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Biomedical subjects

D S Hewick

Publications and source records attributed to D S Hewick.

At least 37 records · Page 2Linked to original sources
PubMed1985

The influence of digoxin antibodies on digoxin disposition and effect: studies in guinea-pigs and HeLa cells.

Pretreatment of guinea-pigs with digoxin-specific Fab (fragment antigen binding) fragments reduced the cardiotoxicity of intravenously infused digoxin (the lethal doses in Fab-treated and control animals were 1.0 and 0.6 mgkg-1, respectively). At death the serum digoxin concentration was elevated 2 fold in the Fab-treated animals, while the tissue concentrations were generally lower. The 30-40% lower cardiac digoxin concentration (seen in whole homogenate and throughout the subcellular fractions examined) was surprising; presumably this reflects a difference from the controls in the proportion of pharmacologically active/inactive digoxin in this organ. Adding digoxin-specific immunoglobulin G or the Fab fragments to HeLa cells before incubation with digoxin, reduced specific digoxin binding (Na pump-bound) slightly more than the non-specific binding. Adding specific antibody after digoxin, however, did not reduce digoxin binding or effect a recovery in Na pump activity. It seems that the protective effect of digoxin-specific antibodies seen in the guinea-pig can to some extent be simulated using HeLa cells. However, this is apparently not so regarding the widely-reported ability of these antibodies to reverse the action of digoxin.

Animals↗
PubMed1984

The effect of immunization with digoxin-specific antibodies on digoxin disposition in the mouse.

After intravenous dosing, digoxin was rapidly distributed to tissues, with a distribution half-life of 3.0 min. The highest digoxin concentrations at 1 hr post dosing were found in lymph nodes, adrenals, gallbladder (including contents), liver and kidney respectively. Digoxin concentrations in the heart, spleen, brain, lung, skeletal muscle and fat were similar to, or lower than, those in the plasma. The apparent volume of distribution (AVd) was 1 l/kg, and the plasma elimination half-life and clearance (Cl) 2.8 hr and 0.25 l/kg per hr respectively. When digoxin was given one day after passive immunization with digoxin-specific immunoglobulin G (IgG) or Fab fragments the respective plasma digoxin concentrations were elevated some 26- and 5-fold respectively compared with control values. Consequently there were reductions in AVd (93 and 32%) and Cl (94 and 50%). The effect of IgG treatment on clearance was still apparent when the hapten was given up to 14 days after immunization, while the weaker effect of Fab-treatment was less persistent. Although tissue digoxin concentrations were slightly lower in the immunised mice, it was only in the lymph nodes at 10 and 14 days after IgG treatment that the reduction in hapten concentration was statistically significant.

Animals↗
PubMed1983

The influence of age on lithium efficacy and side-effects in out-patients.

One hundred and sixty-six unipolar and bipolar out-patients (21-78 years) on long-term lithium treatment were studied on a prospective basis. Although there was a possible tendency for manic attacks to increase in prevalence and severity with age, it was difficult to demonstrate a general age-related decline in lithium efficacy. There was a tendency for the prevalence and severity of fine hand tremor to increase with age. This was not seen with polydipsia/polyuria, the other typical lithium side-effect.

Adult↗
PubMed1977

Age as a factor affecting lithium therapy.

1 We examined the case notes of 82 psychiatric out-patients (aged 21-84 years) receiving lithium prophylaxis and with steady-state plasma lithium levels. 2 The mean weight-related daily dose of lithium prescribed decreased by about 50% between the third and eight decades. 3 The corresponding steady-state plasma lithium levels showed a less marked tendency to decrease, this only being seen in the seventh and eighth decades. 4 In patients aged 50 years or over the daily lithium dose required to give a plasma level of 1 mmol l-1 (0.50 mmol kg-1) was significantly lower than that (0.65 mmol kg-1) in patients aged under 50 years (P less than 0¿5, Student's t-test). In patients aged 70-79 years this dose was 31% lower than in patients under 50 years. However, interindividual variation was great and it was estimated that age only contributed about 14% to the total interpatient variation. 5 Of the 36 patients under 50 years of age, 42% had minor lithium side-effects and 17% were not optimally controlled with lithium. The corresponding figures for the 46 'older' patients were 46% and 28%. 6 Generally the 50% dosage reduction seemed necessary to compensate for an age-related decrease in lithium excretion and to reduce lithium side effects to a level comparable to that acceptable in younger patients.

Adult↗
PubMed1977

Age as a determinant of sensitivity to warfarin.

1 Parallel human and rat studies were carried out to confirm the previous suggestion of an increased sensitivity to warfarin in old age. 2 The anticoagulant response to warfarin was found to be greater in the elderly groups despite, in the case of the patient study, the elderly subjects being given a smaller weight-related dose. 3 At the same plasma warfarin concentrations there was greater inhibition of vitamin K-dependent clotting factor synthesis in the elderly. There was no difference in the rate of clotting factor degradation in the two age groups. 4 There was no appreciable difference in warfarin pharmacokinetics (plasma half-life, apparent volume of distribution, plasma clearance, plasma protein binding or plasma warfarin alcohol levels) in the two age groups. 5 There appeared to be no major age-related differences in warfarin pharmacokinetics and the increased effect of warfarin in the elderly seemed to result from an increased intrinsic sensitivity to warfarin.

Adult↗