Pion absorption on 3He at T pi =62.5 and 82.8 MeV.
Explore the source record for details and available documents.
Journal Article↗
Biomedical subjects
J Vincent
Publications and source records attributed to J Vincent.
The pharmacokinetics of doxazosin in elderly normotensives.
The pharmacokinetics of doxazosin were studied in 12 normotensive elderly volunteers aged 62-89 years. There was marked inter-individual variability in all the parameters derived but the disposition of doxazosin was similar in both sexes. These results were compared to those of a group of young normotensive volunteers aged 23-39 years studied previously under comparable conditions. The volume of distribution increased significantly with age although the bioavailability and clearance were not significantly different in the two groups. These results suggest that age is unlikely to influence the disposition of doxazosin to a clinically significant extent.
Administration, Oral↗
Clinical pharmacological studies with doxazosin.
The clinical pharmacology of doxazosin is reviewed from studies in normotensive young (21-39 years) and elderly (62-89 years) subjects following oral (2 mg) and intravenous (1 mg) administration. In young subjects the mean bioavailability was 65% and the mean terminal elimination half-lives were 9.5 and 10.5 h following acute intravenous and oral administration respectively. These parameters were similar in the elderly with bioavailability of 69% and half-lives of 8.8 and 11.9 h. The apparent volume of distribution and clearance were significantly higher in elderly (1.7 1 kg-1 and 140 ml min-1) than in young subjects (1.01 kg-1 and 83 ml min-1). In both groups blood pressure reductions were most marked in the standing position and the maximum effect did not occur until 5-6 h, even after intravenous administration. The blood pressure reduction produced by doxazosin was associated in the young with a significant increase in heart rate to 108 beats min-1 (placebo, 82 beats min-1) but this increase was significantly attenuated in the elderly at 91 beats min-1 (placebo, 77 beats min-1). Pressor response studies in the young subjects confirmed the alpha 1-adrenoceptor antagonist activity of doxazosin with significant rightward shifts of the dose-response curves for the selective alpha 1-adrenoceptor agonist phenylephrine. Using the technique of concentration-effect analysis, both the degree of alpha 1-adrenoceptor antagonism and the hypotensive effect can be correlated with the concentration of doxazosin in the 'effect compartment'.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenergic alpha-Antagonists↗
Racial differences in drug responses--a comparative study of trimazosin and alpha 1-adrenoceptor responses in normotensive Caucasians and West Africans.
The possible racial differences in alpha 1-adrenoceptor responsiveness and the blood pressure and heart rate responses following alpha 1-adrenoceptor antagonism with trimazosin have been investigated in matched groups of six Caucasians and six Nigerians. There were no significant differences between the racial groups in the blood pressure and heart rate responses to oral (200 mg) and intravenous (100 mg) trimazosin. alpha 1-adrenoceptor responsiveness was similar in both groups after placebo and following both active treatments. There were only minor pharmacokinetic differences with the Caucasians having a larger volume of distribution, and a longer terminal elimination half-life for the metabolite, 1-hydroxy-trimazosin. These results suggest a similarity in peripheral vascular alpha 1-adrenoceptor mechanisms and show no major significant racial differences in the pharmacokinetics and pharmacodynamics of trimazosin.
Adult↗
The cardiovascular effects of trimazosin and prazosin in the rabbit.
