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Benzodiazepine Poisoning

Clinical and Pharmacological Considerations and Treatment

  • Review Article
  • Poisoning Management
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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.

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References

  • Aarskog D. Association between maternal intake of diazepam and oral clefts. Lancet 2: 921–922, 1975

    PubMed  CAS  Google Scholar 

  • 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, 1982

    PubMed  CAS  Google Scholar 

  • 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, 1983a

    PubMed  CAS  Google Scholar 

  • 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, 1983b

    PubMed  CAS  Google Scholar 

  • Acosta D, Chappell R. Cardiotoxicity of diazepam in cultured heart cells. Toxicology 8: 311–317, 1977

    PubMed  CAS  Google Scholar 

  • 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, 1983

    PubMed  CAS  Google Scholar 

  • Allen MD, Greenblatt DJ, Lacasse Y, Shader RI. Pharmacokinetic study of lorazepam overdosage. American Journal of Psychiatry 137: 1414–1415, 1980

    PubMed  CAS  Google Scholar 

  • Allonen G, Ziegler G, Klotz U. Midazolam kinetics. Clinical Pharmacology and Therapeutics 30: 653–661, 1981

    PubMed  CAS  Google Scholar 

  • Alvan G, Siwers B, Vessman J. Pharmacokinetics of oxazepamin healthy volunteers. Acta Pharmacologica et Toxicologica 40(Suppl. 1): 40–51, 1977

    PubMed  CAS  Google Scholar 

  • 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, 1987

    PubMed  CAS  Google Scholar 

  • Ananth J. Side effects in the neonate from psychotropic agents excreted through breast-feeding. American Journal of Psychiatry 135: 801–805, 1978

    PubMed  CAS  Google Scholar 

  • Andreasen PB, Hendel J, Greisen G, Hvidger EF. Pharmacokinetics of diazepam in disordered liver function. European Journal of Clinical Pharmacology 10: 115–120, 1976

    PubMed  CAS  Google Scholar 

  • 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, 1983

    Google Scholar 

  • Ayd Jr FJ. Benzodiazepines: dependence and withdrawal. Journal of the American Medical Association 242: 1401–1402, 1979

    PubMed  Google Scholar 

  • Aziz K. Drugs-of-abuse testing: screening and confirmation. Clinics in Laboratory Medicine 10: 493–502, 1990

    PubMed  CAS  Google Scholar 

  • Baehrendtz S, Hojer J. Flumazenil in self-induced benzodiazepine poisoning. European Journal of Anaesthesiology (Suppl. 2): 287–293, 1988

  • 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, 1989

    PubMed  CAS  Google Scholar 

  • 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, 1984

    Google Scholar 

  • Bansky G, Meier PJ, Ziegler WH, et al. Reversal of hepatic coma by benzodiazepine antagonist (Ro 15-1788). Lancet 1: 1324–1325, 1985

    Google Scholar 

  • Barry WS, St Clair SM. Exposure to benzodiazepines in utero. Lancet 1: 1436–1437, 1987

    PubMed  CAS  Google Scholar 

  • Bell EF. The use of naloxone in the treatment of diazepam poisoning. Journal of Pediatrics 87: 803–804, 1975

    PubMed  CAS  Google Scholar 

  • Berger R, Green G, Melnick A. Cardiac arrest caused by oral diazepam intoxication. Clinical Pediatrics 14: 842–844, 1975

    PubMed  CAS  Google Scholar 

  • Bergman U, Boethius G, Swartling PG, Isacson D, Smedby B. Teratogenic effects of benzodiazepine use during pregnancy. Journal of Pediatrics 116: 490–491, 1990

    PubMed  CAS  Google Scholar 

  • Besunder JB, Blumer JL. Neonatal drug withdrawal syndromes.In Koren (Ed.) Maternal-fetal toxicology: a clinicians’ guide, Marcel Dekker Inc., New York, 1990

    Google Scholar 

  • 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, 1986

    Google Scholar 

  • Bodenham A, Brownlie G, Dixon JS, Park GR. Reversal of sedation by prolonged infusion of flumazenil (Anexate, Ro 15-1788). Anaesthesia 43: 376–378, 1988

    PubMed  CAS  Google Scholar 

  • 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, 1989

    PubMed  CAS  Google Scholar 

  • 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, 1977a

    PubMed  CAS  Google Scholar 

  • 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, 1977b

    PubMed  CAS  Google Scholar 

  • 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, 1987

    Google Scholar 

  • Burkhart KK, Kulig KW. The diagnostic utility of flumazenil (a benzodiazepine antagonist) in coma of unknown etiology. Annals of Emergency Medicine 19: 319–321, 1990

