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Biomedical subjects

G N Volans

Publications and source records attributed to G N Volans.

At least 37 records · Page 2Linked to original sources

The relationship between plasma ibuprofen concentrations and toxicity in acute ibuprofen overdose.

1. The information available from the literature and from a prospective survey of ibuprofen overdose being undertaken by the London centre of the National Poisons Information Service (NPIS) was examined utilizing the Generalized Linear Interactive Modelling (GLIM) statistical computing package. 2. This confirmed that timed ibuprofen plasma concentrations were related to the symptoms of tachycardia, dizziness, tinnitus, ocular symptoms and coma/stupor as well as to reversible renal impairment and plasma hepatic enzyme elevation. 3. The best model of the relationship between symptomatic toxicity and timed ibuprofen plasma concentrations, was an exponential equation in time. Because of the lack of specificity or sensitivity in this model, and absence of demonstrable clinical advantages from its application, we do not recommend its use as a guide to predict toxicity. 4. However analysis of a larger information base utilizing similar methodology could, by increasing the statistical power of the resultant model, provide a useful means of predicting ibuprofen toxicity. 5. A previously postulated relationship between post-ingestion ibuprofen plasma concentrations and toxicity was not confirmed.

Humans↗

Who needs molar units for drugs?

The standardisation of units for drug concentration measurement in clinical medicine is an urgent necessity. The obvious choice is mass units based on the litre. A change to molar units for drug concentrations would make no sense unless drugs were also prescribed in moles, which would cause disruption and inconvenience. There would be considerable danger to patients and the change would be expensive. Most importantly, molar units for drugs will not benefit doctors or their patients. Mass units should be retained and proposals for the adoption of molar units should be abandoned.

Humans↗

The epidemiology and prevention of paraquat poisoning.

In the UK there was an increase in the annual number of deaths associated with paraquat poisoning between 1966 and 1975. Since that time there has been little change in numbers. High mortality is associated commonly with suicidal intent. Serious accidental poisoning from paraquat has never been frequent in the UK and there have been no deaths reported in children since 1977. The National Poisons Information Service has monitored in detail all reports of paraquat poisoning since 1980. Of the 1074 cases recorded there were 209 deaths. In recent years serious poisoning has been more commonly associated with ingestion of concentrated products by males. Local exposure to paraquat has not resulted in systemic poisoning. International data for paraquat poisoning is incomplete and difficult to compare. There is a scarcity of morbidity data at both international and national levels. Information obtained from Poison Control Centres indicates that paraquat poisoning occurs in many countries but detailed comparisons are hindered by lack of standardised methods of recording. Various measures to prevent paraquat poisoning have been introduced. Their effectiveness has not been studied in detail. Some support is provided by the low incidence of serious accidental paraquat poisoning in the UK, but because of the suicidal nature of paraquat poisoning it is unlikely that current preventative measures will influence the number of deaths occurring each year. Preventative measures against paraquat poisoning should be tailored to national needs, based on and assessed by epidemiological studies.

Adolescent↗

Ibuprofen overdose: the first two years of over-the-counter sales.

Experience during 14 years of prescription only use indicates that the non-steroidal anti-inflammatory drug (NSAID) ibuprofen is of low toxicity in acute overdose. In August 1983 ibuprofen was licensed for over-the-counter (OTC) use in the UK and it was recognised that this change could have an impact upon the epidemiology of analgesic overdose in this country. The London centre of the National Poisons Information Service (NPIS) began a new prospective survey of ibuprofen overdose at the time of OTC release. The first 2 years of this survey detected a marked increase in enquiries concerning ibuprofen overdose but there was no evidence to contradict the former claims of low toxicity. The importance of continued monitoring is stressed.

Adult↗

Mercury poisoning after disc-battery ingestion.

A case is described of a 2-year-old girl who swallowed an alkaline disc battery containing mercuric oxide. Two days after ingestion it disintegrated in the stomach necessitating laparotomy to remove the battery casing and most of its contents. Postoperatively her blood mercury concentration rose to 340 micrograms/l and subsequently she developed small bowel obstruction due to adhesions. She was treated with dimercaprol but blood mercury concentrations did not fall until after a second laparotomy to relieve the obstruction and to remove residual mercury salts from the colon. The corrosive effects of swallowed disc batteries are well documented. The maximum blood concentration of mercury reported in this case is 17 times the 'acceptable level of mercury in the blood' and nearly double the highest level recorded previously after disc-battery ingestion. A policy for management of swallowed batteries is suggested.

Child, Preschool↗

Accidental poisoning in childhood: a multicentre survey. 1. General epidemiology.

As background to a study of the effectiveness of packaging in preventing childhood poisoning, the National Poisons Information Service coordinated a prospective survey, in which 9 Accident and Emergency (A & E) departments and 5 paediatric departments, between July 1982 and February 1984, recorded 2043 cases of suspected accidental poisoning in children aged 0-60 months. The products implicated were drugs (59%), household products (37%) and plants (3%). The drugs most frequently implicated were analgesics, anxiolytics, cough medicines, oral contraceptives and drugs to supplement diet or treat dietary disorders. The most frequently implicated household products were cleaners such as bleach, detergent and disinfectant, and petroleum distillate. Seventy-five per cent of the children were 2 and 3-year-olds. Fifty-six per cent were male. Only 22% of the children had signs or symptoms on admission. In only 2 cases were these serious. Treatment other than ipecacuanha and/or oral fluids was seldom required. Of the cases where outcome was recorded, 56% were discharged from A & E. The rest were admitted to a ward; only 7 children were admitted to intensive care units. No child died. Comparison with HASS and other epidemiological surveys shows that these results are representative of national trends.