The cardiovascular effects of trimazosin, a quinazoline derivative similar in structure to prazosin, were investigated and compared with prazosin in the rabbit. Radioligand binding to cerebral membranes showed that trimazosin has roughly 100-fold less affinity for the alpha 1-adrenoceptor. This was further supported by its lower pA2 derived from phenylephrine contractile responses in isolated thoracic aorta preparations. Trimazosin is less extensively distributed and has a lower clearance from whole blood than prazosin although their whole blood elimination half-lives are comparable. In addition, although it is a less potent alpha 1-adrenoceptor antagonist in vivo, its peripheral vascular depressor effect tends to be greater than prazosin. Trimazosin at the dose used and under the conditions of study did not reverse the peripheral pressor effect of angiotensin II or B-HT920 but at higher concentrations, unlike prazosin, it relaxed the K+ contracted thoracic aorta. In addition, following pharmacological autonomic blockade and treatment with prazosin in vivo, trimazosin caused a further depressor response. A similar though shorter lasting non-alpha 1-receptor mediated action was also observed with prazosin. 1-Hydroxytrimazosin (CP23445), the major metabolite of trimazosin in man, showed little affinity for either the alpha 1- or alpha 2-adrenoceptor from radioligand binding studies. In addition to alpha 1-adrenoceptor antagonism, trimazosin may exert an additional direct vasodilator effect in rabbits.
Adrenergic alpha-Antagonists↗
Clinical pharmacology and therapeutic role of prazosin and related alpha-adrenoceptor antagonists.
Prazosin is a quinazoline derivative, which lowers blood pressure by selective alpha-1-receptor antagonism. It has been found that, for similar decreases in blood pressure, prazosin causes less reflex tachycardia than non-selective alpha blockers or direct vasodilators, and that it is as efficacious as other conventional antihypertensive agents (alpha-methyldopa, hydralazine, beta blockers, etc.) in controlling severe hypertension. Prazosin causes a dose-related decrease in blood pressure in humans; twice-daily dosing is sufficient for 24-hour blood pressure control. Prazosin in combination with other drugs has also been shown to control blood pressure effectively, and it has been associated with relatively few side effects. Other agents with selective alpha-1-receptor-blocking activity are under investigation: these include doxazosin, trimazosin, terazosin, and alfuzosin.
Adrenergic alpha-Antagonists↗
[Role of ketotifen in the immunotherapy of atopic asthmatics].
The place of KETOTIFEN in the immunotherapy for atopic asthmatic patients (confirmed by cutaneous test and RAST) has been determined by a study conducted on 48 patients divided into two randomly selected parallel groups. Group one received 2 mg/d. Ketotifen treatment together with a desensitization. Group two: only had a specific hyposensitization treatment. The study was contacted over a period of 18 weeks and showed that the number of local reaction in group one was half as numerous as in group two. In conclusion, KETOTIFEN may be practised an immunotherapy to house dust and acarians, without any difficulties, and with a fast progression.
Adolescent↗
[Spontaneous regression of pulmonary images interpreted as metastases of kidney cancer. Apropos of 2 cases].
The authors report two cases of spontaneous regression of pulmonary metastases from hypernephroma; this is an exceptional event that occurs in 0.8% of metastasized renal carcinomas; spontaneous regression in all cancers as a group occurs in 0.0014% of cases. The theories postulated up till now to explain this phenomenon are unconvincing. The authors suggest the possibility of tumorous emboli: this event, that occurs mainly in those carcinomas with a propensity for extension to veins, such as renal carcinoma, choriocarcinoma, hepatoma and liver metastases, does not necessarily give rise to a metastasis. The evidence that leads to advocate nephrectomy in metastasized renal carcinoma are recalled and discussed.
Carcinoma, Renal Cell↗
The effect of cimetidine on the pharmacokinetics, pharmacodynamics and alpha 1-adrenoceptor responsiveness of trimazosin in man.
The effect of cimetidine treatment on the pharmacokinetics and pharmacodynamics of single doses of trimazosin was studied in 6 normotensive volunteers. Co-administration of cimetidine did not significantly affect the overall magnitude of the hypotensive effect of trimazosin. However, the time profile of the blood pressure response was significantly modified particularly with attenuation of the delayed component. Co-administration of cimetidine did not alter alpha 1-adrenoceptor antagonism by trimazosin. There was no significant change in the clearance and volume of distribution of trimazosin but there was a significant reduction in the area under the concentration-time curve for the metabolite, 1-hydroxy-trimazosin. The reduction in the AUC of 1-hydroxy-trimazosin corresponds in time with the attenuation of the delayed hypotensive response. This is consistent with the suggestion that the delayed hypotensive response is related to an active metabolite, probably 1-hydroxytrimazosin.