    PubMed  CAS  Google Scholar 

  • Busto U, Kaplan HL, Sellers EM. Benzodiazepine-associated emergencies in Toronto. American Journal of Psychiatry 137: 224–227, 1980

    PubMed  CAS  Google Scholar 

  • Busto U, Lanctôt KL, Isaac P, Manuella A. Benzodiazepine use and abuse in Canada. Canadian Medical Association Journal 141: 917–921, 1989

    PubMed  CAS  Google Scholar 

  • 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, 1986

    PubMed  CAS  Google Scholar 

  • Carroll WM, Mastiglia FL. Alpha and beta coma in drug intoxication. British Medical Journal 2: 1518–1519, 1977

    PubMed  CAS  Google Scholar 

  • Castleden CM, George CF, Marcer D, Hallett C. Increased sensitivity to nitrazepam in old age. British Medical Journal 1: 10–12, 1977

    PubMed  CAS  Google Scholar 

  • Cate JC, Jatlow PI. Chlordiazepoxide overdose: interpretation of serum drug concentrations. Clinical Toxicology 6: 553–561,1973

    Google Scholar 

  • Cerqueira Ma J, Olle C, Bellart J, Baro F, Cabero L, et al. Intoxicationby benzodiazepines during pregnancy. Lancet 1: 1341,1988

    PubMed  CAS  Google Scholar 

  • Choux C, Gueugniaud PY, Prost G, Vaudelin T, Bertin-Maghit M, et al. Limites du flumazénil en pratique pré-hospitalière. Presse Médicale 19: 719, 1990

    CAS  Google Scholar 

  • 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, 1982

    PubMed  CAS  Google Scholar 

  • 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, 1986

    PubMed  CAS  Google Scholar 

  • Cook PJ, Flanagan R, James IM. Diazepam tolerance: effect of age, regular sedation and alcohol. British Medical Journal 289: 351–353, 1984

    PubMed  CAS  Google Scholar 

  • 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, 1975

    PubMed  CAS  Google Scholar 

  • 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, 1981

    PubMed  CAS  Google Scholar 

  • Curry SH, Smith CM. Diazepam-ethanol interaction in humans: addiction or potentiation? Communications in Psychopharmacology 3: 101–113, 1979

    PubMed  CAS  Google Scholar 

  • Czeizel A. Diazepam, phenytoin, and etiology of cleft lip and/or cleft palate. Lancet 1: 810, 1976

    PubMed  CAS  Google Scholar 

  • 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, 1982

    PubMed  CAS  Google Scholar 

  • 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, 1980a

    PubMed  CAS  Google Scholar 

  • Desmond PV, Patwardhan RV, Schenker S, Speeg KV. Cimetidine impairs elimination of chlordiazepoxide (Librium) in man. Annals of Internal Medicine 93: 266–268, 1980b

    PubMed  CAS  Google Scholar 

  • Diliberti L, O’Brien ML, Turner T. The use of physostigmine as an antidote in accidental diazepam intoxication. Journal of Pediatrics 86: 106–107, 1975

    CAS  Google Scholar 

  • Divoll M, Greenblatt DJ. Alcohol does not enhance diazepam absorption. Pharmacology 22: 263–268, 1981a

    PubMed  CAS  Google Scholar 

  • 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, 1981b

    PubMed  CAS  Google Scholar 

  • Divoll M, Greenblatt DJ, Harmatz JS, Shader RI. Effect of age and gender on disposition of temazepam. Journal of Pharmaceutical Sciences 70: 1104–1107, 1981a

    PubMed  CAS  Google Scholar 

  • Divoll M, Greenblatt DJ, Lacasse Y, Shader RI. Benzodiazepine overdosage: plasma concentrations and clinical outcome. Psychopharmacology 73: 381–383, 1981b

    PubMed  CAS  Google Scholar 

  • 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, 1983

    PubMed  CAS  Google Scholar 

  • 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, 1985

    PubMed  CAS  Google Scholar 

  • 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, 1983

    Google Scholar 

  • 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, 1987

    PubMed  CAS  Google Scholar 

  • Ellinwood EH, Healtherly DG, Nikardo AM, Bjomsson TD, Kilts C. Comparative pharmacokinetics and pharmacodynamics of lorazepam, alprazolam and diazepam. Psychopharmacology 86: 392–399, 1985

