Advertisement

Drug Safety

, Volume 6, Issue 4, pp 247–265 | Cite as

Benzodiazepine Poisoning

Clinical and Pharmacological Considerations and Treatment
  • Pierre Gaudreault
  • Joanne Guay
  • Robert L. Thivierge
  • Isabelle Verdy
Review Article Poisoning Management

Summary

Benzodiazepines are among the most frequently prescribed drugs worldwide. This popularity is based not only on their efficacy but also on their remarkable safety. Pure benzodiazepine overdoses usually induce a mild to moderate central nervous system depression; deep coma requiring assisted ventilation is rare, and should prompt a search for other toxic substances. The severity of the CNS depression is influenced by the dose, the age of the patient and his or her clinical status prior to the ingestion, and the coingestion of other CNS depressants. In severe overdoses, benzodiazepines can occasionally induce cardiovascular and pulmonary toxicity, but deaths resulting from pure benzodiazepine overdoses are rare.

Quantitative determinations of benzodiazepines are not useful in the clinical management of intoxicated patients since there is no correlation between serum concentrations and pharmacological and toxicological effects.

Benzodiazepine overdoses occurring during pregnancy rarely induce serious morbidity in mothers or fetuses, although large doses administered near delivery can induce respiratory depression in neonates. The teratogenic potential of benzodiazepines remains controversial, but is probably small if it exists at all.

There is clear evidence that the prolonged use of even therapeutic doses of benzodiazepines will lead to dependence. The risk of developing significant withdrawal symptoms is related to dosage and duration of treatment.

Prevention of gastrointestinal absorption should be initiated in all intentional benzodiazepine overdoses. Forced diuresis and dialysis techniques are not indicated since they will not significantly accelerate the elimination of these agents. Intravenous administration of flumazenil, a pure benzodiazepine antagonist, effectively reverses benzodiazepine-induced CNS depression.

