Ampoules, infusions, and filters.
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Drug Contamination↗
Biomedical subjects
D G Waller
Publications and source records attributed to D G Waller.
Clinical and rheological effects of nifedipine in Raynaud's phenomenon.
Thirty-four patients with Raynaud's phenomenon, 28 primary and six secondary, were entered into a double-blind placebo controlled, randomized cross-over trial of nifedipine treatment. Nifedipine was given as a 20 mg biphasic release formulation twice daily. Twenty-nine patients completed the study, during which the mean number of attacks was reduced by 25% during nifedipine treatment (P less than 0.001). Twenty patients scored nifedipine higher than placebo on a five point rating scale (P less than 0.001). Unwanted effects were experienced by 26 patients during active treatment, resulting in withdrawal from the study in five. Red cell deformability and fibrinogen concentrations were not altered by nifedipine.
Adolescent↗
The effects of food and posture on the pharmacokinetics of a biphasic release preparation of nifedipine.
The pharmacokinetics of a novel 20 mg biphasic release tablet of nifedipine were compared with the conventional 10 mg capsule and 20 mg sustained release preparations in healthy volunteers. The influence of food and posture on the pharmacokinetics of the biphasic tablet were studied. In the fasting state, the time to peak concentration of nifedipine was not significantly different between the 20 mg biphasic and 20 mg sustained release tablets, but plasma concentrations were higher between 2 and 4 h after the biphasic tablet. The terminal elimination half-lives of the two formulations were similar. In subjects who fed prior to nifedipine administration there was no significant difference between either the peak plasma concentration or terminal half-life of the biphasic tablet and two 10 mg capsules of nifedipine. When the biphasic preparation was given after a standard breakfast, the time to peak plasma concentration was significantly longer and the terminal half-life shorter than when given in the fasting state. The dissolution characteristics of the biphasic tablet were influenced by prior administration of food to an extent which may be of clinical significance during twice daily administration.
Delayed-Action Preparations↗
Thyroid function and urine-concentrating ability during lithium treatment.
It has been suggested that adenylate cyclase inhibition may be important in the development of both nephrogenic diabetes insipidus and hypothyroidism during lithium treatment. We measured serum thyroxine and urine-concentrating ability (Umax) in response to desmopressin (DDAVP) in 85 patients receiving lithium. Hypothyroidism developed in eight patients while they were taking lithium. Impaired Umax was found in both euthyroid and hypothyroid patients while some hypothyroid patients concentrated their urine well. It is concluded that the dominant mechanisms by which lithium exerts these two effects are different.
Cyclic AMP↗
A comparison of the effects of intravenous propranolol and nadolol on the renal response to hypertonic saline infusion.
Intravenous loading with 500 ml of 2.7% saline increased the clearance of PAH and inulin and urine sodium excretion in 14 healthy subjects. Intravenous propranolol (0.075 and 0.15 mg/kg) did not alter PAH or inulin clearance at rest but abolished the increase expected during saline infusion. There was no consistent effect on urinary sodium excretion. Intravenous nadolol (0.05 and 0.75 mg/kg) reduced resting PAH and inulin clearances by up to 25%. Both clearances fell significantly during saline infusion but natriuresis was not significantly reduced in spite of the changes in renal function. There was no evidence from these studies in normal volunteers that nadolol confers any advantages over propranolol in its effects on renal function.
Adrenergic beta-Antagonists↗
Raynaud's syndrome and carpal tunnel syndrome.
We report three cases of Raynaud's syndrome with digital ischaemic ulceration, in association with carpal tunnel syndrome. In all cases, the aetiology of the Raynaud's syndrome was probably unrelated to the nerve compression. However, symptoms were worse on the side of the median nerve lesion in two patients and worse on the side with the most severe nerve dysfunction in the third; symptoms were relieved by carpal tunnel decompression in two patients. We suggest that carpal tunnel syndrome may exacerbate Raynaud's syndrome and should be considered particularly in patients with asymmetrical digital lesions.
Aged↗
Neuroleptics, lithium and renal function.
