Appendix 1 Cross-Reference of Research, Generic and Trade Names of Benzodiazepines

Transcription

1 Appendix 1 Cross-Reference of Research, Generic and Trade Names of Benzodiazepines Table 1. Benzodiazepine research designations with corresponding generic names Research Designation lactam methyl A 101 AB AB AH 3232 CB 4261 CB 4306 CB 4311 CGS 8216 CI683 CS 370 CS 430 D40TA EGYT 341 ER 115 HR 158 HR376 HR 4723 HR930 K3917 demoxepam nordazepam tetrazepam (antagonist) ripazepam cloxazolam haloxazolam estazolam tofisopam loprazolam clobazam clobazam fosazepam 287

2 THE BENZODIAZEPINES Research Designation LA 111 LM 2717 ORF 8063 Ro Ro Ro Ro Ro Ro Ro Ro Ro Ro Ro Ro Ro Ro Ro Ro Ro Ro RU S 1530 SAH 1123 SAH SB 5833 SCH SCH U U U W4020 We 352 clobazam triflubazam desmethy1 demoxepam desmethyl desmethyl bromazepam flu clonazepam flu (antagonist) midazolam loprazolam nimetazepam isoquinazepam camazepam halazepam quazepam ketazolam alprazolam triazolam prazepam triflubazam 288

3 RESEARCH, GENERIC AND TRADE NAMES Research Designation We 941 Wy 2917 Wy 3467 Wy 3498 Wy 3917 Wy 4036 Wy 4082 Wy 4426 Y 6047 brotizolam lormetazepam ciotiazepam Table 2. Benzodiazepine generic names with corresponding trade names alprazolam bromazepam brotizolam camazepam c10bazam Trade Name(s) Xanax Compendium, Lectopam, Lexatin, Lexomil, Lexotan, Lexotanil Lendorm, Lendormin Albego, Limpidon, Paxor Ansiacal, A-Poxide, Benzodiapin, Binomil, Cebrum, Chlortran, Corax, C-Tran, Decacil, Diazepina, Disarim, Eden-psich, Endequil, Elenium, Equibral, Helogaphen, Huberplex, Klopoxid, Labican, Liberans, Librium, Libritabs, Lixin, Medilium, Menrium, Mesural, Multum, Nack, Normide, Novopoxide, O.CM., Omnalio, Philicorium, Psicofar, Psicoterina, Raysedan, Reposal, Relaxil, Reliberan, Risachief, Risolid, Seren, Silibrin, Sintesedan, Smail, Solium, SonimenTrilium, Tropium, Viansin, Zeisin, Zetran Castilium, Frisin, Frisium, Karidium, Noiafren, Sentil, Urbadan, Urbanol, Urbanyl 289

4 THE BENZODIAZEPINES clonazepam clorazolam clotiazepam cloxazolam estazolam fiu fiu Trade Name(s) Clonopin, Iktorivil, Landsen, Rivotril Azene, Belseren, Covengar, Enadine, Justum, Mendon, Moderane, Nansius, Tencilan, Transene, Tranxen, Tranxene, Tranxilen, Tranxilene, Tranxilium, Uni-Tranxene see triazolam Rize, Trecalmo Enadel, Lubalix, OIcadil, Sepazon, Tolestan Aliseum, Alupram, Amiprol, Ansiolin, Apaurin, Apozepam, Armonil, Atenex, Atensine, Atilen, Avex, Best, Bialzepam, Calmpose, Ceregulart, Cuadel, Cyclopam, Diaceplex, Diapam, Diatran, Diazemuls, Dipam, Dipezona, Dizam, Doval, Drenian, D-Tran, Ducene, E-Pam, Eridan, Euphorin, Evacalm, Faustan, Gradual, Gubex, Lembrol, Levium, Lorinon, Meval, Morostan, Neo-Calme, Neurolytril, Noan, Notense, Novodipam, Pacitran, Pax, Paxate, Paxel, Plidan, Pro-pam, Quetinil, Quievita, Relanium, Relivan X, Saromet, Scriptopam, Sedapam, Sedaril, Seduxen, Serenack, Setonil, Solis, Somasedan, Sonacon, Stesolid, Stesolin, Stess-Pam, Tensium, Tranimul, Tranquase, Tranquirit, Tranquo-Tablinen, Valitran, Valium, Valrelease, Vatran, Vival, Vivol Domnamid, Esilgan, Eurodin, Nuctalon Erispan Darkene, Narcozep, Primun, Rohipnol, Rohypnol, Roipnal, Val sera 290