Keywords

Flumazenil Triazolam Oxazepam Nitrazepam Clobazam 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Aarskog D. Association between maternal intake of diazepam and oral clefts. Lancet 2: 921–922, 1975PubMedGoogle Scholar
  2. Abernethy DR, Greenblatt DJ, Divoll M, Arendt R, Ochs HR, et al. Impairment of diazepam metabolism by low-dose estrogen-containing oral-contraceptive steroids. New England Journal of Medicine 306: 791–792, 1982PubMedGoogle Scholar
  3. Abernethy DR, Greenblatt DJ, Divoll M, Moschitto LJ, Harmatz JS, et al. Interaction of cimetidine with the triazolobenzodi-azepines alprazolam and triazolam. Psychopharmacology 80: 275–278, 1983aPubMedGoogle Scholar
  4. Abernethy DR, Greenblatt DJ, Ochs HR, et al. Lorazepam and oxazepam kinetics in women on low-dose oral contraceptives. Clinical Pharmacology and Therapeutics 33: 628–632, 1983bPubMedGoogle Scholar
  5. Acosta D, Chappell R. Cardiotoxicity of diazepam in cultured heart cells. Toxicology 8: 311–317, 1977PubMedGoogle Scholar
  6. Allen CJ, Gough KR. The effect of doxapram on heavy sedation produced by intravenous diazepam in a patient with tetanus. British Medical Journal 286: 1181–1182, 1983PubMedGoogle Scholar
  7. Allen MD, Greenblatt DJ, Lacasse Y, Shader RI. Pharmacokinetic study of lorazepam overdosage. American Journal of Psychiatry 137: 1414–1415, 1980PubMedGoogle Scholar
  8. Allonen G, Ziegler G, Klotz U. Midazolam kinetics. Clinical Pharmacology and Therapeutics 30: 653–661, 1981PubMedGoogle Scholar
  9. Alvan G, Siwers B, Vessman J. Pharmacokinetics of oxazepamin healthy volunteers. Acta Pharmacologica et Toxicologica 40(Suppl. 1): 40–51, 1977PubMedGoogle Scholar
  10. Amrein R, Leishman B, Bentzinger C, Roncari G. Flumazenil in benzodiazepine antagonism: actions and clinical use in intoxications and anesthesiology. Medical Toxicology 2: 411–429, 1987PubMedGoogle Scholar
  11. Ananth J. Side effects in the neonate from psychotropic agents excreted through breast-feeding. American Journal of Psychiatry 135: 801–805, 1978PubMedGoogle Scholar
  12. Andreasen PB, Hendel J, Greisen G, Hvidger EF. Pharmacokinetics of diazepam in disordered liver function. European Journal of Clinical Pharmacology 10: 115–120, 1976PubMedGoogle Scholar
  13. Arendt RM, Greenblatt DJ, de Jong RH, et al. In vitro correlates of benzodiazepine cerebrospinal fluid uptake, pharmacodynamic action, and peripheral distribution. Journal of Pharmacology and Experimental Therapeutics 227: 95–106, 1983Google Scholar
  14. Ayd Jr FJ. Benzodiazepines: dependence and withdrawal. Journal of the American Medical Association 242: 1401–1402, 1979PubMedGoogle Scholar
  15. Aziz K. Drugs-of-abuse testing: screening and confirmation. Clinics in Laboratory Medicine 10: 493–502, 1990PubMedGoogle Scholar
  16. Baehrendtz S, Hojer J. Flumazenil in self-induced benzodiazepine poisoning. European Journal of Anaesthesiology (Suppl. 2): 287–293, 1988Google Scholar
  17. Bal TS, Johnson B, Kilner EA, Sunter JP, Cowan WK. Three deaths involving triazolam -analytical aspects. Journal of the Forensic Science Society 29: 119–123, 1989PubMedGoogle Scholar
  18. Balter MB, Manheimer DI, Mellinger GD, et al. A cross-nationalcomparison of anti-anxiety/sedative drug use. Current MedicalResearch Opinion 8(Suppl. 4): 5–20, 1984Google Scholar
  19. Bansky G, Meier PJ, Ziegler WH, et al. Reversal of hepatic coma by benzodiazepine antagonist (Ro 15-1788). Lancet 1: 1324–1325, 1985Google Scholar
  20. Barry WS, St Clair SM. Exposure to benzodiazepines in utero. Lancet 1: 1436–1437, 1987PubMedGoogle Scholar
  21. Bell EF. The use of naloxone in the treatment of diazepam poisoning. Journal of Pediatrics 87: 803–804, 1975PubMedGoogle Scholar
  22. Berger R, Green G, Melnick A. Cardiac arrest caused by oral diazepam intoxication. Clinical Pediatrics 14: 842–844, 1975PubMedGoogle Scholar
  23. Bergman U, Boethius G, Swartling PG, Isacson D, Smedby B. Teratogenic effects of benzodiazepine use during pregnancy. Journal of Pediatrics 116: 490–491, 1990PubMedGoogle Scholar
  24. Besunder JB, Blumer JL. Neonatal drug withdrawal syndromes.In Koren (Ed.) Maternal-fetal toxicology: a clinicians’ guide, Marcel Dekker Inc., New York, 1990Google Scholar
  25. Bismuth C, Baud FJ, Du Fretay H, Mellerioi F. Antagoniste Ro 15-1788 dans l’intoxication volontaire par benzodiazepines: valeur diagnostique et thérapeutique. Abstract. Réanimation, Soins Intensifs, Médecine d’Urgence 1: 263, 1986Google Scholar
  26. Bodenham A, Brownlie G, Dixon JS, Park GR. Reversal of sedation by prolonged infusion of flumazenil (Anexate, Ro 15-1788). Anaesthesia 43: 376–378, 1988PubMedGoogle Scholar
  27. Bouget J, Breurec JY, Baert A, Yapo-Ette H, Feuillu A, et al. Intérêt du charbon par voie orale chez des patients admis en service d’urgence pour absorption volontaire de benzodiazepines. Journal de Toxicologie Clinique et Expérimentale 9: 287–289, 1989PubMedGoogle Scholar
  28. Boxenbaum HGI, Geitner KA, Jack MK, Dixon WR, Kaplan SA. Pharmacokinetics and biopharmaceutical profile of chlordi-azepoxide HCl in healthy subjects: single dose studies by intravenous, intramuscular and oral routes. Journal of Pharmacokinetics and Biopharmaceutics 5: 3–23, 1977aPubMedGoogle Scholar
  29. Boxenbaum HG, Geitner KA, Jack ML, Dixon WR, Kaplan SA. Pharmacokinetic and biopharmaceutic profile of chlordiaze-poxide HCI in healthy subjects: multiple-dose oral administration. Journal of Pharmacokinetics and Biopharmaceutics 5: 25–39, 1977bPubMedGoogle Scholar
  30. Brouard A, Perdu E, Bismuth C. Monographie systematisée, réalisée à la demande de l’OMS et de la Communauté Européenne, dans le cadre d’une commission de revision des antidotes. Journal de Toxicologie Clinique et Expérimentale 4: 223–237, 1987Google Scholar
  31. Burkhart KK, Kulig KW. The diagnostic utility of flumazenil (a benzodiazepine antagonist) in coma of unknown etiology. Annals of Emergency Medicine 19: 319–321, 1990PubMedGoogle Scholar
  32. Busto U, Kaplan HL, Sellers EM. Benzodiazepine-associated emergencies in Toronto. American Journal of Psychiatry 137: 224–227, 1980PubMedGoogle Scholar
  33. Busto U, Lanctôt KL, Isaac P, Manuella A. Benzodiazepine use and abuse in Canada. Canadian Medical Association Journal 141: 917–921, 1989PubMedGoogle Scholar
