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Biomedical subjects

D G Waller

Publications and source records attributed to D G Waller.

At least 55 records · Page 3Linked to original sources
PubMed1990

The combination of slow-release nifedipine and atenolol for stable angina.

Beta-adrenoceptor antagonists, such as atenolol and the dihydropyridine calcium antagonist nifedipine, have antianginal actions that should prove complementary when the drugs are used in combination. Atenolol acts primarily by reducing myocardial oxygen demand, while the vasodilator effects of nifedipine can both reduce demand and increase oxygen supply. The slow-release tablet formulation of nifedipine (Nifedipine Retard) provides more persistent plasma concentrations than the conventional capsule formulation, which may prolong the duration of action. There is increasing evidence that the plasma nifedipine concentration is closely related to efficacy, although the absolute concentration required to improve exercise tolerance in patients with angina varies between individuals. Clinical studies indicate that for many patients the duration of action of slow-release nifedipine, particularly when added to atenolol, is less than 12 hours. This reflects the extensive but variable first-pass metabolism of nifedipine, leading to subtherapeutic trough concentrations. To achieve 24-hour symptom relief, slow-release nifedipine will often need to be given three times daily to patients with angina.

Angina Pectoris↗
PubMed1990

Active and inactive urinary kallikrein in man: effects of diuresis and antidiuresis.

1. The urinary excretion of active and inactive kallikrein was studied in volunteers during diuresis induced by water loading or oral frusemide and during antidiuresis induced by desamino-D-arginine-vasopressin. 2. During acute oral water loading, excretion of active kallikrein was unchanged, despite high urine flow rates and low urine osmolalities being achieved. Excretion of inactive kallikrein correlated with the urine flow rate. 3. After desamino-D-arginine-vasopressin in eight water-loaded and six normally hydrated subjects, excretion of inactive kallikrein also correlated with the urine flow rate. There were no significant changes in the excretion of active kallikrein. 4. After frusemide there was a small transient increase in excretion of active kallikrein 1-2 h after dosing which coincided with the maximum diuresis and natriuresis. Excretion of inactive kallikrein again correlated with urine flow rate but the regression relationship between the two variables was different for water-load-induced and frusemide-induced diuresis. 5. These studies do not support a role for urinary kallikrein in the modulation of the antidiuretic action of vasopressin, but suggest that it may contribute to the natriuretic action of frusemide.

Adult↗
PubMed1990

Effect of food and activity on the reproducibility of isotopic GFR estimation.

The reproducibility of the plasma clearance of 99Tcm DTPA was studied in 26 patients under standardized conditions with the subject fasting and at rest. The coefficient of variation of duplicate measurements in patients with glomerular filtration rates (GRF's) ranging from 11-103 ml min-1 was 8%. Mean GFR following a breakfast containing 670 kcal and 31 g protein was increased significantly from 40.7 +/- 28.1 ml min-1 to 43.6 +/- 30.8 ml min-1. When fasted but permitted free exercise there was no consistent trend in GFR but the coefficient of variation of duplicate estimates increased significantly to 12.1%. It is recommended that routine GFR measurement should be carried out fasting or following a light diet with restricted activity.

Food↗
PubMed1990

The influence of levodopa on gastric emptying in man.

1. Simultaneous radioisotopic (99Tc-DTPA) gastric emptying measurements and paracetamol pharmacokinetic studies were performed in eight healthy male volunteers with and without levodopa (125 mg orally). 2. In the absence of levodopa gamma camera imaging showed rapid mono or biexponential emptying in all subjects and the plasma concentration-time curves for paracetamol displayed a single major peak. 3. In the presence of levodopa the time to 90% emptying was prolonged from 32 +/- 24 min to 81 +/- 20 min (P less than 0.01). Gastric emptying was interrupted by a plateau phase in six subjects and this pattern of emptying was associated with double peaks in the plasma concentration-time curves of both levodopa and paracetamol. The time to the end of the plateau phase of emptying correlated with the time to the trough plasma concentrations of paracetamol and levodopa. 4. There was excellent agreement between the plasma concentration-time curves of levodopa and paracetamol, i.e. time to initial peak, r = 0.946, P less than 0.001; time to trough concentration r = 0.943, P less than 0.01; time to second peak r = 0.974, P less than 0.001. 5. The results indicate that levodopa inhibits gastric emptying and thus influences its own absorption. Temporary inhibition of gastric emptying by levodopa (or a metabolite) is the cause of the multiple plasma peaks commonly observed following oral levodopa.

