BENZODIAZEPINES MEL POHL, MD LAS VEGAS .ppt
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1、,BENZODIAZEPINESMEL POHL, MDLAS VEGAS RECOVERY CENTER,Doctors who treat the symptom tend to give a prescription; Doctors who treat the patient are more likely to offer guidance.J. Apley 1978,“Emerging research suggests that optimum benzodiazepine therapy consists of judicious, circumspect, and criti
2、cally monitored use of benzodiazepines in terms of target symptoms and diagnoses”Rickels et al,Secondary Substances for Primary Benzo Admissions,Dasis report 11/21/03,Dosage Conversion Table for Benzodiazepines Benzodiadepines Dosages (mg) Half-life* Alprazolam (Xanax) 1 6-10 Chlordiazepoxide (Libri
3、um) 25 5-100+ Clonazepam (Klonopin) .5 18-50 Clorazepate (Tranxene) 15 30-200 Diazepam (Valium) 10 30-100+ Estazolam (Prosom) 4 20-120 Flurazepam (Dalmane) 30 1-120 Midazolam (Versed) n/a Lorazepam (Ativan) 2 10-20 Oxazepam (Serax) 30 3-21 Quazepam (Doral) 30 20-120 Temazepam (Restoril) 30 10-12 Tri
4、azolam (Halcion) 1 2-3 Zolpidem (Ambien) 20 2.5 Zaleplon (Sonata) 20 1 Adapted from Giannini AJ. Drugs of abuse. 2d ed. Los Angeles: Practice Management Information Corp., 1997:121-5. *Includes metabolites - in hours,new,Short- acting,Imidazo- pyridine,Triazolo ring,Antagonist,Beta- carboline,tetrac
5、yclic,Cyclo- pyrrolone,Other sedative-hypnotics,Barbiturates - pentobarbital,phenobarbital,secobarbital, butalbital (Fiorinal) Barb-like: glutethimide, chloral hydrate, ethhchlorvynol (Placidyl), meprobamate (carisoprodol/Soma) Azapirone: buspirone (2-10 mg TID - max 60 mg/d)-slow onset of action (1
6、-3 wks)-not abused, no withdrawal-effective for anxiety disorders-not for acute-does not block benzo withdrawal -not sedating, anticonvulsant or mm relaxing-no resp dep/ cognitive/psychomotor impair,Non-Benzo Hypnotics,Zolpidem (Ambien) imadozopyridine Zaleplon (Sonata) pyrazolopyrimidine Bind to sp
7、ecifically to BZ-1 sites Both rapid onset (1h-2.5 h) - short action/1/2 life Decrease sleep latency, increase REM sleep 5-20 mg dose range Safe in older adults, metab in liver, no active metabolites Potentiate ETOH impairment Both reinforcing, potentially abusable, and performance-impairing,GHB Gamm
8、a Hydroxybutyrate,Club drug - “G” “liquid ecstasy Aqueous solution - variable concentration Relaxation, disinhibition, euphoria Rapid onset, short half-life (20 minutes) Dependence and withdrawal occur Narrow therapeutic window-side effects: Dizziness, nausea, emesis, dec resp, coma Additive with ET
9、OH and other sed-hypnotics,Therapeutic Uses,Sedative-hypnotic Anxiolytic Panic disorder Generalized anxiety disorder Muscle relaxants Anticonvulsants Alcohol withdrawal Premenstrual syndrome Psychoses Adjunct in mania of bipolar disorder,Sedative/Hypnotic,Transient - lowest effective dose- time-limi
10、ted Insignificant decrease in sleep latency-1 hour increase in sleep duration -? effect on sleeparchitecture ( REM, stages 3 and 4) Rebound insomnia - worsening of sleep - worse than before trying benzos. Daytime drowsiness, dizziness, lightheadedness,Anxiety,benzos good for immediate symptom relief
11、-fasterthan SSRIs for panic. long-acting, low potency preferred (clonazepam or chlordiazepoxide) best used for exacerbations of anxiety-short term vscontinuous use,Adverse Effects,Diminished psychomotor performance Impaired reaction time Loss of coordination, decreased attention Ataxia Falls Excessi
12、ve daytime drowsiness Confusion Amnesia Increase of existing depressed mood Overdose rarely lethal,Treatment of Overdose,Airway assessment and maintenance Ventilatory support if necessary NG suction - activated charcoal Flumazenil - competitive antagonist May need to repeat Q30-60 minutes Can induce
13、 withdrawal seizures in dependent pts.,REINFORCING EFFECTS,Increased with rapid drug effect - eg alprazolam Subjective effects - high - e.g. diazepam, lorazepam, triazolam, flunitrazepam, and alprazolam. Speed of onset of pleasurable effects - eg GHB Increased reinforcement in those with history ofd
14、rug abuse,Tolerance,Time-dependent decrease in effect. Neurochemical basis unclear Varying rates for different behavioral effects: sedative and psychomotor effects diminish first (e.g. few weeks) memory and anxiety effects persist despite chronic use. Varying rates with different benzos. If no histo
15、ry of addiction, rarely see doseescalation or overuse Cross-tolerance with ETOH and other sed-hyp,Dependence,Negative reinforcement of withdrawal - major deterrent to discontinuing use. Difficult to distinguish between wd & reboundanxiety upon discontinuing drug. Withdrawal-time-limited (not part of
16、 original anxiety state) Relapse-reemergence of original anxiety Rebound - increased anxiety baseline Also see insomnia, fatigue, headache, muscletwitching, tremor, sweating, dizziness, tinnitusdifficulty concentrating, nausea, depression, abnormal perception of movement, irritability,Dependence/Wit
17、hdrawal, cont.,rarely -seizures, delirium, confusion, psychosis. triggering of depression, mania, OCD. 90% of long-term users (8mo-1yr) experiencesignificant withdrawal insignificant wd if used less than 2 weeks mild-moderate if used 8 weeks Slow taper (30days) with +/- carbamazepine, valproic acid,
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