The acute effects upon blood pressure and sympathetic outflow of two beta adrenoceptor blocking drugs, propranolol and atenolol, are described in five healthy normotensive subjects. Supine blood pressure, heart rate, plasma noradrenaline, and urinary catecholamine excretion were measured before and at intervals for 24 h after a single oral dose of either propranolol 200 mg, atenolol 100 mg, or placebo. Propranolol caused a fall in blood pressure and heart rate of 17.2/14.1 mm Hg and 20.4 beats/min respectively two hours after dose. Atenolol caused a fall in blood pressure of 11.4/18.6 mm Hg within 7 h of the dose, and a fall in heart rate of 13.8 beats/min after 2 h. The reduction in blood pressure after single high dose beta adrenoceptor blockade is established. The synchronous reduction in blood pressure and heart rate after propranolol was not associated with an increase in peripheral sympathietic activity as assessed by the biochemical indices. It is conceivable that the reduction in blood pressure during beta adrenoceptor blockade may be due in part to inappropriately low sympathetic activity but this cannot be the main mechanism of pressure reduction.

Adrenergic beta-Antagonists↗

PubMed1979

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

1 Measurements of antipyrine clearance in saliva have been made in 128 London factory and office workers. 2 Mean antipyrine clearance in 56 Asian immigrants was 40% slower than in 72 White subjects. 3 Although dietary differences existed between the two groups, analysis of their effect independently of race was impossible since all but one of the vegetarians were Asian and the non-vegetarians were nearly all White. 4 In the White subjects, use of the oral contraceptive reduced clearance by 38% in women, while cigarette smoking increase clearance by 38% in men.

Adolescent↗

PubMed1979

Atenolol and chlorthalidone in combination for hypertension.

1 The hypotensive effect of single daily dosing with atenolol 100 mg and chlorthalidone 25 mg given alone or in combination has been assessed in a double-blind, crossover, placebo controlled trial in fifteen hypertensive patients. 2 Average lying blood pressures were: Placebo 155.4/103.9 mm Hg, atenolol 134.6/85.8 mm Hg, chlorthalidone 139.5/90.1 mm Hg, combination 127.7/82.5 mm Hg. 3 The effect of the combination therapy in reducing lying diastolic pressure compared with placebo (a fall of 21.4 mm Hg) was significantly less than the 31.9 mm Hg fall predicted from the sum of the individual effects (P = 0.01). 4 Observations on blood pressure at rest and under mental, isometric and bicycle ergometer stress were made pre-dose and post-dose for a 12 h period at the end of the last treatment period. 5 Lying blood pressure declined from the zero hour (pre-dose) reading on all treatments to a low at 15.00--18.00 h and then rose again. 6 The rise in systolic blood pressure after isometric exercise and mental stress was of a similar magnitude with all four treatment regimes. 7 Atenolol, alone and in combination with chlorthalidone, reduced the blood pressure and the pulse rate increase on exercise 2 h post-dose when compared with readings 24 h post-dose. 8 Once daily dosing with a combination of atenolol and chlorthalidone produced a fall in supine blood pressure over a 24 h period but the effect on exercise induced changes was not uniform over this period.

Adolescent↗

PubMed1979

The effect of individual dietary constituents on antipyrine clearance in Asian immigrants [proceedings].

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Antipyrine↗

PubMed1979

Reduction of circulating 25-hydroxyvitamin D by antipyrine.

1 Twenty-four Asian vegetarians had significantly lower 25-hydroxyvitamin D (25-OHD) levels and longer antipyrine half-lives than twenty white non-vegetarians (P less than 0.001). 2 Treatment with oral antipyrine over 4 or 5 weeks in seven vegetarian Asians and five racially different non-vegetarians increased drug oxidation significantly in both groups as measured by a fall in antipyrine half-lives and a rise in serum gamma-glutamyltranspeptidase levels and urinary 6 beta-hydroxycortisol/17-hydroxycorticosteroid ratios. 3 Antipyrine treatment produced a fall in circulating 25-hydroxyvitamin D of around 60% in all subjects in whom pretreatment levels could be measured, independent of race and diet. 4. In the Caucasian non-vegetarian group 1,25 dihidroxyvitamin D levels, the most active metabolite of vitamin D, were also measured and remained unaltered despite a substantial fall in 25-hydroxy substrate. 5 The acute fall in 25-hydroxyvitamin D concentration with a maintained level of 1,25 dihidroxyvitamin D may represent the early changes of drug-induced osteomalacia.

Adult↗

PubMed1979

Contribution of environmental factors to variability in human drug metabolism.

