Biomedical subjects

D McTavish

Publications and source records attributed to D McTavish.

At least 19 recordsLinked to original sources

PubMed2000

Change in primary health care: new wine in old bottles?

Describes the findings from the first year of an evaluation of change at a PMS+ site in West Cumbria. The study has used qualitative methods including non-participant observation at the site; face to face interviews with 28 clinical staff; group interviews with administrative and secretarial staff; and the collection of documents. Analysis of the data against a set of "outcome indicators" shows that significant progress has been made towards implementing the model of primary care delivery described in the pilot proposal. Multidisciplinary working is developing in the clinical action groups and the establishment of a primary care emergency unit has changed general practitioner workloads. The new organisation structure is not yet working wholly as anticipated but recently initiated changes are intended to strengthen the role and authority of the management board.

Data Collection↗

PubMed2000

The NHS--is Scotland different? A case study of the management of health care in the hospital service in the west of Scotland 1947-1987.

Management of the health service in Scotland and England, has since its creation, shown both divergence and congruence. In the initial decades in Scotland the executive hospital boards (which contained strong medical professional membership) and central government had a clearer relationship than in England. The health service-civil service machinery in Scotland was without doubt more to the forefront with higher status in the Scottish 'polity' than was the case in England. The 1970s reforms also indicated difference: despite the pro managerialist tones of the Farquarson Lang report in Scotland, a managerial emphasis was more apparent in the English reforms. By the 1980s, the government's clear intention that their 'radical' agenda should apply in Scotland and England was implemented in many instances: aspects of the new managerialism were applied as vigorously in the case examined than anywhere in England; the attempt to draw clinicians into resource management (as advocated in the Griffiths report) appeared to have advanced further in Scotland until well into the 1990s. Yet in other aspects, Scotland diverged from parts of England in the implementation of the 1980's agenda most notably in the growth of private practice though the case indicated significant Scottish developments here too. The article concludes by speculating on some Scottish differences in the coming years.

England↗

PubMed1998

Cerivastatin.

Cerivastatin is a synthetic HMG-CoA reductase inhibitor with high liver selectivity, which lowers plasma cholesterol levels by inhibiting endogenous cholesterol synthesis. In vitro, the affinity of cerivastatin for HMG-CoA reductase was higher than that of lovastatin, simvastatin and pravastatin. This higher enzyme affinity was reflected in vivo, with a lower ED50 (dose causing 50% inhibition) for cerivastatin in rats and beagle dogs compared with lovastatin. Cerivastatin 0.2 mg/day significantly reduced low density lipoprotein (LDL)-cholesterol, total cholesterol and triglyceride levels, and increased high density lipoprotein (HDL)-cholesterol levels, in patients with type IIa hypercholesterolaemia. Available data indicate that cerivastatin has a tolerability profile similar to that of other HMG-CoA reductase inhibitors. No drug interactions were observed when cerivastatin was coadministered with digoxin, warfarin, cimetidine or the antacid magnesium/aluminium hydroxide.

Animals↗

PubMed1997

Pravastatin. A reappraisal of its pharmacological properties and clinical effectiveness in the management of coronary heart disease.

