Calcium antagonists in cardiovascular disease.
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Calcium Channel Blockers↗
Biomedical subjects
D G Waller
Publications and source records attributed to D G Waller.
Class II antiarrhythmic agents.
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Adrenergic beta-Agonists↗
Age-related changes in the pharmacokinetics and pharmacodynamics of nifedipine.
1. The effects of age on the pharmacology of nifedipine were investigated in 11 young and six elderly normotensive volunteers. 2. Following 2.5 mg of nifedipine i.v. the plasma clearance of nifedipine was 348 +/- 83 (s.d.) ml min-1 in the elderly compared with 519 +/- 125 ml min-1 in the young (P less than 0.05) and the AUC in the elderly was significantly greater at 125 +/- 28 ng ml-1 h compared with 83.9 +/- 19 ng ml-1 h (P less than 0.05). The Vss was similar in both age groups. 3. Following 10 mg oral sustained release nifedipine the AUC was 281 +/- 64 ng ml-1 h in the elderly compared with 136 +/- 56 ng ml-1 h in the young (P less than 0.002) and Cmax in the elderly was significantly greater at 36.8 +/- 11.8 ng ml-1 compared with 22.3 +/- 5.8 ng ml-1 (P less than 0.05). The trend towards an increased bioavailability in elderly subjects (36%) was supported by a significantly lower nitropyridine metabolite/nifedipine ratio in the elderly. 4. Absorption rate limited kinetics of the sustained release formulation were indicated by the prolonged t1/2 compared with i.v. administration. In the elderly t1/2 (oral) was significantly greater than in the young (elderly 6.7 +/- 2.2 h, young 3.8 +/- 1.4 h, P less than 0.05). 5. Haemodynamic changes in the young were confined to a tachycardia following i.v. administration. In the elderly, supine BP fell significantly following both oral and i.v. nifedipine while the heart rate remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Oral↗
Comparative effects of fluoxetine and amitriptyline on cardiac function.
1. The effects of fluoxetine and amitriptyline on the electrocardiogram (ECG) and systolic time intervals (STIs) were measured during a double-blind parallel-group study in depressed patients. 2. ECGs and STIs were measured after a 1 week placebo run-in, following 1 week's treatment with fluoxetine 40 mg daily or amitriptyline 100 mg daily, and then after 3 weeks' treatment with fluoxetine 60-80 mg daily or amitriptyline 150-200 mg daily. 3. Fluoxetine had no effect on the ECG or STIs at any dose. Amitriptyline 150-200 mg daily shortened the sinus cycle length by a mean of 12%, prolonged the PR interval by 8% and the QRS duration by 10%. Amitriptyline did not significantly alter the STIs.
Adult↗
The pharmacokinetics of oral nifedipine--a population study.
1. The pharmacokinetics and metabolism of nifedipine have been studied in a population of 59 young male volunteers following administration of a 10 mg capsule. 2. The area under the plasma concentration-time curves (AUC) for nifedipine demonstrated a skewed but not a bimodal distribution (mean 154 ng ml-1 h; range 54-306 ng ml-1h). 3. Calculation of the ratio of the AUC of nifedipine to the AUC of its nitropyridine metabolite did not separate those individuals with high AUC values of nifedipine from the remainder of the population. 4. Similarly there was no evidence for bimodality in the excretion of the major urinary metabolite. Those subjects with high plasma AUC values for nifedipine excreted similar amounts to the remainder of the population. 5. In contrast to a previous study using a 20 mg oral dose, there was no evidence of polymorphism in the pharmacokinetics or metabolism of nifedipine following a single 10 mg oral dose.
Administration, Oral↗
The effect of nisoldipine on whole blood platelet aggregation in patients with Raynaud's phenomenon.
