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Biomedical subjects

J C Mucklow

Publications and source records attributed to J C Mucklow.

At least 37 records · Page 2Linked to original sources
PubMed1984

The comparative beta-adrenoceptor blocking effects of penbutolol, atenolol and sustained-release metoprolol in healthy volunteers.

The effects of penbutolol (40 mg), atenolol (100 mg) and sustained-release metoprolol (metoprolol SA) (200 mg) upon heart rate (HR) and blood pressure (BP) at rest and during bicycle ergometer exercise, have been compared in 12 healthy young men using a double-blind crossover design. Measurements of each drug's effect were made before and at 3, 10 and 24 h after a single dose, and again at 24 h after the last of seven consecutive daily doses. Resting HR and systolic BP were reduced to an equivalent extent by all three drugs. During the third minute of exercise, the effects of penbutolol and atenolol upon HR and systolic BP were consistently similar and greater than those of metoprolol SA.

Adolescent↗
PubMed1984

Partial reversal of carbamazepine-induced water intolerance by demeclocycline.

The anti-diuretic action of carbamazepine, before and after concurrent treatment with demeclocycline, has been studied in a single epileptic subject, in whom two episodes of status epilepticus had been associated with excessive fluid intake and hyponatraemia. After addition of demeclocyline, free water clearance, plasma arginine vasopressin concentration and serum osmolality (all appreciably reduced after carbamazepine alone) increased but did not revert to normal. The findings are consistent with direct antagonism by demeclocycline of the enhancing effect of carbamazepine on endogenous ADH activity.

Adult↗
PubMed1983

Acetylator phenotype and the effect of dapsone in rheumatoid arthritis.

Acetylator phenotype was determined in 54 patients with rheumatoid arthritis (RA) taking dapsone in the course of 2 comparative clinical studies. No significant differences were demonstrated in the assessments, either of efficacy or adverse effects. There appears to be no clinical advantage in assessing acetylator phenotype in patients with RA being treated with dapsone.

Acetylation↗
PubMed1982

Family study of antipyrine clearance.

Antipyrine clearance was measured in 208 healthy volunteers from 78 families. After the values had been corrected for weight and sex, antipyrine clearance was observed to be significantly correlated between siblings (r = 0.590) and between spouses (r = 0.320), but not between parents and their offspring. After the clearance values had been corrected for tobacco and oral contraceptive use, there was still no significant correlation between parents and offspring. These results are incompatible with the hypothesis that antipyrine clearance is primarily determined by genetic factors and indicate that environmental influences predominate.

Adolescent↗
PubMed1982

The relationship between individual dietary constituents and antipyrine metabolism in Indo-Pakistani immigrants to Britain.

1 Antipyrine clearance has been measured from serial saliva samples in 36 healthy adult Indo-Pakistani immigrants to Britain, to assess the effect of dietary differences within this population. 2 Clearance (mean +/- s.e. mean) was significantly slower in 16 lactovegetarians (0.54 +/- 0.06 ml min -1 kg -1) than in the subjects who ate meat regularly (0.91 +/-0.07 ml min -1 kg -1). 3 The absence of meat from the diet was associated with a significantly smaller daily intake of dietary protein, which was abnormally low by Western standards. 4 It is likely that the contrast in daily protein intake between the dietary subgroups was largely responsible for the differences observed in antipyrine clearance.

Adult↗
PubMed1982

Therapeutic progress: review IV. Therapeutic drug monitoring: can it improve the treatment of epilepsy?

Our ability to measure plasma drug concentrations under steady-state conditions has meant that the daily dose of phenytoin, and a few other anticonvulsants drugs, can be safely adjusted to suit the individual epileptic's seizure pattern and drug metabolizing capacity. With correct timing of samples and interpretation of results, therapeutic drug monitoring can lead to, and maintain, complete freedom from seizures for some patients and an appreciable reduction in frequency for many others. There are large numbers of epileptics, however, who continue to suffer needlessly because clinical practice has lagged behind our expertise in drug assay and our understanding of pharmacokinetics. We are not using our knowledge sufficiently to benefit the epileptic population as a whole.

Anticonvulsants↗
PubMed1982

N-acetylation phenotype in bladder cancer.

1 N-acetylation phenotype has been examined in 30 patients with bladder cancer and in 27 controls of similar age. 2 59% of controls and 70% of bladder cancer patients were phenotypically 'slow' acetylators. This difference was not significant (P greater than 0.30). 3 Within phenotypes, isoniazed half life was similar in controls and bladder cancer patients. 4 N-acetylation phenotype is unlikely to be a major determinant in the pathogenesis of bladder cancer in the population studied.

Acetylation↗
PubMed1982

Benzodiazepine withdrawal in general practice.