Pravastatin is an HMG-CoA reductase inhibitor which lowers plasma cholesterol levels by inhibiting de novo cholesterol synthesis. Pravastatin produces consistent dose-dependent reductions in both total and low density lipoprotein (LDL)-cholesterol levels in patients with primary hypercholesterolaemia. Favourable changes in other parameters such as total triglyceride and high density lipoprotein (HDL)-cholesterol levels are generally modest. Combination therapy with other antihyperlipidaemic agents such as cholestyramine further enhances the efficacy of pravastatin in patients with severe dyslipidaemias. Available data suggest that pravastatin is effective in elderly patients and in patients with hypercholesterolaemia secondary to diabetes mellitus or renal disease. The benefit of cholesterol-lowering in terms of patient outcomes is currently an area of considerable interest. Recently completed regression studies (PLAC I, PLAC II, KAPS and REGRESS) show that pravastatin slows progression of atherosclerosis and lowers the incidence of coronary events in patients with mild to moderately severe hypercholesterolaemia and known coronary heart disease. Large scale primary (WOSCOPS) and secondary (CARE) prevention studies, moreover, demonstrate that pravastatin has beneficial effects on coronary morbidity and mortality. In WOSCOPS, all-cause mortality was reduced by 22%. Pravastatin is generally well tolerated by most patients (including the elderly), as evidenced by data from studies of up to 5 years in duration. As with other HMG-CoA reductase inhibitors, myopathy occurs rarely (< 0.1% of patients treated with pravastatin): approximately 1 to 2% of patients may present with raised serum levels of hepatic transaminases. Thus, with its favourable effects on cardiovascular morbidity/mortality and total mortality, pravastatin should be considered a first-line agent in patients with elevated cholesterol levels, multiple risk factors or coronary heart disease who are at high risk of cardiovascular morbidity.

Anticholesteremic Agents↗

PubMed1997

Alendronate. A review of its pharmacological properties and therapeutic efficacy in postmenopausal osteoporosis.

Alendronate is an aminobisphosphonate which appears to attenuate, rather than completely inhibiting bone turnover, by suppressing the activity of osteoclasts. Clinical trials have established that 10 mg/day orally administered alendronate is the optimum dosage. Despite its poor bioavailability after oral administration, alendronate is highly effective at preventing bone loss associated with the absence of endogenous estrogen. A sustained increase in bone mass was observed during alendronate therapy without accelerated loss after withdrawal of the drug. Increased bone mass was associated with a reduction in the risk and rate of occurrence of vertebral fractures. A recent study demonstrated a 47% reduction in the risk of developing new radiographic vertebral fractures over 3 years in women with low bone mass and pre-existing vertebral fractures. There have been few direct comparisons in clinical trials. However, when compared with calcium or low dosages of salmon calcitonin (salcatonin) therapy in women with postmenopausal osteoporosis, alendronate induced a sustained increase in bone mass during therapy that was not seen with the comparator. In clinical trials alendronate was generally well tolerated when taken as recommended. Adverse events tended to be transient and usually associated with the upper gastrointestinal tract; the most common events included abdominal pain, nausea, dyspepsia, constipation and diarrhoea, which are also common with other bisphosphonates. Of potential concern are the small number of reports of patients developing oesophageal ulceration; however, this adverse event was attributed to noncompliance with the manufacturer's recommendations for administration of the drug. In addition, alendronate has not been associated with osteomalacia. Studies are still required to establish the long term efficacy of alendronate, particularly with regard to other available therapies. Although estrogen replacement therapy is generally considered the treatment of choice for the management of postmenopausal osteoporosis, many women are unable or unwilling to receive estrogens on a long term basis. Thus, alendronate, with its demonstrated beneficial effects and its good tolerability profile (when taken as recommended), is a promising alternative treatment option for the management of postmenopausal osteoporosis.

Alendronate↗

PubMed1997

Atorvastatin. A review of its pharmacology and therapeutic potential in the management of hyperlipidaemias.