    PubMed  Google Scholar 

  • 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, 1988

  • Farley TA. Severe hypernatremic dehydration after use of an activated charcoal-sorbitol suspension. Journal of Pediatrics 109: 719–722, 1986

    PubMed  CAS  Google Scholar 

  • 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, 1989

    PubMed  CAS  Google Scholar 

  • 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, 1979

    PubMed  CAS  Google Scholar 

  • 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, 1987

    Google Scholar 

  • 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, 1983

    PubMed  CAS  Google Scholar 

  • Friedman H, Greenblatt DJ, Burnstein ES, Harvatz JS, Shader RI. Population study of triazolam pharmacokinetics. British Journal of Clinical Pharmacology 22: 639–642, 1986

    PubMed  CAS  Google Scholar 

  • 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, 1977

    Google Scholar 

  • 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, 1984

    PubMed  CAS  Google Scholar 

  • Garriott JC, Latman N. Drug detection in cases of driving under the influence. Journal of Forensic Sciences 21: 398–415, 1976

    PubMed  CAS  Google Scholar 

  • Garzone PD, Kroboth PD. Pharmacokinetics of the newer benzodiazepines. Clinical Pharmacokinetics 16: 337–364, 1989

    PubMed  CAS  Google Scholar 

  • George CF, Robertson D. Clinical consequences of abrupt drug withdrawal. Medical Toxicology 2: 367–382, 1987

    PubMed  CAS  Google Scholar 

  • Ghoneim MM, Mewaldt SP. Benzodiazepines and human memory: a review. Anesthesiology 72: 926–938, 1990

    PubMed  CAS  Google Scholar 

  • Goethe JW, Edelman SL. Chlordiazipoxide toxicity in Limbitrol overdose. American Journal of Psychiatry 142: 774, 1985

    PubMed  CAS  Google Scholar 

  • Greenblatt DJ, Abernethy DR, Divoll M, Harmatz JS, Shader RI. Pharmacokinetic properties of benzodiazepine hypnotics. Journal of Clinical Psychopharmacology 3: 129–132, 1983a

    PubMed  CAS  Google Scholar 

  • 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, 1985

    PubMed  CAS  Google Scholar 

  • Greenblatt DJ, Allen MD, Locniskar A, Harmatz JS, Shader RI. Lorazepam kinetics in the elderly. Clinical Pharmacology and Therapeutics 26: 103–113, 1979

    PubMed  CAS  Google Scholar 

  • Greenblatt DJ, Allen MD, Noel BJ, Shader RI. Acute overdosage with benzodiazepine derivatives. Clinical Pharmacology and Therapeutics 21: 497–514, 1977a

    PubMed  CAS  Google Scholar 

  • Greenblatt DJ, Divoll M, Abernethy DR, Moschitto LJ, Smith RB, et al. Alprazolam kinetics in the elderly. Archives of General Psychiatry 40: 287–290, 1983c

    PubMed  CAS  Google Scholar 

  • 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, 1983d

    PubMed  CAS  Google Scholar 

  • Greenblatt DJ, Divoll M, Abernethy DR, Ochs HR, Shader RI. Diazepam disposition determinants. Clinical Pharmacology and Therapeutics 27: 301–312, 1980a

    PubMed  CAS  Google Scholar 

  • Greenblatt DJ, Divoll M, Harmatz JS. Pharmacokinetic comparison of sublingual lorazepam with intravenous, intramuscular, and oral lorazepam. Journal of Pharmaceutical Sciences 71: 248–252, 1982

    PubMed  CAS  Google Scholar 

  • Greenblatt DJ, Divoll M, Harmatz JS, Shader RI. Oxazepam kinetics: effects of age and sex. Journal of Pharmacology and Experimental Therapeutics 215: 86–91, 1980b

    PubMed  CAS  Google Scholar 

  • 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, 1981

    PubMed  CAS  Google Scholar 

  • 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, 1983b

    PubMed  CAS  Google Scholar 

  • 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, 1989

    PubMed  CAS  Google Scholar 

  • 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, 1976

    PubMed  CAS  Google Scholar 

  • Greenblatt DJ, Shader RI. Prazepam and lorazepam, two new benzodiazepines. New England Journal of Medicine 299: 1342–1344, 1978

    PubMed  CAS  Google Scholar 

  • 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, 1977b

    PubMed  CAS  Google Scholar 

  • Greenblatt DJ, Shader RI, Macleod SM, Sellers EM. Flurazepam hydrochloride. Clinical Pharmacology and Therapeutics 17: 1–14, 1975

