Referral patterns and diagnoses in women attending a urodynamic unit.
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Adolescent↗
Biomedical subjects
A M Shepherd
Publications and source records attributed to A M Shepherd.
Comparative bioavailability of a sustained-release ion-exchange hydralazine product with a potassium (cation) challenge.
A sustained-release formulation of hydralazine was manufactured by binding hydralazine to an ion-exchange resin and coating the drug-resin complex with a semipermeable membrane. Because the sustained-release characteristics are due in part to displacement of drug from the drug-resin complex by gastrointestinal ions, the stability of the sustained-release formulation could be compromised if challenged by a high concentration of ions. In this study, 12 healthy male volunteers participated in a two-way crossover trial that was designed to test the bioavailability and release of drug from the sustained-release formulation both with and without concomitant ingestion of a solution of KCl. Blood samples were collected over a 14-h period after administration of either treatment. Analysis of whole blood for hydralazine and comparison of the values of the area under the curve of the concentration of hydralazine versus time, the maximum concentration of hydralazine, and the time to reach the maximum concentration between the two experimental groups showed that KCl had no influence on the bioavailability or release characteristics of hydralazine from the sustained-release formulation.
Adult↗
Resting and maximal forearm skin blood flows are reduced in hypertension.
To find whether the vasodilator capacity of nonacral skin is reduced in hypertension, we measured forearm blood flow by venous occlusion plethysmography in 10 seated normotensive (mean +/- SD mean arterial pressure, 94 +/- 5 mm Hg) and 10 hypertensive (112 +/- 9 mm Hg) men at rest for 39 minutes while the forearm was heated with water at 42 degrees C, a maneuver known to selectively and maximally vasodilate skin. Blood pressure, measured every 5 minutes, did not change with heating. We found that in the normotensive group resting forearm blood flow was higher (3.64 +/- 1.12 versus 2.48 +/- 0.58 ml/100 ml tissue per minute, p less than 0.001; normotensive group versus hypertensive group) and resting forearm vascular resistance lower (30.17 +/- 10.99 versus 48.88 +/- 17.37 mm Hg.min.100 ml tissue per minute, p less than 0.05; normotensive group versus hypertensive group), and maximal forearm blood flow with local heating was higher (29.32 +/- 11.99 versus 18.19 +/- 4.50 ml/100 tissue per minute, p less than 0.018; normotensive group versus hypertensive group and vascular resistance lower (4.07 +/- 1.04 versus 6.54 +/- 1.17 mm Hg.min.100 ml tissue per minute, p less than 0.005; normotensive group versus hypertensive group). To find whether this degree and duration of local warming maximally vasodilated the skin in hypertensive subjects (as it does in normotensive subjects), we measured forearm skin blood flow before and during local heating plus 10 minutes of ischemia using a laser Doppler flowmeter.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Determination of alpha-adrenergic blocking potency.
Determination of the alpha-adrenergic blocking potency of drugs in humans is usually done by measuring the shift in the blood pressure versus logarithm of intravenous phenylephrine dose-response relationship. Change in blood pressure activates homeostatic reflexes that may change this relationship. This study examines the effect of autonomic (beta 1- and beta 2-adrenergic, parasympathetic, and alpha-adrenergic) blockade on the dose versus blood pressure response relationship to sequential doses of phenylephrine in humans. Phenylephrine dose responses were conducted under controlled conditions, during propranolol and atropine infusion, during prazosin-induced alpha 1-adrenergic blockade, and during prazosin, propranolol, and atropine administration. Propranolol-atropine infusion decreased the threshold dose of phenylephrine required to increase mean blood pressure (p less than 0.00001), increased the slope of the phenylephrine dose versus increase in mean blood pressure relationship (p = 0.019), and and decreased the dose of phenylephrine required to increase mean blood pressure by 20 mm Hg (p less than 0.00001). Determination of the alpha-adrenergic blocking potency of prazosin was not affected by autonomic blockade with propranolol and atropine (dose ratio 5.2 before and 5.0 after autonomic blockade; p = 0.465). We conclude that beta 1- and beta 2-adrenergic and muscarinic blockade increase sensitivity to phenylephrine by increasing the slope and decreasing the threshold dose of the phenylephrine dose-response curve, and that alpha-adrenergic-blocking potency of prazosin may be determined with or without blocking homeostatic blood pressure regulatory mechanisms in humans.
