Altered pharmacokinetics of tricyclic antidepressants in burns.

A case of self-inflicted burns which occurred in the setting of a major depression with psychotic features is described. The case emphasises the difficulties in utilising plasma (serum) tricyclic antidepressant levels to determine adequacy of treatment and risk of toxicity. The case discussion demonstrates the altered pharmacokinetics of tricyclic antidepressants that can occur during disorders such as burns, surgery and medical illness.

A review of the management of oral drug overdose in the Accident and Emergency Department of the Royal Brisbane Hospital.

Two-hundred and eighty-nine patients who made a total of 323 presentations to the Royal Brisbane Hospital Accident and Emergency Department with a known or suspected oral drug overdose were reviewed. The majority of patients (76%) could be managed in a 24 h Accident and Emergency observation unit. Activated charcoal given orally or via a nasogastric tube was the recommended method of preventing further absorption of an ingested drug. The use of syrup of ipecac was not encouraged and orogastric lavage was used in only specific situations. The morbidity and mortality of these patients when compared with other studies, was not adversely affected by this protocol which dramatically reduced the indications for the use of orogastric lavage and syrup of ipecac.

Pharmacokinetics in acute illness.

Severe illness at any age is accompanied by organ dysfunction, the administration of numerous drugs and complex changes in drug absorption, disposition and action. The clinician faced with a seriously ill patient should be aware of the important principles of drug treatment in critical illness. With acute illness of all types, the premature infant and the octogenarian lie at opposite ends of an age spectrum which encompasses the gamut of human disease and changeable organ pathophysiology. The common requirement of this host of variables is a flexible management plan, and careful observation of the patient's response to a therapeutic regimen which has been based on a sound knowledge of drug pharmacokinetics.

Frontal sinus osteoma with complicating intracranial aerocele.

An elderly man, who presented initially with clinical features of dementia, was found to have an intracranial tension aerocele due to an underlying osteoma of the frontal sinus. Plain skull roentgenograms and computerized tomography did not reveal the osteoma, although a communication between the frontal sinus and the aerocele was present. Surgical aspiration of the aerocele and excision of the osteoma produced an excellent clinical result.

Distribution of sodium valproate in normal whole blood and in blood from patients with renal or hepatic disease.

Sodium valproate at a concentration of 300 mumol/l in whole blood, partitioned between the red blood cell and plasma to produce a red blood cell/plasma partition ratio of 0.20. Red blood cell uptake was proportional to percent free drug in plasma and uptake was maximal when plasma was replaced by buffer, producing a red blood cell/buffer ratio of 0.87. Reduction of plasma protein binding by plasma dilution, by increasing the total sodium valproate plasma concentration, or by renal or hepatic disease in 24 patients, caused a predictable rise in red blood cell uptake of drug. The red blood cell represented a relatively small compartment for free sodium valproate in blood, however uptake of the drug into this compartment increased considerably in states of reduced plasma protein binding. Because the concentration of drug in the red blood cell reflects free drug concentration in plasma, the red blood cell may serve as an indicator of free drug changes in blood.

Discrimination between five oral frusemide preparations using renal chloride excretion and frusemide recovery.

The bioavailabilities of five preparations of frusemide (an aqueous solution, Diurin, Frusid, Lasix and Selemide tablets) were studied in healthy subjects, using Latin square designs and administering doses at weekly intervals. Relative to the solution, Lasix had reduced chloride excretion (0.88) and frusemide recovery (0.80) while Diurin and Frusid had reduced frusemide recoveries (0.90 and 0.92 respectively) There were no other significant differences. Potassium excretion tended to fall as the trials progressed.

The influence of various factors in the in vitro distribution of haloperidol in human blood.

Haloperidol is 89.6+/-0.3% bound (mean+/-s.e. mean) in human plasma under in vitro conditions and the free drug distributes rapidly between the plasma and the cellular elements of blood. The cell/plasma partition ratio was 1.12+/-0.06 (mean+/-s.e. mean). Alteration of plasma binding by dilution with buffer showed that uptake of haloperidol by the cellular elements of blood was proportional to free drug concentration. Bishydroxycoumarin (95 ot 286 mug/ml) reduced plasma binding of haloperidol and the displaced haloperidol was taken up by the cellular blood elements. The experiments indicate that the cellular compartment of blood as well as the plasma compartment may act as a sink for haloperidol and drug displacement interactions should therefore be interpreted with a knowledge of both of these compartments.

Propranolol and skilled human performance.

In a double-blind crossover experiment 18 young men received on one occasion 6 doses of 40 mg propranolol and in the other placebo. Medication was given at 6 hour intervals. One hr after the last capsule was ingested subjects were measured with various physiological and behavioral tests. At the conclusion of testing mean plasma propranolol concentration was 67.6 ng/ml. Propranolol significantly reduced systolic blood pressure and heart rate. There was an increased variability on one behavioral measure but the results of other tests were not affected. The findings are discussed in terms of therapeutic use of this and other beta-adrenergic receptor blocking agents.

General practitioner prescribing habits; The Western Australian experience, 1972-1973.

A research project to assess the possibility of modifying general practitioner prescribing habits in Western Australia is described. The results suggest a high level of acceptance of the drug information provided, and a significant alteration in prescribing habits is reported along the lines which might have been predicted.