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Biomedical subjects

I M Whyte

Publications and source records attributed to I M Whyte.

At least 19 recordsLinked to original sources
PubMed1998

Serotonin syndrome resulting from drug interactions.

We describe six patients diagnosed with serotonin syndrome after exposure to drugs with serotonergic activity. Drug interactions occurred as a result of a combination of tricyclic antidepressants, selective serotonin reuptake inhibitors, selective noradrenaline reuptake inhibitors or monoamine oxidase inhibitors. Management included supportive care and the use of non-specific serotonin antagonists (cyproheptadine, benzodiazepines and chlorpromazine). All patients made uneventful recoveries.

Adolescent↗
PubMed1998

Features and toxicokinetics of clozapine in overdose.

One hundred patients were commenced on clozapine in the Hunter region of Australia from July 1993 to September 1995. Of these, one ingested clozapine as a self-poisoning on two occasions. Over the same period, there were four other self-poisonings with clozapine in the region. Another case from a different region is described. The cases were identified from the Hunter Area Toxicology Service Database and regional psychiatric hospitals. The severity of the poisoning is related to prior exposure and tolerance. Marked sedation at relatively low doses occurred in the absence of prior exposure. No reversible electrocardiographic changes or biochemical abnormalities were demonstrated. Anticholinergic effects were minimal. All seven cases made full recovery. A high-pressure liquid chromatography (HPLC) method for assaying clozapine and its major metabolite, norclozapine, in plasma is described. Approximate retention times were norclozapine, 3.8 minutes; clozapine, 5 minutes; and propyl-norclozapine, 7 minutes. The lower limit of analysis for this assay was 20 ng/ml for clozapine and the metabolite. Using the HPLC assay, serial clozapine and norclozapine plasma concentrations were measured in three of these cases of clozapine self-poisoning. Toxicokinetic modeling was conducted by simultaneous analysis of clozapine and norclozapine observations. A two-compartment model with a metabolite compartment attached to the central compartment was used. Clozapine metabolism to norclozapine was best described by linear elimination of norclozapine and nonlinear norclozapine formation. The Km (1918 +/- 2093 micrograms/l) relative to observed concentration (3396 +/- 962 micrograms/l) suggests that norclozapine formation was saturated at the time of the first observation.

Adult↗
PubMed1997

Health care. A model for the management of self-poisoning.

OBJECTIVE: To describe the development and activity of a multidisciplinary service to manage self-poisoning. DESIGN: Descriptive, comparative study with prospective data collection. SETTING: Regional toxicology treatment centre in the Hunter area of New South Wales (NSW) with primary and secondary referral service to 385,000 people and tertiary referral service to a further 100,000. PATIENTS: All patients (1987-1995) with poisoning or envenomation presenting to the Hunter Area Toxicology Service (HATS). MAIN OUTCOME MEASURES: Average length of stay for HATS compared with national and NSW hospitals; mortality data for HATS compared with NSW. RESULTS: Average length of stay for HATS was 0.53-1.22 days shorter than for all Australian hospitals, potentially saving 518 bed-days, valued at $468,000 per year. Average length of stay was 0.94-3.39 days shorter than for all NSW hospitals, saving 1470 bed-days at $1.4 million per year. Inpatient mortality (0.2%; 95% confidence interval, 0.0-1.1) was not significantly different from NSW (0.5%; 95% CI, 0.2-0.8). Standardised mortality ratios showed no greater all-cause suicide mortality. CONCLUSIONS: In our centralised model for managing self-poisoning, all toxicology patients in an area health service are diverted to one hospital, where all patients with deliberate self-poisoning are admitted under the one multidisciplinary team, and all receive psychiatric assessment. This model has substantially reduced bed stay, with considerable savings to the Hunter Area Health Service manifested as an increase in beds available for other purposes.

Critical Pathways↗
PubMed1996

Interrater agreement in the measurement of QRS interval in tricyclic antidepressant overdose: implications for monitoring and research.