  34. Busto U, Sellers EM, Naranjo CA, Cappeli H, Sanchez-Craig M, et al. Withdrawal reaction after long-term therapeutic use of benzodiazepines. New England Journal of Medicine 315: 854–859, 1986PubMedGoogle Scholar
  35. Carroll WM, Mastiglia FL. Alpha and beta coma in drug intoxication. British Medical Journal 2: 1518–1519, 1977PubMedGoogle Scholar
  36. Castleden CM, George CF, Marcer D, Hallett C. Increased sensitivity to nitrazepam in old age. British Medical Journal 1: 10–12, 1977PubMedGoogle Scholar
  37. Cate JC, Jatlow PI. Chlordiazepoxide overdose: interpretation of serum drug concentrations. Clinical Toxicology 6: 553–561,1973Google Scholar
  38. Cerqueira Ma J, Olle C, Bellart J, Baro F, Cabero L, et al. Intoxicationby benzodiazepines during pregnancy. Lancet 1: 1341,1988PubMedGoogle Scholar
  39. Choux C, Gueugniaud PY, Prost G, Vaudelin T, Bertin-Maghit M, et al. Limites du flumazénil en pratique pré-hospitalière. Presse Médicale 19: 719, 1990Google Scholar
  40. Cimbura G, Lucas DM, Bennett RC, Warren RA, Simpson HM. Incidence and toxicological aspects of drugs detected in 484 fatally injured drivers and pedestrians in Ontario. Journal of Forensic Sciences 27: 855–867, 1982PubMedGoogle Scholar
  41. Ciraulo DA, Barnhill JG, Boxenbaum HG, Greenblatt DJ, Smith RB. Pharmacokinetics and clinical effects of alprazolam following single and multiple oral doses in patients with panic disorder. Journal of Clinical Pharmacology 26: 292–298, 1986PubMedGoogle Scholar
  42. Cook PJ, Flanagan R, James IM. Diazepam tolerance: effect of age, regular sedation and alcohol. British Medical Journal 289: 351–353, 1984PubMedGoogle Scholar
  43. Costa E, Guidotti A, Mao CC. Evidence for the involvement of GABA in the action of benzodiazepines: studies on rat cerebellum. Advances in Biochemical Psychopharmacology 14: 113–130, 1975PubMedGoogle Scholar
  44. Crevoisier C, Eckert M, Heizmann P, Thurneysen DJ, Ziegler WH. Relation entre l’effet clinique et al pharmacocinétique du midazolam après l’administration IV ou IM. Arzneimittel-Forschung 31: 2211–2215, 1981PubMedGoogle Scholar
  45. Curry SH, Smith CM. Diazepam-ethanol interaction in humans: addiction or potentiation? Communications in Psychopharmacology 3: 101–113, 1979PubMedGoogle Scholar
  46. Czeizel A. Diazepam, phenytoin, and etiology of cleft lip and/or cleft palate. Lancet 1: 810, 1976PubMedGoogle Scholar
  47. Darragh A, Lambe R, Kenny M, Brick I, Taffe W, et al. RO 15-1788 antagonises the central effects of diazepam in man without altering diazepam unavailability. British Journal of Clinical Pharmacology 14: 677–682, 1982PubMedGoogle Scholar
  48. Desmond PV, Patwardhan RV, Schenker S, Hoyumpa AM. Short-term ethanol administration impairs the elimination of chlordiazepoxide (Librium) in man. European Journal of Clinical Pharmacology 18: 275–278, 1980aPubMedGoogle Scholar
  49. Desmond PV, Patwardhan RV, Schenker S, Speeg KV. Cimetidine impairs elimination of chlordiazepoxide (Librium) in man. Annals of Internal Medicine 93: 266–268, 1980bPubMedGoogle Scholar
  50. Diliberti L, O’Brien ML, Turner T. The use of physostigmine as an antidote in accidental diazepam intoxication. Journal of Pediatrics 86: 106–107, 1975Google Scholar
  51. Divoll M, Greenblatt DJ. Alcohol does not enhance diazepam absorption. Pharmacology 22: 263–268, 1981aPubMedGoogle Scholar
  52. Divoll M, Greenblatt DJ. Plasma concentrations of temazepam, a 3-hydroxy benzodiazepine, determined by electron-capture gas-liquid chromatography. Journal of Chromatography 222: 125–128, 1981bPubMedGoogle Scholar
  53. Divoll M, Greenblatt DJ, Harmatz JS, Shader RI. Effect of age and gender on disposition of temazepam. Journal of Pharmaceutical Sciences 70: 1104–1107, 1981aPubMedGoogle Scholar
  54. Divoll M, Greenblatt DJ, Lacasse Y, Shader RI. Benzodiazepine overdosage: plasma concentrations and clinical outcome. Psychopharmacology 73: 381–383, 1981bPubMedGoogle Scholar
  55. Divoll M, Greenblatt DJ, Ochs HR, Shader RI. Absolute bioavailability of oral and intramuscular diazepam: effects of age and sex. Anesthesia and Analgesia 62; 1–8, 1983PubMedGoogle Scholar
  56. Dorian P, Sellers EM, Kaplan HL, Hamilton C, Greenblatt DJ, et al. Triazolam and ethanol interaction: kinetic and dynamic consequences. Clinical Pharmacology and Therapeutics 37: 558–562, 1985PubMedGoogle Scholar
  57. Eckert M, Ziegler WH, Cano JP, et al. Pharmacokinetics and pharmacodynamics of flurazepam in man: part I. Drugs under Experimental and Clinical Research 9: 77–84, 1983Google Scholar
  58. El-Khordagui LK, Saleh AM, Khalil SA. Adsorption of benzodiazepines on charcoal and its correlation with in vitro and in vivo data. Pharmaceutica Acta Helvetiae 62: 28–32, 1987PubMedGoogle Scholar
  59. Ellinwood EH, Healtherly DG, Nikardo AM, Bjomsson TD, Kilts C. Comparative pharmacokinetics and pharmacodynamics of lorazepam, alprazolam and diazepam. Psychopharmacology 86: 392–399, 1985PubMedGoogle Scholar
  60. Fantozzi R, Caramelli L, Barattini M, et al. Clinical experiences with Ro 15–1788 (Anexate) in benzodiazepine and mixed-drug overdoses. Resuscitation (Suppl. 16): S79-S82, 1988Google Scholar
  61. Farley TA. Severe hypernatremic dehydration after use of an activated charcoal-sorbitol suspension. Journal of Pediatrics 109: 719–722, 1986PubMedGoogle Scholar
  62. Ferslew KE, Hagardorn AN, McCormick WF. Postmortem determination of the biological distribution of sufentanil and midazolam after an acute intoxication. Journal of Forensic Sciences 34: 249–257, 1989PubMedGoogle Scholar
  63. Finkle BS, McCloskey KL, Goodman LS. Diazepam and drug-associated deaths: a survey in the United States and Canada. Journal of the American Medical Association 242: 429–434, 1979PubMedGoogle Scholar
  64. Ford S, Ankier SI, Corless D, et al. Pharmacokinetics of loprazolam and its principal metabolite in young subjects and elderly hospital patients. Xenobiotica 8: 1001–1009, 1987Google Scholar
  65. Forster AF, Morel DM, Bachmann M, et al. Respiratory depressant effects of different doses of midazolam and lack of reversal with naloxone: a double-blind randomized study. Anesthesia and Analgesia 62: 920–924, 1983PubMedGoogle Scholar
  66. Friedman H, Greenblatt DJ, Burnstein ES, Harvatz JS, Shader RI. Population study of triazolam pharmacokinetics. British Journal of Clinical Pharmacology 22: 639–642, 1986PubMedGoogle Scholar