1. Whole blood platelet aggregation was measured by electrical impedance in 28 controls and 28 patients with primary Raynaud's phenomenon. 2. The patients were entered into a double-blind, placebo-controlled cross-over trial of the calcium antagonist nisoldipine, in which they received, in random order, three, 4 week treatments with placebo and nisoldipine (5 and 10 mg day-1). 3. Platelet aggregation responses to two concentrations (5.0 and 0.5 micrograms ml-1) of collagen were determined before treatment and at the end of each treatment phase. 4. There were no differences in aggregation response to either collagen concentration between controls and patients with primary Raynaud's phenomenon, or between placebo and active treatment phases. 5. These data do not support the suggestion that nisoldipine has a significant anti-platelet effect.
Adult↗
Inter-individual differences in response to cardiovascular drug therapy.
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Cardiovascular Diseases↗
A longitudinal assessment of renal function during treatment with lithium.
Renal function was studied during lithium treatment in 28 patients on two occasions separated by a mean interval of 4.7 years. Glomerular filtration rate, assessed by creatinine clearance and serum creatinine concentrations, showed no impairment. Albumin excretion rate, a marker of glomerular permeability, showed no consistent change. In contrast, a decline in urine concentrating ability (mean 140 mOsm/kg) was found in all patients, exceeding the reduction to be expected from ageing in all but three. These results support the view that treatment with lithium long-term does not damage renal glomerular function, but that progressive impairment of the distal tubular responsiveness to arginine vasopressin is common.
Adult↗
Attitudes to prescribing iron supplements in general practice.
In response to a postal questionnaire general practitioners in the Southampton and New Forest area indicated a considerable understanding of the principles of iron prescribing and use of laboratory tests to determine iron deficiency. Many respondents, however, chose slow release and compound iron preparations as first treatments for iron deficiency. The role of parenteral iron appeared to be poorly understood. The use of and response to laboratory investigations for iron deficiency were generally appropriate, but many practitioners probably do not check for a response to oral iron sufficiently early during treatment or stop prescribing supplements before iron stores have been replenished. There is scope for further education in the biology and management of iron deficiency in general practice.
Clinical Laboratory Techniques↗
Measurement of glomerular filtration rate with 99mTc-DTPA: a comparison of gamma camera methods.
A comparison has been made between three gamma camera methods for estimation of glomerular filtration rate (GFR) using 99mTc-DTPA in a group of 27 patients with widely different renal function. Plasma clearance of 99mTc-DTPA by multiple blood sampling was used as the reference. Percentage uptake of chelate in the bladder and kidneys at 20 min after injection gave the lowest standard error of 8.0 ml/min. Techniques using early uptake of isotope in the kidneys at 2 min after injection gave less accurate estimates. Correction for the vascular activity in the renal region of interest improved the results for the 2 min uptake technique. Gamma camera techniques provide rapid estimates of GFR which are less accurate than those obtained by plasma clearance of labelled chelate.
Glomerular Filtration Rate↗
Longitudinal assessment of glomerular filtration rate by gamma camera and portable external detector.
Noninvasive isotope chelate methods to assess glomerular filtration rate (GFR) are less accurate than blood sampling. However, some measurement errors would be expected to be constant for an individual, and repeat estimations may be less variable. In 18 patients, estimates of GFR were obtained by 2 gamma camera techniques and a portable external detector at a mean interval of 1 year, to assess accuracy in predicting a change of GFR. Errors in these techniques were not significantly better than those predicted from two independent estimates. Most GFR measurement error for noninvasive methods appears to be random.
Adult↗
Factors affecting the pharmacokinetics of nifedipine.
The plasma pharmacokinetics of nifedipine and the formation of its metabolites have been studied in volunteers under conditions which would affect the activity of the cytochrome P-450 system. The pharmacokinetics of a 10-mg capsule of nifedipine were not significantly different between smokers and non-smokers of similar age. After pretreatment with cimetidine, which inhibits the activity of cytochrome P-450, the peak plasma concentration and area under the plasma-time concentration curve for nifedipine were increased by a mean 84%. In contrast, pre-treatment with ranitidine which has little effect on cytochrome P-450, did not significantly alter nifedipine pharmacokinetics. Smoking does not contribute significantly to the variability in nifedipine pharmacokinetics. However, the interaction between nifedipine and cimetidine, but not ranitidine, may be of clinical importance.
