Aspects of drug use in schizophrenia, cardiac surgery and palliative care

The research in this thesis involved four studies of the variability in plasma concentrations and effects of a selection of drugs used in schizophrenia, cardiac surgery and palliative care. 1. Fluphenazine study Steady-state pre-dose plasma concentrations of fluphenazine were measured using a gas chromatography I mass spectrometry assay in 24 patients with schizophrenia who were receiving continuous treatment with depot intramuscular fluphenazine decanoate. Clinical response was measured using the Andreasen Scale for positive and negative symptoms. Poorer clinical control was related to higher log transformed plasma concentrations of fluphenazine and higher fluphenazine decanoate dosage. The log transformed plasma concentrations of fluphenazine and the fluphenazine decanoate dosages were weakly related. These results indicated the useful role that plasma level monitoring can fulfill in identifying patients who are therapy-resistant despite optimal or high plasma levels. 2. CPB study This study examined the effect of cardiopulmonary bypass (CPB) surgery on the total and unbound plasma concentrations of fentanyl and the total plasma concentrations of alcuronium in sixteen patients. Due to the large number of factors which may affect pharmacokinetics during CPB, the results were difficult to deal with mathematically. Despite marked declines in the plasma concentrations of both drugs on initiation of CPB, suitable plasma concentrations for anaesthesia were maintained throughout the procedure. 3. Subcutaneous fentanyl This study investigated the steady-state total and unbound plasma concentrations of fentanyl during continuous subcutaneous administration in 20 palliative care patients. Infusion rates and both total and unbound plasma concentrations of fentanyl were correlated. Even with standardisation for dosage, there was an 8-fold variation in total plasma concentrations and a 3.5-fold variation in unbound plasma concentrations of fentanyl. There was considerable inter-patient variability in the pharmacokinetics of fentanyl with subcutaneous infusion in the palliative care setting, which necessitated careful titration of dosage according to individual clinical response. 4. Nebulised morphine trial The final study involved a trial of nebulised morphine for dyspnoea in eleven palliative care patients. Due to patient attrition and the resulting small sample size, a significant improvement in respiratory function and assessment of dyspnoea could not be found overall. Individual patients, however, reported an improvement in their symptoms. More studies with increased numbers are needed to statistically prove the benefit of nebulised morphine over saline alone for the relief of dyspnoea.