A rapid bioassay technique for arginine-vasopressin.
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Animals↗
Biomedical subjects
J C Mucklow
Publications and source records attributed to J C Mucklow.
Transepithelial water movement in response to carbamazepine, chlorpropamide and demeclocycline in toad urinary bladder.
1. Osmotic water movement across toad isolated hemibladders was measured by a gravimetric method. 2. The influence of carbamazepine, chlorpropamide and demeclocycline on the antidiuretic hormone (ADH)-induced water flow rate was examined. 3. No antidiuretic activity due to carbamazepine alone was observed but a slight inhibition due to ADH-induced water flow was observed in the presence of carbamazepine over a selected dose-range. This was unexpected and is inconsistent with data from in vivo studies in man. 4. Chlorpropamide potentiated ADH-induced water flow, in keeping with the hypothesis that chlorpropamide sensitizes the renal tubules to ADH-induced water flow. 5. Demeclocycline inhibited ADH-induced water flow. The mechanism of action remains unclear.
Animals↗
Perceptions of pain relief after surgery.
OBJECTIVE: To assess patients' satisfaction with postoperative pain relief. DESIGN: A descriptive and questionnaire study of patients' experience. SETTING: Two surgical and two gynaecological wards. PATIENTS: 50 Patients admitted to hospital for cholecystectomy and 51 admitted for hysterectomy. MAIN OUTCOME MEASURES: Visual analogue scales with no divisions were completed by the patients immediately after each dose of postoperative analgesia was administered throughout their stay in hospital. A questionnaire completed on the fifth postoperative day recorded patients' recollections of their experience. Opinions were also sought from medical and nursing staff. RESULTS: During the first 24 hours after surgery recorded pain levels were 60% of the maximum and were not influenced by age, sex, or the type of operation performed. The median interval between the return of pain and a further injection of analgesic was 2 hours (interquartile range 1 to 3.5 hours). Expectations of pain relief were low, and for 70% of the patients the pain was at least as bad as they had expected. Only half of the medical and nursing staff questioned thought that postoperative analgesia should relieve pain completely; drugs were prescribed and administered with too little attention to the patient's response and too much concern about adverse effects and opioid dependence. CONCLUSIONS: The results suggest that the standard of postoperative pain relief is poor because of inadequate education of patients in what to expect (and demand), and of medical and nursing staff in how to prescribe and administer analgesia with reference to individual drug response.
Analgesics↗
A single oral dose method for predicting steady state theophylline concentrations in clinical practice.
A single dose, single point method of predicting patients' oral maintenance theophylline dosage has been compared with a noninvasive method. Twenty patients with obstructive lung disease received an oral dose (6 mg kg-1) of micro-crystalline theophylline. The plasma theophylline concentration after 8-10 h was then used to calculate the optimum maintenance dose of sustained release aminophylline required to achieve steady state concentrations between 55 and 110 mumols l-1. The mean steady state plasma theophylline concentration for this dosage schedule was also predicted by a method using population average pharmacokinetic parameters (assumed clearance method). These predictions were then compared with observed concentration-time profiles at steady state. The mean difference between the observed values and those predicted from a morning test dose was -0.11 mumol l-1 (95% CI -7.0 to +7.2). A larger difference (-7.4 mumol l-1 95% CI -18.2 to +3.4) was found for the assumed clearance method. Since the confidence intervals contain zero, these differences are not significantly different from zero at the 5% level, although the morning test dose method allowed prediction of the whole concentration-time profile and was more precise. An evening test dose was also used in the study, but the mean difference between the observed values and those predicted from this method was larger at -24.8 mumol l-1 (95% CI -32.89 to -17.21) and was significantly different from zero. This study indicates that a morning test dose followed by a single blood sample can be used to establish maintenance theophylline therapy quickly and safely in selected patients.
Adult↗
Environmental factors affecting drug metabolism.
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Animals↗
The fate of drugs in pregnancy.
The response of mother and fetus/neonate to drugs administered to the pregnant woman is determined largely by drug disposition and elimination within and between mother and fetus. Physiological changes occurring in pregnancy may result in reduced plasma protein binding, an increase in the apparent volume of distribution, and more rapid metabolic and renal clearance of certain drugs than are usually found in non-pregnant women. The consequences are relevant for the peak concentration of drug achieved after a single dose, the half-life of the drug, and the drug concentration to which the fetus is exposed via the placenta. Drugs whose dosage may need to be altered in pregnancy include most anticonvulsants, lithium, digoxin, certain beta-blockers, ampicillin and cefuroxime; for drugs which have not been specifically investigated, no generalizations are possible. Very few drugs given in pregnancy fail to cross the placenta and, as a rule, drug molecules not bound to plasma protein diffuse along a concentration gradient to establish and maintain an equilibrium. Because movement of drug molecules is bidirectional, the placenta is the main portal of exit from, as well as entry to, the fetus. The pharmacological response of the fetus to drugs which it receives depends mainly on the unbound concentration of drug in fetal blood--unwanted effects seldom occur if the maternal dose is correct; exceptions include tetracycline, antithyroid drugs, coumarin anticoagulants, aspirin, indomethacin and cerebral depressant drugs (opiates, barbiturates and phenothiazines). The total (bound plus unbound) drug concentration on the fetal side of the placenta is usually lower than on the maternal side except where differences in blood pH and/or protein binding lead to 'trapping' of drug in the fetus; the latter phenomenon may prove hazardous after birth because of the neonate's limited capacity to eliminate drugs by metabolism and excretion.
Adrenal Cortex Hormones↗
A comparative study of the bioavailability of five different phenytoin preparations.
The concentration of phenytoin in saliva has been measured in 8 healthy volunteers at intervals after an intravenous dose and after single oral doses of five formulations commercially available in the United Kingdom. The six doses (all 300 mg) were given in random order and at least one week apart. There were no significant differences in the mean values of the peak saliva concentration, the time-to-peak and the area under the saliva concentration-time curve between the five oral formulations. The absolute bioavailability of phenytoin varied between 68 and 74%.
Adult↗
Drugs for epilepsy.
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Drug Therapy, Combination↗
Compliance with drug treatment.
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Age Factors↗
Blood pressure and plasma noradrenaline during single high-dose beta adrenoceptor blockade.
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↗
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↗
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↗
The effect of individual dietary constituents on antipyrine clearance in Asian immigrants [proceedings].
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Antipyrine↗
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↗
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↗
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↗
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↗