Accidents, Home↗

Accidental poisoning in childhood: a multicentre survey. 2. The role of packaging in accidents involving medications.

To assess the effectiveness of child-resistant closures (CRCs) and unit dose packaging in preventing childhood poisoning with medications, a survey by 14 hospitals of accidental suspected poisoning in children under 5-years-old, was compared with a survey of a representative sample of households with children under 5 living in the catchment areas of the hospitals. Nine hundred and thirty-eight medications thought to have been ingested by 877 children were compared with 5827 medications found in households with children. The relationship between availability of packs or medications in the home and their involvement in accidents was quantified by means of an Accident Association Index (AAI). A low AAI indicated that the involvement of a pack or medication was less than expected from availability and therefore safe. A high AAI indicated that involvement was greater than expected and therefore unsafe. Medications involved in suspected poisoning were most frequently packed in containers without CRCs (63%) or transparent blisters (20%); both had high AAIs. CRCs, strips, sachets and opaque blisters had low AAIs. Analgesics, expectorants and gastrointestinal medications, had low AAIs, while oral contraceptives, hypnotics, sedative/tranquillizers, antidepressants, anticonvulsants, anti-emetics, and anti-infectives had high AAIs. Prescription medications were more frequently involved in accidents than over-the-counter (OTC) medications and had a higher AAI. Comparison of the AAIs of different kinds of medication in each of their various pack types showed that safe packaging reduced the risk from medications which had a high average AAI. Only 40% of medications were in their normal storage place at the time of the accident. Medicine and bathroom cabinets, and kitchen cupboards and drawers were the safest places to store medications. Handbags, fridges, and shelves or ledges in the bathroom were the most unsafe places. No pack had a low AAI when stored on open shelves indicating that safe packaging cannot compensate for unsafe storage. Other factors which influenced the involvement of medications in accidents were the intended user and the duration of storage. The results of the study have important implications for design of packaging for medications and for education of the public.

Accidents, Home↗

Haemoperfusion: a useful therapy for a severely poisoned patient?

Although it is many years since a haemodialysis and haemoperfusion over uncoated and later coated charcoal columns have been used for the treatment of intoxicated patients, the clinical efficacy of these extracorporeal techniques in the treatment of severely poisoned patients remains a matter of debate. Some of the reasons for this controversy may be the indiscriminate use of haemoperfusion in any form of intoxication, the lack of well-controlled studies and the wrong interpretation of the high haemoperfusion clearance values sometimes obtained. Simple pharmacokinetic principles are applied to this type of treatment and some practical guidelines as to how and when haemoperfusion should be applied or presented are reviewed. The limited place of haemoperfusion in the treatment of severe poisoning, its further declining use in the future, at least in its present design, and some promising new treatments are emphasized.

Forecasting↗

Digoxin and cimetidine: investigation of the potential for a drug interaction.

The potential for a pharmacokinetic interaction between digoxin and cimetidine was investigated in a series of studies. 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. 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. 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. 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. 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.

Adult↗

Adverse reactions to acetylcysteine and effects of overdose.

Since the introduction in 1979 of intravenous acetylcysteine (Parvolex) as an antidote for overdosage of paracetamol the National Poisons Information Service and the manufacturer have been notified of 38 adverse reactions that were anaphylactoid in nature and 19 accidental overdoses. The most common feature of the anaphylactoid reaction to normal dosage was rash; other features reported included angioedema, hypotension, and bronchospasm; all the patients recovered. The features associated with an overdose of acetylcysteine were similar but more severe; two patients died, but the extent to which the overdose of acetylcysteine may have been implicated was not clear in either case.

Acetylcysteine↗

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.

Adrenergic beta-Antagonists↗

An investigation of the role of the specific opioid antagonist naloxone in clinical toxicology.

1 An assessment of the current role of naloxone in clinical toxicology has been made in a series of three separate epidemiological studies. 2 Through the National Poisons Information Service we found that the role of naloxone in opioid poisoning is often not appreciated by the enquirer and that toxicological screening is often requested before the diagnostic use of naloxone. 3 The recommended dose of naloxone (0.4--1.2 mg i.v.) is not always adequate. In 51 cases where naloxone was effective, doses of up to 3.2 mg were necessary (mean 1.8 +/- 0.3 mg SEM i.v.). 4 In 31 cases of non-opioid poisoning, naloxone in doses of 0.4--1.2 mg i.v. caused no deterioration, whilst six patients in whom no opioids were detected showed clinical improvement. 5 In 300 cases of suspected ethanol-induced coma, 49 showed reversal of coma with naloxone, and in 38 cases ethanol was the sole cause of coma (mean plasma concentration 3.54 +/- 0.62 g/l SEM). 6 These results suggest that the role of naloxone in clinical toxicology is not fully appreciated. There is a need for further education as to its indications in opioid poisoning, together with additional studies to define more accurately the dose/response relationship. In addition, the role of naloxone in coma induced by ethanol and certain other non-opioids needs to be evaluated further.

Alcoholic Intoxication↗