5 RESEARCH, GENERIC AND TRADE NAMES Trade Name(s) flutazolam halazepam haloxazolam ketazolam loprazolam lormetazepam mexazolam midazolam nimetazepam Benozil, Dalmane, Dalmadorm, Dalmate, Domodor, Dormodor, Felison, Felmane, Flunox, Fordrim, Insumin, Lunipax, Midorm AR, Natam, Niotal, Remdue, Somlan, Valdorm Coreminal Paxipam Some lin Anxon, Contamex, Loftran, Solatran, Unakalm Avlane, Dormonoet Almazine, Aplaeasse, Ativan, Control, Emotieal, Emotival, Kalmalin, Loraus, Lorax, Lorsilan, Lorenin, NIC, Orfidal, Plaeidia, Psieopax, Quait, Seeurit, Sedarkey, Sedatival, Sidenar, Tavor, Temesta, Trapax, Wypax Loramet, Noetamid Ansilan, Anxitol, Azepamid, Benson, Diepin, Elbrus, Esmail, Lerisum, Medazepol, Megasedan, Metonas, Mezepan, Narsis, Navizil, Nivelton, Nobrium, Pazital, Psiquium, Raporan, Resmit, Rudotel, Serenium, Siman, Templane, Tranquilax Melex Dormieum Elimin, Erimin, Hypnon 291

6 THE BENZODIAZEPINES Trade Name(s) nordazepam oxazolam oxazolazepam pinazepam prazepam tetrazepam tofisopam tofizopam triazolam Apodorm, Arem, Benzalin, Calsmin, Dormicum, Dumolid, Eatan, Eunoctin, Hipsal, Hypnotin, Mitidin, Mogadan, Mogadon, Nelbon, Neuchlonic, Nipam, Nitrados, Nitrenpax, Noctene, Pacisyn, Paxisyn, Pelson, Persopir, Prosonno, Quill, Radedorm, Relact, Remnos, Sindepres, Somnased, Somnibel, Somnite, Sonebon, Sonnolin, Surem, Unisomnia Calmday, Demadar, Madar, Stilny Adumbran, Aplakil, Benzotran, Enidrel, Isodin, Limbial, Murelax, Nesontil, Nulans, Oxadin, Oxepam, Praxiten, Psiquiwas, Purata, Quen, Quilibrex, Sedokin, Serax, Serenal, Serenid-D, Serenid Forte, Serepax, Seresta, Serpax, Sobile, Sobril, Wakazepam Convertal, Hializan, Serenal Tranquit see oxazolam Domar, Duna Centrax, Demetrin, Equipaz, Lysanxia, Mono Demetrin, Prazene, Reapam, Sedapran, Trepidan, Verstran Cerepax, Euhypnos, Lenal, Levanxene, Levanxol, Mabertin, Maeva, Normison, Planum, Remestan, Restoril, Signopam Clinoxan, Musaril, Myolastan Grandaxin, Grandaxine, Seriel see tofisopam Halcion 292

7 RESEARCH, GENERIC AND TRADE NAMES Table 3. Benzodiazepine trade names with corresponding generic names Trade Name Adumbran Albego Aliseum Almazine Alupram Amiprol Ansiacal Ansilan Ansiolin Anxitol Anxon Apaurin Aplacasse Aplakil Apodorm A-Poxide Apozepam Arem Armonil Atenex Atensine Atilen Ativan Avex Avlane Azene Azepamid Belseren Benozil Benson Benzalin camazepam ketazolam loprazolam c!orazepate c!orazepate 293

