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Amphetamine Use Disorders Michael J. Mancino, M.D. University of Arkansas for Medical Sciences © AMSP 2011 1 Substance Use/Problems % Lifetime Substance Use → → → • Alcohol: Lifetime Problems 80 60 • Cannabinoids: 40 50 • Cocaine: 15 50 • Amphetamine: 10 60 © AMSP 2011 2 Why Problems Arise • Mimic medical/psych dx • ↑ symptoms • Direct side effects • Occur in patient populations • Recent ↑ in use © AMSP 2011 3 This Talk Will Review • History/nature of amphetamines • Epidemiology • Problems • Treatment © AMSP 2011 4 History • 1887- Amphetamine synthesized • 1919 - Methamphetamine synthesized • 1930’s – AMPH OTC bronchodilator • 1937 – AMPH prescription only • 1939 – WWII troops, factory workers • 1959 – FDA bans inhalers • 1970 - AMPH Schedule II © AMSP 2011 5 Drug Classification • Depressants:↑sleep, ETOH high, disinhibit • Cannabinoids → ↓ drive, ↑ appetite • Opioids → ↓ pain, ↓ cough • Stimulants → ↑ energy/attention/activity © AMSP 2011 6 Amphetamines • Routes of use – Oral – Nasal – Intravenous • Amphetamine high short-lived – Drug half-life = 12-13 hours – Post high letdown © AMSP 2011 7 Amphetamines © AMSP 2011 8 Structure Adrenaline Amphetamine © AMSP 2011 9 Structure → Function • Adrenaline = Epinephrine • “Fight or flight” • Bind to sympathetic system • Mobilize defense system –↑ glucose –Shift blood © AMSP 2011 10 How Neurons Communicate Neurotransmitters are: 1.Synthesized in cell 1 5 2.Released 6 3.Bound to post-synaptic receptors 2 4 4.Recycled by transporters 3 5.Broken down by enzymes 6.Bound to pre-synaptic receptors © AMSP 2011 11 Effect of AMPH at the Synapse DA AMPH DA-R DA-T © AMSP 2011 12 1. AMPH enters in exchange for DA DA AMPH DA-R DA-T © AMSP 2011 13 2. AMPH enters pre-synaptic vesicles DA AMPH DA-R DA-T © AMSP 2011 14 3. ↑ release of DA in pre-synapse DA AMPH DA-R DA-T © AMSP 2011 15 4.↑ DA in pre-synapse and synapse DA AMPH DA-R DA-T © AMSP 2011 16 Medical Uses • Narcolepsy: sleep disorder –Modafinil (Provigil) –Armodafinil (Nuvigil) • ADHD: developmental d/o – Amph/d-amphetamine (Adderall) – Methylphenidate (Ritalin) © AMSP 2011 17 This Talk Will Review History/nature of amphetamines • Epidemiology • Problems • Treatment © AMSP 2011 18 Epidemiology • US lifetime use 2009 ≈ 10% –Highest rate age 26-34 (>12%) –Rate males = females –Rate 2X white > black • Past month use ≈ 0.5 % • Lifetime dependence ≈ 1.5 % © AMSP 2011 19 Drug Dependence • Presence of ≥ 3 in 12 months – Tolerance – Withdrawal – Larger amounts – Desire/attempts to cut down – ↑ time spent – Give up activities – Ongoing use despite problems © AMSP 2011 20 Drug Abuse • Presence of ≥ 1 in 12 months –Fulfill obligations –Physically hazardous situations –Legal consequences –Interpersonal problems Never dependent on this drug © AMSP 2011 21 This Talk Will Review History/nature of amphetamines Epidemiology • Problems • Treatment © AMSP 2011 22 Amphetamine Problems • Medical –Overdose –Withdrawal –Other • Psychiatric –Psychosis –Anxiety/depression © AMSP 2011 23 Overdose Copyright © 2010 Meth Kills © AMSP 2011 24 OD: Sympathetic Symptoms • ↑ heart rate (> 100 beats/min) • ↑blood pressure (>160 /110) • ↑ respiratory rate (>30/min) • ↑ temperature (> 0 102 F) • Dilated pupils • Seizures © AMSP 2011 25 OD: Sympathetic Symptoms • Chest pain / heart attack • Stroke • Arrhythmias = irregular heart beat • Muscle rigidity → shock © AMSP 2011 26 OD: Psychological Effects • Restlessness • Higher doses → –Suspiciousness • Dizziness –Stereotypy • Irritable/violent • Insomnia –Bruxism –Punding © AMSP 2011 27 OD Treatment • Basic life support (ABC’s) • ↑ temp - dantroline (Dantrium): 1-2mg/kg • Seizures (diazepam): 10mg IV • ↑ BP- phentolamine (Regitine): 5-15mg • Chest pains/heart attack • Urine tox: ID other drugs © AMSP 2011 28 Agitation Treatment • Benzodiazepines • Diazepam (Valium): 10-30mg PO, 2-10 mg IV • Lorazepam (Ativan): 2-4 mg PO, IM, IV • Hi potency antipsychotics (anticholinergic SE) • Haloperidol (Haldol): 5-10 mg PO, IM, IV • Risperidone (Risperdal): 2-4 mg PO © AMSP 2011 29 Withdrawal • Begins ≥ 2 hrs, peaks day 1-2 • Symptoms opposite intoxication – Sleepy, depressed, ↓ concentration, ↑ appetite – Craving • Symptoms ↓ over 3-4 days • ↓ concentration/↑ sad last ≥ 2 months © AMSP 2011 30 Other Medical Problems • Infection (contaminated needles) –Endocarditis (heart valve inflammation) –Skin abcesses –HIV → AIDS • Intranasal → holes in nasal septum • Heart attack • Stroke (hemorrhagic or ischemic) © AMSP 2011 31 Psychiatric © AMSP 2011 32 Stimulant Psychosis vs Schizophrenia Stimulant Psychosis Schizophrenia • Labile mood • Bland mood • Develops rapidly • Develops slowly • Physical findings • Rare findings • Resolve days/wk • Worsen with time © AMSP 2011 33 Treatment • History, physical & labs • Hospitalization • Monitor vitals • Behavioral • Antipsychotics • Avoid benzodiazepines • Drug rehab © AMSP 2011 34 Anxiety • Intoxication (mimic panic attacks) – ↑ Heart rate, palpitations – Nervousness, hyperventilation • Obsessive-compulsive picture – Take apart / reassemble mechanical objects – High levels of use © AMSP 2011 35 Depression • Related to withdrawal • “Atypical depression” – Impaired mood – Sleepiness – Excessive appetite • Cessation → mood swings wks/mos © AMSP 2011 36 Treatment Depression/Anxiety • Counseling • Reassurance • Medication rarely necessary • Evaluate medical illness – Heart attack, hyperthyroidism • Rule out pre-existing disorders – Major depression or anxiety © AMSP 2011 37 This Talk Will Review History/nature of amphetamines Epidemiology Problems • Treatment © AMSP 2011 38 Rehabilitation Goals • Drug free forever • Interim goals to reduce – Use – HIV risk and other med issues – Unemployment – Crime • Engage in treatment © AMSP 2011 39 Rehabilitation Focus • Engage in treatment • Support abstinence • Prevent/reduce relapse • Life management skills • Cope with anxiety/stress © AMSP 2011 40 Rehab Tools • Individual & group counseling • Urine toxicology • Psychosocial treatments – Contingency management – Motivational interviewing – Cognitive behavioral therapy (CBT) – Self help groups • Vocational rehab © AMSP 2011 41 Medications • Other substance use disorders –Alcohol –Opiates • No efficacious meds for AMPH © AMSP 2011 42 Summary • Amphetamine structure → action • Amphetamine use common & serious • Problems mimic med/psych problems • Tx required for acute & chronic use © AMSP 2011 43