PubMed Health⌕ Search

Biomedical subjects

A Breckenridge

Publications and source records attributed to A Breckenridge.

At least 19 recordsLinked to original sources
PubMed1992

Different vasodilating mechanisms--different peripheral effects?

Many factors, both local and systemic, are known to influence the caliber of peripheral vessels and regional blood flow. Methods of studying limb blood flow and its alteration by disease and drugs present considerable problems. We compared the effects of a series of antihypertensive drugs on limb blood flow and their functional effects in patients with hypertension and peripheral vascular disease. Results from studies with new antihypertensive drugs such as carvedilol are awaited.

Adrenergic beta-Antagonists↗
PubMed1992

Clinical significance of interactions with antifungal agents.

Antifungal drugs act by a variety of mechanisms. Agents such as substituent imidazoles and triazoles, which act by inhibiting the fungal cytochrome P-450-dependent enzyme lanosterol N-demethylase, have the potential to inhibit host cytochrome P-450-dependent drug metabolism. This is discussed with respect to ketoconazole, fluconazole and itraconazole. In contrast, allylamines, which have a different mode of action and a weaker ability to bind to cytochrome P-450, are not expected to inhibit clinical drug oxidation. Inducers of drug metabolism, especially rifampicin, phenobarbitone and phenytoin, may lower plasma (and tissue) concentrations of those antifungals metabolized by mixed function oxidases, with therapeutic consequences.

Antifungal Agents↗
PubMed1992

Double-blind comparison of captopril with nifedipine in hypertension complicated by intermittent claudication.

In a double-blind, crossover trial 12 patients with hypertension and peripheral arterial disease were randomized to three months' treatment with captopril 25-50 mg twice daily or nifedipine SR 20-40 mg twice daily. While both treatments were equally effective at lowering blood pressure, postexercise calf blood flow availability was greater during treatment with captopril (P less than 0.04). This was not reflected in walking capacity assessed by treadmill exercise. The results suggest that both captopril and nifedipine are appropriate antihypertensive agents in patients with peripheral arterial disease.

Blood Pressure↗
PubMed1991

Angiotensin converting enzyme inhibitors and quality of life.

The term quality of life implies more than adverse effects that make treatment intolerable. It is not new but has only relatively recently become a parameter to be measured in patients treated for cardiovascular disease. Lessons can be learned from other conditions in which the Karnovsky Index and the Arthritis Impact Measurement Scale have been used. Several investigators have used questionnaires to assess quality of life during antihypertensive therapy. However, assessment of the effect of angiotensin converting enzyme (ACE) inhibition on quality of life has only been done recently. The largest and best known study, of 625 white men with mild hypertension, reported that patients given captopril showed a significant improvement after 6 months in general well-being, work performance, and those skills associated with cognitive function. No such improvement was found with methyldopa and there was significant worsening in measures associated with depression, sexual dysfunction, and life satisfaction. The propranolol group, while showing improvement in cognitive functioning and social participation, manifested worsening of sexual function and physical symptoms. Diuretic therapy had a greater negative impact on the quality of life of hypertensive patients than captopril, propranolol, or methyldopa alone. Whether these results will be seen in other patient populations, and the pharmacological basis for these results, remains to be determined. As newer agents become available (eg, beta-blockers with ancillary properties, calcium channel blockers with allegedly more selective actions on various vascular beds), comparative studies between these agents and ACE inhibitors old and new are awaited with interest.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Antihypertensive treatment in concomitant peripheral vascular disease: current experience and the potential of carvedilol.

The relative importance of hypertension as a risk factor for peripheral vascular disease is of the same order as coronary artery disease. The design of drug studies in occlusive vascular disease presents several problems. First, investigations must be placebo-controlled and crossover in design. Second, since these patients are very much at risk from other vascular occlusions, length of treatment phase is critical. Third, drug doses are also critical--probably best chosen by titration to similar antihypertensive effect. Fourth, patients must be trained in treadmill procedure. Fifth, measurements of limb blood flow must be accompanied where possible by "functional" assessment, e.g., claudication distance. With respect to the specific problem of low perfusion pressure distal to the blockage of peripheral vasculature, resting blood flow may remain normal, implying compensatory reduction in tone of arteriolar resistance vessels. Thus, regional circulation distal to blockage is sensitive to changes in perfusion pressure. There is the risk of "steal" with vasodilator agents; however, conflict exists in the literature over effects of beta-blockers in this situation. In view of its peripheral hemodynamic profile, the theoretical possibilities with the beta-blocker/vasodilator carvedilol in patients with hypertension and peripheral vascular disease seem extremely rewarding, but remain to be borne out in practice.

