Search PubMed⌕ Search

Biomedical subjects

A M Hayler

Publications and source records attributed to A M Hayler.

17 recordsLinked to original sources
PubMed1986

Measurement of plasma disopyramide as a guide to paediatric use.

We have studied the relationship between age, daily dose, plasma concentration and clinical efficacy of disopyramide in a group of paediatric patients. Twelve children with ventricular and 3 with supraventricular arrhythmias were treated with oral disopyramide. The initial dose was 3-6 mg/kg per day. This was adjusted until a pre-dose plasma concentration greater than 2 mg/I was achieved. Seven patients were judged to have responded to the treatment on clinical criteria. No symptoms or signs of toxicity were observed. In some of the children the dose of disopyramide required to achieve a plasma concentration greater than 2 mg/l was greatly in excess of the normal adult dose. Generally the youngest children required the highest dose, but the variation was wide. The dose could not be predicted from the age, the body weight or the surface area of the patient. In children high doses of disopyramide may be needed to achieve effective plasma concentrations of the drug; such doses are not associated with adverse effects. Measurement of the plasma concentration is necessary to guard against premature termination of therapy.

Administration, Oral↗
PubMed1985

Is fibreoptic bronchoscopy in patients with lung cancer and hepatic metastases potentially dangerous?

Plasma lignocaine levels were measured in 18 patients with lung cancer undergoing fibreoptic bronchoscopy to determine whether those with hepatic metastases and disturbed hepatic function were at special risk from lignocaine toxicity. Peak plasma lignocaine levels were in fact lower in six patients with hepatic metastases and deranged hepatic function tests than in the nine patients with no evidence of hepatic metastases or dysfunction (mean +/- SEM 1.89 +/- 0.2 mg/litre and 2.60 +/- 0.3 mg/litre respectively, P not significant). The peak plasma lignocaine level did not correlate with tests of liver function but did correlate with age. Using a total dose of lignocaine of less than 400 mg, plasma lignocaine levels remained below the toxic range in all patients. The peak plasma lignocaine level correlated significantly with the amount of drug administered directly into the bronchial tree (P less than 0.05) rather than total dose administered. Patients with hepatic metastases from lung cancer do not appear to be at an increased risk from the toxic effects of lignocaine topical anaesthesia if moderate doses are used.

Administration, Topical↗
PubMed1982

Plasma disopyramide concentrations following a 300-mg oral loading dose in acute myocardial infarction.

Plasma disopyramide concentrations were measured in 19 patients with suspected myocardial infarction (MI) following an oral loading dose of 300 mg. Infarction was confirmed in 17 patients. In 10 patients blood samples were collected frequently over a period of 6 h, and in the remaining nine, blood samples were collected for 60 h whilst they were receiving a maintenance dose of 100 mg six hourly. There was a wide variation in the absorption of the drug, and only 8 patients achieved plasma concentrations in the range 2-4 mg/L within one hour of ingestion; 8 of the patients on maintenance therapy were within this range 24 h following the start of therapy. Although only 2 noninfarct patients were observed, they achieved the highest plasma disopyramide concentrations--above the therapeutic range--within 1 h of receiving the loading dose. Narcotic analgesia was associated with poor absorption of the drug, but this does not exclude severity of infarction or vomiting after the loading dose from contributing to the wide variation in plasma concentrations in the early stages following the loading dose. It is concluded that this regime is unsuitable for prophylactic use in acute MI.

Adult↗
PubMed1980

Successful management of serious disopyramide poisoning.

A case of deliberate disopyramide overdosage is described. Circulatory collapse was treated by means of a large dose of isoprenaline, and charcoal haemoperfusion was used in an attempt to enhance the elimination of disopyramide. The suitability of this treatment regime is discussed in the light of findings from animal studies and the implications for the management of the disopyramide-poisoned patient are considered.

Adult↗
PubMed1979

Simple gas-liquid chromatographic method for the measurement of mexiletine and lignocaine in blood-plasma or serum.

A simple method has been developed for the measurement of mexiletine and lignocaine in blood-plasma or serum at the concentrations attained during therapy. A relatively small (200 microliter) sample volume is made basic and extracted with 50 microliter of chloroform containing internal standards, and the extract is analysed directly by gas-liquid chromatography with flame-ionisation detection on two separate columns. The instrument calibrations are linear and pass through the origin of the graphs. Neither solvent transfer nor evaporation steps are used in the extraction procedure, which takes less than 3 min to complete, and no interference from either endogenous sample constituents or other drugs has been observed.

Chromatography, Gas↗
PubMed1979

Cardiac consequences and treatment of disopyramide intoxication: experimental evaluation in dogs.

A slow (1.18 mumol.kg-1.mm-1) intravenous infusion of disopyramide (mol.wt 339) was given to 8 adult Beagle dogs. An initial phase of slow decline in cardiac output and broadening of the QRS complex on the ECG, with systolic blood pressure maintained above 13.5 kPa (100 mmHg), was followed by a phase of rapid circulatory failure without a correspondingly dramatic change in ECG appearances. Underventilation and cardiac arrhythmias were observed only in the agonal phase after several minutes of circulatory arrest. They were not therefore the primary cause of death, which was due to failure of myocardial contractility. Three positively inotropic drugs (isoprenaline, dopamine, and glucagon) are shown to be capable of restoring the failing circulation, provided they are given before the phase of complete circulatory standstill. In this respect isoprenaline appears superior to dopamine and glucagon.

Animals↗
PubMed1978

Simple gas-liquid chromatographic method for the measurement of disopyramide in blood-plasma or serum and in urine.

A simple method has been developed for the measurement of disopyramide in blood-plasma or serum at the concentrations attained during therapy. A relatively small (200 microliter) sample volume is made basic and extracted with 50 microliter of chloroform containing an internal standard, and the extract is analysed directly by gas-liquid chromatography with flame-ionization detection. The instrument calibration is linear and passes through the origin of the graph. Neither solvent transfer nor evaporation steps are used in the extraction procedure, which takes less than 3 min to complete, and urine specimens may be analysed by an analogous technique. No interference from either endogenous sample constituents or other drugs has been observed, although a simple back-extraction procedure is described which eliminates potential interference from a small number of basic and neutral drugs.

Chromatography, Gas↗
PubMed1978

Fatal overdosage with disopyramide.

The most common clinical finding in five patients who died after deliberately taking overdoses of disopyramide was an early loss of consciousness after an apnoeic episode. An initial response to resuscitation and antiarrhythmic drugs in four patients was not sustained and these patients deteriorated rapidly with cardiac arrhythmias and loss of spontaneous respiration. At necropsy the appearance of the lungs in four cases was consistent with pulmonary congestion secondary to left ventricular failure.

Adolescent↗
PubMed1976

Penetration of digoxin into cerebrospinal fluid.

The concentration of digoxin in the cerebrospinal fluid (CSF) of ten patients receiving conventional oral doses of this cardiac glycoside has been measured by a radioimmunoassay technique. Digoxin was undetected in eight patients and barely detectable in two, suggesting the presence of a significant blood-CSF barrier for digoxin. The implication of these findings is discussed.

Adult↗