8 THE BENZODIAZEPINES Trade Name Benzodiapin Benzotran Best Bialzepam Binomil Calmday nordazepam Calmpose Calsmin Castilium c!obazam Cebrum Centrax prazepam Ceregulart Cerepax Chlortran Clinoxan tetrazepam Clonopin c!onazepam Compendium bromazepam Contamex ketazolam Control Convertal oxazolam Corax Coreminal fiutazolam Covengar c!orazepate C-Tran Cuadel Cyc!opam Dalmane fiurazepam Dalmadorm fiurazepam Dalmate fiurazepam Darkene fiu Decacil Demadar nordazepam Demetrin prazepam 294

9 Trade Name Diaceplex Diapam Diatran Diazemuls Diazepina Diepin Dipam Dipezona Disarim Domar Domnamid Domordor Dormicum Dormodor Dormonoct Doval Drenian D-Tran Ducene Dumolid Duna Eatan Eden-psich Edenquil Elbrus Elenium Elimin Emotical Emotival Enadel Enadine Enidrel E-Pam RESEARCH, GENERIC AND TRADE NAMES pinazepam estazolam midazolam, loprazolam pinazepam nimetazepam cloxazolam 295

10 THE BENZODIAZEPINES Trade Name Equibral Equipaz prazepam Eridan Erimin nimetazepam Erispan flu Esilgan estazolam Esmail Euhypnos Eunoctin Euphorin Eurodin estazolam Evacalm Faustan Feliston Felmane Flunox Fordrim Frisin c10bazam Frisium c10bazam Gradual Grandaxin tofisopam Grandaxine tofisopam Gubex Ha1cion triazolam Helogaphen Hializan oxazolam Hipsal Huberplex Hypnon nimetazepam Hypnotin Iktorivil c10nazepam Insumin Isodin 296

11 Trade Name Justum Kalmalin Karidium Klopoxid Labican Landsen Lectopam Lembrol Lenal Lendorm Lendormin Lerisum Levanxene Levanxol Levium Lexatin Lexomil Lexotan Lexotanil Liberans Limbial Librium Libritabs Limpidon Lixin Loftran Loramet Loraus Lorax Lorinon Lorsilan Lorenin Lubalix RESEARCH, GENERIC AND TRADE NAMES GenericName c10razepate c10bazam c10nazepam bromazepam brotizolam brotizolam bromazepam bromazepam bromazepam bromazepam camazepam ketazolam lormetazepam c1oxazolam 297

12 THE BENZODIAZEPINES Trade Name GenericName Lunipax Lysanxia prazepam Mabertin Madar nordazepam Maeva Medazepol Medilium Megasedan Melex mexazolam Mendon Menrium Mesural Metonas Meval Mezepan Midorm AR Mitidin Moderane Mogadan Mogadon Mono Demetrin prazepam Morostan Multum Murelax Musaril tetrazepam Myolastan tetrazepam Nack Nansius Narcozep flu Narsis Natam Navizil Nelbon 298

13 Trade Name Neo-Calme Nesontil Neuchlonic Neurolytril NrC Niotal Nipam Nitrados Nitrenpax Nivelton Noan Nobrium Noctamid Noctene Noiafren Normide Normison Notense Novodipam Novopoxide Nuctalon Nulans O.C.M. Okadil Omnalio Orfidal Oxadin Oxepam Pacisyn Pacitran Pax Paxate Paxel RESEARCH, GENERIC AND TRADE NAMES lormetazepam clobazam estazolam cloxazolam 299

14 THE BENZODIAZEPINES Trade Name Paxipam halazepam Paxisyn Paxor camazepam Pazital Pelson Persopir Philicorium Placidia Planum Plidan Praxiten Prazene prazepam Primun flu Pro-Pam Prosonno Psicofar Psicopax Psicoterina Psiquium Psiquiwas Purata Quait Quen Quetinil Quievita Quilibrex Quill Radedorm Raporan Raysedan Reapam prazepam Reposal Relact 300

15 RESEARCH, GENERIC AND TRADE NAMES Trade Name Relanium Relaxil Reliberan Relivan X Remdue Remestan Remnos Resmit Restoril Risachief Risolid Rivotril Rize Rohipnol Rohypnol Roipnal Rudotel Saromet Scriptopam Securit Sedapam Sedapran Sedaril Sedarkey Sedativil Sedokin Seduxen Sentil Sepazon Serax Seren Serenack Serenal clonazepam clotiazepam flu flu flu prazepam clobazam cloxazolam, oxazolam 301