Adrenergic beta-Antagonists↗
PubMed1990

Adverse effects of captopril in hospital outpatients with hypertension.

Hypertensive patients prescribed captopril while attending a hospital hypertension clinic were studied, to identify the benefits of the drug, its adverse effects and factors predisposing to them. One hundred and eighty two patients were followed for a mean of 18 months; 24 received captopril alone, and 158 combinations of captopril and other antihypertensive drugs, especially loop diuretics (91/158), or thiazide diuretics (57/158), or other vasodilators (57/158). The mean final dose of captopril was 67 mg/day. Blood pressure (BP) was effectively controlled in 73% of patients (mean fall in systolic BP 29 mmHg, CI 24 to 34, P less than or equal to 0.001; mean fall in diastolic BP 18 mmHg, CI 16 to 20, P less than or equal to 0.001). Blood urea and creatinine rose slightly in all patients (urea by 0.9 mmol/l [13%], CI 0.5-1.3, P less than or equal to 0.001 and creatinine by 9 mumols/l [8%], CI 4-13, P less than or equal to 0.001). Twenty six patients were withdrawn from captopril therapy: 6 because of poor control of their blood pressure, two because it was no longer necessary and 12 (7.7%) because of extrarenal adverse effects--10 for rashes, one each for gastric upset and impotence. Captopril was withdrawn in a further 6 patients, because of deteriorating renal function. Factors discriminating those at risk of renal dysfunction were high doses of captopril, concomitant high dose diuretic therapy and undiagnosed renovascular disease.

Adult↗
PubMed1990

The chemotherapy of onchocerciasis. XIV. Studies with mebendazole citrate.

Twenty patients from an area of vector control in the savannah region of northern Ghana with moderate to heavy infection with Onchocerca volvulus were randomised to receive two priming doses of levamisole 150 mg on two occasions followed either by mebendazole-citrate (500 mg) given daily or twice daily for 14 days. The two dose levels produced a similar effect on skin microfilariae (80-88% reduction) with a very mild systemic clinical reaction: low levels were maintained over 42 weeks. Both regimes were embryotoxic for O. volvulus; an effect which was transient in the single dose group but persisted for more than three months in the twice daily dose group. Mebendazole-citrate appeared to be absorbed more predictably than has been observed previously for mebendazole. The degree of systemic exposure as determined by measurement of AUC (0-24 h) was 2.5 times greater for the twice daily dose as compared to the single dose and this fact was reflected in the efficacy of the two dose regimes against the adult female worms at three months.

Adult↗
PubMed1988

Current controversies in the treatment of hypertension.

Three controversies in the treatment of hypertension are reviewed. The first involves the decision whether to treat mild hypertension. Little consensus currently exists in this area and recent trial evidence is reviewed. Second, the basis of choosing specific drugs is discussed; biochemical profiling has not been overly successful, but demographic profiling and benefit profiling are to be commended. Third, the salt controversy is reviewed. On a population basis, lowering salt intake may be beneficial.

Aging↗
PubMed1988

Serotoninergic mechanisms in hypertension. Focus on the effects of ketanserin.

Aggregating platelets release serotonin, which induces contraction of most vascular smooth muscle by activation of S2-serotoninergic receptors. Serotonin released in the circulation may contribute to the increase in peripheral resistance of hypertension as the responsiveness of blood vessels from hypertensive animals and humans to the vasoconstrictor action of the monoamine is augmented. The data obtained with the new antihypertensive agent ketanserin may favor that interpretation. Ketanserin is a selective S2-serotoninergic antagonist with additional alpha 1-adrenergic blocking properties. In humans, it has a terminal half-life of 12 to 25 hours and is eliminated predominantly by the liver. The hemodynamic profile of ketanserin is that of a vasodilator drug with actions on both resistance and capacitance vessels. On short-term intravenous administration, it lowers blood pressure in hypertensive patients with minimal reflex changes in cardiovascular function. When given orally long term to hypertensive patients, ketanserin causes a sustained reduction in arterial blood pressure, comparable to that obtained with either beta-adrenergic blockers or diuretics. Several studies have shown a greater efficacy in older (greater than 60 years of age) than in younger patients independent of starting pressure. Side effects mainly consist of dizziness, somnolence, and dry mouth, but they are usually not severe. The mechanism underlying the antihypertensive effect of ketanserin is unclear. It cannot be attributed to either S2-serotoninergic or alpha 1-adrenergic blockade alone, but an interaction between the two effects appears to be required.