Acetaminophen↗
PubMed1990

The pharmacokinetics of doxazosin in patients with hypertension and renal impairment.

1. The pharmacokinetics of doxazosin, following a single oral dose (1 mg) and chronic oral dosing (doubling doses up to a maximum of 16 mg day-1), were studied in 18 patients with mild to moderate hypertension and stable renal function varying from normal to severely impaired. In addition, the effect of chronic administration of doxazosin on renal haemodynamics was evaluated. 2. Significant accumulation of doxazosin occurred with chronic dosing, but comparison of dose-adjusted AUC after single and chronic dosing suggested that there was no change in clearance or bioavailability during chronic administration. 3. There was no significant relationship between plasma elimination half-life or the AUC for doxazosin and the degree of renal impairment. 4. Symptomatic postural hypotension occurred in six patients following the initial dose of 1 mg doxazosin. Systolic and diastolic blood pressure measured 24 h after the previous dose were significantly reduced during chronic administration of doxazosin by a mean of 12/6 mm Hg supine and 10/7 mm Hg on standing. 5. During chronic administration of doxazosin, there was a significant reduction of 13% in glomerular filtration rate compared with pre-treatment, but no change in effective renal plasma flow.

Adult↗
PubMed1990

Splenic and renal abscesses following Salmonella virchow septicaemia--conservative management with ciprofloxacin.

Splenic abscess formation is a serious condition which usually requires prompt surgical intervention. We report on a patient with Salmonella virchow septicaemia, complicated by peritonitis and multiple splenic and renal abscesses. This is an uncommon manifestation of non-typhoid salmonella infection, which was managed conservatively with oral ciprofloxacin, leading to satisfactory resolution and cure.

Abscess↗
PubMed1990

Doxazosin in renal impairment.

The pharmacokinetics of doxazosin given once daily are similar in patients both with normal and with impaired renal function and consequently doxazosin can be used effectively in both at similar doses. Renal blood flow is well preserved during long-term treatment but effects on glomerular filtration rates are less consistent and small reductions may occur. It is uncertain whether these reflect a reduction in perfusion pressure, progression of the underlying renal disease or a combination of the two. Postural hypotension may occur in some patients after an initial dose of 1 mg.

Administration, Oral↗
PubMed1989

Beta-adrenoceptor antagonists plus nifedipine in the treatment of chronic stable angina pectoris.

The antianginal effects of beta-adrenoceptor antagonists are achieved by a reduction in myocardial oxygen demand. This is a rational approach to treatment in patients whose angina is caused by a fixed stenosis. However, dynamic coronary vasospasm is an important factor in patients with chronic stable angina. Nifedipine increases myocardial oxygen supply by reducing coronary vascular tone and is a logical approach to treatment in these patients. For monotherapy of angina, nifedipine is less effective than the beta-adrenoceptor antagonists, but the combination has additive effects in reducing the frequency of anginal episodes and improving exercise tolerance. Plasma concentrations of nifedipine are closely related to clinical efficacy, and the variable first-pass metabolism of the drug leads to wide interindividual differences in peak concentrations and duration of action. Increasing the size of individual doses of nifedipine carries a risk of enhanced side effects due to high peak plasma concentrations. Optimal treatment may be more appropriately achieved in some patients by a slow release formulation, but with an increased frequency of administration.

Adrenergic beta-Antagonists↗
PubMed1989

Clinical efficacy of xamoterol, a beta 1-adrenoceptor partial agonist, in mild to moderate heart failure. U.K. Xamoterol Study Group.