    PubMed  CAS  Google Scholar 

  • Greenblatt DJ, Shader RI, Weinberger DR, Allen MD, Mac-Laughlin DS. Effect of cocktail on diazepam absorption. Psychopharmacology 57: 199–203, 1978b

    PubMed  CAS  Google Scholar 

  • 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, 1978a

    PubMed  CAS  Google Scholar 

  • Haefely WE. Pharmacology of the benzodiazepine receptor. European Archives of Psychiatry and Neurological Sciences 238: 294–301, 1989

    PubMed  CAS  Google Scholar 

  • 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, 1975

    PubMed  CAS  Google Scholar 

  • 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, 1984

    PubMed  CAS  Google Scholar 

  • Hayes SL, Pablo G, Radomski T, Palmer RF. Ethanol and oral diazepam absorption. New England Journal of Medicine 296: 186–189,1977

    PubMed  CAS  Google Scholar 

  • Heizmann P, Eckert M, Zeigler WH. Pharmacokinetics and bioavailability of midazolam in man. British Journal of Clinical Pharmacology 16: 43S–49S, 1983

    PubMed  Google Scholar 

  • Heyndrickx B. Fatal intoxication due to flunitrazepam. Journal of Analytical Toxicology 11: 278, 1987

    PubMed  CAS  Google Scholar 

  • Higgitt AC, Lader MH, Fogany P. Clinical management of benzodiazepine dependence. British Medical Journal 291: 688–691, 1985

    PubMed  CAS  Google Scholar 

  • Hiss J, Hepler BR, Falkowski AJ, Sunshine I. Fatal bradycardia after intentional overdose of cimetidine and diazepam. Lancet 2: 982, 1982

    PubMed  CAS  Google Scholar 

  • Hofer P, Scollo-Lavizzari G. Benzodiazepine antagonist Ro 15-1788 in self-poisoning: diagnostic and therapeutic use. Archives of Internal Medicine 145: 663–664, 1985

    PubMed  CAS  Google Scholar 

  • 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, 1988

    PubMed  Google Scholar 

  • 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, 1989

    PubMed  Google Scholar 

  • 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, 1988

    PubMed  Google Scholar 

  • Hoyumpa A, Patwardhan R, Maples M, Desmond P, Johnson R, et al. Effect of short-term ethanol administration on lorazepa mmetabolism. Gastroenterology 79: 1027, 1980

    Google Scholar 

  • 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, 1965

    PubMed  CAS  Google Scholar 

  • Hunkeler W, Mönier H, Pieri L, et al. Selective antagonists of benzodiazepines. Nature 290: 514–516, 1981

    PubMed  CAS  Google Scholar 

  • Jatlow P, Dobular K, Bailey D. Serum diazepam concentrations in overdose: their significance. American Journal of Clinical Pathology 72: 571–577, 1979

    PubMed  CAS  Google Scholar 

  • Jeffrey DI, Withfield MF. Lorazepam poisoning. British Medical Journal 4: 719, 1974

    Google Scholar 

  • 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, 1982

    PubMed  CAS  Google Scholar 

  • 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, 1986

    CAS  Google Scholar 

  • 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, 1983

    PubMed  Google Scholar 

  • Jones DJ, Stehling LC, Zauder HL. Cardiovascular responses to diazepam and midazolam maleate in the dog. Anesthesiology 51: 430–434, 1979

    PubMed  CAS  Google Scholar 

  • Jordan C, Lehaue JR, Jones JG. Respiratory depression following diazepam: reversal with high dose naloxone. Anesthesiology 53: 293–298, 1980

    PubMed  CAS  Google Scholar 

  • Kangas L, Breimer DD. Clinical pharmacokinetics of nitrazepam. Clinical Pharmacokinetics 6: 346–366, 1981

    PubMed  CAS  Google Scholar 

  • Kanto JH. Use of benzodiazepines during pregnancy, labour, and lactation, with particular reference to pharmacokinetic consideration. Drugs 23: 354–380, 1982

    PubMed  CAS  Google Scholar 

  • 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, 1973

    PubMed  CAS  Google Scholar 

  • Kelly RC, Krent L, Sunshine I. Association of benzodiazepines with death in a major metropolitan area. Journal of Analytical Toxicology 6: 91–96, 1982