Adrenergic beta-Antagonists↗
Effect of food on oral availability of apresoline and controlled release hydralazine in hypertensive patients.
Hydralazine is a vasodilator antihypertensive drug that has been in use for many years. Efficacy after oral administration correlates well with the levels of the drug in blood. Factors such as food ingestion that affect blood levels of hydralazine may therefore be of importance. There is dispute regarding the effect of food intake on blood levels of hydralazine and on the antihypertensive response. This randomized cross-over study examined the effect of food (642 K calories, 25 g protein, 43 g fat, 40 g carbohydrates, 32 mEq sodium, 17 mEq potassium) ingested immediately before hydralazine (taken as Apresoline, Ciba Geigy, or as slow-release hydralazine, SRH, Pennwalt Corporation) on the blood levels of hydralazine in 16 essential hypertensive patients who were slow acetylators currently taking at least 100 mg Apresoline daily. Peak blood hydralazine levels were reduced by food after both Apresoline and SRH, by 69 and 66%, respectively. Time to peak blood hydralazine concentration was delayed significantly with SRH. We could detect a statistically significant food-related reduction of area under blood hydralazine concentration versus time curves (AUC) only with Apresoline (by 44%). The AUC for SRH was decreased only 29% by food. Hydralazine should be taken at a consistent time with respect to meals.
Administration, Oral↗
High-pressure liquid chromatographic assay for hydralazine in human plasma.
A specific high-performance liquid chromatographic assay for hydralazine in human plasma was developed. Plasma hydralazine is reacted with 10 microliter of p-anisaldehyde for 7 min at room temperature to form hydralazine p-anisaldehyde hydrazone. This derivative is extracted into ethyl acetate, and the solvent is removed by evaporation. The residue is reconstituted in 100 microliter of methanol, and 90 microliter is injected onto a reversed-phase column. The mobile phase is 32% acetonitrile in 0.75 M acetate buffer, pH 3.4, at a flow rate of 2 ml/min. The retention time of hydralazine p-anisaldehyde hydrazone is 6.5 min. The average coefficient of variation over 10-200 ng/ml is 5.5%, and the sensitivity limit is 5 ng/ml. Under the assay conditions, hydralazine pyruvic acid hydrazone, a known plasma metabolite of hydralazine, yields less than 0.1% hydralazine. Detectable plasma hydralazine levels of 5-20 ng/ml were found 10-30 min after a 0.5-mg/kg oral dose of hydralazine hydrochloride was given to a male volunteer.
Adult↗
Urinary incontinence: prevalence and needs.
The prevalence of recognised urinary incontinence in a community was found to be 1%; the prevalence of unrecognised incontinence was 3.3% in men and 8% in women in a group practice of 7000 patients. The approach to investigation and management of urinary incontinence in a urodynamic unit and the staffing of this unit are described.
Adolescent↗
Pharmacokinetics and cardiovascular effects in rabbits of a major hydralazine metabolite, the hydralazine pyruvic-acid hydrazone.
The hydrazone of hydralazine and pyruvic acid (HPH) has been recognized as a quantitatively important metabolite of hydralazine in human plasma. We evaluated the disposition of [14C] HPH after its i.v. administration to normal, anephric and probenecid-pretreated rabbits. Renal clearance of HPH in normal rabbits exceeded the glomerular filtration rate by a factor of 3 to 4 and accounted for 80 to 90% of the total body clearance. Active tubular secretion was established by the effect of probenecid pretreatment to reduce the renal clearance of HPH by 80%. Total body clearance of HPH in anephric rabbits was 10% of that of normal animals, emphasizing the minor importance of metabolic conversion for the overall disposition of HPH. HPH in a maximum dose of 50 mumol/kg i.v. had no hypotensive effect in renal hypertensive rabbits and did not interfere with the subsequent hypotensive response to hydralazine. This HPH dose produced plasma levels at least 50 times in excess of those reported in humans after administration of therapeutic doses of parent hydralazine. HPH is consequently of negligible clinical significance, despite the relatively high plasma concentration of this metabolite which occurs after administration of parent hydralazine.
Animals↗
Pharmacokinetics of hydralazine, apparent hydralazine and hydralazine pyruvic acid hydrazone in humans.
