Migraine and drug absorption.

The majority of migraine attacks are associated with gastrointestinal symptoms which add considerably to the distress and inconvenience caused by the headache. When salicylate absorption from effervescent aspirin tablets was studied during migraine, the rate of absorption was found to be reduced relative to that found in non-migrainous volunteers and in the same patients when headache-free. There is evidence that this reduced rate of absorption is caused by gastrointestinal stasis and reduced rate of gastric emptying. Patients in whom aspirin absorption was delayed were more likely to take longer to respond and to require additional treatment. Metoclopramide, which increases gastric emptying rate, has been shown to improve the rate of absorption of aspirin during migraine and also increase the rate of recovery from the attack and avoid the need for additional treatment; effects which were not shown by thiethylperazine. It is likely that delayed absorption during migraine affects some drugs other than aspirin, such as ergotamine, and it is therefore recommended that the most rapidly absorbable formulation should be used. If such treatment is ineffective, metoclopramide may be a useful addition and should be tried before resorting to other routes of administration.

Features, prevention and management of acute overdose due to antidiabetic drugs.

Hypoglycaemic medication forms a disparate group of therapeutic compounds including insulin, the sulphonylureas and biguanides. They are all designed to prevent hyperglycaemia and in general are well tolerated. Careful prescribing practice and patient education by the physician can do much to reduce the risk of adverse effects from diabetic therapy. However, the presentation of adverse effects, together with accidental and non-accidental overdose, is a frequent clinical problem. Furthermore, the possible impairment of hypoglycaemic awareness in patients prescribed human insulin has added complexity to diabetic management. The cardinal features of insulin overdose are hypoglycaemia and hypokalaemia. The sulphonylureas predominantly cause hypoglycaemia, while the biguanides may precipitate lactataemia and acidosis. Recognition of hypoglycaemia is therefore crucial in avoidance of toxicity. Intravenous dextrose is the mainstay of therapy following gut decontamination (for the oral agents). The efficacy of glucagon is dependent on hepatic glycogen stores and should therefore be used with caution. Diazoxide is not recommended. More recently, octreotide has been shown to be effective in sulphonylurea overdose. Patients should be admitted and monitored with serial blood sugar measurements for a minimum of 1 to 2 days as clinically warranted.

A preliminary controlled evaluation of the antihypertensive effect of indapamide.

A controlled, single-blind trial was carried out in 10 hypertensive patients to compare the effectiveness of a single daily dose (2.5 mg to 5 mg) of indapamide with that of placebo. Blood pressure was measured with a bias-free sphygmomanometer. Indapamide produced a significant reduction in mean systolic and diastolic pressures in both supine and erect positions. It was generally well tolerated: few side-effects were reported and no significant changes were noted in laboratory tests. It is concluded that further long-term studies of indapamide are indicated in larger numbers of patients.

Preliminary experience with diacetylrhein in the treatment of osteoarthritis.

A single-blind, placebo controlled study was carried out over a 12-week period in 12 patients with osteoarthritis of the hip or knee to assess the effectiveness of 50 mg diacetylrhein per day. The 4 weeks of active treatment were preceded and followed by periods on placebo. Response to treatment as assessed by pain score, walking time and the number of 'rescue' analgesic tablets (paracetamol) consumed showed that 6 patients improved, 4 were unchanged and 2 deteriorated. Improvement was not apparent for several weeks after starting active treatment and remission lasted for 2 weeks to 3 or more months after the drug was withdrawn. The action of diacetylrhein is not yet established, but it does not appear to be related to analgesia or inhibition of prostaglandin synthetase activity. It is considered that further studies of this interesting drug are warranted to determine the most effective dose and duration of treatment.

Pharmacokinetics of oral indoramin.

A randomized crossover study was carried out in 7 healthy subjects to investigate the pharmacokinetics of indoramin from two oral formulations (film-coated and uncoated 50 mg tablets) and to determine the effect of a standard mean on the plasma concentration time curve of the film-coated form. The results indicated that peak plasma concentrations occurred in 1 to 4 hours after treatment with a single dose of 2 tablets, with an overall elimination half-life of 5 hours. No significant differences could be shown between treatments in any of the pharmacokinetic variables determined. However, administration of film-coated indoramin after a standard meal narrowed the range of peak concentrations but the time at which peak concentrations of the drug occurred did not appear to be related to whether or not indoramin was given after the meal.

Management of cardiac drug overdose.

Although overdoses from cardiac drugs are uncommon, these are compounds with narrow therapeutic indices and they may give rise to serious acute toxicity from accidental, deliberate or even iatrogenic overdosage. Through the National Poisons Information Service for England and the Poisons Unit laboratory, we monitor reports of serious toxicity from this group of drugs and use the information gained to assess our recommendations for treatment. This article reviews the toxicity and the management of overdosage with digoxin and representative drugs from each class of anti-arrhythmic drugs. From these observations, a general plan of management applicable to all cardiac drugs is proposed and its is suggested that this form of monitoring should be continued.

Apparent poisoning by wood preservatives: an attributional syndrome.