Atorvastatin is a synthetic HMG-CoA reductase inhibitor which lowers plasma cholesterol levels by inhibiting endogenous cholesterol synthesis. It also reduces triglyceride levels through an as yet unproven mechanism. Dose-dependent reductions in total cholesterol, low density lipoprotein (LDL)-cholesterol and triglyceride levels have been observed with atorvastatin in patients with hypercholesterolaemia and in patients with hypertriglyceridaemia. In large trials involving patients with hypercholesterolaemia, atorvastatin produced greater reductions in total cholesterol, LDL-cholesterol, apolipoprotein B and triglyceride levels than lovastatin, pravastatin and simvastatin. In patients with primary hypercholesterolaemia, the combination of atorvastatin and colestipol tended to produce larger reductions in LDL-cholesterol levels and smaller reductions in triglyceride levels than atorvastatin monotherapy. Although atorvastatin induced smaller reductions in triglyceride levels and more modest increases in high density lipoprotein (HDL)-cholesterol levels than either fenofibrate or nicotinic acid in patients with combined hyperlipidaemia, it produced larger reductions in total cholesterol and LDL-cholesterol. As with other HMG-CoA reductase inhibitors, the most frequently reported adverse events associated with atorvastatin are gastrointestinal effects. In comparative trials, atorvastatin had a similar adverse event profile to that of other HMG-CoA reductase inhibitors. Clinical data with atorvastatin are limited at present. However, with its ability to markedly reduce LDL-cholesterol levels, atorvastatin is likely to join other members of its class as a first-line agent for the treatment of patients with hypercholesterolaemia, if changes in lipid levels with atorvastatin convert to reductions in CHD mortality and morbidity. Atorvastatin may be particularly suitable for patients with heterozygous or homozygous familial hypercholesterolaemia because of the marked reductions in LDL-cholesterol experienced with the drug. Additionally, because of its triglyceride-lowering properties, atorvastatin appears to have the potential to become an appropriate treatment for patients with combined hyperlipidaemia or hypertriglyceridaemia.

Anticholesteremic Agents↗

PubMed1997

Fosinopril. A review of its pharmacology and clinical efficacy in the management of heart failure.

Fosinopril is the prodrug of the active diacid ACE inhibitor fosinoprilat. In patients with heart failure, fosinopril reduces pulmonary capillary wedge pressure, mean arterial blood pressure, mean right atrial pressure and heart rate, and increases stroke volume index and cardiac index. The drug has compensatory dual elimination routes via renal and hepatic systems and accumulates to a lesser extent than enalapril and lisinopril in patients with chronic renal insufficiency with or without heart failure. Comparative studies of 3 or 6 months' duration with fosinopril 10 to 40 mg/day have demonstrated clinical efficacy significantly superior to that of placebo in patients with heart failure [mostly New York Heart Association (NYHA) functional class II or III]. Fosinopril treatment consistently increased exercise duration and improved heart failure symptoms in these patients. Significantly fewer fosinopril than placebo recipients withdrew or were hospitalised because of worsening heart failure. Additionally, significantly more fosinopril than placebo recipients showed improvement, and fewer patients had deteriorated, in terms of NYHA functional class. Fosinopril and enalapril showed similar clinical efficacy over 6 and 12 months' treatment in patients with NYHA functional class II to IV heart failure. As yet, there are no data showing a mortality benefit with fosinopril. Fosinopril was well tolerated in clinical trials in patients with heart failure. Dizziness (11.9 vs 5.4% for placebo), cough (9.7 vs 5.1%) and hypotension (4.4 vs 0.8%) were the most commonly reported adverse events. In 6- or 12-month comparative studies, fosinopril therapy was associated with a lower incidence of dizziness and hypotension, but a higher incidence of vertigo, than enalapril therapy. 0.8% of patients discontinued the drug because of cough, which occurred to a similar extent with fosinopril and enalapril. Thus, based on available clinical evidence, fosinopril is an effective and well tolerated option for the management of patients with heart failure. Although clinical data are limited, fosinopril may be especially useful in patients with renal or hepatic impairment.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1997

Salmeterol. A review of its pharmacological properties and clinical efficacy in the management of children with asthma.

Salmeterol xinafoate is a selective beta 2-adrenoceptor agonist indicated for the maintenance treatment of adults and children with asthma. When administered as a dry powder or aerosol, salmeterol produces bronchodilation for at least 12 hours and protects against methacholine and exercise-induced bronchoconstriction. Salmeterol is not recommended for the treatment of acute exacerbations of asthma. Recent clinical studies have demonstrated the efficacy and tolerability of inhaled salmeterol in the management of asthma in children. Salmeterol improved symptom control and lung function more effectively than placebo or regularly administered salbutamol. In children who were symptomatic despite regular inhaled corticosteroid therapy, the addition of salmeterol to treatment produced a significant improvement in morning and evening peak expiratory flow and forced expiratory volume in 1 second, and a significant reduction in the incidence of asthma exacerbations compared with placebo. Notably, the long duration of action of salmeterol makes it particularly suitable for the prevention of nocturnal asthma symptoms and exercise-induced asthma (EIA) in children. Current data suggest that salmeterol should not be used as a substitute for corticosteroid therapy in children, but rather as an adjunct to therapy. Thus, salmeterol may be a suitable adjunct to therapy in children with asthma receiving inhaled corticosteroids. In addition, salmeterol also has a potentially important role in the prevention of EIA and nocturnal asthma symptoms.

