Neurobiology of Opioid Addiction & Physical Health Impacts Thomas Kosten, M.D. Baylor College of Medicine 1 1
Faculty Disclosure • Dr. Kosten —Speakers Bureau: Cephalon, Forest, Reckitt Benckiser; Consultant: Novartis, Bristol-Myers Squibb, Celtic, Alkermes, Synosia, Catalyst, Lannacher, Gerson Lerman Consultants 2
Addiction • Chemical dependency is a compulsive, pathological, impaired control over drug use, leading to an inability to stop using drugs in spite of adverse consequences 3
Essential Definitions • Physical Dependence: Pharmacologic effect characteristic of opioids; withdrawal or abstinence syndrome manifest on abrupt cessation of medication • Tolerance: Pharmacologic effect characteristic of opioids; need to increase dose to achieve the same effect or diminished effect from the same dose 4
Essential Definitions • Pseudo-Addiction: Pattern of drug-seeking behavior of pain patients receiving inadequate pain management that can be mistaken for addiction; resolves with re-establishing analgesia 5
Neurotransmitters • Dopamine • Opioid • Glutamate • GABA • Cannabinoid • Norepinephrine 6
Drug Abuse Acute Effects Chronic Effects • Positive Effects • Tolerance • Reward • Dependence • Reinforcement • Sensitization 7
Drug Abuse • Addiction • Detoxification-Withdrawal • Craving • Relapse 8
Current Theory: Reward Pathway • There is reward pathway in the brain which is activated by – Food, water and sex – Nurturing and caring for others – “Thrills” – Exercise • This reward pathway is also activated by – Drugs, including alcohol – Gambling • Project Cork 9
Neural Circuitry of Reward • Present in all animals • Produces pleasure for behaviors needed for survival: • eating • drinking • sex • Nurturing Project Cork 10
All drugs of abuse bind to the neural circuitry of reward 11
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Your Brain on Drugs 1-2 Min 3-4 5-6 6-7 7-8 8-9 9-10 10-20 20-30 14
Your Brain After Drugs Normal Cocaine Abuser (10 da) Cocaine Abuser (100 da) 15
All drugs of abuse increase dopamine in the nucleus accumbens • alcohol • amphetamines • cocaine • sedatives • heroin • hallucinogens • marijuana • pcp • nicotine 16
Definition • “Addiction is a cycle of spiraling dysregulation of brain reward systems that progressively increases, resulting in compulsive drug use and a loss of control over drug taking” George Koob 17
Compulsion to use The brain is altered by abuse of a psychoactive chemical and use becomes the only way to experience feeling good or normal – No one ever starts drinking or using a drug intending to become an alcoholic or drug addicted – The focus of life is on obtaining access to, using, and recovering from a chemical that makes you high….OR IN THE END TO AVOID WITHDRAWAL OR FEEL NORMAL – Everything—social time, job performance, recreational opportunities—are given up or reduced because of this focus 18
Medical History Associated with Substance Abuse • Medical history findings associated with substance abuse: hepatitis C, HIV, TB, cellulitis, sexually transmitted diseases, elevated liver function tests • Social history: motor vehicle accidents, DUIs, domestic violence, legal history, loss of property in fire • Psychiatric history 19
Clinical Assessment: Psychosocial History • Current psychiatric symptoms • History of addictive disease • Change in social function – work – family and relationships – recreation • Medical-legal status 20
Pain and Addiction • Nearly 1/3 of the US population has used illicit drugs and an estimated 6-15% have a substance abuse disorder of some type • An individual with chronic pain AND untreated addictive disease WILL NOT get better with an opioid prescription 21
Pain History • Provocative or Palliative Features • Quality • Radiation • Severity • Timing 22
Predictors of Opioid Misuse • Behavior that Suggests Addiction – Multiple episodes of prescription “loss” – Repeatedly seeking prescriptions from other clinicians or from the emergency rooms without informing prescriber, or after warnings to desist – Evidence of deterioration in the ability to function at work, in the family , or socially, which appears to be related to drug use – Repeated resistance to changes in therapy despite clear evidence of adverse physical or psychological effects from the drug – Positive urine drug screen-other substance abuse 23