Adult↗
Nisoldipine in primary Raynaud's phenomenon.
The efficacy and tolerability of the dihydropyridine derivative nisoldipine was assessed in 36 patients with primary Raynaud's phenomenon. Nisoldipine was given at doses of 5 mg and 10 mg daily for one month each in a placebo controlled double-blind cross-over trial. There was no subjective improvement in symptoms or changes in resting finger blood flow, platelet aggregability or red cell deformability after nisoldipine. The incidence of unwanted effects was similar to that previously described with nifedipine, suggesting that plasma concentrations of nisoldipine were sufficient to cause pharmacodynamic effects. Nisoldipine, in contrast to nifedipine is ineffective in the treatment of primary Raynaud's phenomen when given in a dose of up to 10 mg/day.
Adult↗
Measurement of glomerular filtration rate with a portable cadmium telluride detector.
The plasma clearance rate constant of 99Tcm-DTPA was measured with a portable cadmium telluride detector over anterior chest wall and lateral leg sites to obtain an empirical estimate of glomerular filtration rate (GFR). Thirteen patients with a range of renal dysfunction were studied to compare the accuracy of the estimates over various time periods compared to GFR estimated from plasma sampling. The chest site was more accurate for GFR assessment over all time periods assessed up to 4 h following injection. The clearance rate constants obtained up to 1 h after injection from the chest site were not significantly less accurate then those from later time periods.
Cadmium↗
Food and nifedipine pharmacokinetics.
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Adult↗
The trans-hepatic extraction of nifedipine.
1. The trans-hepatic extraction of nifedipine during steady state infusion was studied in six patients undergoing cardiac catheterisation for suspected coronary disease. 2. Mean extraction ratio across the liver was 0.64 but hepatic clearance accounted for a mean of only 65% of total body clearance. 3. These results are consistent with the liver as the major site of metabolism of nifedipine, but also suggest that significant metabolism occurs outside the liver.
Adult↗
Amiloride, frusemide and urinary kallikrein excretion.
Intravenous administration of the loop diuretic frusemide caused a rapid but short-lived increase in the urinary excretion of kallikrein-like activity in healthy volunteers. Indomethacin alone did not alter urinary electrolyte or kallikrein excretion, but when given concurrently with frusemide it blunted the natriuresis without altering the urinary kallikrein excretion. A single oral dose of amiloride, a distal tubular diuretic, caused a natriuresis but no significant change in urinary kallikrein excretion. The results do not support a direct role for the renal kallikrein-kinin system in mediating the natriuresis induced by diuretics.
Adult↗
Measurement of glomerular filtration rate with technetium-99m DTPA: comparison of plasma clearance techniques.
We have compared several techniques for measuring [99mTc]DTPA plasma clearance following single injection to estimate glomerular filtration rate (GFR). Half hourly measurements of disappearance of plasma activity were used to calculate a reference GFR corrected for one-pool assumption and body surface area. Alternative methods involving (i) single blood sample, (ii) two blood samples, (iii) external detector clearance rate, and (iv) a combination of (i) and (iii) were then compared. Closest correlations were obtained with (i) two blood samples at 2 hr and 4 hr (s.e.e. 2.8 ml/min) and (i.v.) external rate constant from 2-5 hr with a blood sample at 3 hr (s.e.e. 3.0 ml/min). Correlations with single blood sample were closest at 3 hr and 4 hr postinjection (s.e.e. 5.4 and 4.5 ml/min, respectively). External detector disappearance rate constant alone was least accurate (s.e.e. greater than 10 ml. min).
Glomerular Filtration Rate↗