  67. Fucella LM, Bolcioni G, Tamassia V, Ferrario L, Tognoni G. Human pharmacokinetics and bioavailability of temazepam administered in soft gelatin capsules. European Journal of Clinical Pharmacology 12: 383–386, 1977Google Scholar
  68. Garnier R, Medemach C, Harbach S, Fournier E. Agitation et hallucinations lors des intoxications aiguës par le lorazépam chez l’enfant. Annales de Pédiatrie 31: 286–289, 1984PubMedGoogle Scholar
  69. Garriott JC, Latman N. Drug detection in cases of driving under the influence. Journal of Forensic Sciences 21: 398–415, 1976PubMedGoogle Scholar
  70. Garzone PD, Kroboth PD. Pharmacokinetics of the newer benzodiazepines. Clinical Pharmacokinetics 16: 337–364, 1989PubMedGoogle Scholar
  71. George CF, Robertson D. Clinical consequences of abrupt drug withdrawal. Medical Toxicology 2: 367–382, 1987PubMedGoogle Scholar
  72. Ghoneim MM, Mewaldt SP. Benzodiazepines and human memory: a review. Anesthesiology 72: 926–938, 1990PubMedGoogle Scholar
  73. Goethe JW, Edelman SL. Chlordiazipoxide toxicity in Limbitrol overdose. American Journal of Psychiatry 142: 774, 1985PubMedGoogle Scholar
  74. Greenblatt DJ, Abernethy DR, Divoll M, Harmatz JS, Shader RI. Pharmacokinetic properties of benzodiazepine hypnotics. Journal of Clinical Psychopharmacology 3: 129–132, 1983aPubMedGoogle Scholar
  75. Greenblatt DJ, Abernethy DR, Locniskar A, Ochs HR, Harmatz JS, et al. Age, sex, and nitrazepam kinetics: relation to antipyrine disposition. Clinical Pharmacology and Therapeutics 38: 697–703, 1985PubMedGoogle Scholar
  76. Greenblatt DJ, Allen MD, Locniskar A, Harmatz JS, Shader RI. Lorazepam kinetics in the elderly. Clinical Pharmacology and Therapeutics 26: 103–113, 1979PubMedGoogle Scholar
  77. Greenblatt DJ, Allen MD, Noel BJ, Shader RI. Acute overdosage with benzodiazepine derivatives. Clinical Pharmacology and Therapeutics 21: 497–514, 1977aPubMedGoogle Scholar
  78. Greenblatt DJ, Divoll M, Abernethy DR, Moschitto LJ, Smith RB, et al. Alprazolam kinetics in the elderly. Archives of General Psychiatry 40: 287–290, 1983cPubMedGoogle Scholar
  79. Greenblatt DJ, Divoll M, Abernethy DR, Moschitto LJ, Smith RB, et al. Reduced clearance of triazolam in old age: relation to antipyrine oxidizing capacity. British Journal of Clinical Pharmacology 15: 303–309, 1983dPubMedGoogle Scholar
  80. Greenblatt DJ, Divoll M, Abernethy DR, Ochs HR, Shader RI. Diazepam disposition determinants. Clinical Pharmacology and Therapeutics 27: 301–312, 1980aPubMedGoogle Scholar
  81. Greenblatt DJ, Divoll M, Harmatz JS. Pharmacokinetic comparison of sublingual lorazepam with intravenous, intramuscular, and oral lorazepam. Journal of Pharmaceutical Sciences 71: 248–252, 1982PubMedGoogle Scholar
  82. Greenblatt DJ, Divoll M, Harmatz JS, Shader RI. Oxazepam kinetics: effects of age and sex. Journal of Pharmacology and Experimental Therapeutics 215: 86–91, 1980bPubMedGoogle Scholar
  83. Greenblatt DJ, Divoll M, Puri SK, Ho I, Zinny MA, et al. Clobazam kinetics in the elderly. British Journal of Clinical Pharmacology 12: 631–636, 1981PubMedGoogle Scholar
  84. Greenblatt DJ, Divoll M, Puri SK, Ho I, Zinny MA, et al. Reduced single-dose clearance of clobazam in elderly men predicts increased multiple-dose accumulation. Clinical Pharmacokinetics 8: 83–94, 1983bPubMedGoogle Scholar
  85. Greenblatt DJ, Ehrenberg BL, Gunderman J, et al. Pharmacokinetic and electroencephalographic study of intravenous diazepam, midazolam, and placebo. Clinical Pharmacology and Therapeutics 45: 356–365, 1989PubMedGoogle Scholar
  86. Greenblatt DJ, Schillings RT, Kyriakopoulos AA, et al. Clinical pharmacokinetics of lorazepam: I. Absorption and disposition of oral 14C-Lorazepam. Clinical Pharmacology and Therapeutics 20: 329–341, 1976PubMedGoogle Scholar
  87. Greenblatt DJ, Shader RI. Prazepam and lorazepam, two new benzodiazepines. New England Journal of Medicine 299: 1342–1344, 1978PubMedGoogle Scholar
  88. Greenblatt DJ, Shader RI, Harmatz JS, Franke K, Kosch-Weser J. Absorption rate, blood concentrations, and early response to oral chlordiazepoxide. American Journal of Psychiatry 134: 559–562, 1977bPubMedGoogle Scholar
  89. Greenblatt DJ, Shader RI, Macleod SM, Sellers EM. Flurazepam hydrochloride. Clinical Pharmacology and Therapeutics 17: 1–14, 1975PubMedGoogle Scholar
  90. Greenblatt DJ, Shader RI, Weinberger DR, Allen MD, Mac-Laughlin DS. Effect of cocktail on diazepam absorption. Psychopharmacology 57: 199–203, 1978bPubMedGoogle Scholar
  91. Greenblatt DJ, Woo E, Divoll M, Allen M, Orsulak PJ, et al. Rapid recovery from massive diazepam overdose. Journal of the American Medical Association 240: 1872–1874, 1978aPubMedGoogle Scholar
  92. Haefely WE. Pharmacology of the benzodiazepine receptor. European Archives of Psychiatry and Neurological Sciences 238: 294–301, 1989PubMedGoogle Scholar
  93. Haefely W, Kulcsar A, Möhler H, et al. Possible involvement of GABA in the central actions of benzodiazepines. Advances in Biochemical Psychopharmacology 14: 131–151, 1975PubMedGoogle Scholar
  94. Harrison M, Busto U, Naranjo CA, Kaplan HL, Sellers EM. Diazepam tapering in detoxification for high-dose benzodiazepine abuse. Clinical Pharmacology and Therapeutics 36: 527–533, 1984PubMedGoogle Scholar
  95. Hayes SL, Pablo G, Radomski T, Palmer RF. Ethanol and oral diazepam absorption. New England Journal of Medicine 296: 186–189,1977PubMedGoogle Scholar
  96. Heizmann P, Eckert M, Zeigler WH. Pharmacokinetics and bioavailability of midazolam in man. British Journal of Clinical Pharmacology 16: 43S–49S, 1983PubMedGoogle Scholar
  97. Heyndrickx B. Fatal intoxication due to flunitrazepam. Journal of Analytical Toxicology 11: 278, 1987PubMedGoogle Scholar
  98. Higgitt AC, Lader MH, Fogany P. Clinical management of benzodiazepine dependence. British Medical Journal 291: 688–691, 1985PubMedGoogle Scholar
  99. Hiss J, Hepler BR, Falkowski AJ, Sunshine I. Fatal bradycardia after intentional overdose of cimetidine and diazepam. Lancet 2: 982, 1982PubMedGoogle Scholar
  100. Hofer P, Scollo-Lavizzari G. Benzodiazepine antagonist Ro 15-1788 in self-poisoning: diagnostic and therapeutic use. Archives of Internal Medicine 145: 663–664, 1985PubMedGoogle Scholar
  101. Höjer J, Baehrendtz S. The effect of flumazenil (Ro 15-1788) in the management of self-induced benzodiazepine poisoning. Acta Medica Scandinavica 224: 357–365, 1988PubMedGoogle Scholar