Hydralazine is an antihypertensive vasodilator agent. Lack of specific assay techniques for its measurement have delayed elucidation of its pharmacokinetic profile. This study compares the plasma profiles of hydralazine, measured both by a specific and by a previously published nonspecific assay and of a major plasma metabolite, hydralazine pyruvic acid hydrazone. After po and iv administration of hydralazine, peak hydralazine levels were lower (7-33%) and plasma half lives were shorter (15-31%) when measured by the specific technique. The mean plasma half life of the pyruvic acid hydrazone was 156 min and mean urinary clearance, 28 ml/min. The plasma profile of hydralazine and of the major metabolite, the pyruvic acid hydrazone, do not appear to correspond to the duration of antihypertensive effect of administered hydralazine.
Acetylation↗
Altered warfarin metabolism in iron-deficient patient.
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Adult↗
Reduced induction of drug metabolism in the elderly.
Young and elderly subjects were given the hypnotic dichloralphenazone (Welldorm) in a dose of 20 mg/kg nightly for two weeks and the extent of induction of liver microsomal drug metabolism was assessed from alteration in the plasma elimination of quinine and antipyrine (phenazone). With both indices, there was a significant increase in plasma drug clearance in young subjects following dichloralphenazone treatment but no significant alterations occured in the elderly group. These results indicate that, in addition to being less able to metabolize some drugs, elderly patients show a reduced induction response. They may therefore be less likely to become tolerant to those drugs which are inactivated by metabolism.
Adult↗
Drug prescribing patterns in the elderly: a cross-sectional study of in-patients.
A cross-sectional one-day survey of drug prescribing and use in elderly in-patients was carried out in Dundee hospitals. Altogether 873 patients were studied and analyses of prescribing patterns were carried out by patient categories--medical, surgical, geriatric, psychiatric and mentally subnormal--and by major drug groups. While the average number of drugs prescribed per patient on the study day was 3.3, which was not excessive, other results highlighted some possible problems of therapy, viz. the wide range of drugs used within drug groups, the common use of psychotropic drugs, dose regimes which although used in a geriatric population differed little from general adult dosages, and which sometimes involved many administrations per day. Examples were described relating to the use of nitrazepam, phenothiazines and tricyclic antidepressants.
Aged↗
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↗
Measurement of cardiac muscle relaxation in hypothyroidism.
The isovolumetric relaxation time of the left ventricle (IRT) in 20 hypothyroid patients (133 +/- (SE of mean) 4 ms) was significantly longer than that in 23 normal subjects (95 +/- 3 ms). During a trial of thyroxine replacement the IRT in 12 hypothyroid patients fell from 143 +/- 4 ms to 107 +/- 4 ms. The IRT seems to be a useful index of end-organ function in hypothyroidism.
Adolescent↗
The plasma elimination of the enantiomers of phenprocoumon in man.
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Adult↗
Haemoglobin and serum iron responses to periodic intravenous iron-dextran infusions during maintenance haemodialysis.
Patients with chronic renal failure who were on maintenance haemodialysis, were given monthly 600 mg iron intravenously as iron-dextran complex to a body replacement total of 5-6 g iron. Those patients who had been on maintenance haemodialysis for a long period and had received numerous blood transfusions failed to show a rise in haemoglobin levels. Those patients who received iron from the commencement of maintenance dialysis, and who had not received blood transfusions, showed a significant increase in haemoglobin concentrations which has been maintained for more than 18 months after iron therapy ceased, despite a concurrent decrease in serum iron concentrations. Pre-treatment and post-treatment levels of serum iron are not of predictive value for the success of iron treatment, neither for the haemoglobin nor the serum iron response. A body replacement dose of iron given intravenously over a year benefits the majority of patients on maintenance haemodialysis and is recommended for the treatment of their anaemia.
Anemia↗
The effect of desferrioxamine on the colorimetric determination of iron in human serum and plasma.
The effect of a range of concentrations of desferrioxamine on a colorimetric determination of serum, or plasma, iron concentration is described. The method of iron estimation used was an autoanalyzer method using tripyridyltriazine as chromogen. There was found to be a small, reproducible diminution in the serum iron estimation in the presence of desferrioxamine. This was independent of the concentration of desferrioxamine. High serum concentrations of iron can be measured reproducibly in the presence of desferrioxamine after dilution of the serum with saline.
Autoanalysis↗
Drugs and the elderly. The nature of the problem.
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Aged↗