Recent reports have pointed to an increased number of patients presenting with multisystem symptoms which they attribute to chemical exposures or to heightened chemical sensitivity. Twenty patients exposed to wood preservative products, who attended a joint toxicology and psychiatric clinic, were reviewed by a retrospective case note analysis. Thirteen patients attributed their symptoms to the wood preservative soon after the exposure, and seven patients developed the attribution only at a later date. Reported symptoms referred to all body systems, but there were few physical signs. Clinical findings suggest that the acute symptoms were consistent with the expected toxic effects, but the chronic symptoms could not be explained physically. Patient's beliefs about chemical poisoning could be understood as arising in the context of an attributional process, representing a sociopsychosomatic syndrome precipitated by wood preservative exposure. Patient management included a discussion of findings from assessments, published information, along with counseling where appropriate. Follow-up information from their general practitioners indicated a possible improvement in 50% of patients.

Paracetamol overdose in pregnancy analysis of the outcomes of 300 cases referred to the Teratology Information Service.

A prospective study was carried out to investigate the outcome of pregnancy in 300 women who had self-administered an overdose of paracetamol, either alone, or as part of a combined preparation. Exposure occurred in all trimesters. The most striking feature of this study is that the majority of the pregnancies had normal outcomes. Over half of the mothers (160 = 53%) required treatment for the overdose, and 49 of these had specific antidotes (33 mothers had acetylcysteine and 16 mothers had methionine). The rest of the mothers were given nonspecific treatments including ipecacuanha (52), gastric lavage (42), and charcoal (16). None of the mothers died. There were 219 liveborn infants with no malformations, 61 of whom had been exposed in the first trimester. Eleven liveborn infants had malformations; none was exposed in the first trimester. On other infant exposed at 18 weeks had a diaphragmatic hernia; this pregnancy was terminated at 22 weeks. In none of these 12 infants can the malformations be directly associated with paracetamol exposure. There were no apparent differences either in the sex ratio or the body weights of term infants. There were seven full-term infants with neonatal problems that seem unrelated to paracetamol exposure. Six premature infants also had neonatal problems, which were more likely to be related to their degree of prematurity rather than paracetamol exposure. There was no obvious relationship between the time of exposure and the time of delivery. The overall conclusion is that paracetamol overdose per se is not an indication for termination of pregnancy.

Paracetamol poisoning in pregnancy: an analysis of the outcomes of cases referred to the Teratology Information Service of the National Poisons Information Service.

A study was carried out to investigate the outcome of pregnancy in 115 women who had been exposed to paracetamol overdose. Follow up was obtained in 48 cases. Exposure occurred in all trimesters, and the most striking feature of this series is that the majority of the pregnancy outcomes were normal. None of the mothers died. There were 39 live born infants with no malformation, 14 of whom had been exposed in the first trimester. Four babies, exposed in the third trimester had neonatal problems, but these seem unrelated to paracetamol. There were two live born infants with gross malformations (spina bifida occulta; and cleft lip and palate). However, as the overdoses occurred at weeks 26 and 28 respectively, long after the structural development of these organs, the malformations could not have been caused by the paracetamol. There were two spontaneous abortions, both in the first trimester, which occurred two weeks after the overdose which may be related to the paracetamol. The overall conclusion is that paracetamol overdose per se is not necessarily an indication for termination of pregnancy.

A study of self poisoning with oral salbutamol--laboratory and clinical features.

1. The recent increase in asthma mortality coupled with reports of fatal asthma associated with beta-2-agonist therapy, has stimulated interest in the plasma concentrations of beta-2-agonists that produce systemic toxicity. 2. We prospectively studied 17 patients (9 male), mean age 23 years (range 2-72), who attended the emergency departments of hospitals throughout the United Kingdom having recently ingested an overdose of salbutamol. 3. Clinical, laboratory, ECG data, plasma and urine samples were obtained from each patient. Plasma was assayed for salbutamol concentration using a high performance TLC-photodensitometric method. 4. The mean (+/- s.d.) salbutamol dose reported to have been ingested was 89(+83)mg and the mean plasma salbutamol concentration was 166 (range 18-449) ng ml-1. The mean plasma potassium was 2.9 (s.d. +/- 0.6) mM (n = 16). None of the patients in this study developed serious cardiac dysrrhythmias. 5. There were significant correlations between the plasma salbutamol concentration and plasma potassium concentration (r = -0.85; P < 0.00005) and between plasma salbutamol concentration and pulse rate (r = 0.66; P < 0.005). 6. We conclude that in these patients, without respiratory decompensation, suprapharmacological plasma concentrations of salbutamol were tolerated without serious cardiac arrhythmias or any fatalities.

A schedule for combined intravenous and oral dosing with mexiletine.

A combined intravenous and oral dosage regime for mexiletine has been evaluated in volunteer subjects. Therapeutically effective plasma concentrations of the drug were achieved rapidly and maintained over a four-hour period. Side-effects were minimal and the scheme would be suitable for the anti-arrhythmic protection of patients being transported to hospital and for the treatment of patients receiving hospital or, even, domicilliary care.

Effects of food and exercise on the absorption of effervescent aspirin.

1 The absorption of effervescent aspirin was studied in normal volunteers of both sexes under varied conditions of activity in both fasting and non-fasting states. 2 Moderate activity resulted in no significant changes in absorption compared with that at rest. 3 In non-fasting subjects the absorption was reduced but this reduction was attenuated with time until after 60 min the plasma levels were similar. 4 There was no interaction between the resting/non-resting and fasting/non-fasting absorption.