or sleep disorders)
• Stimulants (for ADHD and narcolepsy)
http://www.drugabuse.gov/drugsabuse/prescription-drugs-coldmedicines
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General Trends
• Prescription and OTC drugs: third most
commonly abused substances
– After marijuana and alcohol
• In 2013, nearly 2 million Americans either
abused or were dependent on opioids
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http://www.cdc.gov/drugoverdose/epidemic/providers.html
Prescription Drug Abuse Trends
• Young adults (age 18-25) are the most common
abusers of prescription
drugs
• Motivations for use:
–
–
–
–
–
Concentrate/study better
Lose weight
Experiment/“get high”
Deal with problems
Relax/decrease anxiety
http://www.drugabuse.gov/related-topics/trendsstatistics/infographics/abuse-prescription-rx-drugs-affects20
young-adults-most
Risk Factors for Opioid Abuse
http://www.cdc.gov/drugoverdose/epid
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emic/riskfactors.html
Prescription Rates
• In 2012, health care
providers wrote 259
million prescriptions
for opioids
http://www.cdc.gov/drugoverdose/epidemic/providers.html
http://www.cdc.gov/drugoverdose/data/prescribing.html
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Opioid-Related Deaths
• 16,235 drug
poisoning deaths
involving opioids
in 2013
• In 2013, there
were 5.1 deaths
per 100,000
involving opioids
• Each day, 44
people in the U.S.
die from overdose
of opioids
http://www.cdc.gov/nchs/data/databriefs/db190.pdf
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http://www.cdc.gov/drugoverdose/epidemic/index.html
Addressing Opioid Crisis
• Safe prescribing practices
– www.responsibleopioidprescribing.org
• Prescription drug monitoring programs
• U.S. Dept. of Health & Human Services launched
Prescription Drug Overdose Prevention for States
– FY2016 funding: $133 million
– Three priority areas:
1. Providing training and educational resources
2. Increasing use of naloxone
3. Expanding use of Medication-Assisted Treatment (MAT)
http://www.hhs.gov/about/news/2015/03/26/hhstakes-strong-steps-to-address-opioid-drug-related24
overdose-death-and-dependence.html
CLINICAL PRESENTATION OF
OPIOID ABUSE
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Opioid Abuse Clinical Presentation
• Diagnostic and Statistical Manual of Mental
Disorders, Fifth Edition (DSM-5)
– Opioid use disorder: problematic pattern of opioid
use leading to clinically significant impairment or
distress, as manifested by at least two of the
following, occurring within a 12-month period
• Dependence, withdrawal, intoxication,
addiction
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Opioid Abuse Clinical Presentation
• Dependence
– Mental status effects:
• Depression with any or all of its symptoms
– Physiological effects:
• Tolerance develops over time, effects may be difficult
to notice
• Small pupils (miosis), constipation  Only side effects
that mild or no tolerance develops
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Opioid Abuse Clinical Presentation
• Withdrawal
– Due to physical dependence
– Length of withdrawal varies with drug used
– Symptoms
• Mental status effects:
– Purposive behaviors, anxiety
• Physiologic effects:
– Autonomic signs (e.g., tachycardia, high blood pressure, fever,
piloerection [goose flesh]
– Mydriasis, and lacrimation
– CNS arousal (irritability)
– Yawning
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Opioid Abuse Clinical Presentation
• Intoxication
– Mental status effects:
• Euphoria, sedation, decreased anxiety
– Physiological effects:
•
•
•
•
•
•
Respiratory depression
Alteration in temperature regulation
Low blood pressure
Miosis
Needle marks or soft tissue infection
Increase sphincter tone
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Opioid Abuse Clinical Presentation
• Addiction:
– Psychological and behavioral syndrome
• Drug craving
• Compulsive use
• Strong tendency to relapse after withdrawal
• Addiction must be defined by the observation of maladaptive behaviors
– Adverse consequences due to drug use
– Loss of control over drug use
– Preoccupation with obtaining opioids
• Addiction does NOT describe patients who are merely physically
dependent
• Pseudoaddiction
– Undertreatment in patients with pain
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Opioid Abuse Causes
• Pharmacological Factors
• Social Factors
• Psychological Factors
• Genetic Factors
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Recognizing Opioid Abuse
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Routes of Opioid Abuse
• Ingestion
• Injection
• Inhalation (oral and nasal)
• Absorption
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DETERRENTS TO OPIOID ABUSE
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Sources of Abused Opioids
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Abuse Deterrent
Mechanisms
• OxyContin
– Original formulation approved Dec. 1995