  102. Höjer J, Baehrendtz S, Gustafsson L. Benzodiazepine poisoning: experience of 702 admissions to an intensive care unit during a 14-year period. Journal of Internal Medicine 226: 117–122, 1989PubMedGoogle Scholar
  103. Højgaard AD, Andersen PT, Møller-Petersen J. Rhabdomyolisis and acute renal failure following an overdose of doxepin and nitrazepam. Acta Medica Scandinavica 223: 79–82, 1988PubMedGoogle Scholar
  104. Hoyumpa A, Patwardhan R, Maples M, Desmond P, Johnson R, et al. Effect of short-term ethanol administration on lorazepa mmetabolism. Gastroenterology 79: 1027, 1980Google Scholar
  105. Hughes FW, Forney RB, Richards AB. Comparative effect in human subjects of chlordiazepoxide, diazepam, and placebo on mental and physical performance. Clinical Pharmacology and Therapeutics 6: 139–145, 1965PubMedGoogle Scholar
  106. Hunkeler W, Mönier H, Pieri L, et al. Selective antagonists of benzodiazepines. Nature 290: 514–516, 1981PubMedGoogle Scholar
  107. Jatlow P, Dobular K, Bailey D. Serum diazepam concentrations in overdose: their significance. American Journal of Clinical Pathology 72: 571–577, 1979PubMedGoogle Scholar
  108. Jeffrey DI, Withfield MF. Lorazepam poisoning. British Medical Journal 4: 719, 1974Google Scholar
  109. Jochemsen R, Van Der Graaff, Boeijinga JK, Breimer DD. Influence of sex, menstrual cycle, and oral contraception on the disposition of nitrazepam. British Journal of Clinical Pharmacology 13: 319–324, 1982PubMedGoogle Scholar
  110. Jochemsen R, Van Rijn PA, Hazelet TGM, Van Boxtel CJ, Breimer DD. Comparative pharmacokinetics of midazolam and loprazolam in healthy subjects after oral administration. Biopharmaceutics and Drug Disposition 7: 53–61, 1986Google Scholar
  111. Jochemsen R, Wesselman JGJ, Van Boxtel CJ, Hermans J, Breimer DD. Comparative pharmacokinetics of brotizolam and triazolam in healthy subjects. British Journal of Clinical Pharmacology 16 (Suppl. 2): 291S–298S, 1983PubMedGoogle Scholar
  112. Jones DJ, Stehling LC, Zauder HL. Cardiovascular responses to diazepam and midazolam maleate in the dog. Anesthesiology 51: 430–434, 1979PubMedGoogle Scholar
  113. Jordan C, Lehaue JR, Jones JG. Respiratory depression following diazepam: reversal with high dose naloxone. Anesthesiology 53: 293–298, 1980PubMedGoogle Scholar
  114. Kangas L, Breimer DD. Clinical pharmacokinetics of nitrazepam. Clinical Pharmacokinetics 6: 346–366, 1981PubMedGoogle Scholar
  115. Kanto JH. Use of benzodiazepines during pregnancy, labour, and lactation, with particular reference to pharmacokinetic consideration. Drugs 23: 354–380, 1982PubMedGoogle Scholar
  116. Kaplan SA, Jack ML, Alexander K, Weinfeld RE. Pharmacokinetic profile of diazepam in man following single intravenous and oral and chronic oral administrations. Journal of Pharmaceutical Sciences 62: 1789–1796, 1973PubMedGoogle Scholar
  117. Kelly RC, Krent L, Sunshine I. Association of benzodiazepines with death in a major metropolitan area. Journal of Analytical Toxicology 6: 91–96, 1982PubMedGoogle Scholar
  118. King LA. Synergistic effect of benzodiazepines in fatal amitriptyline poisonings. Lancet 2: 982–983, 1982PubMedGoogle Scholar
  119. Klotz U, Antonin KH, Bieck PR. Comparison of the kinetics of diazepam after single and subchronic doses. European Journal of Clinical Pharmacology 10: 121–126, 1976PubMedGoogle Scholar
  120. Klotz U, Duka T, Dorow R, Doenicke A. Flunitrazepam and lormetazepam do not affect the pharmacokinetics of the benzodiazepine antagonist Ro 15-1788. British Journal of Clinical Pharmacology 19: 95–98, 1985bPubMedGoogle Scholar
  121. Klotz U, Reimann I. Delayed clearance of diazepam due to cimetidine. New England Journal of Medicine 302: 1012–1014, 1980PubMedGoogle Scholar
  122. Klotz U, Ziegler G, Ludwig L, Reimann IW. Pharmacodynamic interaction between midazolam and a specific benzodiazepine antagonist in humans. Journal of Clinical Pharmacology 25: 400–406, 1985aPubMedGoogle Scholar
  123. Klotz U, Ziegler G, Reimann IW. Pharmacokinetics of the selective benzodiazepine antagonist Ro 15-1788 in man. European Journal of Clinical Pharmacology 24: 115–117, 1984Google Scholar
  124. Klotz U, Ziegler G, Rosenkranz B, Mikus G. Does the benzodiazepine antagonist Ro 15-1788 antagonize the action of ethanol? British Journal of Clinical Pharmacology 22: 513–520, 1986PubMedGoogle Scholar
  125. Knudsen L, Lonka L, Sorensen BH, Kirkegaard L, Jensen OV, et al. Benzodiazepine intoxication treated with flumazenil (Anexate, Ro 15-1788). Anaesthesia 43: 274–276, 1988PubMedGoogle Scholar
  126. Kraus JW, Desmond PV, Marshall JP, Johnson RF, Schenker S, et al. Effect of aging and liver disease on disposition of lorazepam. Clinical Pharmacology and Therapeutics 24: 411–419, 1978PubMedGoogle Scholar
  127. Krieger J, Perianu M, Bertagna C, Manfen P, Kurtz D. Hypnotic benzodiazepines: relationship between sleep parameters and pharmacokinetics of loprazolam. Drug Development and Research 3: 143–152, 1983Google Scholar
  128. Kumar A, Mohan M, Anand NK. Aminophylline in neonatal diazepam intoxication. Indian Pediatrics 24: 602–604, 1987PubMedGoogle Scholar
  129. Laegreid I, Olegard R, Conradi N, Hagberg G, Wahlström J, et al. Congenital malformations and maternal consumption of benzodiazepines: a case-control study. Developmental Medicine and Child Neurology 32: 432–441, 1990PubMedGoogle Scholar
  130. Laegreid L, Olegard R, Wahlström J, Conradi N. Abnormalities in children exposed to benzodiazepines in utero. Lancet 1: 108–109, 1987PubMedGoogle Scholar
  131. Laegreid L, Olegard R, Wahlström J, Conradi N. Teratogenic effects of benzodiazepine use during pregnancy. Journal of Pediatrics 114: 126–131, 1989PubMedGoogle Scholar
  132. Leykin Y, Halpern P, Silbiger A, et al. Acute poisoning treated in the intensive care unit: a case series. Israel Journal of Medical Sciences 25: 98–102, 1989PubMedGoogle Scholar
  133. Lheureux P, Askenasi R. Treatment of benzodiazepine overdose with Ro 15-1788. Archives of Internal Medicine 146: 1241,1986PubMedGoogle Scholar
  134. Lheureux P, Askenasi R. Specific treatment of benzodiazepine overdose. Human Toxicology 7: 165–170, 1988PubMedGoogle Scholar
  135. Lheureux P, Askenasi R. Agonism and antagonism at the benzodiazepine-receptor: a new concept for new approach of common drug poisoning. Acta Anaesthesiologica Belgica 40: 23–28, 1989PubMedGoogle Scholar