STUDY OBJECTIVE: To assess interobserver agreement when experienced clinicians measure QRS-interval duration in tricyclic antidepressant (TCA) overdose. METHODS: We studied the admission ECGs of 231 patients with ICA poisoning. Three of the authors, with experience in the management of TCA poisoning, independently measured QRS intervals manually. Each rater was blinded to patient outcome and the measurements made by the other raters. Our main outcome measure was agreement among raters, particularly as it applies to clinically used QRS cutoff points for the determination of treatment and disposition. RESULTS: Agreement on the measurement of QRS intervals was good (intraclass correlation coefficient, 60; 95% confidence interval [CI], 53 to .66) for transformed data and .82 (95% CI, 7B to .85) for raw data. When assigning patients to categories of QRS interval, the raters agreed on 169 of 231 patients (73%) (weighted kappa = 83; P < .0001). However, the raters did not agree unanimously on whether the QRS interval was less than 100 milliseconds or 100 milliseconds or greater in 45 of 231 of patients (19.5%) (kappa = 69; P < .0001). CONCLUSION: Reliance on the manually measured QRS interval to determine management in TCA poisoning is not justified because of substantial observer variation in the determination of whether the interval falls below the clinical cutoff point of 100 milliseconds. Agreement is sufficient to make the measurements useful as part of the overall assessment of toxicity.

Antidepressive Agents, Tricyclic↗
PubMed1996

An analysis of age and gender influences on the relative risk for suicide and psychotropic drug self-poisoning.

Psychiatric illness is a significant risk factor for both attempted and completed suicide and psychotropic medications account for 80% of all drug overdoses involving prescription medications. One challenge facing clinicians is to balance the benefit of treatment against the risk of drug overdose. The aim of the present study was to compare the age and gender distribution of patients prescribed psychotropic drugs with patients attempting and completing suicide with these drugs. Data were obtained from the Australian census and studies of general practitioner prescribing, patients who committed suicide or presented with self-poisoning within a defined geographic area. The characteristics of these populations were compared to calculate odds ratios for attempting or completing suicide with psychotropic drugs, before and after correction for rates of prescription, in different age and gender groups. The odds ratios (ORs) for self-poisoning were higher for those aged less than 45 years and yet this group was least likely to be prescribed psychotropic drugs. Men had a much higher rate of completed suicide using more lethal methods. The ORs for self-poisoning and suicide with psychotropic drugs, after correction for prescription rates, for those aged 15 to 24 years were 11.1 and 1.7, respectively. Those aged 25 to 44 years had ORs of 4.9 and 4.3, and, by contrast, those over 75 years had ORs of 0.03 and 0. Women were slightly more likely to poison themselves with psychotropic drugs (OR 1.2). However, the situation reversed after correction for prescription rates (OR 0.69). It is concluded that greater caution should be exercised in prescribing for those under 45 years of age, given their relatively higher risk of drug overdose, and that the least toxic compounds should be used. The risk (of self-poisoning) among the elderly may have been overstated, so that some patients may have been denied the benefit of adequate treatment.

Adolescent↗
PubMed1996

Relative toxicity of beta blockers in overdose.

OBJECTIVE: To compare the toxicity of beta blockers in overdose and to identify clinical features predictive of serious toxicity. DESIGN: Comparison of clinical data collected prospectively on a relational database of subjects presenting to hospital with self-poisoning, coroner's data and prescription data. SETTING: Newcastle and Lake Macquarie, Australia, 1987-1995. MAIN OUTCOME MEASURES: Death, seizure, cardiovascular collapse, hypoglycemia, coma and respiratory depression. SUBJECTS: Fifty-eight self-poisonings with beta blockers and two deaths investigated by the coroner with evidence of propranolol poisoning. RESULTS: All patients who developed toxicity did so within six hours of ingestion. The use of ipecac was temporally associated with cardiorespiratory arrest in one patient. Propranolol was the only beta blocker associated with seizure; of those who ingested more than 2 g of propranolol, two thirds had a seizure. There was a significant association between a QRS duration of > 100 ms and risk of seizures. Propranolol was over represented in beta blocker poisoning when prescription data were also examined. Propranolol was the only beta blocker associated with death. Propranolol was taken by a younger age group. CONCLUSIONS: Propranolol should be avoided in patients at risk of self-poisoning. Propranolol poisonings should be observed closely for the first six hours post ingestion. Syrup of ipecac should not be used to decontaminate the gastrointestinal tract after beta blocker overdose.

Adolescent↗
PubMed1995

Self-poisoning in Newcastle, 1987-1992.