The clinical efficacy of xamoterol, alpha beta 1-adrenoceptor partial agonist, was determined in a multicentre double-blind, randomized, parallel group study of 240 patients with mild to moderate heart failure. At entry, 62% of patients were receiving diuretics (thiazides, or loop diuretics at a dose no greater than the equivalent of 80 mg of frusemide); 32% were taking nitrate formulations and 14% digoxin for control of atrial fibrillation. Assessments were carried out after a 1-week placebo run-in and after 3 months of treatment with either xamoterol or placebo. 198 patients completed the study of whom 186 had valid exercise tests. Mean exercise duration increased by 7% after placebo and by 19% after xamoterol during a progressive treadmill exercise protocol. Xamoterol significantly reduced peak exercise heart rate compared with placebo. Subjectively, there was improvement in breathlessness on the visual analogue scale after treatment with xamoterol compared with placebo, but no change in fatigue. We conclude that xamoterol produces sustained improvement in symptoms and exercise duration in mild to moderate heart failure.

Adrenergic beta-Agonists↗
PubMed1989

The effect of age on the pharmacokinetics of levodopa administered alone and in the presence of carbidopa.

1. The effect of age on the pharmacokinetics of levodopa administered alone and in the presence of carbidopa was investigated in young and elderly healthy volunteers. 2. The plasma clearance of levodopa following intravenous administration of 50 mg was 14.2 +/- 2.8 (s.d.) ml min-1 kg-1 in the elderly compared with 23.4 +/- 4.1 ml min-1 kg-1 in the young (P less than 0.01) which resulted in a 49% greater area under the plasma concentration-time curve (AUC) in the older subjects (P less than 0.01). The volume of distribution (Vss) was lower in the elderly (1.01 +/- 0.29 l kg-1) than in the young (1.65 +/- 0.39 l kg-1) (P less than 0.002). 3. Following oral administration of 250 mg of levodopa the AUC was 2512 +/- 588 ng ml-1h in the elderly compared with 1056 +/- 282 ng ml-1h in the young (P less than 0.002). Cmax was also significantly greater in the elderly (P less than 0.05). The bioavailability of levodopa was significantly greater in the elderly (0.63 +/- 0.12 compared with 0.41 +/- 0.16, P less than 0.01). 4. In the presence of carbidopa, the plasma clearance of intravenous levodopa (50 mg) was reduced in both age groups but remained lower in the elderly (5.8 +/- 0.9 ml min-1 kg-1 compared with 9.3 +/- 1.0 ml min-1 kg-1; P less than 0.01). This resulted in a 54% greater AUC in the older subjects (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1989

Prodrugs.

Explore the source record for details and available documents.

Animals↗
PubMed1989

Slow release nifedipine plus atenolol in chronic stable angina pectoris.

1. The effects of adding slow release nifedipine in doses of 20 mg and 40 mg twice daily to atenolol therapy (50 mg twice daily) were assessed in 18 patients with chronic stable angina. 2. The addition of the lower dose of nifedipine to atenolol did not significantly alter the weekly consumption of glyceryl trinitrate or the mean number of anginal attacks as assessed by diary cards. However, 2 h after dosing there was a significant prolongation during stress testing in the time to onset of both 1 mm ST depression on the ECG (by 28%) and to angina (by 37%) compared with atenolol alone, but no benefit was apparent by 12 h after dosing. 3. At a dose of 40 mg twice daily, nifedipine significantly reduced glyceryl trinitrate consumption by 25% and the number of anginal attacks by 36%. The times to onset of ST depression and angina were increased by 37% and 55% respectively at 2 h and by 24% and 26% respectively 12 h after dosing. 4. Analysis of the frequency distribution of anginal attacks showed decreasing efficacy with time after administration of nifedipine. The overall results also suggest a relationship between efficacy and the plasma nifedipine concentration, with a mean 20% improvement in time to development of angina occurring at a nifedipine plasma concentration of approximately 30-40 ng ml-1. 5. In conclusion, the reduction of effort-related angina by nifedipine is related to its plasma concentration and the effective duration of action of the 20 mg slow release formulation is less than 12 h.