    PubMed  Google Scholar 

  • King LA. Synergistic effect of benzodiazepines in fatal amitriptyline poisonings. Lancet 2: 982–983, 1982

    PubMed  CAS  Google Scholar 

  • 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, 1976

    PubMed  CAS  Google Scholar 

  • 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, 1985b

    PubMed  CAS  Google Scholar 

  • Klotz U, Reimann I. Delayed clearance of diazepam due to cimetidine. New England Journal of Medicine 302: 1012–1014, 1980

    PubMed  CAS  Google Scholar 

  • 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, 1985a

    PubMed  CAS  Google Scholar 

  • 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, 1984

    Google Scholar 

  • 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, 1986

    PubMed  CAS  Google Scholar 

  • 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, 1988

    PubMed  CAS  Google Scholar 

  • 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, 1978

    PubMed  CAS  Google Scholar 

  • 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, 1983

    CAS  Google Scholar 

  • Kumar A, Mohan M, Anand NK. Aminophylline in neonatal diazepam intoxication. Indian Pediatrics 24: 602–604, 1987

    PubMed  CAS  Google Scholar 

  • 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, 1990

    PubMed  CAS  Google Scholar 

  • Laegreid L, Olegard R, Wahlström J, Conradi N. Abnormalities in children exposed to benzodiazepines in utero. Lancet 1: 108–109, 1987

    PubMed  CAS  Google Scholar 

  • Laegreid L, Olegard R, Wahlström J, Conradi N. Teratogenic effects of benzodiazepine use during pregnancy. Journal of Pediatrics 114: 126–131, 1989

    PubMed  CAS  Google Scholar 

  • 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, 1989

    PubMed  CAS  Google Scholar 

  • Lheureux P, Askenasi R. Treatment of benzodiazepine overdose with Ro 15-1788. Archives of Internal Medicine 146: 1241,1986

    PubMed  CAS  Google Scholar 

  • Lheureux P, Askenasi R. Specific treatment of benzodiazepine overdose. Human Toxicology 7: 165–170, 1988

    PubMed  CAS  Google Scholar 

  • 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, 1989

    PubMed  CAS  Google Scholar 

  • 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, 1974

    PubMed  CAS  Google Scholar 

  • Linnoila M, Mattila MJ. Drug interaction on psychomotor skills related to driving: diazepam and alcohol. European Journal of Clinical Pharmacology 5: 186–194, 1973a

    CAS  Google Scholar 

  • 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, 1973b

    PubMed  CAS  Google Scholar 

  • Litovitz T. Fatal benzodiazepine toxicity? American Journal of Emergency Medicine 5: 472–473, 1987

    Google Scholar 

  • 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, 1987

    PubMed  CAS  Google Scholar 

  • 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, 1989

    PubMed  CAS  Google Scholar 

  • 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, 1988

    CAS  Google Scholar 

  • 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, 1979

    PubMed  CAS  Google Scholar 

  • MacLeod SM, Sellers EM, Giles HG, et al. Interaction of disulfiram with benzodiazepines. Clinical Pharmacology and Therapeutics 24: 583–589, 1978

    PubMed  CAS  Google Scholar 

  • Mandelli M, Tognoni G, Garattini S. Clinical pharmacokinetics of diazepam. Clinical Pharmacokinetics 3: 72–91, 1978

    PubMed  CAS  Google Scholar 

  • Marks J. Techniques of benzodiazepine withdrawal in clinical practice: a consensus workshop report. Medical Toxicology 3: 324–333, 1988

    PubMed  CAS  Google Scholar 

  • Martin CD, Chan SC. Distribution of temazepam in body fluids and tissues in lethal overdose. Journal of Analytical Toxicology 10: 77–78, 1986

    PubMed  CAS  Google Scholar 

  • 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, 1983

    Google Scholar 

  • McCormick SR, Nielsen J, Jatlow PI. Alprazolam overdose: clinical findings and serum concentrations in two cases. Journal of Clinical Psychiatry 46: 247–248, 1985

    PubMed  CAS  Google Scholar 

  • 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, 1982

    CAS  Google Scholar 

  • Mignée C, Garnier R, Conso F, Efthymiou ML, Fournier E. Intoxication aiguë par le flunitrazépam. Thérapie 35: 581–589, 1980

    PubMed  Google Scholar 

  • Möhler H, Okada T. Benzodiazepines receptors: demonstration in the central nervous system. Science 198: 849–851, 1977

