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Driving under the influence of Oxazepam: Guilt without Responsability
223
glucose and glycosylated haemoglobin (normal 4’9-8-1%) determinations are summarised in the table. There were no differences in metabolic control after the change of treatment. The
patients reported
a
tendency
to more
frequent
hypoglycaemic episodes and, therefore, a tendency to lower insulin doses on human insulin. These tendencies were not significant. Others have reported the same.4,5 This point apart no subjective or objective differences between porcine and human insulin were found. No side-effects were observed. These results are not surprising: a small, short-term study would probably not allow for recognition of any minor differences between the two insulin types. However, it does seem that human semisynthetic insulin can be safely and effectively used in
outpatient treatment. Department of Medicine, Faaborg Hospital,
K. EGSTRUP J. OLSEN
DK-5600 Faaborg, Denmark
DIHYDROCODEINE INCREASES DENTAL
PAIN
SIR,-We were impressed by the finding of Seymour and colleagues (June 26, p. 1476) that intravenous dihydrocodeine increases pain after dental extraction, and felt it merited more detailed discussion of possible mechanisms. Seymour et al. make the point that dihydrocodeine is an effective analgesic in other situations, and the apparent anomaly of dental pain therefore demands explanation. If, as they suggest, dihydrocodeine (or a metabolite) acts as a partial agonist, it could act as an antagonist in situations where acute pain is accompanied by high opioid activity, and thus increase dental pain by antagonising endogenous opioids at receptor sites. This is probably the mechanism by which the opioid antagonist naloxone acutely enhances pain in man. 1-3 The suggestion follows that opioid analgesics (particularly partial agonists) may be less effective than non-opioid analgesics in relieving those types of acute pain where there is already a high level of endogenous opioid activity. In addition, it might provide an alternative explanation to the prostaglandin hypothesis for the success of diclofenac sodium, in relieving the pain of renal colic when compared with a narcotic analgesic (Dr Landstam and colleagues, May 15, p. 1096), and could account for the efficacy of indomethacin as an adjunct to narcotic analgesia following abdominal surgery as reported by Mr Reasbeck and colleagues in last week’s Lancet (p. 115). The potential of non-opioid analgesia in acute severe pain merits further assessment. Poisons Unit, New Cross Hospital,
J. A. HENRY
London SE14 5ER
DIAZEPAM AND CANCER
SIR,-D. W. Kaufman and colleagues (March 6, p. 537) reported that diazepam did not accelerate the development of breast cancer as opposed to cancers of other organs. They suggested that this was a test of my hypothesis relating to diazepam and cancer. The study was not a test of my hypothesis since I have suggested that diazepam may enhance the development of all cancers. Kaufman et al. were careful to note that their work did not evaluate the possibility that diazepam may influence the risk of cancer in general. Media reports of their paper have not been so scrupulous. It is therefore important to emphasise just what has and has not been elucidated. P.O. Box 10, Nuns’ Island,
Montreal, Canada H3E 1J8
DAVID F. HORROBIN
4. Laube H,
Velkovsky HG, Federlin K. Semisynthetisches Humaninsulin: Vergleichende Untersuchung über Stoffwechseleffekte beim Menschen. Akta
Endokrinol 1981; 2: 102. S, Hauff C, Cüppers HJ, Broerman C, Schütte M, Berger M. Absorptionskinetik und biologische Aktivität von semisynthetischem HumanInsulin (Novo). Akta Endokrinol 1981; 2: 116. 1. Levine JD, Gordon NC, Jones RT, Fields HL. The narcotic antagonist naloxone enhances clinical pain. Nature 1978; 272: 826-27. 2.Levine JD, Gordon NC, Fields HL. Naloxone dose-dependently produces analgesia and hyperalgesia in postoperative pain. Nature 1979; 278: 740-41. 3.Willer JC, Dehen H, Cambier J. Stress-induced analgesia in humans. Endogenous opioids and naloxone-reversible depression of pain reflexes. Science 1981; 212: 5 Sundermann
689-91.