Adult↗
PubMed1989

Long-term studies with xamoterol in heart failure.

1. Xamoterol (Corwin, Carwin, Corwil, Xamtol, ICI 118,587) is a beta 1-adrenoceptor partial agonist which, unlike full beta-adrenoceptor agonists, does not down-regulate beta-adrenoceptors in the rat ventricle during chronic administration. 2. Improvements in myocardial performance have been demonstrated following acute administration of xamoterol to patients with mild or moderate heart failure, and these are sustained during at least 1 year of continued treatment. 3. Exercise duration is increased by xamoterol in patients with left ventricular dysfunction and benefit is still apparent after at least 1 year of therapy. 4. Despite sustained cardiac stimulation, xamoterol does not appear to affect adversely mortality in patients with mild or moderate heart failure. 5. Few adverse events directly attributable to xamoterol were reported during 3 month efficacy studies in more than 600 patients, and the laboratory safety profile over 1 year of treatment is good. 6. Xamoterol is a promising, well-tolerated addition to established therapies for chronic mild or moderate heart failure.

Adrenergic beta-Agonists↗
PubMed1989

Renal and pulmonary effects of angiotensin converting enzyme inhibition in chronic hypoxic lung disease.

The effects of 28 days' treatment with captopril or with placebo on renal and pulmonary function were evaluated in nine patients with stable pulmonary heart disease. Captopril (25 mg twice daily) caused a 17% rise in effective renal plasma flow but no change in glomerular filtration rate, resulting in a fall in filtration fraction likely to favour natriuresis. Captopril did not alter FEV1, lung volumes, or arterial oxygen or carbon dioxide tension.

Aged↗
PubMed1989

Vibrotactile sensation and response to nifedipine dose titration in primary Raynaud's phenomenon.

The clinical response to two doses of sustained-release nifedipine was assessed during a double-blind, randomized, placebo-controlled trial in 22 patients with primary Raynaud's phenomenon. Nifedipine at doses of 20 mg and 40 mg daily reduced the mean number of attacks by 40% compared with placebo with no significant differences between the two doses in the number of attacks or their severity. Unwanted effects were more common and more persistent with the higher dose of nifedipine. Fingertip vibrotactile thresholds measured at 31.5 and 125 Hz were unchanged by treatment with nifedipine. There was, however, a correlation between the pretreatment threshold at 125 Hz and the response to treatment with nifedipine, the most favorable responses occurring in patients with the lowest thresholds.

Adolescent↗
PubMed1989

Maximising safety when prescribing non-steroidal anti-inflammatory drugs.

Current knowledge on side-effects of non-steroidal anti-inflammatory drugs (NSAIDs) is reviewed. These occur most commonly in the gastro intestinal tract and include peptic ulceration and haemorrhage as well as effects on the small and large bowel. Renal effects with many manifestations are also increasingly described. Photosensitivity is the most common adverse dermatological effect. The role of various NSAIDs in causing asthma is now well recognised. Many less common side-effects occur, the most significant of which is marrow aplasia. Phenylbutazone and indomethacin are rarely but definitely associated with this, but other NSAIDs including ibuprofen are also suspected, but unproven, causes. A strategy for minimising side-effects is outlined. Where there is not a strong indication for use of an NSAID, local physical measures or a pure analgesic can be substituted. If an NSAID is really necessary, it is best to commence with a drug of lesser potency in the first instance, unless the patient is suffering from a severe inflammatory disorder. Indomethacin and piroxicam should be reserved for when other NSAIDs have not been effective. Patients who have a past or present history of peptic ulceration but still need to continue their NSAID therapy, should combine it with an anti-ulcer drug. In the case of younger patients a H2 receptor antagonist is the drug of first choice, whereas in the older patient a mucosal protective agent such as sucralfate is preferred. In the event of ulcer relapse, combination with a prostaglandin analogue is the next step. The growing awareness of side-effects with NSAIDs suggests that monitoring of patients commencing NSAIDs and on long-term treatment, should be increasingly practiced.

Anemia, Aplastic↗