Adrenal Cortex Hormones↗

PubMed1997

Insulin lispro: a review of its pharmacological properties and therapeutic use in the management of diabetes mellitus.

Insulin lispro, a recombinant insulin analogue, is identical to human insulin except for the transposition of proline and lysine at positions 28 and 29 in the C-terminus of the B chain. The resultant reduced capacity for self-association in solution translates into more rapid absorption of insulin lispro than human regular insulin from subcutaneous sites. Maximum insulin concentrations are higher and are reached earlier with insulin lispro than with human regular insulin, and insulin concentrations return to baseline values more quickly with insulin lispro; consequently, insulin lispro has a more rapid onset and a shorter duration of glucose-lowering activity. These pharmacological properties provided the rationale for comparative clinical trials of subcutaneous insulin lispro (administered within 15 minutes before meals, preferably immediately before meals) and subcutaneous human regular insulin (administered 20 to 45 minutes before meals) in patients with type 1 diabetes (insulin-dependent diabetes mellitus) or type 2 diabetes (non-insulin-dependent diabetes mellitus) requiring premeal insulin therapy plus basal insulin therapy. Available clinical trials are well designed and results suggest that 1- and 2-hour postprandial blood glucose levels with insulin lispro are similar to or lower than those with human regular insulin; 1- and 2-hourpostprandial glucose excursions are similar to or less pronounced than those with human regular insulin. Glycated haemoglobin A values were generally similar with both agents. Continuous subcutaneous insulin infusion was associated with greater improvements in postprandial blood glucose levels and glycated haemoglobin A1 values with insulin lispro than with human regular insulin. Confirmatory data are required. The incidence of hypoglycaemia with insulin lispro was similar to or lower than that with human regular insulin. In particular insulin lispro appears to be associated with a lower incidence of night-time and severe hypoglycaemic episodes. Evidence also suggests that patients perceive their quality of life to be improved with insulin lispro compared with human regular insulin, and that satisfaction with treatment is greater with the insulin analogue. Thus, in patients with type 1 or 2 diabetes requiring premeal insulin therapy, insulin lispro appears to provide greater postprandial glycaemic control than human regular insulin without increasing the risk of hypoglycaemia. Furthermore, the reduced injection-meal interval with this agent offers greater convenience for the patient than regular human insulin. If longer term clinical experience supports these promising results it is likely that insulin lispro will offer important advantages over human regular insulin.

Amino Acid Sequence↗

PubMed1997

Simvastatin. A reappraisal of its cost effectiveness in dyslipidaemia and coronary heart disease.

The Scandinavian Simvastatin Survival Study (4S) has confirmed the link between the cholesterol-reducing effects of simvastatin and improved survival in patients with hypercholesterolaemia and pre-existing coronary heart disease (CHD). Pharmacoeconomic analyses of the 4S trial, using prospectively collected data for cost-generating events, demonstrate that the cost per year of life saved for simvastatin in such patients falls within the range considered cost effective. Reductions in resource utilisation costs (numbers of hospitalisations and revascularisation procedures) largely offset the acquisition cost of long term simvastatin treatment in the US. Models of primary prevention incorporating epidemiological data to predict CHD events generally suffer from deficiencies in the methods and assumptions used, and no firm conclusions can be made at present regarding relative cost effectiveness of the drugs studied, including simvastatin. It is generally agreed that cost effectiveness will improve in patients with higher absolute risk of CHD. In summary, simvastatin has been shown in a major clinical trial and its companion economic analyses to reduce mortality and to be cost effective in patients with hypercholesterolaemia and existing CHD. As is the case for others of its class, its cost-effectiveness ratio in primary prevention remains to be ascertained. This issue aside, simvastatin is a rational choice of cholesterol-lowering agent in secondary prevention whose use can be justified on an economic basis.