OBJECTIVE: To examine the morbidity and mortality associated with self-poisoning with different drug classes. DESIGN: Prospective cohort study with limited follow-up. Retrospective analysis of coronial data. SETTING: Primary and tertiary referral toxicology centre covering Newcastle and Lake Macquarie, Australia, 1987-1992. RESULTS: There were 1969 admissions after ingestion of 3724 substances (2424 prescription drugs and 1300 non-prescription items). The coroner investigated 83 drug-related deaths. Only 12 of these people presented to hospital and, for most of these, death was inevitable at presentation. The most frequently ingested substances were benzodiazepines, alcohol, paracetamol, antidepressants, neuroleptics and anticonvulsants. Since 1980, the percentage of self-poisonings involving benzodiazepines has fallen, while it has risen for those involving antidepressants. Over 50% of deaths were due to tricyclic antidepressants or opioid analgesics. CONCLUSIONS: As death usually occurs out of hospital, interventions to decrease mortality from self-poisoning must focus on prevention, and targeting drugs that are frequently taken or frequently lethal in overdose. Consideration should be given to the use of antidepressants that are safer in overdose. The use of antidepressants, barbiturates or chloral hydrate as sedatives should be discouraged.

Adolescent↗
PubMed1995

Correlations between prescriptions and drugs taken in self-poisoning. Implications for prescribers and drug regulation.

OBJECTIVE: To compare prescription data for Australia with drugs ingested in self-poisoning and suicide, to determine which drugs are over-represented. DESIGN: Comparison of data on drugs taken in self-poisoning admissions and suicides with Australian prescription drug dispensing data from the Drug Utilization SubCommittee (DUSC). SETTING: Newcastle and Lake Macquarie, Australia, 1989-1992. SUBJECTS: Between July 1989 and June 1992, 1159 prescription drugs were taken in overdose. Eighty-three drug-related deaths were investigated by the coroner between 1987 and 1992. On 48 occasions a prescription drug was the primary cause of death. RESULTS: Drugs over-represented in self-poisoning (relative to Australian prescriptions) included not only those prescribed for psychiatric conditions (antidepressants, neuroleptics and lithium), but also benzodiazepines, barbiturates and other anticonvulsants. The highest odds ratios for death when adjusted for prescription numbers were for short-acting barbiturates (523.7; 95% confidence interval [CI], 207-1322), chloral hydrate (58.1; 95% CI, 18.1-187), colchicine (27.9; 95% CI, 3.8-202), dextropropoxyphene (20.8; 95% CI, 8.8-48.9), tricyclic antidepressants (13.3; 95% CI, 7.2-24.5) and anticonvulsants (11.6; 95% CI, 4.1-32.2). CONCLUSIONS: Short-acting barbiturates, chloral hydrate and dextropropoxyphene have little or no clinical advantage over alternatives and excessive toxicity in overdose. They should be removed from the market. The toxicity of anticonvulsants and colchicine should be considered when they are prescribed, and smaller amounts per prescription may be advisable for high risk patients using these and other toxic drugs.

Drug Prescriptions↗
PubMed1995

Relative toxicity of benzodiazepines in overdose.

OBJECTIVE: To assess the sedative effects in overdose of temazepam and oxazepam compared with other benzodiazepines to determine if this explains reported differences in fatal toxicity. DESIGN: Cohort study of patients admitted with benzodiazepine poisoning. SETTING: Newcastle, Australia. SUBJECTS: 303 patients who had ingested benzodiazepine alone or in combination with alcohol and presented to a general hospital which served a well defined geographical area. MAIN OUTCOME MEASURES: Degree of sedation: Glasgow coma score, McCarron Score, and whether patients were stuporose or comatose. RESULTS: Oxazepam produced less and temazepam more sedation than other benzodiazepines. Unadjusted odds ratios for coma with oxazepam and temazepam compared with other benzodiazepines were 0.0 (95% confidence interval 0.0 to 0.85) and 1.86 (0.68 to 4.77) respectively, chi 2 = 7.08, 2df, P = 0.03. After adjustment for potentially confounding effects of age, dose ingested, and coingestion of alcohol, the odds ratios were 0.22 (0.0 to 1.43) for oxazepam and 1.94 (0.57 to 6.23) for temazepam. Similar results were obtained for other measures of sedation. CONCLUSIONS: These results were in accordance with fatal toxicity indices derived from coroners' data on mortality and rates of prescription. The relative safety of benzodiazepines in overdose should be a consideration when they are prescribed.

Adolescent↗
PubMed1995

Cardiotoxicity more common in thioridazine overdose than with other neuroleptics.