    PubMed  Google Scholar 

  • 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, 1981

    PubMed  Google Scholar 

  • Möhler H, Richards JG. Agonist and antagonist benzodiazepine receptor interaction in vitro. Nature 294: 763–765, 1981

    PubMed  Google Scholar 

  • 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, 1974

    PubMed  CAS  Google Scholar 

  • Nagy J, Decsi L. Physostigmine, a highly potent antidote for acute experimental diazepam intoxication. Neuropharmacology 17: 469–475, 1978

    PubMed  CAS  Google Scholar 

  • Norman TR, Burrows GD. Plasma concentrations of benzodiazepines: a review of clinical findings and implications. Progress in Neuropsychopharmacology and Biological Psychiatry 8: 115–126, 1984

    CAS  Google Scholar 

  • 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, 1983

    Google Scholar 

  • Ochs HR, Greenblatt DJ, Gugler R, Muntefering G, Locniskar A, et al. Cimetidine impairs nitrazepam clearance. Clinical Pharmacology and Therapeutics 34: 227–230, 1983

    PubMed  CAS  Google Scholar 

  • Ochs HR, Greenblatt DJ, Roberts GM, Dengler HJ. Diazepam interaction with antituberculosis drugs. Clinical Pharmacology and Therapeutics 29: 671–678, 1981

    PubMed  CAS  Google Scholar 

  • Oliver JS, Smith H. Determination of nitrazepam in poisoning cases. Forensic Science 4: 183–186, 1974

    PubMed  CAS  Google Scholar 

  • Olson KR, Yin L, Osterloh J, Tani A. Coma caused by trivial triazolam overdose. American Journal of Emergency Medicine 3: 210–211, 1985

    PubMed  CAS  Google Scholar 

  • Oreland L. The benzodiazepines: a pharmacological overview. Acta Anaesthesiologica Scandinavica 32 (Suppl. 88): 13–16, 1987

    Google Scholar 

  • 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, 1987

    PubMed  Google Scholar 

  • Owen RT, Tyrer P. Benzodiazepine dependence: a review of the evidence. Drugs 25: 385–398, 1983

    PubMed  CAS  Google Scholar 

  • Pacifici GM, Placidi GF, Fornaro P, Gomeni R. Pinazepam: a precursor of N-desmethyldiazepam. European Journal of Clinical Pharmacology 22: 225–228, 1982

    PubMed  CAS  Google Scholar 

  • Patwardhan RV, Yarborough GW, Desmond PV, Johnson RF, Schenker S, et al. Cimetidine spares the glucuronidation of lorazepam and oxazepam. Gastroenterology 79: 912–916, 1980

    PubMed  CAS  Google Scholar 

  • Peel HW, Perrigo BT, Mikhael NZ. Detection of drugs in saliva of impaired drivers. Journal of Forensic Sciences 29: 185–189, 1984

    PubMed  CAS  Google Scholar 

  • Perry PJ, Wilding DC, Fowler RC, et al. Absorption of oral and intramuscular chlordiazepoxide by alcoholics. Clinical Pharmacology and Therapeutics 23: 535–541, 1978

    PubMed  CAS  Google Scholar 

  • Petursson H, Lader MH. Withdrawal from long term benzodiazepine treatment. British Medical Journal 283: 643–645, 1981

    PubMed  CAS  Google Scholar 

  • Pevnick JS, Jasinski DR, Haertzen CA. Abrupt withdrawal from therapeutically administered diazepam. Archives of General Psychiatry 35: 995–998, 1978

    PubMed  CAS  Google Scholar 

  • Pond SM, Phillips M, Benovitz NL, et al. Diazepam kinetics in acute alcohol withdrawal. Clinical Pharmacology and Therapeutics 25: 832–836, 1979

    PubMed  CAS  Google Scholar 

  • 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, 1982

    PubMed  CAS  Google Scholar 

  • Rada RT, Kellner R, Buchanan JG. Chlordiazepoxide and alcohol: a fatal overdose. Journal of Forensic Sciences 20: 544–547, 1974

    Google Scholar 

  • 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, 1978

    PubMed  CAS  Google Scholar 

  • Rementeria JL, Bhatt K. Withdrawal symptoms in neonates from intrauterine exposure to diazepam. Pediatric Pharmacology 90: 123–126, 1977

    CAS  Google Scholar 

  • Richman S, Harris RD. Acute pulmonary edema associated with librium abuse. Radiology 103: 57–58, 1972