A study of benzodiazepine prescribing in a single-handed general practice was carried out over a period of three months. It seemed that the existing pattern of prescribing was indiscriminate and ineffective, and that repeat prescriptions were poorly controlled. A programme of controlled withdrawal was instituted for patients whose consumption of benzodiazepines was felt to be no longer appropriate. Of 103 patients identified who had been taking benzodiazepines for longer than three months, 78 were entered into the programme. On completion, 45 patients (58 per cent) had discontinued benzodiazepines completely, and a further 13 (17 per cent) were taking less than half their original dose. Four patients had failed to reduce consumption at all and two were lost to follow-up. At follow-up between three and five months later, 49 patients (63 per cent) had discontinued benzodiazepines completely and only two had restarted treatment. The median time taken to complete the programme was 3.2 weeks, with 95 per cent of patients completing within six weeks. Withdrawal was generally well tolerated, with a temporary increase in insomnia as the main symptom. Two patients experienced severe symptoms, but both had stopped treatment abruptly.

Adult↗
PubMed1981

Placebo-controlled study of phenobarbitone and phenytoin in the prophylaxis of febrile convulsions.

Of 138 children who had a first febrile convulsion before their second birthday, 48 were treated with phenobarbitone, 47 with phenytoin, and 43 with a placebo for 12 months. Drug levels were monitored and adverse effects of the drugs were noted. Compared with placebo, phenobarbitone significantly reduced recurrences among children under 14 months old at the time of their first convulsion, but nor among older children. Phenytoin was an ineffective prophylactic agent. Ideal drug levels were difficult to maintain, and many recurrences occurred when concentrations were suboptimal. Behavioural disturbance in children taking phenobarbitone was not a serious problem. The decision to give continuous prophylaxis for febrile convulsions is complex, and each case must be judged on its merits. For children who have a first seizure before 14 months of age prophylaxis may be advisable and phenobarbitone is effective.

Age Factors↗
PubMed1981

Monitoring of phenobarbitone and phenytoin therapy in small children by salivary samples.

Concentrations of phenytoin or phenobarbitone have been measured serially using saliva samples in 75 very young children receiving one of these drugs for prevention of recurrent febrile convulsions. Saliva samples were easily obtained and the measured concentrations were a valuable guide to drug dosage during the treatment period. Mean (+/- SD) saliva concentrations were, for phenytoin, 1.0 +/- 0.8 mg/litre (3.8 +/- 3.0 mumol/litre) and, for phenobarbitone, 7.9 +/- 2.6 mg/litre (24.0 +/- 11.3 mumol/litre) and did not alter significantly during the period of observation. Despite frequent review with assessment of compliance, it proved difficult to achieve and maintain target drug concentrations. Paired samples of saliva and plasma were obtained from 36 children before treatment was terminated. Drug concentrations in saliva correlated well with those in plasma and mean plasma: saliva ratios (phenytoin, 8.4; phenobarbitone, 2.2) were comparable to results obtained previously in adults.

Dose-Response Relationship, Drug↗
PubMed1981

Pharmacokinetics of phenytoin in children.

1 Apparent Vmax and Km for phenytoin were estimated in 40 children (aged 8--33 months) and 21 adults (aged 18--66 years). 2 The derived values of Vmax and Km were used to predict the plasma and salivary concentrations of phenytoin following a change in dose. There was a highly significant correlation between observed and predicted steady-state concentration in both children and adults (P less than 0.001). 3 The apparent Km was similar in children (7.5 +/- 1.2 mg/l) and adults (9.4 +/- 2.3 mg/l). 4 Vmax differed significantly (P less than 0.001) between children (20.4 +/- 2.1 mg kg-1 day-1) and adults (8.7 +/- 0.7 mg kg-1 day-1). 5 After correction for differences in the ratio of liver weight to body weight in children and adults, Vmax was similar in the two groups.

Body Weight↗
PubMed1980

Environmental factors affecting paracetamol metabolism in London factory and office workers.

A Paracetamol elimination was measured, using serial saliva samples, in 114 London factory and office workers, 76 Whites and 38 Asian immigrants. 2. Use of social drugs such as alcohol, tobacco and the oral contraceptive varied considerably within the sample, being appreciably greater in White subjects. 3. Paracetamol clearance was 21% slower in Asians than in Whites and half-life 18% longer. The total range of clearance was 1.86--6.78 ml min-1 kg-1. 4. Clearance was slower in women than in men, increased with increasing alcohol intake and cigarett consumption, and was more rapid in those women using the oral contraceptive. The effects of alcohol and the oral contraceptive were also found in White subjects alone. 5 The variables found to correlate independently with paracetamol clearance accounted for only 27% of the total sample variance, however, and are unlikely to be the major determinants of paracetamol elimination in man.

Acetaminophen↗
PubMed1980

Antipyrene clearance in Indian villagers.

1 Antipyrine clearance has been measured using saliva samples in 50 Maharashtrans from a village to the north of Bombay. 2 All subjects were very lean and were also anaemic probably as a result of hookworm infestation. 3 Antipyrine clearance was 36% faster than in White Londoners studied previously and more than twice as fast as in Asian immigrants living in London. 4 Clearance was 25% faster in men than in women but volume of distribution was also greater in men and mean half-lives did not differ significantly between the sexes. 5 There was a negative correlation between antipyrine clearance and haemoglobin concentration. 6 The study has identified geographic differences in antipyrine metabolism which could be clinically important. The role of anaemia merits further study.

Adult↗