Predictors of Opioid Misuse • Dangerous Behavior – Motor vehicle crash/arrest related to opioid or illicit drug or alcohol intoxication effects – Intentional overdose or suicide attempt – Aggressive/threatening/belligerent behavior in the clinic 24
Define Your Role in Medication Prescribing 25
Patient Medication Agreement • A patient medication agreement establishes clear expectations between physician and patient and specifies – purpose of opioid therapy – side effects – treatment goals – physician’s role in responsible opioid prescribing – patient’s role in responsible opioid use 26
Opioid Agreement • Opioid prescriptions are provided by only one Provider • Patients agree not to ask for opioid medications from any other doctor without the knowledge and assent of the provider • Patients agree to keep all scheduled medical appointments • Urine drug screens will be obtained as indicated 27
Opioid Agreement • Patients agree to comply fully with all aspects of the treatment program including behavioral medicine and physical therapy if recommended • A prohibition on use with alcohol, other sedating medications or illegal medications • Agreement not to drive or operate heavy machinery until medication-related drowsiness is cleared 28
Adjuncts and Alternatives to Opioid Therapy • Heat • Antidepressants • Prosthetic supports • NSAIDS • Physical therapy • Anticonvulsants • Exercise • Acetaminophen • Cognitive-behavioral • Muscle Relaxers therapy • Interventional Pain • Tramadol Management • Medications for sleep • TENS Unit • Topical Agents • Orthopedic Consultation 29
Exercise is important for everyone 30
Don’t Forget to Look at Lifestyle 31
Don’t forget about lifestyle changes 32
Monitoring – Opioid Treatment Guidelines • Clinicians should reassess patients on COT periodically as warranted by changing circumstances. Monitoring should include documentation of pain intensity and level of functioning, assessment of progress toward achieving therapeutic goals, presence of adverse events, and adherence to prescribed therapies. 33
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Urine Drug Screen • Urine drug screens typically check for evidence of opiate, alcohol, benzodiazepine, cocaine, marijuana, amphetamine and barbiturate use • Some opiates may need to be specifically requested such as oxycodone, fentanyl, and methadone 35
Length of Time Drugs of Abuse Can Be Detected in Urine • Alcohol 7-12 hours • Amphetamine 48 hours • Barbiturate 24 hours to 3 weeks • Benzodiazepines 3 days to 1 month • Cocaine 3 days • Marijuana 3 days to over 1 month • Opioids 48 hours to 4 days 36
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Urine Drug Screens Parameter Diluted Adulterated Creatinine Less than 20 ph Less than 3 Greater than 11 s.g. Less than 1.003 nitrite Greater than 500 40
Substances that can be detected with u/a, color check and temperature • Bleach • Table salt • Laundry detergent • Toilet bowl cleaner 41
Aberrant Behavior that Requires Attention • Aggressive complaining about needing more of the drug • Drug hoarding during periods of reduced symptoms • Requesting specific drugs • Openly acquiring similar drugs from other medical sources • Unsanctioned dose escalation or other noncompliance with therapy on one or two occasions 42
Aberrant Behavior that Requires Attention • Unapproved use of the drug to treat other symptoms • Reporting psychic effects not intended by the clinician • Resistance to a change in therapy associated with adverse effects • Missing appointments • Not following other components of the treatment plan (physical therapy, exercise, etc) 43
Rationale for a primary care based chronic pain program Patients who do not follow-up with pain consultation are at high risk for substance abuse diversion psychiatric illness They frequently come back to the primary care provider demanding opiate therapy for their chronic pain 44
Problems with high risk patients in a typical primary care visit • Time constraints attempting to provide primary care, adequate pain control, pain education • Disruptive behavior related to patient attempts to get inappropriate opiate prescriptions • Increased stress on the primary care providers which further limits their ability to care for other patients in the clinic 45
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