16 THE BENZODIAZEPINES Trade Name Serenid-D Serenid Forte Serenium Serepax Seresta Seriel tofisopam Serpax Setonil Sidenar Signopam Silibrin Siman Sindepres Sintesedan Smail Sobile Sobri! Solatran ketazolam Solis Solium Somasedan Some1in haloxazolam Somlan Somnased Somnibel Somnite Sonacon Sonebon Sonimen Sonnolin Stesolid Stesolin Stess-Pam 302

17 Trade Name Stilny Surem Tavor Temesta Templane Tencilan Tensium Tolestan Tranimul Tranquase Tranquilax Tranquirit Tranquit Tranquo-Tablinen Transene Tranxen Tranxene Tranxilen Tranxilene Tranxilium Trapax Trecalmo Trepidan Trilium Tropium Unakalm Unisomnia Uni-Tranxene Urbadan Urbanol Urbanyl Valdorm Valitran RESEARCH, GENERIC AND TRADE NAMES nordazepam cloxazolam oxazolam clotiazepam prazepam ketazolam clobazam clobazam clobazam 303

18 THE BENZODIAZEPINES Trade Name Valium Val release Val sera Vatran Verstran Viansin Vival Vivol Wakazepam Wypax Xanax Zeisin Zetran fiu prazepam alprazolam 304

19 Appendix 2: Books on Benzodiazepines Costa E (ed): The Benzodiazepines: From Molecular Biology to Clinical Practice. New York, Raven Press, CostaE, Di Chiari G, Gessa GL (eds): GABA and Benzodiazepine Receptors. New York, Raven Press, Costa E, Greengard P (eds): Mechanisms of Action of Benzodiazepines. New York, Raven Press, Garattini S, Mussini E, Randall LO (eds): The Benzodiazepines. New York, Raven Press, Greenblatt DJ, Shader RI: Benzodiazepines in Clinical Practice. New York, Raven Press, Marks, J: The Benzodiazepines: Use, Overuse, Misuse, Abuse. 2nd Edn. Lancaster, England, MTP Press Limited, Priest RG, Vianna Filho U, Amrein R, et al. (eds): Benzodiazepines Today and Tomorrow. Lancaster, England, MTP Press Limited, Skolnick P, Tallman JF, Jr., et al. (eds): Pharmacology of Benzodiazepines. London, The Macmillan Press, Ltd., Scientific and Medical Division, Szara SI, Ludford JP: Benzodiazepines: A Review of Research Results, NIDA Research Monograph 33. Rockville, Maryland, National Institute on Drug Abuse,

20 Index absorption rates factors affecting 49 hypnotics 122, 124, 125, oral benzodiazepines 46-8 abuse 35,36 behavioral effects 193,194 negative 193 benzodiazepine avoidance 95 benzodiazepines used 189, 190 new 190 cortical atrophy 194 definition 181 and dependence differences 194,195, Third World 172 disorder classification 181 experimental assessment drug abuse human self-administration 205,206 human studies phenothiazine comparison 215 placebo comparison 215 forecasting potential animal studies 191 human volunters international legislation liability 202 multiple 186,187 potential 2, 117 primary international data 184 secondary 179,186-90,194,195 and alcohol 186 euphoriant 189 narcotics and 187 reasons and narcotics 188, 189 urine test 187 socio-medical appraisal 195 street cost 188 Switzerland, drug incidence 186 activity onset 45-9,99 and hypnotic use 124,125 intravenous 46 oral 46-8 adaptation 52 addiction see dependence, abuse and withdrawal adverse drug reactions 2 see also tolerance, toxicity, dependence and withdrawal amnesia 10 behavioral 131 and benzodiazepine abuse 95 clobazam 154 clonazepam 165 ens depressant 99 early morning insomnia fiurazepam 139 hangover 49 hypnotics daytime sedation memory 129 initial treatment 53,60 metabolism 102 performance 10 psychotropic 60 sedation 93,117 social tricyclic antidepressants 117 triazolam 131, 139 tryptophan 161 aggression enhancement 100,101 reduction 9 alcohol use and abuse anxiety 112 benzodiazepine reinforcement 210,212, 213 benzodiazepine social cost 282 cross-tolerance 93, 95 psychotropic drugs 76,77 withdrawal alprazolam, half-life 97,98 307