Coronary Disease↗

PubMed1996

Intranasal salcatonin (salmon calcitonin). A review of its pharmacological properties and role in the management of postmenopausal osteoporosis.

Osteoporosis is a common problem among postmenopausal women and is associated with significant morbidity, mortality and costs primarily resulting from osteoporotic fractures. Salcatonin (salmon calcitonin) inhibits osteoclastic bone resorption and is approximately 40 to 50 times more potent than human calcitonin. In most randomised trials in which intranasal salcatonin (usually 50 to 200 IU/day plus oral calcium supplements) was administered for 1 to 5 years to postmenopausal women for prevention of osteoporosis, bone mineral density or content of the lumbar spine increased by approximately 1 to 3% from baseline. In contrast, postmenopausal women receiving only oral calcium supplements typically had reductions in bone mineral density or content of about 3 to 6%. The difference between treatment groups was statistically significant in essentially all studies. Although changes in bone mineral density or content were broadly similar in studies of postmenopausal women with established osteoporosis to those in postmenopausal women receiving therapy for prevention of the disease, studies in women with established osteoporosis did not usually demonstrate statistically significant differences between treatment groups. Also in postmenopausal women with established osteoporosis, intranasal salcatonin reduced pain and/or analgesic consumption in some trials and, in a limited number of studies of relatively short duration (i.e. < or = 2 years), the incidence of osteoporotic fractures. A large multicentre 5-year study with adequate statistical power to confirm the effect of intranasal salcatonin on reducing osteoporotic fracture rates in postmenopausal women is currently under way. The intranasal formulation of salcatonin offers a more convenient and better tolerated alternative to the parenteral formulation of the drug which is administered by regular subcutaneous or intramuscular injections. Adverse events associated with the intranasal formulation are generally mild and transient, usually involving local reactions such as nasal discomfort, rhinorrhoea or rhinitis. Thus, for postmenopausal women unable or unwilling to tolerate long term hormone replacement therapy, intranasal salcatonin is an attractive alternative for the management of osteoporosis.

Administration, Intranasal↗

PubMed1996

Clarithromycin and omeprazole as helicobacter pylori eradication therapy in patients with H. pylori-associated gastric disorders.

Helicobacter pylori is susceptible to many antibacterial drugs in vitro but has proved difficult to eradicate in vivo. The macrolide clarithromycin has good activity against H. pylori in vitro and has demonstrated the highest eradication rate for any antibacterial monotherapy in vivo. However, it is clear that antibacterial monotherapy is not a sufficiently effective treatment for patients with H. pylori infection. The suggestion that high intragastric acidity impairs the action of antibacterial drugs led to the evaluation of combination H. pylori eradication regimens including H+,K+-ATPase inhibitors and antibacterial drug(s) with or without bismuth compounds. Noncomparative studies evaluating the efficacy of dual therapy with clarithromycin plus omeprazole in patients with H. pylori infection have reported eradication rates of between 58 and 83% > or = 4-weeks after therapy. In comparative studies, clarithromycin plus omeprazole was at least as effective as amoxicillin plus omeprazole. However, direct comparisons have shown that eradication rates achieved by dual therapy are not as high as those achieved by triple therapy. Indeed, triple therapy with clarithromycin plus omeprazole in combination with amoxicillin or a nitroimidazole has achieved eradication rates of up to 100%. Although 14-day triple drug regimes were initially considered necessary for effective eradication, it now seems clear that 7-day regimes are equally effective. Factors known to influence response to H. pylori eradication therapy include bacterial resistance and patient compliance. A review of 4 studies evaluating the efficacy of dual eradication therapy with clarithromycin plus omeprazole reported an overall incidence of adverse events (patient or investigator reported, whether related to treatment or not) of 45%. The most common adverse event was taste disturbance (an adverse event commonly reported during the development of clarithromycin); nausea, headache, diarrhoea, vomiting and abdominal pain occurred less frequently. Although dual therapy might be expected to cause fewer adverse events than triple therapy this has not been the case in direct comparisons conducted to date. Thus, although clarithromycin plus omeprazole is associated with an H. pylori eradication rate of approximately 70%, 1 week of triple therapy with these 2 drugs together with amoxicillin or a nitroimidazole, which eradicates the organism in approximately 90% of cases, may represent optimal H. pylori eradication therapy.