    PubMed  CAS  Google Scholar 

  • 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, 1990

    PubMed  CAS  Google Scholar 

  • 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, 1978

    PubMed  CAS  Google Scholar 

  • 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, 1986

    PubMed  CAS  Google Scholar 

  • 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, 1983

    PubMed  CAS  Google Scholar 

  • 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, 1979

    PubMed  CAS  Google Scholar 

  • Ruff RL, Kutt H, Hafler D. Prolonged benzodiazepine coma. New York State Journal of Medicine 81: 776–777, 1981

    PubMed  CAS  Google Scholar 

  • 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, 1979

    PubMed  Google Scholar 

  • Safra MJ, Oakley GP. Association between cleft lip with or without cleft palate and prenatal exposure to diazepam. Lancet 2: 478–480, 1975

    PubMed  CAS  Google Scholar 

  • Saxen I. Associations between oral clefts and drugs taken during pregnancy. International Journal of Epidemiology 4: 37–44, 1975

    PubMed  CAS  Google Scholar 

  • Scavone JM, Greenblatt DJ, Friedman H, Shader RI. Enhanced bioavailability of triazolam following sublingual versus oral administration. Clinical Pharmacology 26: 208–210, 1986

    CAS  Google Scholar 

  • Scavone JM, Greenblatt DJ, Shader DJ. Alprazolam kinetics following sublingual and oral administration. Journal of Clinical Psychopharmacology 7: 332–334, 1987

    PubMed  CAS  Google Scholar 

  • Schneiderman JF. Nonmedical drug and chemical use in pregnancy. In Koren (Ed.) Maternal-fetal toxicology: a clinicians’ guide, Marcel Dekker, Inc., New York, 1990

    Google Scholar 

  • 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, 1965

    PubMed  CAS  Google Scholar 

  • Scollo-Lavizzari G. First clinical investigation of the benzodiazepine antagonist Ro 15-1788 in comatose patients. European Neurology 22: 7–11, 1983

    PubMed  CAS  Google Scholar 

  • Scollo-Lavizzari G, Matthis H. Benzodiazepine antagonist Ro 15-1788 in ethanol intoxication: a pilot study. European Neurology 24: 352–354, 1985

    PubMed  CAS  Google Scholar 

  • Sellers EM, Busto U. Benzodiazepines and ethanol: assessment of the effects and consequences of psychotropic drug interaction. Journal of Psychopharmacology 2: 249–262, 1982

    CAS  Google Scholar 

  • Sellers EM, Giles GH, Greenblatt DJ, Naranjo CA. Differential effects on benzodiazepine disposition by disulfiram and ethanol. Arzneimittel-Forschung 30: 882–886, 1980b

    PubMed  CAS  Google Scholar 

  • Sellers EM, Greenblatt DJ, Giles HG, et al. Chlordiazepoxide and oxazepam disposition in cirrhosis. Clinical Pharmacology and Therapeutics 26: 240–246, 1979

    PubMed  CAS  Google Scholar 

  • 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, 1978

    PubMed  CAS  Google Scholar 

  • Sellers EM, Naranjo CA, Giles HG, et al. Mechanism of ethanoldiazepam pharmacokinetic interactions. Clinical Pharmacology and Therapeutics 27: 286, 1980a

    Google Scholar 

  • 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, 1975

    PubMed  CAS  Google Scholar 

  • 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, 1975b

    PubMed  CAS  Google Scholar 

  • 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, 1978

    PubMed  CAS  Google Scholar 

  • 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, 1981

    PubMed  CAS  Google Scholar 

  • Shader RI, Greenblatt DJ, Salzman C, Kochansky G, Harmatz JS. Benzodiazepines: safety and toxicity. Diseases of the Nervous System 5: 23–26, 1975

    Google Scholar 

  • Shiono PH, Mills JL. Oral clefts and diazepam use during pregnancy. New England Journal of Medicine 311: 919–920, 1984

    PubMed  CAS  Google Scholar 

  • Skerrit JH, Johnston GAR. Enhancement of GABA binding by benzodiazepines and related anxiolytics. European Journal of Pharmacology 89: 193–198, 1983

    Google Scholar 

  • Smith MT, Eadie MJ, O’Rourke Brophy T. The pharmacokinetics of midazolam in man. European Journal of Clinical Pharmacology 19: 271–278, 1981

    PubMed  Google Scholar 

  • 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, 1983

    PubMed  CAS  Google Scholar 

  • 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, 1984a

    PubMed  CAS  Google Scholar 

  • Smith RB, Kroboth PD, Phillips JP. Temporal variation in triazolam pharmacokinetics and pharmacodynamics after oral administration. Journal of Clinical Pharmacology 26: 120–124, 1986