21 BENZODIAZEPINES American Psychiatric Association, abuse classification 181,182 'Y aminobutyric acid see also GABA agonists 16 CNSroie 7 inhibitory neurotransmission 14 presynaptic inhibition 14 amnesia, anterograde 10 anesthesia 88, 165 in Third World 171, 172 animal studies abuse potential 191 self-administration 205 anti-anxiety drugs overprescription III sex bias and use 255,258 structures 88 synonyms 112 anticonvulsant activity 7, 8 neuronal activities 34 antiepileptic action 34 anxiety acute and chronic 113,114 assessment 114 benzodiazepinetherapy 253,254 benzodiazepine use III causes 115 and change 116 chronic treatment daytime 129,133 definitions 112, 113 non-psychotic 97 non-psychotropic treatment 112 physician response III rebound 242 treatment 116, 117!3-blockers 117, 118 guidelines 118, 119 tricyclic antidepressants 117 views of III anxiolytic effects benzodiazepines mechanism 34,35 non-sedative role 10 area under the time-action curve 218 assessment anxiety 114 benzodiazepine uses 284 autonomic affects 10, 11 autoradiography, benzodiazepine binding sites 21,22 barbiturates, benzodiazepine receptor actions 30 Beck Depression Scale 115 behavioral effects anti punishment 9 exploratory 9 behavioral inhibition system 35 behavioral tests, anxiolytic 9 behavioral toxicity see also toxicity benefit/cost aspects, drug controls 278,279 benefit/risk ratio 116 Benzodiazepine Research and Training Project 3 bicuculline 16 binding sites CNS 21-4 and receptors 24 blood-brain barrier 45 brain regions and benzodiazepine effects 17 brain stem, benzodiazepine effects 17 breast milk, infant drug exposure 228 bromazepam abuse 190 caffeinism 80 anxiety 115 tranquilo-sedative use 80 cancer risk and use 260,261 cerebellar cortex, benzodiazepine effects 17 cerebral cortex 17!3-CCE, benzodiazepine antagonism 26,27!3-CCM, benzodiazepine antagonist 26,27!3-CCPr, benzodiazepine antagonism 26,27 central nervous system, onset of effects and plasma invasion 60 CGS 8216, receptor blocking 26 abuse 189,221 alcohol withdrawal 160,161 anxiolytic half-life 97,98 discovery 1 eclamptic seizures 154 pentobarbital abuse comparison 218 chloroquine toxicity incidence 170,171 mortality and 170, 171 cimetidine alcohol withdrawal 160 interaction 56 cirrhosis and clearance 56 clobazam anticonvulsant use 153 serum concentrations 5 I clonazepam anticonvulsant interaction 152 gradual onset 152 mania 164 status epilepticus 150, 15 I abuse 222 half-life, anxiolytic 97,98 seizure use 153 cocaine 231 cognitive impairment 229 commercial availability, international comparison 69,70 conjugation, factors affecting 55,56 308

