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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 4 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 6 &rank=5%7E127&source=see_link&search=tramadol&utdPopup=true PAIN MEDICATIONS: AN OVERVIEW 7 Pain Medication Options • • • • • • • Non-opioid agents Tramadol Opioids Antidepressants Antiepileptic drugs Muscle relaxants Topical analgesics 8 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 17 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 18 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 19 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 21 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 22 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 23 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 25 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 26 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 27 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 28 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 29 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 30 Opioid Abuse Causes • Pharmacological Factors • Social Factors • Psychological Factors • Genetic Factors 31 Recognizing Opioid Abuse 32 Routes of Opioid Abuse • Ingestion • Injection • Inhalation (oral and nasal) • Absorption 33 DETERRENTS TO OPIOID ABUSE 34 Sources of Abused Opioids 35 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 36 OxyContin OC vs OxyContin OP 37 Other Abuse Deterrents • • • • • • • • • • 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 38 OPIOID DEPENDENCE AND TREATMENT 39 Opiate Withdrawal • Detoxification: – Commonly used pharmacologic methods of detoxification • Methadone • Buprenorphine • Alpha-2 agonists (clonidine) 40 Quick Receptor Pharmacology 41 Opioid Classification Pure agonists Antagonists PURE Mixed agonists/ antagonists Nonopioid naloxone FULL morphine oxycodone fentanyl tramadol naltrexone buprenorphine PARTIAL butorphanol pentazocine nalbuphine 42 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 43 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! 44 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 45 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 46 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 47 Questions? Andrea Winterswyk, PharmD [email protected] Joe Berendse, PharmD [email protected] 48 References • • • • • • • • • • • • • • • 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 49