    PubMed  CAS  Google Scholar 

  • Smith RB, Kroboth PD, Vanderlugt JT, Phillips JP, Juhl RP. Pharmacokinetics and pharmacodynamics of alprazolam after oral and IV administration. Psychopharmacology 84: 452–456, 1984b

    PubMed  CAS  Google Scholar 

  • Squires RF, Braestrup C. Benzodiazepine receptors in rat brain. Nature 266: 732–734, 1977

    PubMed  CAS  Google Scholar 

  • 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, 1983

    PubMed  CAS  Google Scholar 

  • 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, 1985

    PubMed  CAS  Google Scholar 

  • Stirt JA. Aminophylline is a diazepam antagonist. Anesthesia and Analgesia 60: 767–768, 1981

    PubMed  CAS  Google Scholar 

  • Stringer MD. Adult respiratory distress syndrome associated with flurazepam overdose. Journal of the Royal Society of Medicine 78: 74–75, 1985

    PubMed  CAS  Google Scholar 

  • Sury MRJ, Billingham I, Russell GN, et al. Acute benzodiazepine withdrawal syndrome after midazolam infusions in children. Critical Care Medicine 17: 301–302, 1989

    PubMed  CAS  Google Scholar 

  • Taeuber K, Badian M, Brettel HF, et al. Kinetic and dynamic interaction of clobazam and alcohol. British Journal of Clinical Pharmacology 7: 91S–97S, 1979

    PubMed  Google Scholar 

  • 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, 1981

    PubMed  CAS  Google Scholar 

  • 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, 1973

    Google Scholar 

  • 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, 1976

    PubMed  CAS  Google Scholar 

  • Torry JM. A case of suicide with nitrazepam and alcohol. Practioner 217: 648–649, 1976

    CAS  Google Scholar 

  • Trappler B, Bezeredi T. Triazolam intoxication. Canadian Medical Association Journal 126: 893–894, 1982

    Google Scholar 

  • Tyrer P, Rutherford D, Huggett T. Benzodiazepine withdrawal symptoms and propranolol. Lancet 1: 520–523, 1981

    PubMed  CAS  Google Scholar 

  • 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, 1971

    Google Scholar 

  • 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, 1976

    PubMed  CAS  Google Scholar 

  • 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, 1979

    Google Scholar 

  • von Staak M, Moosmayer A. Pharmacokinetic studies on interactions between dipotassium chlorazepate and alcohol after oral administration. Arzneimittel-Forschung 28: 1187–1191, 1978

    PubMed  CAS  Google Scholar 

  • Welch TR, Rumack BH, Hammond K. Clonazepam overdose resulting in cyclic coma. Clinical Toxicology 10: 433–436, 1977

    PubMed  CAS  Google Scholar 

  • 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, 1981

    PubMed  CAS  Google Scholar 

  • Whitelaw AGL, Cummings AJ, McFadyen IR. Effect of maternal lorazepam on the neonate. British Medical Journal 282: 1106–1108, 1981

    PubMed  CAS  Google Scholar 

  • 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, 1979

    PubMed  CAS  Google Scholar 

  • 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, 1980

    PubMed  CAS  Google Scholar 

  • Winter RM, Czeizel A, Lendvay A, Gerhardsson M, Alfredsson L. In-utero exposure to benzodiazepines. Lancet 1: 627–628, 1987

    Google Scholar 

  • Ziegler G, Ludwig L, Klotz U. Relationships between plasma levels and psychological effects of benzodiazepines. Pharmacopsychiatry 16: 71–76, 1983

    CAS  Google Scholar 

  • Zileli MS, Telatar F, Deniz S, Ilter E, Adalar N. Pseudohyperosmolar nonketoacidotic coma due to oxazepam intoxication. Clinical Toxicology 5: 337–341, 1972

    PubMed  CAS  Google Scholar 

  • Zuber M, Elasser S, Ritz R, Scollo-Lavirazzi G. Flumazenil (Anexate®) in severe intoxication with carbamazepine (Tegretol®). European Neurology 28: 161–163, 1988

    PubMed  CAS  Google Scholar 

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Gaudreault, P., Guay, J., Thivierge, R.L. et al. Benzodiazepine Poisoning. Drug-Safety 6, 247–265 (1991). https://doi.org/10.2165/00002018-199106040-00003

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