Anti-Bacterial Agents↗

PubMed1996

Fosinopril: a reappraisal of its pharmacology and therapeutic efficacy in essential hypertension.

Fosinopril is a phosphinic acid derivative which undergoes rapid hydrolysis after oral administration to the active diacid ACE inhibitor fosinoprilat. Cardiotropic effects have been associated with the drug, and the compensatory dual elimination route of fosinopril via renal and hepatic systems offers an opportunity for ACE inhibitor treatment of hypertension in patients with renal or hepatic impairment. Comparative trials of monotherapy with fosinopril 10 to 40 mg/day have demonstrated antihypertensive efficacy equivalent to that of sustained release nifedipine 40 mg/day, hydrochlorothiazide 25 to 50 mg/day, enalapril 5 to 10 mg/day amlodipine 5 to 10 mg/day and sustained release verapamil 240 to 480 mg/day, and superior to that of isradipine 5 mg/day. The efficacy of combination therapy with fosinopril 10 to 20 mg/day and hydrochlorothiazide 12.5 mg/day was significantly superior to that of hydrochlorothiazide alone, tended to be superior to that of fosinopril 20 mg/day alone and was similar to that of sustained release nifedipine 40 mg/day alone. The combination of fosinopril/chlorthalidone 20 to 40/25 mg/day was as effective as propranolol/chlorthalidone 80 to 160/25 mg/day. The incidence of adverse effects associated with fosinopril is low, and cough may possibly occur less often with this drug than with other ACE inhibitors. Fosinopril thus offers an effective and well tolerated option for the treatment of hypertension in adult and elderly patients, including those with renal or hepatic impairment.

Adult↗

PubMed1996

Reteplase. A review of its pharmacological properties and clinical efficacy in the management of acute myocardial infarction.

Reteplase (BM 06.022; r-PA) is a recombinant peptide which consists of the kringle 2 and protease domains of human tissue-type plasminogen activator. It has been developed as a thrombolytic treatment for acute myocardial infarction (AMI). The half-life of reteplase allows administration as a double-bolus injection (second injection given 30 minutes after the first) rather than by the prolonged and, in some cases, more complex intravenous infusion regimens that are required for most other thrombolytic agents. Reteplase produced rapid and effective coronary artery thrombolysis in a number of dose-finding and comparative studies. Double-bolus administration of reteplase 10U + 10U produced significantly higher coronary artery patency rates than accelerated alteplase (100mg as a 1.5-hour infusion) in patients with AMI in the RAPID-II study. The 10U + 10U reteplase regimen produced a 35-day survival rate at least equivalent to that seen with a 1-hour infusion of streptokinase 1.5 million units in 5986 patients in the INJECT study, which was designed to demonstrate equivalence between treatments. As with other thrombolytics, bleeding was the most common adverse event seen in reteplase recipients. No significant differences in the overall risk of haemorrhage were observed between reteplase and either accelerated alteplase or standard streptokinase treatment in clinical trials. The risk of stroke in reteplase recipients appears to be similar to that for other thrombolytic agents [1.2% incidence in 3288 patients treated with reteplase 10U + 10U in clinical trials (0.76% for haemorrhagic stroke)], although accurate statistical assessment of the relative risk is not possible for the data available to date. Thus, reteplase is an effective thrombolytic agent which can be administered as a double-bolus injection regimen rather than as a prolonged infusion. Together with acquisition cost and general pharmacoeconomic data (which are not yet available), the results of GUSTO-III (a trial comparing double-bolus reteplase with accelerated alteplase in 15 000 patients) will have a major influence on the pattern of use of reteplase. In the meantime, data from the available clinical trials suggest that reteplase is a fast-acting and effective thrombolytic treatment for patients with AMI.