On the basis of case reports and small non-comparative series it has been suggested that thioridazine has greater cardiotoxicity in overdose. Limited evidence also suggests an increased association with sudden death in therapeutic doses. The aim of our study is to examine the clinical and electrocardiographic features associated with neuroleptic poisoning and compare thioridazine with other neuroleptics. Consecutive adult patients with neuroleptic poisoning presenting to metropolitan hospitals in Newcastle between 1987 and 1993 were studied. The main outcome measures examined were ECG changes (QRS, QT and QTc intervals), arrhythmias, seizures, degree of sedation, heart rate and blood pressure. Two-hundred ninety-nine patients had ingested thioridazine (104), chlorpromazine (69), trifluoperazine (36), pericyazine (35), haloperidol (33), prochlorperazine (18), fluphenazine (8), or other neuroleptics (7). Sixteen patients had ingested more than one neuroleptic and were excluded from comparative analysis. Thioridazine was more likely to cause tachycardia (odds ratio 1.7, 95% CI 1.1-2.9, p = 0.03), a prolonged QT interval (odds ratio 5.2, 95% CI 1.6-17.1, p = 0.006), prolonged QTc > 450 ms1/2 (odds ratio 4.7, 95% CI 2.7-7.9, p = 0.001), a widened QRS (> 100 ms) (odds ratio 3.1, 95% CI 1.5-6.3, p = 0.001) and arrhythmias (odds ratio infinity, 95% CI 2.4- infinity, p = 0.004). There were no significant differences in the odds of coma (odds ratio 0.5 (0.2-1.5)), hypotension (odds ratio 0.9 (0.4-1.9)) or seizures (odds ratio 3.9 (0.3-43.5)). Adjustment for age, sex, dose ingested and co-ingestion of tricyclic antidepressants or lithium had no major effect on the odds ratios observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Pheniramine--a much abused drug.

OBJECTIVES: To assess the relative clinical toxicity of pheniramine compared with other antihistamines taken in overdose and its relative use for self-poisoning. DESIGN: A prospective follow-up cohort study of antihistamine self-poisonings. Local pharmacists were surveyed to ascertain the approximate market share of pheniramine. SETTING: Newcastle, Australia. SUBJECTS: 102 patients giving rise to 118 consecutive admissions to hospital for antihistamine self-poisoning after ingestion of pheniramine (43) or other antihistamines (75). MAIN OUTCOME MEASURES: Generalised seizures, delirium/psychosis, sedation, QRS width, mean blood pressure. RESULTS: Pheniramine accounted for only 3.0% of antihistamine items dispensed, 5.5% of defined daily doses (DDDs) dispensed, but 33.9% of antihistamine self-poisonings. Fourteen admissions were complicated by seizures and 43 by delirium/psychosis. Patients admitted after ingestion of pheniramine were more likely to have generalised seizures (13 of 43) than those ingesting other antihistamines (one of 75). Other complications (sedation, need for ventilation, prolongation of QRS interval, change in blood pressure) were comparable. A very high proportion of the pheniramine group had a history of drug or alcohol abuse (79.9%). This included 60.5% with a history of antihistamine abuse. The figures for those who ingested other antihistamines were 46.7% and 6.7% respectively. CONCLUSIONS: Pheniramine is taken in overdose more frequently than other antihistamines relative to its market share. It is also more likely to be abused than other antihistamines. In overdose, it appears to be more proconvulsant than other antihistamines. Consideration should be given to the use of alternative antihistamines in patients at risk of seizures. In the light of these findings, regulatory authorities should review the over-the-counter availability of pheniramine.

Adult↗
PubMed1994

Greater toxicity in overdose of dothiepin than of other tricyclic antidepressants.

