Peter Crome

Fatal tricyclic antidepressant poisoning.

Introduction In 1975 there were 234 deaths in the United Kingdom attributed to tricyclic antidepressants and a further 111 cases where these drugs had been taken along with others. Thus, these drugs were involved in 11.6% of the total 2984 deaths from solid and liquid poisons (OPCS 1977). There have been numerous case reports describing the clinical features of poisoning but only a few of these have included large numbers of fatal cases (Frejaville et al. 1965, 1966). Because fatal poisoning appears to be a growing problem, we decided to conduct a survey of all deaths from these drugs, in a single year, to ascertain the epidemiological and clinical features and to see in which particular areas management proved most difficult.

ORAL METHIONINE IN THE TREATMENT OF SEVERE PARACETAMOL (ACETAMINOPHEN) OVERDOSE

30 patients at risk of hepatic damage from paracetamol (acetaminophen) ingestion were given 2-5 g oral methionine every four hours up to a total dose of 10 g. The first dose was given within ten hours of the overdose. There were no deaths and no reports of hepatic encephalopathy or other complications. In 21 patients plasma aspartate-aminotransferase remained within normal limits. These results suggest that methionine may be effective in reducing the frequency and severity of paracetamol-induced liver damage and may provide an effective non-toxic alternative to cysteamine.

Effect of delayed administration of activated charcoal on nortriptyline absorption

SummaryActivated charcoal is known to reduce the absorption of therapeutic doses of nortriptyline in vivo when administered 30 min after drug ingestion. In a group of volunteers, one sachet (10 g) of a new activated charcoal preparation, ‘Medicoal’ was found to produce a highly significant reduction in nortriptyline absorption when given as long as four hours after nortriptyline dosing. Activated charchoal may therefore be useful in the treatment of tricyclic antide-pressant poisoning even if a delay of several hours ensues before medical help is sought.

Experience with fixed-bed charcoal haemoperfusion in the treatment of severe drug intoxication

SummaryFifteen patients who were severely poisoned with either hypnotic drugs or salicylate were treated by charcoal haemoperfusion. The device contained 100 g of activated charcoal immobilised by fixation to a polyester film. Two patients showed no response and eventually died. The remainder showed marked lightening of coma and recovered uneventfully. Complications of platelet loss and, in one patient, fibrinolysis were observed, but these had no serious consequences. No significant biochemical disturbances occurred with the exception of one patient who presented with hypocalcaemia and required intravenous calcium throughout the treatment. Drug clearance values were comparable with those obtained with columns containing 300 g of acrylic polymer coated charcoal.

A Comparison of the Effects of Single Doses of Mianserin and Amitriptyline on Psychomotor Tests in Normal Volunteers

Eight healthy volunteers received single doses of either mianserin 10 mg, mianserin 20 mg, amitriptyline 25 mg or placebo. Critical flicker frequency, reaction time, digit substitution and addition times were tested up to six hours afterwards. Mianserin 20 mg and amitriptyline 25 mg significantly prolonged reaction time and mianserin 10 mg and 20 mg significantly reduced critical flicker frequency. No other significant effects were found. Patients should be warned of possible sedation when first starting treatment with mianserin.

The Use of Methionine for Acute Paracetamol Poisoning

Since September 1974 the London Centre of the National Poisons Information Service has advocated the use of methionine for acute paracetamol poisoning and this paper presents a preliminary report of its outcome. Seventeen patients, all of whom had high plasma paracetamol levels, received oral methionine within ten hours of the ingestion of the overdose. Eleven of these patients suffered no hepatic damage, while the remaining six showed varying degrees of liver failure with a mean maximum aspartate aminotransferase (AST) of 1,098 iu/l. There were no deaths in this group. Among fourteen patients who had taken similar paracetamol overdoses and received no antidotal treatment, all developed liver damage and seven of these died. These two groups were not, however, accurately matched for dose of paracetamol, plasma paracetamol levels or interval before reaching hospital. Comparison was therefore made with two other recently published series of untreated patients. A significant reduction was noted in the incidence of liver damage and in the mean maximum AST. Although this survey was not controlled, it is suggested that oral methionine, which has a low incidence of side-effects, may be effective in reducing the incidence and severity of paracetamol-induced liver damage, provided the overdose is not massive.