Renal function test results in 26 patients on neuroleptic treatment, who had never received lithium or antidepressants, were compared with those in a matched group, treated with lithium; also, their tubular response to DDAVP was compared with that of 25 control subjects. Measurements of serum creatinine, creatinine clearance, and urinary albumin excretion showed no abnormality attributable to either neuroleptics or lithium. The maximum urine concentrating ability after DDAVP was significantly lower in the neuroleptic group than in controls, but significantly higher than in the lithium-treated patients. There was a significant correlation between excretion of urinary beta 2-microglobulin and duration of neuroleptic treatment, but mean excretion rates were the same in both treatment groups. The results suggest that neuroleptics as well as lithium impair urine concentrating ability.
Acetylglucosaminidase↗
The effect of hemodilution upon patients with intermittent claudication.
Seventeen patients with stable intermittent claudication and a PCV of more than 0.45 were venesected until a PCV of 0.35 was achieved. Only patients that were not considered candidates for surgical treatment were entered into the study. Each patient acted as their own control and was studied twice before the venesection at a mean PCV of 0.49 then after achieving a PCV of 0.35 or less (mean PCV of 0.33), and finally one month after the last venesection (mean PCV of 0.37). Angina developed in one patient after the third venesection and was withdrawn from the study. In the remaining sixteen patients, blood flow of the calf muscle during exercise increased significantly after venesection from 5.90 to 8.84 milliliters per 100 grams per minute (p = 0.02). This was measured by xenon 133 clearance and a cadmium telluride detector. There was also a substantial decrease (p less than 0.001) in whole blood viscosity at both low and high shear stresses, but there was no change in plasma viscosity or plasma fibrinogen. Treadmill claudication distance improved in only two patients. Ten patients were tired when the PCV decreased to 0.35 and subjective claudication distance deteriorated in four of these patients. Subsequent isovolemic venesection with dextran 70 volume replacement to a PCV of 0.35 did not improve the response in the six patients restudied. We conclude that venesection did not benefit these patients with intermittent claudication and there was an unacceptable incidence of side effects. Therefore, we suggest that reducing the PCV to 0.35 should be avoided in patients with intermittent claudication who have been refused surgical treatment.
Adult↗
Adverse effects of beta-adrenoceptor antagonists on the kidney.
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Adrenergic beta-Antagonists↗
The effect of captopril on autonomic reflexes in human hypertension.
The effects of acute administration of captopril on heart rate, blood pressure and physiological responses to head-up tilt, hand-grip, exercise and Valsalva manoeuvre were studied in 25 hypertensive subjects (10 untreated, 15 previously treated). After chronic administration for 8-12 weeks the effect on heart rate, blood pressure and the response to head-up tilt were studied again in 15 of these subjects. After the first dose of captopril (0.5 mg/kg), both systolic and diastolic blood pressures fell significantly, with no change in heart rate. Head-up tilting produced a significant increase in heart rate without any alteration in the blood pressure; hand-grip produced a significant increase in heart rate and blood pressure. These responses and exercise-induced tachycardia were unaltered by captopril. There was a significant reduction in the Valsalva ratio. After chronic administration the hypotensive efficacy was maintained for 10-12 h after the last dose, suggesting that twice daily dosage may be sufficient. There was a significant reduction in the basal supine heart rate by captopril. Head-up tilt produced the same physiological changes as in the acute study. These findings suggest that captopril has a vagotonic effect, possibly associated with resetting of baroceptor mechanisms. This could be one explanation for the hypotensive effect of captopril even in low-renin states.
Autonomic Nervous System↗
Investigating renal function during lithium treatment.
The tests that have been used to assess glomerular and tubular function in patients receiving treatment with lithium have been reviewed. The advantages and disadvantages of these are discussed. The most useful tests are the creatinine clearance, which may be predicted from the serum creatinine using a formula or nomogram, and the measurement of urine osmolality, followed if necessary by assessment of the maximum urine concentrating ability after desamino cys-1-8-D arginine vasopressin.
Acetylglucosaminidase↗
Investigation of renal tubular function during treatment with lithium.