  136. Linnoila M, Hakkinen S. Effects of diazepam and codeine, alone and in combination with alcohol, on simulated driving. Clinical Pharmacology and Therapeutics 15: 368–373, 1974PubMedGoogle Scholar
  137. Linnoila M, Mattila MJ. Drug interaction on psychomotor skills related to driving: diazepam and alcohol. European Journal of Clinical Pharmacology 5: 186–194, 1973aGoogle Scholar
  138. Linnoila M, Mattila MJ. Proceedings: drug interaction on driving skills as evaluated by laboratory tests and by driving simulator. Pharmakopsychiatrie, Neuro-Psychopharmakologie 6: 127–132, 1973bPubMedGoogle Scholar
  139. Litovitz T. Fatal benzodiazepine toxicity? American Journal of Emergency Medicine 5: 472–473, 1987Google Scholar
  140. Litovitz TL, Martin TG, Schmitz B. 1986 Annual report of the American association of poison control centers national data collection system. American Journal of Emergency Medicine 5: 405–445, 1987PubMedGoogle Scholar
  141. Litovitz TL, Schmitz BF, Holm KC. 1988 Annual report of the American Association of Poison Control Centers national data collection system. American Journal of Emergency Medicine 7: 495–545, 1989PubMedGoogle Scholar
  142. Litovitz TL, Schmitz BF, Matyunas N, Martin TG. 1987 Annual report of the American Association of Poison Control Centers national data collection system. American Journal of EmergencyMedicine 6: 479–515, 1988Google Scholar
  143. Lundberg GD, White JM, Hoffman KI. Drugs (other than or in addition to ethyl alcohol) and driving behavior a collaborative study of the California Association of Toxicologists. Journal of Forensic Sciences 24: 207–215, 1979PubMedGoogle Scholar
  144. MacLeod SM, Sellers EM, Giles HG, et al. Interaction of disulfiram with benzodiazepines. Clinical Pharmacology and Therapeutics 24: 583–589, 1978PubMedGoogle Scholar
  145. Mandelli M, Tognoni G, Garattini S. Clinical pharmacokinetics of diazepam. Clinical Pharmacokinetics 3: 72–91, 1978PubMedGoogle Scholar
  146. Marks J. Techniques of benzodiazepine withdrawal in clinical practice: a consensus workshop report. Medical Toxicology 3: 324–333, 1988PubMedGoogle Scholar
  147. Martin CD, Chan SC. Distribution of temazepam in body fluids and tissues in lethal overdose. Journal of Analytical Toxicology 10: 77–78, 1986PubMedGoogle Scholar
  148. Massault J, d’Hollander A, Barvais L, Dubois-Primo J. Haemodynamic effects of midazolam in anaesthetized patients with coronary artery disease. Acta Anaesthesiologica Scandinavica 27: 299–302, 1983Google Scholar
  149. McCormick SR, Nielsen J, Jatlow PI. Alprazolam overdose: clinical findings and serum concentrations in two cases. Journal of Clinical Psychiatry 46: 247–248, 1985PubMedGoogle Scholar
  150. Mennini T, Cotecchia S, Caccia S, Garattini S. Benzodiazepines: relationship between pharmacological activity in the rat and in vivo receptor binding. Pharmacology, Biochemistry and Behavior 16: 529–532, 1982Google Scholar
  151. Mignée C, Garnier R, Conso F, Efthymiou ML, Fournier E. Intoxication aiguë par le flunitrazépam. Thérapie 35: 581–589, 1980PubMedGoogle Scholar
  152. Möhler H, Okada T. Benzodiazepines receptors: demonstration in the central nervous system. Science 198: 849–851, 1977PubMedGoogle Scholar
  153. Möhler H, Burkard WP, Keller HH, Richards JG, Haefely W. Benzodiazepine antagonist RO 15-1788: binding characteristics and interaction with drug-induced changes in dopamine turnover and cerebellar cGMP levels. Journal of Neurochemistry 37: 714–722, 1981PubMedGoogle Scholar
  154. Möhler H, Richards JG. Agonist and antagonist benzodiazepine receptor interaction in vitro. Nature 294: 763–765, 1981PubMedGoogle Scholar
  155. Morland J, Setekleiv J, Haffher JFW, et al. Combined effects of diazepam and ethanol on mental and psychomotor functions. Acta Pharmacologica et Toxicologica 34: 5–15, 1974PubMedGoogle Scholar
  156. Nagy J, Decsi L. Physostigmine, a highly potent antidote for acute experimental diazepam intoxication. Neuropharmacology 17: 469–475, 1978PubMedGoogle Scholar
  157. Norman TR, Burrows GD. Plasma concentrations of benzodiazepines: a review of clinical findings and implications. Progress in Neuropsychopharmacology and Biological Psychiatry 8: 115–126, 1984Google Scholar
  158. O’Boyle C, Lambe R, Darragh A, Taffe W, Brick I, et al. RO 15-1788 antagonizes the effects of diazepam in man without affecting its bioavailability. British Journal of Anaesthesiology 55: 349–356, 1983Google Scholar
  159. Ochs HR, Greenblatt DJ, Gugler R, Muntefering G, Locniskar A, et al. Cimetidine impairs nitrazepam clearance. Clinical Pharmacology and Therapeutics 34: 227–230, 1983PubMedGoogle Scholar
  160. Ochs HR, Greenblatt DJ, Roberts GM, Dengler HJ. Diazepam interaction with antituberculosis drugs. Clinical Pharmacology and Therapeutics 29: 671–678, 1981PubMedGoogle Scholar
  161. Oliver JS, Smith H. Determination of nitrazepam in poisoning cases. Forensic Science 4: 183–186, 1974PubMedGoogle Scholar
  162. Olson KR, Yin L, Osterloh J, Tani A. Coma caused by trivial triazolam overdose. American Journal of Emergency Medicine 3: 210–211, 1985PubMedGoogle Scholar
  163. Oreland L. The benzodiazepines: a pharmacological overview. Acta Anaesthesiologica Scandinavica 32 (Suppl. 88): 13–16, 1987Google Scholar
  164. O’Sullivan GF, Wade DN. Flumazenil in the management of acute drug overdosage with benzodiazepines and other agents. Clinical Pharmacology and Therapeutics 42: 254–259, 1987PubMedGoogle Scholar
  165. Owen RT, Tyrer P. Benzodiazepine dependence: a review of the evidence. Drugs 25: 385–398, 1983PubMedGoogle Scholar
  166. Pacifici GM, Placidi GF, Fornaro P, Gomeni R. Pinazepam: a precursor of N-desmethyldiazepam. European Journal of Clinical Pharmacology 22: 225–228, 1982PubMedGoogle Scholar
  167. Patwardhan RV, Yarborough GW, Desmond PV, Johnson RF, Schenker S, et al. Cimetidine spares the glucuronidation of lorazepam and oxazepam. Gastroenterology 79: 912–916, 1980PubMedGoogle Scholar
  168. Peel HW, Perrigo BT, Mikhael NZ. Detection of drugs in saliva of impaired drivers. Journal of Forensic Sciences 29: 185–189, 1984PubMedGoogle Scholar
  169. Perry PJ, Wilding DC, Fowler RC, et al. Absorption of oral and intramuscular chlordiazepoxide by alcoholics. Clinical Pharmacology and Therapeutics 23: 535–541, 1978PubMedGoogle Scholar
  170. Petursson H, Lader MH. Withdrawal from long term benzodiazepine treatment. British Medical Journal 283: 643–645, 1981PubMedGoogle Scholar