Animals↗

PubMed1996

Tamsulosin. A review of its pharmacological properties and therapeutic potential in the management of symptomatic benign prostatic hyperplasia.

Tamsulosin is the first subtype-selective (alpha IA) alpha 1 adrenoceptor antagonist with specificity for prostatic alpha 1 adrenoceptors (alpha 1A adrenoceptors are thought to be involved in prostatic smooth muscle contraction) to become available for the treatment of patients with symptomatic benign prostatic hyperplasia (BPH). With tamsulosin, the incidence of adverse events commonly associated with alpha 1 adrenoceptor antagonism is similar to that with placebo (except for ejaculation disorders) and alfuzosin. The incidence of other adverse events is similar with tamsulosin and placebo. Furthermore, blood pressure and heart rate are not significantly affected by tamsulosin in patients with symptomatic BPH. In contrast, blood pressure is significantly reduced by alfuzosin compared with tamsulosin. Tamsulosin is available as a controlled release formulation suitable for once daily administration; dose titration is not required. The overall efficacy of this agent administered at a dosage of 0.1 to 0.4 mg/day in Japan, 0.4 mg/day in Europe and 0.4 to 0.8 mg/day in the US to patients with symptomatic BPH is greater than that of placebo was similar to that of alfuzosin or prazosin in the 2 available studies. Efficacy was primarily assessed by changes in maximum and average urinary flow rates, residual urinary volume and total symptom scores. Improvements in these parameters in short term trials (< or = 13 weeks) appear to be maintained in the longer term (< or = 60 weeks). Quality-of-life effects also appear to be similar with tamsulosin and alfuzosin. In conclusion, the pharmacodynamic properties of this agent appear to translate into tolerability and administration advantages over other alpha 1 adrenoceptor antagonists. If future investigations confirm its promising efficacy and tolerability, tamsulosin will be ideally placed as a valuable therapeutic option for patients with symptomatic BPH and in patients awaiting surgery or in those unable to undergo surgery.

Adrenergic alpha-Agonists↗

PubMed1995

Nilvadipine. A review of its pharmacodynamic and pharmacokinetic properties, therapeutic use in hypertension and potential in cerebrovascular disease and angina.

Nilvadipine, a calcium antagonist of the dihydropyridine class, selectively blocks calcium channels in vascular smooth muscle. Compared with nifedipine, the prototype of the dihydropyridines, nilvadipine has a longer duration of action. The antihypertensive efficacy of nilvadipine appears to be comparable with that of nicardipine and nitrendipine, enalapril and captopril and hydrochlorothiazide/triamterene, although further clinical experience is required to establish the claimed advantages nilvadipine may have over the other dihydropyridine derivatives currently used to treat hypertension. Preliminary studies suggest that nilvadipine may also be useful in the treatment of patients with stable exertional or variant angina. Studies conducted in Japan indicate that nilvadipine improves symptoms resulting from cerebral infarction in some patients, but further comparative studies are required to confirm these results. The tolerability of nilvadipine appears to be comparable with that of nicardipine and better than that of nifedipine with respect to flushes, oedema and liver function abnormalities. As is typical of calcium antagonists, there is no evidence of tolerance to the antihypertensive effects of nilvadipine. The drug is equally effective in treating hypertension in elderly and younger patients and does not appear to adversely affect glucose or lipid metabolism. Thus, provided its apparently good tolerability is confirmed by wider clinical experience, it should be a suitable alternative to other calcium antagonists when used alone or in conjunction with other drugs for the majority of patients with mild to moderate hypertension.