22 INDEX controls international 268,269 local, psychotropics 267,268 convulsions, electroshock-induced 8 cross-dependence 202 cross-tolerance 93,95 crutch phenomena 79, 183 daytime sedation defined daily dose 71-3 dependence 11, 12 see a/so withdrawal and alcoholism 179, 241 animal studies 203 anxiolytics 103 caffeinism 80,81 continuous therapy 259 definition 201 WHO 181 dosing 81 factors affecting 183 high-dose 235,236 importance 179 incidence 78 low, therapeutic dose 203,204, etiologies 237 sedative-hypnotic withdrawal 242 signs 245 treatment 243,244 neonatal 242, 243 physical 112 physiological 201, 204 prone individuals 79,81 prospective studies need 241, 242 physiological 201,209 evaluation 204 reports 185 routes to 184,186 sedative-hypnotic 235,236,238 propranolol 244, 245 treatment 244,245 symptoms and desmethyl 241 therapeutic use 182, 183 Third World and 172 types 78,79 WHO Expert Committee 270,273 and withdrawal 185,204 depression anxiety 113 benzodiazepines 164 desmethylclobazam, serum concentrations 51, 52 desmethyl half-life 54 plasma levels 48 dependence symptoms 240,241 precursors 54, 98 diagnostic criteria, anxiolytics 101,102 abuse 189,258, anxiolytic half-life 97,98 biotransformations 55 and cancer 260,261 abuse comparison 221 chlorpromazine abuse comparison 215, 216 abuse comparison 222 conditions prescribed 254 eclamptic seizures 154 halazepam abuse comparison 221 initial response and outcome 102 life saving 165 abuse comparison 221, 222 methaqualone abuse comparison 218,219 onset of action 99 oral clefts 262 abuse comparison pentobarbital abuse comparison pentobarbital withdrawal 202,203 prazepam abuse comparison 222 self administration in humans 205,206 long-term 206 slow release 47 plasma levels 48 status epilepticus, regimen 149, 150 Third World uses anesthesis 171, 172 eclampsia 171 emotional disorders 167, 168 malaria 169,170 tetanus 168, 169 use patterns 255 USuse 89 DMCM, structure and actions 26-8 doctor warmth 118 dose high- and low- designations 243 international variations 68 minimal effective hypnotic 93 psychotropic effects 60,61 therapeutic withdrawal 96 titration 92-4 drug abuse history see a/so abuse and abuse liability 214 aftercare 230 benzodiazepine reinforcement drug accumulation 51-4,125 scheme and effects 52 drug combinations 74 drug companies and education role 263, 264 drug holidays 119 drug interactions, alcohol and benzodiazepines 227, 228 drug response assessment 94,95 drug-seeking behaviour 13 duration of action determinants lipophilic properties 50

23 BENZODIAZEPINES duration of action contd termination mechanisms 49, 50 eclampsia, mortality and in Zambia 171 education 263, 264 endocrine effects 10, 11 Europe, benzodiazepine use 72-4 females and overmedication 2 anxiolytic use 255, 256 health system use 256 tranquillizer treatment, reasons 75 FG 7142, structure 27 Finland, alcohol and psychotropic drug use 76,77 flu PH] brain binding 22, 23 anxiolytic effect 139 drug accumulation 139 effectiveness and sleep 126,127 carry-over 132 half-life 94 and hypnotic use 125 insomnia, drug of choice 138 use 189 withdrawal and sleep disturbance 136 Food and Drugs Administration, benzodiazepines introduction 69 France, benzodiazepine availability 70 GABA see (:I-aminobutyric acid GABAergic action, benzodiaepines 7 GABAergic neurons firing facilitation 34 interneurons 15 presynaptic inhibition 16 wiring diagrams 14 GABAergic transmission, benzodiazepine effects 16, 17 potentiation 32 selflimiting 33,34 GABA-facilitation mechanism 17 GABA potentiation andcnsactivity 19 intensity 33 GABA synapse benzodiazepineaction 13-19,33 postsynaptic inhibition 15 generic names Germany, benzodiazepine availability 70 Gilbert's syndrome 55 halazepam abuse 221 half-life 97,98 half-lives and accumulation 51-4 anxiolytic 97, 98 classification 61, 94 hypnotic, clinical comparison onset of action 100 plasma clearance rebound 63 ranges, benzodiazepines 54 short and tapering 53 and symptom return 100 heterocyclic ring variations 71 high pressure liquid chromatography, retention procedure 44 hypnotics activity onset 124, 125 adjunctive use doseandreboundinsomnia dose-titration 93 efficacy 126, 127 intermediate term 127,128 short term 126, 127 half-lives, comparison 125 insomnia 121 choice 140 early morning selection 122 limits to use 92 long acting 92 short term efficacy 127 side effects structural relationships 89 withdrawal effects Iceland, benzodiazepine use 72 indications 67, 68, 87, 89 anxiolyticuse 101,102 DSM-IlI diagnostic criteria 101, 102 proper use 90, 91 insomnia 10 actual sleep 90 alcohol use 123 description 123 drug history 124 drug-induced 123 drug aggravating 91 early morning 125, non-drug management 91 prescribing 121 prevalence 122 psychiatricfactors 124 rebound 123,124,132 dose drugs causing 132-4, 136 and metabolism 135 treatment and pharmacokinetics 124, 125 adjunctive and hypnotics international legislation and control application, variability 275,276 assessment 280,281 cost/benefit outlines 278,279 environmental factors 270 psychotropics inclusion