Drug metabolism in 96 London factory and office workers has been studied after simultaneous single doses of antipyrine (phenazone) and paracetamol (acetaminophen). Metabolic clearance of both drugs was significantly greater in subjects eating meat more than once a week than in those who ate meat less frequently. The precise contribution of diet could not be clearly defined since 90% of "meat-eaters" were European while all except one of the "vegetarians" were Asian. Clearance of both drugs increased with both alcohol and cigarette consumption. Regular intake of coffee and/or tea had a similar effect but, in the case of paracetamol, this did not attain statistical significance. Antipyrine clearance was lower among women who took the oral contraceptive pill than among those who did not, while paracetamol clearance was not significantly different. These findings may have implications for the use of drugs which are administered regularly in order to achieve steady-state plasma and tissue concentrations.

Adolescent↗

PubMed1979

Compliance with prescribed medicines: a study of elderly patients in the community.

Compliance with regular medicine taking has been assessed in 81 patients, aged 65 and over, living at home. Interview assessment, home tablet count, and retrospective review of general practice prescription record cards provided three indices of compliance.Deviation by more than 10 per cent from absolute adherence to the prescription was found in 53 per cent of all tablet counts and was significantly more common in women than in men. Errors were also more common when medicines were to be taken more than once daily.The compliance index obtained by inspection of prescription records correlated closely with the index calculated from tablet counts (r(s) = 0.68; p < 0.001) for 129 separate medicines taken regularly. Poor compliance with an individual medicine could be predicted accurately in 66 per cent of cases. A combination of prescription record inspection and interview assessment increased the accuracy of this prediction to 86 per cent.These findings suggest that, using simple methods, the level of compliance can be accurately predicted in a substantial number of elderly patients at home.

Aged↗

PubMed1978

Drug concentration in saliva.

It is possible to predict plasma concentrations of drugs by measurement in saliva, obviating the need for venipuncture. Using a selection of weakly acidic and basic drugs, we have found this prediction reliable for drugs largely nonionized at normal plasma pH (phenytoin, phenobarbital, antipyrine) but unreliable for ionized drugs (chlorpropramide, tolbutamide, propranolol, meperidine). Deliberate alteration of saliva flow rate and pH using different stimuli have produced twofold changes in saliva drug concentrations. Wide interindividual variability of saliva pH is the likely explanation for the inconstancy of saliva to plasma concentration ratios for ionized drugs.

Adolescent↗

PubMed1978

A method for obtaining saliva samples from infants and young children.

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Child, Preschool↗

PubMed1978

Compliance with anticonvulsant therapy in a hospital clinic and in the community.

1 Seizure control, saliva anticonvulsant concentration, prescribing habits and compliance with anticonvulsant medication have been compared in 86 epileptic subjects attending either a specialist hospital clinic or general practice surgeries. 2 Of all subjects experiencing recurrent seizures 70% had saliva concentrations of phenytoin below the range equivalent to the 'therapeutic range' of plasma concentration. Mean saliva phenytoin concentrations did not differ significantly between the two treatment settings and were low largely because of the low mean dosage prescribed. 3 Eleven subjects in all had no detectable phenytoin in their and could clearly be identified as noncompliant. Freedom from seizures appeared to predispose to poor compliance in these subjects as well as among those admitting repeated omission of doses.

Adolescent↗

PubMed1977

Environmental effects on antipyrine half-life in man.

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Antipyrine↗

PubMed1976

Factors affecting antipyrine metabolism in West African villagers.

Saliva half-life of antipyrine was studied in 49 healthy Gambians between 20 and 60 yr of age of whom 27 were male (mean age, 44.5) and 22 female (mean age, 39.1). Body wieght, height, ponderal index, albumin, and hemoglobin were moderately reduced compared to accepted normal values. Antipyrine half-life was 13.6 +/- 0.58 (SEM) hr. Multiple regression analysis showed that sex, cola nut consumption, hemoglobin in women, and height in men were statiscally significant independent predictors of antipyrine half-life. Half-life was shorter in women, decreased with an increase in height in men, and was prolonged by cola nut consumption. Half-life in women increased with hemoglobin. These factors explained 36% of the variation and suggest that geographic differences in the environment could be important in drug metabolism in man.

Adult↗

PubMed1976

Assessment of antipyrine kinetics by measurement in saliva.

The half-life of antipyrine has been estimated from saliva samples in ten subjects by a gas chromatographic method. Half-life, apparent volume of distribution and total body clearance estimated from saliva and plasma concentrations of antipyrine are not significantly different. The concentration of antipyrine in saliva is independent of flow rate within the range expected in healthy subjects in response to mechanical and sapid stimuli. Antipyrine estimation in saliva could facilitate many areas of phaamacokinetic research limited by the difficulty of obtaining serial plasma samples.

Adult↗