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Benzodiazepines and Similar Drugs: Misuse, Abuse, and Dependence

2. Benzodiazepines = Useful. Medical disordersMuscular spasmConvulsive disordersPsychiatric disordersAnxiety disordersSituational stressorsJet lagWork shift change. BUT. . .. 3. Key Points. Daily use of benzodiazepines (BZDs) is riskyCertain situations increase riskPrescribing practices Patient characteristicsTaper BZDs slowly if daily use ~2 weeks.

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Benzodiazepines and Similar Drugs: Misuse, Abuse, and Dependence

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    1. 1 Benzodiazepines and Similar Drugs: Misuse, Abuse, and Dependence Randy Brown, MD University of Wisconsin, Madison Alcohol Medical Scholars Program

    2. 2 Benzodiazepines = Useful Medical disorders Muscular spasm Convulsive disorders Psychiatric disorders Anxiety disorders Situational stressors Jet lag Work shift change

    3. 3 Key Points Daily use of benzodiazepines (BZDs) is risky Certain situations increase risk Prescribing practices Patient characteristics Taper BZDs slowly if daily use ~2+ weeks

    4. 4 Overview Pharmacology Adverse effects Situations of ? risk Misuse, abuse, dependence Tapering BZDs

    5. 5 Benzodiazepines (BZDs) Sedative-hypnotic Flurazepam (Dalmane) Temazepam (Restoril) Triazolam (Halcion) Anxiolytic Alprazolam (Xanax) Chlordiazepoxide (Librium) Clonazepam (Klonopin) Diazepam (Valium)

    6. 6 Non-BZD BZD Receptor Agonists (BZRAs) Used as sedative-hypnotic Zaleplon (Sonata) Zolpidem (Ambien) Zopiclone (Imovane)

    7. 7 Pharmacodynamics: “What The Drug Does To The Body” Nerve impulse ? GABA released GABA binding ? chloride (Cl) influx into post-synaptic neuron Post-synaptic neuron inhibited

    8. 8 BZRAs Pharmacodynamics Similar to BZDs Selective for GABA receptor subtype 1 May ? adverse effects Less anxiolytic effects

    9. 9 Pharmacokinetics: “What The Body Does To The Drug”

    10. 10 Lipid Solubility ? lipid solubility ? more rapid effects Low: clonazepam Intermediate: lorazepam High: clorazepate, diazepam

    11. 11 BZD Half-Lives Anxiolytics Oxazepam 8 hrs (6-20 hrs) Alprazolam 11 hrs (6-20 hrs) Diazepam 24 hrs (20-100 hrs) Sedative-hypnotics Triazolam < 6 hrs Temazepam 10 hrs (6-20 hrs)

    12. 12 Half-Lives BZRAs Zolpidem 2 hrs Zopiclone 4 hrs

    13. 13 Adverse Effects: Motor Impairment Slowed response time Increased risk Age > 65 Alcohol or >1 BZD use

    14. 14 Adverse Effects: Cognitive Impairment Anterograde amnesia = impaired recall of new information Sedation/drowsiness

    15. 15 Adverse Effects: Cognitive Impairment Increased risk Patient Age > 65 Alcohol use Medication High lipid solubility

    16. 16 Misuse Long-term use (2+ weeks) = risky ? Side effects, tolerance Non-medical use (to get “high”) ~5% ever, 0.3% in last year ? among age 25-44 & alcoholics

    17. 17 Abuse 1+ in 12 months of: Failure to fulfill major obligations Recurrent hazardous use Recurrent legal consequences Ongoing use despite interpersonal problems Lifetime prevalence ~ 0.4% Risk factors similar to those for dependence

    18. 18 Dependence 3+ in 12 months of: Tolerance Withdrawal Larger amts/longer periods than intended Persistent desire/failed attempts to quit/control use Much time obtaining/using/recovering Important activities sacrificed Continued use despite adverse effects

    19. 19 Physical Dependence: Only Part Of Substance Dependence Physiologic adaptation to substance ? tolerance & withdrawal Withdrawal relieved by substance ? Don’t stop abruptly if taken 2+ weeks

    20. 20 Patient Risk Factors: Misuse, Abuse, & Dependence Substance dependence history BZDs, alcohol + Psychiatric history Anxiety, depression + Social & demographic factors Unemployment, poor social support +

    21. 21 Medication Factors: Misuse, Abuse, & Dependence Dose/duration High dose (outside usual range) > 2 weeks daily use Short half-life Highly lipid soluble BZD

    22. 22 BZRAs: Misuse, Abuse, & Dependence Risk < BZDs Dependence develops with long-term use Risk factors similar to BZDs

    23. 23 Risky Patients Age > 65 Substance dependence history Psychiatric history Life stresses

    24. 24 Risky Practice BZD characteristics ? risk: high lipid solubility/rapid onset short half-life Prescribing practices ? risk: Long-term daily use (2+ weeks) High dose (outside usual range)

    25. 25 Detecting Misuse, Abuse, Dependence Did patient: ? dose on own? take meds for additional reason (euphoria)? have risk factors for abuse/dependence? give a believable story? Consider speaking with close family

    26. 26 Detecting Misuse, Abuse, Dependence Behavior: Early refills, Rx “loss/theft” Functional decline Overly focused on med Fails non-med appointments Adverse effects with use

    27. 27 BZD Withdrawal Chronic use (2+ weeks) ? ? GABAergic inhibitory function ? glutamate/NMDA function Abrupt discontinuation ? unopposed excitatory CNS activity Less severe: anxiety, diaphoresis, ?BP/HR More severe: hallucinosis, seizures

    28. 28 Tapering BZDs: Usual Taper 1) Divide daily dose 2-4 x daily 2) Taper by 25% every 3 days 3) Slow rate during last half of taper Provide support behavioral therapy engage close family

    29. 29 Tapering BZDs: Difficult Taper Unsuccessful taper ? dose/duration or ? t1/2 ? ? difficulty tapering ? Consider longer-acting agent—e.g.: 10 mg alprazolam = 100 mg diazepam Divide 2-4x daily Taper 25% each week Slow during last 1/2

    30. 30 Case Vignette 32 yo ? 6 mo h/o ?ing daily bzd use: 2 mg alprazolam QID Dx: panic disorder Substance use: EtOH 6 drinks on 4-6 nights/mo DWI (BZD + EtOH) x 3 over last 12 mo

    31. 31 Case: Treatment Issues Dx: BZD dependence, EtOH abuse. . . Tx: BZD taper Same agent Alprazolam 2 mg QID x 3 days ? 2 mg TID etc. Long-acting Diazepam 20 mg QID x 3 days ? 20 mg TID etc. Adjuntive Tx (behavioral, social, frequent f/u)

    32. 32 Summary Long-term use (> 2 weeks) ? risk for: Side effects Misuse, abuse, & dependence Physical dependence & withdrawal Prescribing practices & patient characteristics ? risk If taken for > 2 weeks, taper slowly

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