– Product abused frequently (injected, snorted)
– Reformulated in 2010
• More difficult to crush, break, dissolve
• Forms viscous hydrogel and cannot be easily prepared
for injection
– No other generics approval allowed
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OxyContin OC
vs
OxyContin OP
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Other Abuse Deterrents
•
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Checking identification
Monitor for payment type
Verify days supply
Legal requirements
Prescription pads
DEA Schedule
Diagnosis of dependence
Counseling/education
Lab tests (urine, blood, others)
Pain Contracts
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OPIOID DEPENDENCE AND
TREATMENT
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Opiate Withdrawal
• Detoxification:
– Commonly used pharmacologic methods of
detoxification
• Methadone
• Buprenorphine
• Alpha-2 agonists (clonidine)
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Quick Receptor Pharmacology
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Opioid Classification
Pure
agonists
Antagonists
PURE
Mixed
agonists/
antagonists
Nonopioid
naloxone
FULL
morphine
oxycodone
fentanyl
tramadol
naltrexone
buprenorphine
PARTIAL
butorphanol
pentazocine
nalbuphine
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Opioid Maintenance
Methadone
• Methadone: long-acting synthetic
opioid agonist
• Can be dosed once daily
– Replaces the necessity for multiple
daily heroin doses
• Highly regulated Schedule II
medication
– Methadone clinics
• Estimated that established
methadone clinics can
accommodate only 15-20% of US
heroin addicts
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Opioid Maintenance
Buprenorphine
• Buprenorphine (Subutex):
– Partial opioid agonist and potent
antagonist
• Potent analgesic administered once
a day to block withdrawal symptoms
• Partial agonist
– Suppresses withdrawal and cravings
– “Ceiling effect"
• Wider margin of safety than methadone
– Schedule III medication
• X-DEA required!
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Opioid Maintenance
Buprenorphine/Naloxone
• Products:
– Suboxone, Zubsolv (4:1 ratio) – sublingual,
buccal
– Bunavail (6-7:1 ratio) – buccal
– Contains both buprenorphine and naloxone
• Maintenance detoxification treatment
(unsupervised)
– After induction with sublingual
buprenorphine (supervised)
• Naloxone added to guard against IV
abuse of buprenorphine
• Products not equivalent on a mg-per-mg
basis
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Naltrexone
• Inhibit opioid effects
– Revia, Depade, Vivatrol
• Used in combination with clonidine for
rapid detox
• Very effective long-acting opioid antagonist
– Clinical results are not very promising when
compared with methadone maintenance
– Craving may continue during naltrexone
maintenance
• Indicated for prevention of relapse
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Naloxone
• Opioid Reversal Agent
– Evizio, Narcan, Narcan Nasal Spray
• Pure opioid antagonist
– Used to reverse opioid intoxication
• Formulations
– Available in vials and syringes
• 0.4 mg/mL, 1 mg/mL
• For IV/IM/SC administration by healthcare providers
– Available as an autoinjector
• Delivers 0.4 mg IM/SC for home use by family or
caregivers
• Pharmacist prescribing in Idaho!
• Effects last about 30 min to an hour
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Questions?
Andrea Winterswyk, PharmD
[email protected]
Joe Berendse, PharmD
[email protected]
48
References
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http://www.uptodate.com/contents/overview-of-the-treatment-of-chronicpain?source=search_result&search=tramadol&selectedTitle=5%7E127#H45605245
http://www.uptodate.com/contents/image?imageKey=ONC%2F63298&topicKey=ANEST%2F2785&
rank=5%7E127&source=see_link&search=tramadol&utdPopup=true
http://www.uptodate.com/contents/overview-of-the-treatment-of-chronicpain?source=search_result&search=tramadol&selectedTitle=5%7E127#H45605245
http://www.drugabuse.gov/drugs-abuse/prescription-drugs-cold-medicines
http://www.cdc.gov/drugoverdose/epidemic/providers.html
http://www.drugabuse.gov/related-topics/trends-statistics/infographics/abuse-prescription-rxdrugs-affects-young-adults-most
http://www.cdc.gov/drugoverdose/epidemic/riskfactors.html
http://www.cdc.gov/drugoverdose/epidemic/providers.html
http://www.cdc.gov/drugoverdose/data/prescribing.html
http://www.cdc.gov/nchs/data/databriefs/db190.pdf
http://www.cdc.gov/drugoverdose/epidemic/index.html
http://www.hhs.gov/about/news/2015/03/26/hhs-takes-strong-steps-to-address-opioid-drugrelated-overdose-death-and-dependence.html
http://emedicine.medscape.com/article/287790-clinical
Opioid Abuse and Dependence, Maritza Lagos MD, Michigan State University, Presentation
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm348252.htm
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