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Enzymes↗
Cyclic AMP responses to parathyroid hormone and glucagon during lithium treatment.
Inhibition of adenylate cyclase has been proposed as a mechanism for hypothyroidism and nephrogenic diabetes insipidus occurring during lithium treatment, but these disorders are rarely found in the same patients. We have measured plasma levels of adenosine 3':5'-cyclic monophosphate (cyclic AMP) after an intravenous injection of glucagon in eight patients receiving long term lithium treatment and in six control subjects. Urinary cyclic AMP levels after an intravenous injection of bovine parathyroid hormone (PTH) were also measured in the patients. The plasma cyclic AMP response to glucagon in the patient group was significantly lower than that of the controls. No correlation was demonstrated between the plasma cyclic AMP response after glucagon and the urinary cyclic AMP response after PTH. We have previously shown that impairment of the response to PTH correlates with reduced urine concentrating ability during lithium treatment. In contrast, there was no correlation between the responses to PTH and glucagon in individual patients. These results are consistent with the hypothesis that inhibition of adenylate cyclase is an important factor in lithium-induced endocrine dysfunction.
Adult↗
Hypoglycaemia due to azapropazone-tolbutamide interaction.
We report a case of hypoglycaemia due to a 'first-dose' interaction between azapropazone and tolbutamide. The mechanism was probably by displacement of tolbutamide from protein binding sites, and it is recommended that azapropazone should be avoided in patients receiving tolbutamide.
Apazone↗
The acute effects of nifedipine on red cell deformability in angina pectoris.
In a randomised double-blind study, the effects on red cell deformability of a single sublingual dose of nifedipine were compared with placebo in eight patients with stable angina pectoris. Red cell deformability, measured by filtration and centrifugation techniques, was significantly increased at rest in all eight patients 1 h after nifedipine, while no change occurred after placebo. The improvement in deformability after nifedipine was maintained at the end of a period of exercise and unchanged from resting values after placebo. The results suggest that the increased deformability of red cells after nifedipine could contribute to the therapeutic effects of the drug in myocardial ischaemia.
Aged↗
The first pass metabolism of nifedipine in man.
Oral administration of nifedipine (20 and 30 mg tablets) to six volunteers was associated with a bioavailability of 0.43 and the presence of its nitropyridine analogue in the plasma. This metabolite was present in only trace amounts in samples taken from the same volunteers following i.v. administration of nifedipine. The peak plasma concentrations and area under the plasma concentration-time curve suggest that the nitropyridine analogue is a major, first pass, metabolite of nifedipine.
Administration, Oral↗
Lithium and the kidney.
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Acid-Base Equilibrium↗
Renal function during lithium treatment.
Renal function tests were performed in 101 unselected patients who had been on lithium for two weeks to 12 years. None had a recorded episode of lithium intoxication. The glomerular filtration rate (GFR), was not correlated with the cumulative dose of lithium or the duration of use of other psychotropic drugs. Nine patients had creatinine clearances lower than predicted; in six of these, no cause was identified and the small reductions in GFR may have been related to lithium use. Urinary concentrating ability (Umax) declined with age, and total dose of lithium received. Although the concurrent use of neuroleptics did not significantly reduce the Umax, the total duration of treatment with these drugs showed a negative correlation. The results suggest that prolonged use of neuroleptics, particularly in patients treated with lithium, may be responsible for an irreversible reduction in urine concentrating ability. Microalbuminuria was present in 40 per cent of the patients, although the rate of albumin excretion was not correlated with duration of use of psychotropic drugs. beta 2 microglobulin excretion was only raised in nine of these patients, suggesting that increased glomerular permeability rather than impaired proximal tubular protein reabsorption was responsible for the proteinuria. The urinary excretion of beta 2 microglobulin and N-acetyl-beta-glucosaminidase were slightly increased in small numbers of patients, indicating little evidence for proximal tubular damage. Increased NAG excretion did not correlate with reduced distal tubular function. However, there was a tendency to higher urinary beta 2 microglobulin excretion in patients with a reduced Umax.
Adult↗