Medicine and the Law Driving under the Influence of Oxazepam: Guilt without Responsibility? ON June 16 magistrates at Havering, Essex, heard the case of a 19-year-old man charged with careless driving. One Wednesday morning in December, on his way to work, he had driven into the back of the car in front of him, damaging three cars altogether. On the preceding Friday his doctor had prescribed oxazepam (’Serenid D’) 10 mg twice daily to help relieve tightness of the chest, sleeplessness, and anxiety at work. The defendant stated that the doctor had not mentioned possible side-effects or warned him about driving (a warning which the data sheet mentions unequivocally). The doctor could not recall what he had said in the consultation. I gave evidence for the defendant on the pharmacological aspects of the case. Three points appeared relevant: (1) The accident happened 40-50 min after the defendant had taken his morning dose of oxazepam. At this time the concentration of the drug in the blood would have been approaching its peak, which occurs between 1 and 2 h after an oral dose. (2) The elimination half life of the drug ranges from 5 to 20 h,1so that the drug could have accumulated during the 41/z days of treatment with it. (3) Benzodiazepines can blunt perception, confuse thought, and cause amnesia. The defendant described feeling "fuddled and muddled" and driving less sharply than usual. This state of mind, if it was induced by the drug, would aggravate the difficulty of
understanding that something was wrong, and of taking appropriate action, let alone suspecting a connection between the state of mind and taking the drug. For such a defence to succeed against the charge of careless driving, the accused must satisfy the court beyond reasonable doubt that he was acting in a state of "automatism".zThis concept is not defined by statute, but has evolved in case law. Automatism in the legal sense has been very narrowly construed as involuntary behaviour the individual took reasonable steps to prevent, could not reasonably have foreseen, and which was not self-induced (as for example by excessive drinking). In this case Mr Andrew Phillips (Bates, Wells and Braithwaite) the defending solicitor, contended that the necessary element of involuntarism was perfectly satisfied in that the defendant had suddenly become unconscious (i.e., nodded off) at the wheel. Furthermore, this unconsciousness was not necessarily avoidable by prior feelings of drowsiness, since the drug’s action itself would have weakened the defendant’s perceptions generally and particularly his ability to recognise drowsiness as requiring action. Since he had not been warned either by his doctor or by labelling of the tablets about the possible sideeffects of the drug, and had no independent knowledge of them, it was unreasonable to expect him to have foreseen or avoided the accident. Mr Gopal Hooper, counsel for the prosecution, rejected this contention because the defendant had admitted feeling sleepy during his drive, and, he argued, should therefore have stopped
driving. The three lay magistrates decided that the case was proved but, in view of the unusual circumstances, granted the defendant an absolute discharge, did not endorse his licence, and refused the prosecution’s application for costs and expenses. This compromise neatly avoided the hazards of any fresh interpretation of the law (which might have provided a popular precedent) while doing some justice to the defendant. The case underlines the importance of warning patients about the possible effects of drugs on driving and other potentially dangerous activities. A doctor who fails to warn his patient at least shares the responsibility for any accident that occurs as a result; in such a case the patient would seem to be entitled to recover damages from the doctor. As yet there appears to be no case on the point. Charing Cross Hospital Medical School,
ANDREW HERXHEIMER
London W6 8RF
HJ, Spector RG, Trounce JR. A textbook of clinical pharmacology. London: Hodder and Stoughton, 1981 205. 2. Halnan P, Spencer J. Wilkinson’s road traffic offences, 10th ed. London: Oyez 1. Rogers
Publishing,
1980: 27, 225-27.
glucose and glycosylated haemoglobin (normal 4’9-8-1%) determinations are summarised in the table. There were no differences in metabolic control after the change of treatment. The
patients reported
a
tendency
to more
frequent
hypoglycaemic episodes and, therefore, a tendency to lower insulin doses on human insulin. These tendencies were not significant. Others have reported the same.4,5 This point apart no subjective or objective differences between porcine and human insulin were found. No side-effects were observed. These results are not surprising: a small, short-term study would probably not allow for recognition of any minor differences between the two insulin types. However, it does seem that human semisynthetic insulin can be safely and effectively used in
outpatient treatment. Department of Medicine, Faaborg Hospital,
K. EGSTRUP J. OLSEN
DK-5600 Faaborg, Denmark
DIHYDROCODEINE INCREASES DENTAL
PAIN
SIR,-We were impressed by the finding of Seymour and colleagues (June 26, p. 1476) that intravenous dihydrocodeine increases pain after dental extraction, and felt it merited more detailed discussion of possible mechanisms. Seymour et al. make the point that dihydrocodeine is an effective analgesic in other situations, and the apparent anomaly of dental pain therefore demands explanation. If, as they suggest, dihydrocodeine (or a metabolite) acts as a partial agonist, it could act as an antagonist in situations where acute pain is accompanied by high opioid activity, and thus increase dental pain by antagonising endogenous opioids at receptor sites. This is probably the mechanism by which the opioid antagonist naloxone acutely enhances pain in man. 1-3 The suggestion follows that opioid analgesics (particularly partial agonists) may be less effective than non-opioid analgesics in relieving those types of acute pain where there is already a high level of endogenous opioid activity. In addition, it might provide an alternative explanation to the prostaglandin hypothesis for the success of diclofenac sodium, in relieving the pain of renal colic when compared with a narcotic analgesic (Dr Landstam and colleagues, May 15, p. 1096), and could account for the efficacy of indomethacin as an adjunct to narcotic analgesia following abdominal surgery as reported by Mr Reasbeck and colleagues in last week’s Lancet (p. 115). The potential of non-opioid analgesia in acute severe pain merits further assessment. Poisons Unit, New Cross Hospital,
J. A. HENRY
London SE14 5ER
DIAZEPAM AND CANCER
SIR,-D. W. Kaufman and colleagues (March 6, p. 537) reported that diazepam did not accelerate the development of breast cancer as opposed to cancers of other organs. They suggested that this was a test of my hypothesis relating to diazepam and cancer. The study was not a test of my hypothesis since I have suggested that diazepam may enhance the development of all cancers. Kaufman et al. were careful to note that their work did not evaluate the possibility that diazepam may influence the risk of cancer in general. Media reports of their paper have not been so scrupulous. It is therefore important to emphasise just what has and has not been elucidated. P.O. Box 10, Nuns’ Island,
Montreal, Canada H3E 1J8
DAVID F. HORROBIN
4. Laube H,
Velkovsky HG, Federlin K. Semisynthetisches Humaninsulin: Vergleichende Untersuchung über Stoffwechseleffekte beim Menschen. Akta
Endokrinol 1981; 2: 102. S, Hauff C, Cüppers HJ, Broerman C, Schütte M, Berger M. Absorptionskinetik und biologische Aktivität von semisynthetischem HumanInsulin (Novo). Akta Endokrinol 1981; 2: 116. 1. Levine JD, Gordon NC, Jones RT, Fields HL. The narcotic antagonist naloxone enhances clinical pain. Nature 1978; 272: 826-27. 2.Levine JD, Gordon NC, Fields HL. Naloxone dose-dependently produces analgesia and hyperalgesia in postoperative pain. Nature 1979; 278: 740-41. 3.Willer JC, Dehen H, Cambier J. Stress-induced analgesia in humans. Endogenous opioids and naloxone-reversible depression of pain reflexes. Science 1981; 212: 5 Sundermann
689-91.