  171. Pevnick JS, Jasinski DR, Haertzen CA. Abrupt withdrawal from therapeutically administered diazepam. Archives of General Psychiatry 35: 995–998, 1978PubMedGoogle Scholar
  172. Pond SM, Phillips M, Benovitz NL, et al. Diazepam kinetics in acute alcohol withdrawal. Clinical Pharmacology and Therapeutics 25: 832–836, 1979PubMedGoogle Scholar
  173. Polc P, Bonetti EP, Schaffner R, Haefely WE. A three-state model of the benzodiazepine receptor explains the interactions between the benzodiazepine antagonist Ro 15-1788, benzodiazepine tranquilizers, β-carbolines and phenobarbitone. Naunyn-Schmiedeberg’s Archives of Pharmacology 321: 260–264, 1982PubMedGoogle Scholar
  174. Rada RT, Kellner R, Buchanan JG. Chlordiazepoxide and alcohol: a fatal overdose. Journal of Forensic Sciences 20: 544–547, 1974Google Scholar
  175. Reidenberg MM, Levy M, Warner H, et al. Relationship between diazepam dose, plasma level, age, and central nervous system depression. Clinical Pharmacology and Therapeutics 23: 371–374, 1978PubMedGoogle Scholar
  176. Rementeria JL, Bhatt K. Withdrawal symptoms in neonates from intrauterine exposure to diazepam. Pediatric Pharmacology 90: 123–126, 1977Google Scholar
  177. Richman S, Harris RD. Acute pulmonary edema associated with librium abuse. Radiology 103: 57–58, 1972PubMedGoogle Scholar
  178. Ritz R, Zuber M, Elasser S, Scollo-Lavizzari G. Use of flumazenil in intoxicated patients with coma: a double-blind placebo-controlled study in ICU. Intensive Care Medicine 16: 242–247, 1990PubMedGoogle Scholar
  179. Roberts RK, Wilkinson GR, Branch RA, Schenker S. Effect of age and parenchymal liver disease on the disposition and elimination of chlordiazepoxide (Librium). Gastroenterology 75: 479–485, 1978PubMedGoogle Scholar
  180. Roncari G, Ziegler WH, Guentert TW. Pharmacokinetics of the new benzodiazepine antagonist Ro 15-1788 in man following intravenous and oral administration. British Journal of Clinical Pharmacology 22: 421–428, 1986PubMedGoogle Scholar
  181. Rosenberg L, Mitchell AA, Parsell JL, Pashayan H, Louik C, et al. Lack of relation of oral clefts to diazepam use during pregnancy. New England Journal of Medicine 309: 1282–1285, 1983PubMedGoogle Scholar
  182. Rothman KJ, Fyler DC, Goldblatt A, Kreidberg MB. Exogenous hormones and other drug exposures of children with congenital heart disease. American Journal of Epidemiology 109: 433–439, 1979PubMedGoogle Scholar
  183. Ruff RL, Kutt H, Hafler D. Prolonged benzodiazepine coma. New York State Journal of Medicine 81: 776–777, 1981PubMedGoogle Scholar
  184. Rupp W, Badian M, Christ O, Hajdú P, Kulkarni RD, et al. Pharmacokinetics of single and multiple doses of clobazam in humans. British Journal of Clinical Pharmacology 7: 51S–57S, 1979PubMedGoogle Scholar
  185. Safra MJ, Oakley GP. Association between cleft lip with or without cleft palate and prenatal exposure to diazepam. Lancet 2: 478–480, 1975PubMedGoogle Scholar
  186. Saxen I. Associations between oral clefts and drugs taken during pregnancy. International Journal of Epidemiology 4: 37–44, 1975PubMedGoogle Scholar
  187. Scavone JM, Greenblatt DJ, Friedman H, Shader RI. Enhanced bioavailability of triazolam following sublingual versus oral administration. Clinical Pharmacology 26: 208–210, 1986Google Scholar
  188. Scavone JM, Greenblatt DJ, Shader DJ. Alprazolam kinetics following sublingual and oral administration. Journal of Clinical Psychopharmacology 7: 332–334, 1987PubMedGoogle Scholar
  189. Schneiderman JF. Nonmedical drug and chemical use in pregnancy. In Koren (Ed.) Maternal-fetal toxicology: a clinicians’ guide, Marcel Dekker, Inc., New York, 1990Google Scholar
  190. Schwartz MA, Koechlin BA, Postma E, Palmer S, Krol G. Metabolism of diazepam in cat, dog and man. Journal of Pharmacology and Experimental Therapeutics 149: 423–435, 1965PubMedGoogle Scholar
  191. Scollo-Lavizzari G. First clinical investigation of the benzodiazepine antagonist Ro 15-1788 in comatose patients. European Neurology 22: 7–11, 1983PubMedGoogle Scholar
  192. Scollo-Lavizzari G, Matthis H. Benzodiazepine antagonist Ro 15-1788 in ethanol intoxication: a pilot study. European Neurology 24: 352–354, 1985PubMedGoogle Scholar
  193. Sellers EM, Busto U. Benzodiazepines and ethanol: assessment of the effects and consequences of psychotropic drug interaction. Journal of Psychopharmacology 2: 249–262, 1982Google Scholar
  194. Sellers EM, Giles GH, Greenblatt DJ, Naranjo CA. Differential effects on benzodiazepine disposition by disulfiram and ethanol. Arzneimittel-Forschung 30: 882–886, 1980bPubMedGoogle Scholar
  195. Sellers EM, Greenblatt DJ, Giles HG, et al. Chlordiazepoxide and oxazepam disposition in cirrhosis. Clinical Pharmacology and Therapeutics 26: 240–246, 1979PubMedGoogle Scholar
  196. Sellers EM, Greenblatt DJ, Zilm DH, Degani N. Decline in chlordiazepxoside plasma levels during fixed-dose therapy of alcohol withdrawal. British Journal of Clinical Pharmacology 6: 370–372, 1978PubMedGoogle Scholar
  197. Sellers EM, Naranjo CA, Giles HG, et al. Mechanism of ethanoldiazepam pharmacokinetic interactions. Clinical Pharmacology and Therapeutics 27: 286, 1980aGoogle Scholar
  198. Sellman R, Pekkarinen A, Kangas L, et al. Reduced concentrations of plasma diazepam in chronic alcoholic patients following an oral administration of diazepam. Acta Pharmacologica et Toxicologica 36: 25–32, 1975PubMedGoogle Scholar
  199. Sellman R, Kanto J, Raijola E, et al. Human and animal study on elimination from plasma and metabolism of diazepam after chronic alcohol intake. Acta Pharmacologica et Toxicologica 36: 33–38, 1975bPubMedGoogle Scholar
  200. Shader RI, Georgotas A, Greenblatt DJ, Harmatz JS, Allen MD. Impaired absorption of desmethyldiazepam from clorazepate by magnesium aluminium hydroxide. Clinical Pharmacology and Therapeutics 24: 308–315, 1978PubMedGoogle Scholar
  201. Shader RI, Greenblatt DJ, Ciraulo DA, Divoll M, Harmatz JS, et al. Effect of age and sex on disposition of desmethyldiazepam formed from its precursor clorazepate. Psychopharmacology 75: 193–197, 1981PubMedGoogle Scholar
  202. Shader RI, Greenblatt DJ, Salzman C, Kochansky G, Harmatz JS. Benzodiazepines: safety and toxicity. Diseases of the Nervous System 5: 23–26, 1975Google Scholar