24 INDEX relevance 277,278 rights 276,277 therapeutic use 275 international use anxiety level 74,75 defined daily doses 71-3 illness-treatment fit 74 Italy, benzodiazepine availability 70 Japan, benzodiazepineavailability 70 lipid solubility 43,44 lithium 163 liver microsomal enzymes 117 long-term use 78 anxiolytic concern 183 postcoronary 103 users 253 abuse 221,222 cardiorespiratory depression 151 dependence 80 duration of action 51 half-life 97,98 status epilepticus 151, 152 lormetazepam, rebound insomnia 132 malaria see also chloroquine cerebral and 169, 170 doses 170 management, non-drug 91 mania and clonazepam use 166 media dependence 180 Valium 251,258 memory impairmeqt 129 metabolism and age 227 methadone 161 methaqualone abuse 184,193 midazolam elimination 50 rebound insomnia 132 misuse 77, 89, 90 definition 181 hypnotics, by physicians 121, 122 long-term use 78 motor impairment 228,229 Multiple Sleep Latency Test 130 muscle relaxant 4, 89 National Ambulatory Medical Care Survey (NAMCS) 253 neonate, physical dependence 242,243 neurochemical probes 1 neurons see also GABA benzodiazepine targets 18, 19 secondary targets 19 neurotransmission, benzodiazepines 13,14 abuse 189 rebound insomnia 132 seizure use 153 nocturnal myoclonus 164 Norway, psychotropic drug use 72,73 numbers of benzodiazepines synthesized oral clefts and in pregnancy 262, 263 overdose 228 acute, data mortality, 257,258 overmedication 251 disorder prevalence and use 252 US assessment 254 overuse, definition 181 abuse and dose 100 half-life 97,98, 100 oxidative pathways clinical effects 55,56 factors affecting 55 pain, physical and psychic 90 panic disorder 101 paradoxical rage reaction 194, 229, 230 pentobarbital benzo abuse comparison withdrawal 202,203 peripherally acting benzodiazepines 23 pharmacodynamics, benzodiazepine differences 100 pharmacokinetics blood levels and brain dynamics 70 chronic anxiety treatment international views 69 pharmacological actions 7-13, pentobarbital withdrawal treatment 246 phenothiazines, benzodiazepine abuse comparison 215,216 phobia 113 photoaffinity labelling 23 physico-chemical properties 43-5 placebo effect benzodiazepine abuse comparison 215 and hypnotics 94 plasma clearance and half-lives 63 plasma levels clinical improvement 102 invasion kinetics plateau and half-lives 61,62 steady-state concentration 55,56 plasma protein binding 44,45 prazepam abuse 222 half-life 97,

