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Biomedical subjects

I M Whyte

Publications and source records attributed to I M Whyte.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1992

A computerized method for measurement and analysis of blood pressure in small animals.

A method is described for computerized measurement of blood pressure (BP) in small animals. As described, the system measures BP in up to four experimental animals at one time by sequential sampling but can be expanded to take data from up to 10. It requires an Apple II computer, and is run from a Grass pen-recording system. Pulse rate and systolic and diastolic BP are measured, and these variables are used to calculate mean arterial pressure (MAP) and the time integral of MAP minute by minute. The data are displayed in real time and stored hourly on floppy disc for further analysis.

Animals↗
PubMed1988

Altered aminoglycoside pharmacokinetics in the critically ill.

We studied prospectively 49 patients being treated in an intensive care unit with aminoglycosides for gram-negative sepsis. Pharmacokinetic data were calculated from three post-dose serum levels using a one-compartment model. Doses required to achieve peak levels between 5 and 10 mg/l with trough levels approximately 1.0 mg/l ranged between 2 and 12 mg/kg per day (mean dose 7 mg/kg per day). During therapy 60% of the patients had a change in their apparent volume of distribution (Vd) of greater than 20%. These patients were likely to have confirmed infection and to be febrile at the start of treatment. Two to three weeks after discharge ten patients were restudied after a single dose of aminoglycoside. There was a reduction in mean Vd from 0.24 to 0.18 l/kg (P less than 0.02). Critically ill patients have significantly larger volumes of distribution and may require larger doses per kilogram of body weight of aminoglycoside to achieve therapeutic concentrations. Due to considerable variation in kinetic parameters, the use of standard doses or dosing nomograms is not recommended.

Aminoglycosides↗
PubMed1987

Comparison of the urate lowering effects of allopurinol and diflunisal.

The urate lowering effect of diflunisal, a fluorinated salicylate with an antiinflammatory action, was compared with that of allopurinol in a crossover study. When patients took diflunisal the mean serum urate was significantly greater than on allopurinol but still was within the optimal range in 6 of 8 patients studied. This effect was consistent with its uricosuric action. No inhibition of xanthine oxidase activity by diflunisal was found. Diflunisal could be particularly useful in patients who require a drug with both a uricosuric and an antiinflammatory effect.

Allopurinol↗
PubMedDate not supplied

Management of dapsone poisoning complicated by methaemoglobinaemia.

The currently recommended dosage regimen for methylene blue (intermittent bolus dose) in the treatment of methaemoglobinaemia caused by dapsone is often inadequate. This is due to the long half-life of dapsone which provides a continuing oxidative stress that can cause a recurrence of clinically significant methaemoglobinaemia. Methylene blue infusion is effective, as demonstrated in an illustrative case report, and should be supported by repeated doses of activated charcoal to enhance dapsone elimination. The principles of treatment of methaemoglobinaemia due to dapsone can be applied to methaemoglobinaemia due to any agent producing prolonged oxidative stress.

Adult↗
PubMedDate not supplied

Suspected white-tail spider bite and necrotic ulcers.

AIM: To describe the clinical features, investigation, diagnosis and treatment of ulcers attributed to white-tail (WT) spider bites or necrotic arachnidism. METHODS: The study was a prospective case series of patients referred to the Hunter Area Toxicology Service (a tertiary referral toxicology unit servicing a population of 500 000) with an ulcer or skin lesion that had been attributed to either a suspected WT spider bite or necrotic arachnidism. Eleven patients with skin lesions or necrotic ulcers were referred between January 2000 and June 2002. RESULTS: In two patients that were inpatients in other hospitals, investigation and follow up was not possible. In both cases there was no history of spider bite and Staphylococcus aureus was cultured. In nine patients, a diagnosis other than spider bite was made following appropriate investigation and follow up, including: (i) two cases of dermatophytoses, (ii) three staphylococcal infections, (iii) one case of pyoderma gangrenosum, (iv) one case of cutaneous polyarteritis nodosa, (v) one case of Nocardia braziliensis and (vi) one infected diabetic ulcer. There was only one case where the person recalled seeing a spider bite them, but the patient did not collect the spider for identification. The median time to diagnosis was 3 weeks (interquartile range: 3-9 weeks) and 3.5 years in one case. Appropriate treatment was initiated once the correct diagnosis was made and all cases resolved. CONCLUSIONS: In this series, all cases initially referred as WT spider bites or necrotic arachnidism were found to have alternative diagnoses with appropriate investigations. This demonstrates that spider bites are an unlikely cause of necrotic ulcers and that all ulcers should be properly investigated with bacterial, fungal and mycobacterial cultures and skin biopsy for histopathology.

Adult↗