Aging↗

PubMed1995

Estramustine phosphate sodium. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in prostate cancer.

Estramustine phosphate sodium (estramustine phosphate), a unique antitumour agent, is selectively taken up by prostate cells and exerts antineoplastic effects by interfering with microtubule of dynamics and by reducing plasma levels of testosterone. In noncomparative studies of estramustine phosphate in patients with hormone-refractory disease, objective response rates ranging from 19 to 69% have been reported. Preliminary clinical investigations indicate that combining estramustine phosphate with vinblastine, etoposide or paclitaxel improves objective response rates over single-agent treatment, although no survival benefit over single-agent treatment has been demonstrated to date. In comparative studies, estramustine phosphate produces similar objective response rates to conventional antineoplastic agents in patients with hormone-refractory prostate cancer. In previously untreated patients with advanced metastatic hormone-responsive prostate cancer, objective responses are achieved in approximately 80% of patients. Estramustine phosphate appears to be at least as effective as estrogen or flutamide therapy in these patients. Nausea and vomiting are the most frequently observed adverse effects of treatment with estramustine phosphate. While these symptoms are usually mild to moderate in nature, they may occasionally be more troublesome to the patient and necessitate withdrawal of treatment. Cardiovascular complications are a more serious, though less frequently encountered, adverse effect of the drug. However, these complications may be avoided by careful patient selection and prophylactic treatment measures. Unlike some other antineoplastic agents, estramustine phosphate is rarely associated with myelosuppression. In addition to producing similar objective response rates to other established agents, estramustine phosphate improves the subjective status of many patients and has been shown to reduce the intensity of pain and improve the performance status of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

PubMed1995

Captopril. A review of its pharmacology and therapeutic efficacy after myocardial infarction and in ischaemic heart disease.

Captopril is an angiotensin converting enzyme (ACE) inhibitor which has been used extensively in the treatment of patients with hypertension and congestive heart failure. In recent years, animal and human studies have demonstrated that captopril attenuates left ventricular remodelling (structural changes and enlargement) which occurs after myocardial infarction, and can lead to left ventricular dysfunction and increased risk of death. Subsequently, large clinical trials have shown reduced mortality and morbidity in patients receiving captopril or other ACE inhibitors (in addition to standard therapy) after acute myocardial infarction. Results of the 4th International Study of Infarct Survival (ISIS-4), a factorial trial which randomised more than 58,000 patients, indicate that captopril, initiated within 24 hours of myocardial infarction and titrated to 50 mg twice daily for 1 month, significantly reduced overall mortality at 5 weeks after randomisation compared with placebo (7.19 vs 7.69%; p = 0.02). This corresponds to an absolute benefit of 5 lives saved per 1000 patients treated with captopril over this period. Furthermore, the survival advantage appeared to be maintained at 1 year post-infarction. Although both high- and low-risk patients were included in the ISIS-4 trial, the greatest survival benefit of captopril occurred in patients at greater risk of mortality, such as those with signs of heart failure or previous infarction. A significant relative reduction in overall mortality of 19% was seen in patients with left ventricular dysfunction (but not overt heart failure or ongoing ischaemia) after acute myocardial infarction treated with captopril in the Survival and Ventricular Enlargement (SAVE) study. Captopril was started within 3 to 16 days after myocardial infarction and titrated to 50 mg 3 times daily for a mean duration of 42 months. In this high-risk group of patients, approximately 40 to 50 lives were saved per 1000 patients treated with captopril over this period. This was similar to survival benefits demonstrated with other ACE inhibitors following acute myocardial infarction in high-risk patients in other large randomised trials. Cost-effectiveness analyses using data from the SAVE trial indicate that captopril compares favourably with other interventions used for survivors of myocardial infarction. In general, captopril was well tolerated by patients in SAVE, ISIS-4 and other studies in this clinical setting. Thus, when added to standard therapy after acute myocardial infarction, early or late administration of captopril improves survival and reduces cardiovascular morbidity, particularly in selected high-risk patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