25 BENZODIAZEPINES prazepam coma uses 48 prescribing practices 75 anxiety and risks 116 sex bias 255 social solutions 76 prescription control, removal from 82 guidelines in anxiety 118, 119 rate, women 75,76 refusal 119 presynaptic inhibition 13 spinal cord 16 Profile of Mood States (POMS) 114 propranolol anxiety 117, 118 withdrawal strategy psychiatric morbidity incidence 74 third world drug use 167, 168 tranquillizer use 75 psychic distress index 75 psychosocial stimuli 115 psychotherapy and in anxiety 103 psychotropic, definition 283 quazepam withdrawal and sleep disturbance 136 radioreceptor assay 23 rebound phenomena 79 factors affecting 62,63 receptors mode of action 20 properties 19, 20 supersensitivity and propranolol 95, % receptor, {J -adreno, actions 20 receptor, benzodiazepines 19-32,115,240 adaptation 53 agonists 28 inverse 35 partial and mixed 28,29 antagonists 25-8 see also individual compounds barbiturate differences 205 binding sites 20, 240 classes 23, 24 derivative affinity 22 down-regulation 24 multiplicity 24 specific brain 21-4 {J -carboline effects 26-8 chloride channel complexes effector complexes and benzodiazepines 32 endogenous ligands 29 model complex 30, 31 physiological role 32 rebound 95 receptors, GABA antagonists 16 benzodiazepine receptor model 31 chloride channel proteins 15, 30, 31 -effector mechanisms 18 types and activities 16 receptor, nicotinic cholinoceptor 20 regulation 263 reinforcing properties and drug abuse relapse rates, anxiety treatment 103 restless leg~ 164 RO action 30 benzodiazepine receptor block 13,23 properties 25, 26 structural formula 25 withdrawal precipitation 240 safety 2,81 Schedule IV 263,280 schizophrenia 95 benzodiazepines and GABA activity 163 sedative effects 9 seizures 87, 89 see also status epilepticus alcohol withdrawal 154 benzo use clonazepam use 152, 153 eclamptic treatment 154 head trauma 154 menstrual cycle 153 pentylenetetrazol-induced 8 sleep disturbance 90 assessment and drug use 92 hypnotic effectiveness 126,127 social effects 67 abuse 195 benefits of tranquillizers 76 benzodiazepine, alcohol and tobacco 282 implications of use 76 social phobias 199 spasticity 6~, 69 spinal cord, benzodiazepineeffects 16,17 Stanford Sleepiness Scale 130 State Trait Anxiety Index 115 status epilepticus 68 clonazepam administration 150, 151 use 149, 150 and phenytoin 150 step-wise 150 use 151 stimulant and depressant combination 231 stress features and effects 114 identification 118 illness 115 structure-activity relations 21,87,

26 INDEX suicide 138 Sweden, psychotropic drug use 72,73 symptoms, benzodiazepine withdrawal syndromes 228,238 Taylor Manifest Anxiety Scale 114 absorption 125 anterograde amnesia 140 performance 129 restricted use 138, 139 withdrawal 140 tetanus, use, Third World 168, 169 survival 169 therapeutic applications drug discontinuing 95,96 duration 91,92 therapeuticindex 56 Third World black market 82 use see also use 68 tic dulourex, clonazepam 165 tobacco, benzodiazepine and social costs 282 tolerance II, 12, 104 action termination 50 definition 181 drug holidays 119 toxicity II behavioural see also behaviour trade names triazolam activity onset, intravenous 46 pentobarbital abuse comparison 218 rebound insomnia 132 side-effects and suspension 131 withdrawal and sleep disturbance 136, 140 zopiclone abuse comparison 222,223 tricyclic antidepressants in anxiety 117 L-tryptophan and stimulant withdrawal 161 UK benzodiazepine availability 70 psychotropic drug prescribing 72 United Nations, Division of Mental Health 274 United Nations Convention on Psychotropic Substances (1971) 82,268 data validity inclusion criteria 268, 269 inclusion process problems United Nations Universal Declaration of Human Rights 276 US, benzodiazepine availability 70,98 use cost comparisons 282 international comparisons 253 levels and emotional disorders 252 principles 90-6 users patient patterns 255 volume of distribution 50, 51 withdrawal 12 alcohol 89 benzodiazepines 230,236 regimens 160, 161 seizures 154 barbiturate pretreatment 240 benzodiazepine 159,160 short acting 241 symptoms 236 convulsions and dose 104 definition 159 dose 112 pentobarbital 202,203 in rats 202, 203 dose withdrawal reactions 96 drug half-life 53,78,79 duration of treatment 79,132 effects of sudden 79 hypnotics see also insomnia, rebound incidence 79, narcotics and benzodiazepine use 188 opiate 161 physician support 81 receptor blockers 13 sedative-hypnotic types 235,236,238 stimulant regimen 161 syndromes compared 239 tapering dose 104 treatment strategies 243, 244 tricyclic antidepressants 103 Women in Crisis Conference 256 World Health Organization (WHO) abuse classification 182 essential drugs 167 zopiclone