Medicine and the Law Driving under the Influence of Oxazepam: Guilt without Responsibility? ON June 16 magistrates at Havering, Essex, heard the case of a 19-year-old man charged with careless driving. One Wednesday morning in December, on his way to work, he had driven into the back of the car in front of him, damaging three cars altogether. On the preceding Friday his doctor had prescribed oxazepam (’Serenid D’) 10 mg twice daily to help relieve tightness of the chest, sleeplessness, and anxiety at work. The defendant stated that the doctor had not mentioned possible side-effects or warned him about driving (a warning which the data sheet mentions unequivocally). The doctor could not recall what he had said in the consultation. I gave evidence for the defendant on the pharmacological aspects of the case. Three points appeared relevant: (1) The accident happened 40-50 min after the defendant had taken his morning dose of oxazepam. At this time the concentration of the drug in the blood would have been approaching its peak, which occurs between 1 and 2 h after an oral dose. (2) The elimination half life of the drug ranges from 5 to 20 h,1so that the drug could have accumulated during the 41/z days of treatment with it. (3) Benzodiazepines can blunt perception, confuse thought, and cause amnesia. The defendant described feeling "fuddled and muddled" and driving less sharply than usual. This state of mind, if it was induced by the drug, would aggravate the difficulty of
understanding that something was wrong, and of taking appropriate action, let alone suspecting a connection between the state of mind and taking the drug. For such a defence to succeed against the charge of careless driving, the accused must satisfy the court beyond reasonable doubt that he was acting in a state of "automatism".zThis concept is not defined by statute, but has evolved in case law. Automatism in the legal sense has been very narrowly construed as involuntary behaviour the individual took reasonable steps to prevent, could not reasonably have foreseen, and which was not self-induced (as for example by excessive drinking). In this case Mr Andrew Phillips (Bates, Wells and Braithwaite) the defending solicitor, contended that the necessary element of involuntarism was perfectly satisfied in that the defendant had suddenly become unconscious (i.e., nodded off) at the wheel. Furthermore, this unconsciousness was not necessarily avoidable by prior feelings of drowsiness, since the drug’s action itself would have weakened the defendant’s perceptions generally and particularly his ability to recognise drowsiness as requiring action. Since he had not been warned either by his doctor or by labelling of the tablets about the possible sideeffects of the drug, and had no independent knowledge of them, it was unreasonable to expect him to have foreseen or avoided the accident. Mr Gopal Hooper, counsel for the prosecution, rejected this contention because the defendant had admitted feeling sleepy during his drive, and, he argued, should therefore have stopped
driving. The three lay magistrates decided that the case was proved but, in view of the unusual circumstances, granted the defendant an absolute discharge, did not endorse his licence, and refused the prosecution’s application for costs and expenses. This compromise neatly avoided the hazards of any fresh interpretation of the law (which might have provided a popular precedent) while doing some justice to the defendant. The case underlines the importance of warning patients about the possible effects of drugs on driving and other potentially dangerous activities. A doctor who fails to warn his patient at least shares the responsibility for any accident that occurs as a result; in such a case the patient would seem to be entitled to recover damages from the doctor. As yet there appears to be no case on the point. Charing Cross Hospital Medical School,
ANDREW HERXHEIMER
London W6 8RF
HJ, Spector RG, Trounce JR. A textbook of clinical pharmacology. London: Hodder and Stoughton, 1981 205. 2. Halnan P, Spencer J. Wilkinson’s road traffic offences, 10th ed. London: Oyez 1. Rogers
Publishing,
1980: 27, 225-27.