Digoxin and Cimetidine: Investigation of the Potential for a Drug Interaction

1 The potential for a pharmacokinetic interaction between digoxin and cimetidine was investigated in a series of studies. 2 In a single-dose cross-over study in healthy volunteer subjects cimetidine increased the area under the plasma digoxin concentration curve and the peak plasma digoxin concentration. 3 In a repeated-dose study in healthy volunteer subjects taking digoxin 0.25 mg daily, co-administration of cimetidine resulted in an average increase in plasma digoxin concentration of 0.15 ng/ml. 4 In a repeated-dose study in healthy volunteer subjects taking digoxin 0.5 mg daily, co-administration of cimetidine resulted in an average increase in plasma digoxin concentration of 0.19 ng/ml. 5 In a repeated-dose study in patients receiving long-term digoxin therapy for atrial fibrillation co-administration of cimetidine had no significant effect on plasma digoxin concentrations. 6 We have shown that co-administration of cimetidine and digoxin in volunteer subjects causes a statistically significant but small increase in plasma digoxin concentration but no such increase was found in patients. We conclude that it is doubtful that this interaction is of any clinical significance.

Experience with activated carbon-bead haemoperfusion columns in the treatment of severe drug intoxication

Five patients who were severely poisoned with hypnotic drugs, paracetamol, or theophylline were treated by charcoal haemoperfusion. The device contained 160 g of activated carbon beads with a polyester coating. Four patients made a significant improvement; one subsequently died from a cerebral haemorrhage which had occurred prior to haemoperfusion. Platelet losses were minimal and no fibrinolysis was observed. No significant biochemical abnormality occurred as a result of haemoperfusion, although one patient, who presented with hypocalcaemia, required intravenous calcium throughout the procedure.

Pharmacokinetics of Dextropropoxyphene and Nordextropropoxyphene in Elderly Hospital Patients after Single and Multiple Doses of Distalgesic. Preliminary Analysis of Results

1 The plasma elimination half-life of dextropropoxyphene and its metabolite nordextropropoxyphene was investigated in seven elderly hospital patients after the administration of both single and multiple doses of Distalgesic. 2 The mean elimination half-life of dextropropoxyphene after multiple dosing was 35.7 h (range 24.0-50.6 h) and the mean half-life of nordextropropoxyphene was 53.3 h (range 25.1-76.3 h). 3 The half-lives of both dextropropoxyphene and nordextropropoxyphene are much longer than those reported by other investigators in younger subjects.

What every medical SHO should know.

The Royal College of Physicians is not the most radical of medical organizations, and has only lately dropped the use of Latin for summoning Fellows to meetings. A new document, however, marks a striking change of direction1: for the first time, the College has published a curriculum for senior house officers (SHOs) in medicine and its subspecialties. In his foreword the President says that previous moves towards producing a curriculum had been resisted on the grounds that it would have had to include the whole of medicine. SHOs will be relieved to observe that the 1996 document is less ambitious. The curriculum itself is divided into two principal components-a core for all medical SHOs, and the additional knowledge and skills expected of SHOs working in each of the medical specialties. The requirements for specialties are subdivided into topics and practical skills. Most of the individual specialty curricula are easy to understand though some are probably too extensive. The main weakness is that the balance between core and specialty knowledge and the degree of detail described differ from specialty to specialty. For example, gastroenterology and neurology do not distinguish at all between the knowledge required by all SHOs and those working within the specialty. Neurology requires SHOs to know the costs of investigations such as magnetic resonance angiography whereas information of this sort is not required by, say, cardiology. The inconsistency of approach is also evident in what is included under the term practical skills. In some specialties this is confined to clinical procedures such as lumbar puncture and paracentesis. For others the content is much broader. Renal medicine includes assessment of hydration status. Rehabilitation medicine wishes its SHOs to know when and who to ask for help; apparently this skill is not required for other specialties! The section on psychiatry is too brief and failsf the strong association between psychol( physical medicine that the College has recognized elsewhere2. I am sure that these issues of cross-specialty consistency and degree of detail will be ironed out when the document is revised. All SHO posts in the UK must now have educational approval from the relevant Royal College. It seems logical that, if there is a curriculum in place, then educational approval should in some way be related to the organizing hospitals ability to deliver the curriculum. That this is so is by no means clear. Large hospitals such as North Staffordshire Hospital, where I work, are able to organize a year-round core curriculum course that includes lectures, tutorials and bedside teaching; smaller units will find this difficult if not impossible without inter-hospital cooperation. A final point. Those who aspire to be specialist physicians will have to pass through both general professional training (SHO grade) and higher training (specialist registrar grade). For the latter, satisfactory completion (without an examination) will yield a certificate of specialist training and eventually a consultant appointment. For the former, satisfactory completion does not automatically lead to anything. To become a specialist registrar one must pass the MRCP examination, for which the Colleges still decline to issue a curriculum and which has a low pass rate; until something is done about this, most SHOs will spend their time trying to pass the examination rather than gaining the experience and skills outlined in the core curriculum.