Humans↗
PubMed1988

Ageing, serotonin and ketanserin.

In both acute and long term clinical studies, the antihypertensive effects of the S2-serotonergic receptor antagonist ketanserin are more marked in the elderly than in younger patients. The acute effect of ketanserin 10mg intravenously was studied in 57 patients between 25 and 90 years and a significant negative correlation was shown between age and the decrease in both systolic and diastolic blood pressure. In longer term studies ketanserin has been compared with metoprolol and hydrochlorothiazide in patients below and above 60 years. Both ketanserin and the diuretic showed greater antihypertensive efficacy in the elderly, whereas the beta-blocker did not. Data from 15 double-blind studies from the ketanserin International Data File confirm the relationship between age and antihypertensive efficacy. With respect to adverse effects of ketanserin, dizziness, somnolence and dryness of the mouth were commoner in younger than older patients. These effects were not the result of smaller dose requirements in the elderly, and there was no obvious pharmacokinetic reason (e.g. alteration in drug clearance) for the difference. Two theoretical possibilities for the differential age effect of ketanserin are advanced. First the smaller effect in the young may be due to activation of homeostatic mechanisms limiting its antihypertensive activity, or second, some selective (undefined) effect operative in the elderly may be responsible. It is known from animal studies that serotonin shows increased vasoconstrictor properties in the presence of extensive atheroma. Antagonism of this effect may account for the greater vasodilator and antihypertensive effect of ketanserin in elderly patients. This, however, is speculative and does not take into account the complex antihypertensive action of ketanserin. The role of serotonin in cardiovascular control is complex. Its effects depend on the species studied, the vascular bed being investigated, the dose used and the experimental conditions employed. Serotonin has central cardiac and peripheral vascular actions relevant to cardiovascular control. In the peripheral vasculature it can produce vasodilatation or vasoconstriction by either direct or indirect mechanisms. If this complexity were not confusing enough, the nomenclature of the receptors on which serotonin acts is under intense current debate, and little uniformity exists as to the terminology to be used. The terms of this review will be very specific.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1988

Age-related effects of angiotensin converting enzyme inhibitors.

In spite of the fact that plasma renin activity declines with age and drugs whose action is mediated via the renin-angiotensin system might be expected to be less effective with increasing age, the limited available data suggest that both captopril and enalapril lower blood pressure in the elderly. The quantity and the quality of data to compare hypotensive effects in the young and elderly leave much to be desired. It might be predicted that adverse effects such as hypotension and exacerbation of preexisting renal failure could pose problems for the use of these drugs in the elderly, but documentation of this is also sparse. Clearly, this area of risk versus benefit of angiotensin converting enzyme (ACE) inhibitors in the elderly requires further study.

Aged↗
PubMed1987

Placebo-controlled comparison of captopril, atenolol, labetalol, and pindolol in hypertension complicated by intermittent claudication.

In a six month placebo-controlled cross-over trial twenty patients with hypertension and peripheral arterial disease were randomised to captopril 25 mg twice daily, atenolol 100 mg once daily, labetalol 200 mg twice daily, or pindolol 10 mg twice daily for one month. Although all treatments were equally effective at lowering blood pressure, pain-free and maximum walking distances on a treadmill were decreased by atenolol, labetalol, and pindolol, but not by captopril. Post-exercise calf blood flow availability was impaired by atenolol, labetalol, and pindolol, but not by captopril. Despite ancillary characteristics of cardioselectivity, intrinsic sympathomimetic activity, or combination with alpha-blockade, beta-blockers seem to impair the lower limb circulation in such patients, whereas captopril seems to preserve it, possibly by maintaining the collateral blood supply.

Atenolol↗