  203. Shiono PH, Mills JL. Oral clefts and diazepam use during pregnancy. New England Journal of Medicine 311: 919–920, 1984PubMedGoogle Scholar
  204. Skerrit JH, Johnston GAR. Enhancement of GABA binding by benzodiazepines and related anxiolytics. European Journal of Pharmacology 89: 193–198, 1983Google Scholar
  205. Smith MT, Eadie MJ, O’Rourke Brophy T. The pharmacokinetics of midazolam in man. European Journal of Clinical Pharmacology 19: 271–278, 1981PubMedGoogle Scholar
  206. Smith RB, Divoll M, Gillespie WR, Greenblatt DJ. Effect of subject age and gender on the pharmacokinetics ofr oral triazolam and temazepam. Journal of Clinical Psychopharmacology 3: 172–176, 1983PubMedGoogle Scholar
  207. Smith RB, Heazlewood V, Eadie MJ, O’Rourke Brophy T, Tyrer JH. Pharmacokinetics of midazolam in the aged. European Journal of Clinical Pharmacology 26: 381–388, 1984aPubMedGoogle Scholar
  208. Smith RB, Kroboth PD, Phillips JP. Temporal variation in triazolam pharmacokinetics and pharmacodynamics after oral administration. Journal of Clinical Pharmacology 26: 120–124, 1986PubMedGoogle Scholar
  209. Smith RB, Kroboth PD, Vanderlugt JT, Phillips JP, Juhl RP. Pharmacokinetics and pharmacodynamics of alprazolam after oral and IV administration. Psychopharmacology 84: 452–456, 1984bPubMedGoogle Scholar
  210. Squires RF, Braestrup C. Benzodiazepine receptors in rat brain. Nature 266: 732–734, 1977PubMedGoogle Scholar
  211. Stevens LA, Bevan CD, Salmon J, Krieger J, Perianu M, et al. Single and repeated dose kinetics of the hypnotic agent loprazolam in healthy volunteers. European Journal of Clinical Pharmacology 25: 651–655, 1983PubMedGoogle Scholar
  212. Stevens LA, Pidgen AW, Bevan CD, Igns RMJ, Lawrence JR, et al. Correlation of the clinical pharmacodynamics of loprazolam with serum concentrations. Xenobiotica 15: 623–631, 1985PubMedGoogle Scholar
  213. Stirt JA. Aminophylline is a diazepam antagonist. Anesthesia and Analgesia 60: 767–768, 1981PubMedGoogle Scholar
  214. Stringer MD. Adult respiratory distress syndrome associated with flurazepam overdose. Journal of the Royal Society of Medicine 78: 74–75, 1985PubMedGoogle Scholar
  215. Sury MRJ, Billingham I, Russell GN, et al. Acute benzodiazepine withdrawal syndrome after midazolam infusions in children. Critical Care Medicine 17: 301–302, 1989PubMedGoogle Scholar
  216. Taeuber K, Badian M, Brettel HF, et al. Kinetic and dynamic interaction of clobazam and alcohol. British Journal of Clinical Pharmacology 7: 91S–97S, 1979PubMedGoogle Scholar
  217. Tedeschi G, Riva R, Baruzzi A. Clobazam plasma concentrations: pharmacokinetic study in healthy volunteers and data in epileptic patients. British Journal of Clinical Pharmacology 11: 619–622, 1981PubMedGoogle Scholar
  218. Thearle MJ, Dunn PM, Hailey DM. Exchange transfusion for diazepam intoxication at birth followed by jejunal stenosis. Proceedings of the Royal Society of Medicine 66: 13–14, 1973Google Scholar
  219. Thiessen JJ, Sellers EM, Denbeigh P, Dolman L. Plasma protein binding of diazepam and tolbutamine in chronic alcoholics. Journal of Clinical Pharmacology 16: 345–351, 1976PubMedGoogle Scholar
  220. Torry JM. A case of suicide with nitrazepam and alcohol. Practioner 217: 648–649, 1976Google Scholar
  221. Trappler B, Bezeredi T. Triazolam intoxication. Canadian Medical Association Journal 126: 893–894, 1982Google Scholar
  222. Tyrer P, Rutherford D, Huggett T. Benzodiazepine withdrawal symptoms and propranolol. Lancet 1: 520–523, 1981PubMedGoogle Scholar
  223. Van der Kleijn E, Van Rossum JM, Muskens ETJ, Rijntjes NVM. Pharmacokinetics of diazepam in dogs, mice, and humans. Acta Pharmacologica et Toxicologica 29: 109–129, 1971Google Scholar
  224. Vissuzaine C, Coste F, Bocquet L. Rhabdomyolyse cardiaque et squelettique au cours d’un coma par intoxication médicamenteus. Coeur et Médecine Interne 15: 615–623, 1976PubMedGoogle Scholar
  225. Voltz M, Christ O, Kellner HM, et al. Kinetics and metabolism of clobazam in animals and man. British Journal of Clinical Pharmacology 7: 41S–50S, 1979Google Scholar
  226. von Staak M, Moosmayer A. Pharmacokinetic studies on interactions between dipotassium chlorazepate and alcohol after oral administration. Arzneimittel-Forschung 28: 1187–1191, 1978PubMedGoogle Scholar
  227. Welch TR, Rumack BH, Hammond K. Clonazepam overdose resulting in cyclic coma. Clinical Toxicology 10: 433–436, 1977PubMedGoogle Scholar
  228. White JM, Clardy DO, Graves MH, et al. Testing for sedative-hypnotic drugs in the imparied driver: a survey of 72 000 arrests. Clinical Toxicology 18: 945–957, 1981PubMedGoogle Scholar
  229. Whitelaw AGL, Cummings AJ, McFadyen IR. Effect of maternal lorazepam on the neonate. British Medical Journal 282: 1106–1108, 1981PubMedGoogle Scholar
  230. Whiting B, Lawrence JR, Skellern GG, et al. Effects of acute alcohol intoxication on the metabolism and plasma kinetics of chlordiazepoxide. British Journal of Clinical Pharmacology 7: 95–100, 1979PubMedGoogle Scholar
  231. Winokur A, Rickets K, Greenblatt DJ, Snyder PJ, Schatz NJ. Withdrawal reaction from long term low dosage administration of diazepam: a double blind placebo controlled case study. Archives of General Psychiatry 37: 101–105, 1980PubMedGoogle Scholar
  232. Winter RM, Czeizel A, Lendvay A, Gerhardsson M, Alfredsson L. In-utero exposure to benzodiazepines. Lancet 1: 627–628, 1987Google Scholar
  233. Ziegler G, Ludwig L, Klotz U. Relationships between plasma levels and psychological effects of benzodiazepines. Pharmacopsychiatry 16: 71–76, 1983Google Scholar
  234. Zileli MS, Telatar F, Deniz S, Ilter E, Adalar N. Pseudohyperosmolar nonketoacidotic coma due to oxazepam intoxication. Clinical Toxicology 5: 337–341, 1972PubMedGoogle Scholar
  235. Zuber M, Elasser S, Ritz R, Scollo-Lavirazzi G. Flumazenil (Anexate®) in severe intoxication with carbamazepine (Tegretol®). European Neurology 28: 161–163, 1988PubMedGoogle Scholar

Copyright information

© Adis International Limited 1991

Authors and Affiliations

  • Pierre Gaudreault
    • 1
  • Joanne Guay
    • 1
  • Robert L. Thivierge
    • 1
  • Isabelle Verdy
    • 1
  1. 1.Department of Pediatrics and Department of Anesthesia and ReanimationUniversity of Montreal and Clinical Pharmacology and Toxicology Section and Emergency Room Service, Department of Pediatrics and Anesthesia and Reanimation, Sainte-Justine HospitalMontrealCanada

Personalised recommendations