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Biomedical subjects

L E Mather

Publications and source records attributed to L E Mather.

11 recordsLinked to original sources
PubMed1979

A pharmacokinetic approach to postoperative pain: continuous infusion of pethidine.

In an attempt to improve postoperative pain management an intravenous infusion of pethidine was designed to provide stable therapeutic blood concentrations. Ten female patients undergoing elective abdominal hysterectomy were studied. After commencement of the infusion, blood pethidine concentrations increased rapidly and exceeded 0.46 microgram/ml after four hours. The mean steady-state concentration of 0.67 microgram/ml was reached by twenty-four hours. This infusion regimen resulted in the abolition of severe pain after three hours and analgesia continued for the duration of the two day study. Significant blood concentrations of the metabolite norpethidine were found although clinically no toxic effects were observed. Side effects of pethidine were infrequent. Controlled continuous intravenous infusion of pethidine produced stable blood concentrations and provided excellent pain control.

Adult↗
PubMed1979

Cardiovascular and subjective central nervous system effects of long-acting local anaesthetics in man.

Intravenous infusions of etiodocaine 50, 75 and 100 mg and bupivacaine 75 mg were carried out over ten minutes in healthy young adult males. Cardiovascular sequelae were generally trivial at all doses. A collection of subjective central nervous system symptoms were described which may be regarded as early warning of impending local anaesthetic toxicity. Plasma concentrations of etidocaine were proportional to dose and ranged from 2 micrograms/ml to 5 micrograms/ml at the termination of the infusion. Plasma concentrations of bupivacaine were similar to those from the same dose of etidocaine but declined more slowly on cessation of infusion.

Acetanilides↗
PubMed1975

Effects of peridural block: V. Properties, circulatory effects, and blood levels of etidocaine and lidocaine.

Ten healthy, unpremedicated, male volunteers, aged 21-33 years, were given 20 ml 1 per cent etidocaine with 5 mug/ml epinephrine for peridural analgesia via a catheter placed L2. On a different occasion they were given 20 ml 2 per cent lidocaine with 5 mug/ml epinephrine in the same manner. Initial onset of sensory analgesia to pin prick was faster for etidocaine (7 min) than for lidocaine (9 min). Analgesia lasted significantly longer after etidocaine with respect to both two-segment regression (177 plus or minus SE min vs. 114 plus or minus 8 min) and total duration (379 plus or minus 22 min vs. 190 plus or minus 8 min). Onset of maximal motor blockade was significantly faster with etidocaine (15.4 plus or minus 2.5 min) than with lidocaine (31.7 plus or minus 3.3 min); blockade lasted longer with etidocaine (331 plus or minus 25 min vs. 167 plus or minus 13 min). Changes in mean arterial pressure cardiac output, central venous pressure, limb blood flows, total peripheral resistance, and stroke volume were similar with the two drugs, although those after etidocaine were more prolonged as a result of the longer blockade. Mean maximum arterial concentrations of etidocaine were 0.96 plus or minus 0.05 SE mug/ml (plasma) and 0.55 plus or minus 0.03 mug/ml (whold blood), achieved at 17 plus or minus 2 min. Mean maximum arterial concentrations of lidocaine were 2.22 plus or minus 0.09 mug/ml (plasma) and 1.85 plus or minus mug/ml (whold blood), achieved at 24 plus or minus 2 min. No sign of central toxicity was observed with either drug, although subjects receiving lidocaine tended to sleep, which was not the case with etidocaine. Hematologic screening, blood chemistries, and urinalyses performed 24 hours before and after each study showed no abnormality.

Acetanilides↗
PubMedDate not supplied

Clinical pharmacokinetics of pethidine.

Pethidine is commonly used in single doses as a preoperative medication or in multiple doses as an analgesic. The clinical consequences of altered disposition are more likely to result from its analgesic use. Correlations between plasma pethidine concentration, analgesia and side effects such as respiratory depression, have been established, but considerable overlap exists between concentrations producing therapeutic and non-therapeutic effects. The current practice of intermittent pethidine administration (intravenous, intramuscular and oral) for analgesia results in fluctuations in pethidine plasma concentrations which are associated with incomplete pain relief and side effects. Continuous intravenous infusion of pethidine may avoid these difficulties. Changes in pethidine disposition have been observed in patients with liver disease and in the elderly. Measurement of plasma pethidine concentrations may be helpful as an aid to the management of such patients. In renal disease, metabolites may accumulate and cause side effects.

Administration, Oral↗
PubMedDate not supplied

Clinical pharmacokinetics of local anaesthetics.

The introduction of the new long acting local anaesthetics, bupivacaine and etidocaine, has stimulated an expansion of interest in regional anaesthesia, particularly for obstetrical applications and pain therapy. System toxicity following injection of local anesthetics occurs albeit infrequently, and tentative correlations have been made between the onset of CNS and cardiovascular effects and circulating drug concentrations in both adults and neonates. Amongst other factors, interpretation of these relationships depends upon blood distribution and plasma binding of the agents, sampling sites and acid-base balance. The disposition kinetics and placental transfer of the amide type agents have been well characterised. In adults their clearance is almost entirely hepatic but in neonates an increase in the renal component is, in part, a reflection of the immaturity of some of the enzymes responsible for their metabolism. Ester type agents are rapidly hydrolysed by plasma pseudocholinesterase and this has led to a preference for chloroprocaine in some obstetric procedures. Major determinants of the systemic absorption of the agents after perineural administration include their physicochemical and vasoactive properties, perfusion and tissue binding at the site of injection and whether or not adrenaline has been added. In respect of blood drug concentrations achieved after various regional anaesthetic procedures, the margin of systemic safety appears to favour bupivacaine and etidocaine compared to shorter acting analogues such as lignocaine and mepivacaine. The time course of local anaesthetic remaining at the site of injection has been calculated following intravenous regional anaesthesia and peridural block. This has allowed prediction of the local and systemic accumulation of the drugs following contined dosage. Blood concentrations of local anaesthetics after perineural injection are not closely related to age, weight or pregnancy but may be influenced by diseases associated with haemodynamic changes and by other drugs given at or around the time of regional blockade.

Adult↗