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Biomedical subjects

G Farrell

Publications and source records attributed to G Farrell.

46 records · Page 3Linked to original sources
PubMedDate not supplied

Disposition and metabolism of metronidazole in patients with liver failure.

A pharmacokinetic study of metronidazole disposition was performed in 10 patients with severe liver disease, the majority of whom also had impaired renal function. Following a single intravenous dose, systemic clearance of metronidazole was decreased by 66% in patients compared with healthy controls (p less than 0.001). The apparent volume of distribution for metronidazole was also decreased in patients (by 21%), but the greater effect on clearance resulted in the elimination half-life being prolonged 152%. Total urinary excretion of unaltered metronidazole was not reduced in patients compared with controls, and systemic clearance of metronidazole did not correlate with creatinine clearance. Hepatic production of hydroxymetronidazole [1-(2-hydroxyethyl)-2-hydroxymethyl-5-nitroimidazole], the major oxidative metabolite of metronidazole, was significantly lowered in patients with liver failure. Peak plasma levels of this metabolite were lower, the time taken to achieve peak levels was longer and the area under the plasma concentration approximately time curve (AUC0-25h) was reduced in patients compared to controls (p less than 0.05). Similarly, urinary recovery of hydroxymetronidazole was lower in patients with liver disease while excretion of the other major oxymetabolite, 1-acetic acid-2-methyl-5-nitroimidazole, appeared reduced to an even greater extent. Thus, while the presence of renal function impairment in a patient with cirrhosis indicates that metronidazole elimination is likely to be abnormal, the principal mechanism for delayed elimination is impaired hepatic drug metabolism rather than reduced renal clearance of metronidazole and its major metabolites.

Adult↗
PubMedDate not supplied

Halothane hepatitis: damage to peripheral blood mononuclear cells produced by electrophilic drug metabolites is Ca(2+)-dependent.

Peripheral blood mononuclear (PBM) cells from patients with halothane hepatitis are unusually susceptible to damage from phenytoin metabolites generated by an in vitro drug metabolising system. In order to provide more information about the nature of this susceptibility factor, the effect of removing calcium ions (Ca2+) from the incubation medium of the test system was examined. Phenytoin metabolites were generated by incubating phenytoin with beta-naphthoflavone-induced rat liver microsomes in the presence of 1,1,1-trichloropropene oxide (TCPO), an epoxide hydrase inhibitor. When PBM cells from patients who had recovered from halothane hepatitis were incubated in this system and then maintained in Ca(2+)-containing tissue culture medium (without alpha-tocopherol) for 16 h, cell death, as measured by trypan blue exclusion, was greatly increased (53% and 78% at 0.06 mmol/l and 0.12 mmol/l phenytoin, respectively) compared with control incubations (TCPO omitted). Removal of Ca2+ from the tissue culture medium effectively abolished reactive metabolite-induced cell death. Resting cytosolic free Ca2+ concentration in PBM cells was also measured using the quin-2 fluorescence method and total Ca2+ content was measured by atomic absorption spectrometry. Although variability appeared greater among patients, mean values for these parameters among 12 patients with halothane hepatitis did not differ from controls. It is concluded that enhanced permeability of PBM cells to extracellular Ca2+ may be an important factor in the pathogenesis of drug metabolite-induced cell death in patients susceptible to halothane hepatitis. Such permeability to Ca2+ is not evident in resting cells and presumably results from an interaction between electrophilic metabolites and the pumps which regulate cell calcium homeostasis.

Calcium↗
PubMedDate not supplied

Aggression: therapeutic response to verbal abuse.

Increasing numbers of nurses in a variety of settings have to deal with physical and verbal aggression meted out by their patients. This article concentrates on suitable therapeutic responses to verbal abuse, and urges the nurse to consider aggression in a wider context, looking at the predisposing factors and methods to defuse potentially violent situations. The author stresses that self-evaluation is crucial if skills are to be learned and applied to subsequent episodes.

Aggression↗