Epidemiological studies have implicated dothiepin in a greater number of self-poisoning deaths than would be expected from its use. We have prospectively assessed the clinical toxicity of dothiepin and other tricyclic antidepressants (TCAs) in overdose. We followed-up consecutively admitted patients with TCA poisoning managed by our department between January, 1987, and August, 1992. 75 patients had taken dothiepin, 101 amitriptyline, 83 doxepin, and 61 other TCAs. Death after TCA poisoning is rare nowadays, so we used intermediate outcome measures--general seizures, tachyarrhythmias, sedation, and QRS width on the electrocardiogram. 15 patients had seizures and 7 tachyarrhythmias. When we excluded patients who had taken more than one TCA, general seizures were more likely after dothiepin than after other TCAs (9/67 vs 5/220) as were arrhythmias (4/67 vs 3/220). Rates of other complications were similar. The dothiepin group had ingested a larger dose, attributable to the larger average tablet strength, than patients who took other TCAs. The odds ratio for seizures with dothiepin versus other TCAs was 6.7 (95% Cl 2.2-20.7) unadjusted and 7.1 (2.2-23.2) after adjustment for sex, age, and ingested dose. The corresponding odds ratios for arrhythmias were 4.6 (1.0-21.1) and 3.4 (0.7-16.3). Dothiepin in overdose seems to be proconvulsant. Patients with only minor sedation and normal limb-lead QRS width may still have major complications. Consideration should be given to the use of other antidepressants in patients at risk of seizures or suicide. Regulatory authorities should review the need for a 75 mg strength tablet of any TCA.

Adult↗
PubMed1994

Calcium channel blocking drug overdose: an Australian series.

1. A descriptive case study of calcium channel-blocking drug (CCB) overdoses in the Hunter Region of NSW was performed to analyse the in-hospital morbidity and mortality of CCB drug overdoses in an Australian population. 2. The patients were admitted to major hospitals within the Hunter Region and treated initially with gastrointestinal decontamination, including the use of oral activated charcoal. Further management was required in most cases and included intravenous calcium, atropine and inotropic support. 3. Of the 15 CCB overdoses, four patients died. Noncardiogenic pulmonary oedema occurred in two other cases. Cardiac conduction defects occurred in 11 cases. 4. Atropine was found to be effective only after intravenous calcium had been administered. 5. Overdose with slow-release verapamil required prolonged treatment with intravenous calcium salts. 6. Overdose with verapamil or diltiazem in doses greater than 300 mg carries a significant risk of death and potentially life threatening arrhythmias occur with lower doses. 7. Recommended initial management includes early, effective gastrointestinal decontamination. High dose intravenous calcium salts should be given to reverse hypotension and bradycardia. Atropine and inotropic support are frequently required.

Adolescent↗
PubMed1994

Organophosphate poisoning: peripheral vascular resistance--a measure of adequate atropinization.

We report severe organophosphate poisoning complicated by hypotension and ischemic sequelae in two patients with pre-existing vascular disease. Both patients had a low total peripheral resistance and high cardiac output that were significantly reversed by doses of atropine in excess of those required to control other muscarinic symptoms. Cerebral infarcts and gangrene requiring a below knee amputation were complications of the poisonings. It is proposed that the ischemic complications are due to paradoxical vasoconstriction by acetylcholine at sites of endothelial injury. One patient, who had taken fenthion, also had a significantly delayed peak and prolonged, 2-3 week, systemic toxicity. We propose that stability of the plasma cholinesterase at 6 to 8 h after temporarily suspending oxime provides a rapid guide to the duration of therapy, especially in patients whose complications make clinical assessment difficult.

Acetylcholinesterase↗
PubMed1993

Slow-release verapamil poisoning. Use of polyethylene glycol whole-bowel lavage and high-dose calcium.

OBJECTIVE: To present three cases of slow-release verapamil poisoning that demonstrate the prolonged absorption of the drug and the role of polyethylene glycol and high-dose calcium in management. CLINICAL FEATURES: Three patients with slow-release verapamil poisoning are presented. An 18-year-old woman took 2.3 g and developed hypotension and bradyarrhythmias 18 hours after ingestion, despite gastric lavage and administration of charcoal at three hours. A 23-year-old woman took 4.8 g and presented two hours later clinically unaffected. A 44-year-old woman presented 24 hours after taking 15-20 g. She had a systolic blood pressure of 50 mmHg, no measurable diastolic blood pressure and bradyarrhythmias. INTERVENTION AND OUTCOME: Case 1 responded to administration of 30 g of calcium and fluids intravenously. Case 2 was given polyethylene glycol on admission which resulted in passage of a tablet bezoar and no toxicity. Polyethylene glycol was ineffective in Case 3. She responded initially to high doses of calcium and other treatments, but subsequently died of hypotension and cardiac conduction block 39 hours after the overdose. CONCLUSION: The severity of poisoning with slow-release verapamil warrants aggressive pre-emptive treatment. Polyethylene glycol should be used routinely irrespective of the clinical state. High doses of calcium may be required to treat conduction block and hypotension.

Adolescent↗