Adult↗
Pharmacokinetic and pharmacodynamic studies with two alpha-adrenoceptor antagonists, doxazosin and prazosin in the rabbit.
The cardiovascular effects of doxazosin, a quinazoline derivative related to prasozin were investigated and compared to prazosin in the rabbit. Radioligand binding studies using rabbit cerebral membranes showed that both doxazosin and prazosin were roughly equipotent at displacing [3H]-prazosin from specific binding sites. However, the lower pA2 value for doxazosin at alpha 1-adrenoceptors in isolated thoracic aorta preparations suggests a lower potency compared to prazosin. The dose-related pressor effects of intravenous phenylephrine were used to assess vascular alpha 1-adrenoceptor antagonism in vivo. There was a close agreement between alpha 1-adrenoceptor antagonist potency and maximum hypotensive effects with both doxazosin and prazosin. The alpha 1-adrenoceptor antagonist effects of doxazosin were more prolonged than those of prazosin. Studies using either radioligand binding or pressor responses to B-HT 920 showed that doxazosin did not show any significant affinity for the alpha 2-adrenoceptor. Similarly, no direct vasodilator effects were observed either in animals administered angiotensin II or in isolated thoracic aorta spiral strip preparations contracted with potassium. Doxazosin has a longer terminal elimination half-life than prazosin. The pharmacokinetics of doxazosin were linear over the dose range examined. Following pharmacological 'autonomic blockade' and treatment with prazosin, doxazosin did not cause any further fall in blood pressure. These observations suggest that doxazosin, like prazosin, appears to exert its hypotensive action through alpha 1-adrenoceptor antagonism. The prolonged fall in blood pressure and well sustained alpha 1-adrenoceptor antagonism after doxazosin raise the possibility of an active metabolite which also has alpha 1-adrenoceptor blocking properties.
Adrenergic alpha-Antagonists↗
The pharmacokinetics of bucindolol and its major metabolite in essential hypertension.
The pharmacokinetics of bucindolol and its major metabolite, 5-hydroxybucindolol, have been studied in eight patients with mild/moderate hypertension. The mean terminal elimination half-life of bucindolol following acute oral dosing was 8.0 +/- 4.5 h, while the elimination half-life of the metabolite was 0.15 +/- 0.13 h. Because of the large intraindividual variation in the pharmacokinetics of the drug and metabolite, no significant differences in the kinetics following acute or chronic dosing were seen. There was very wide interindividual variability in the pharmacokinetics of bucindolol and 5-hydroxybucindolol, and large interindividual differences in the metabolic profiles as assessed by the areas under drug and metabolite concentration-time curves. This latter observation might be associated with a genetic polymorphism of drug metabolism.
Adult↗
Bucindolol in essential hypertension.
The effects of bucindolol a new nonselective beta blocker were studied after short-term dosing and for up to six months in eight patients with essential hypertension. Bucindolol 100 mg acutely lowered supine and erect systolic and diastolic pressure without orthostatic features and without increases or decreases in heart rate. Plasma noradrenaline increased, but plasma renin activity fell. Long-term dosing of 100-400 mg/day led to modest decreases in blood pressure. The duration of the hypotensive effect after multiple dosing ranged from six to ten hours. After long-term dosing there was evidence of marked nonselective beta blockade but not of alpha 1 blockade from the responses to intravenous isoprenaline and phenylephrine respectively. In six out of eight patients the plasma creatinine phosphokinase rose transiently above the normal range. The increase appeared to be of muscle origin and was associated with myalgia in one patient. Bucindolol is a nonselective beta blocker, possibly with other vasodilator properties. These do not appear to be mediated by alpha blockade.
Adrenergic beta-Antagonists↗
The alpha adrenoceptor antagonist properties of idazoxan in normal subjects.
The imidazoline derivative idazoxan, which has been shown to be a potent, selective alpha 2-adrenoceptor antagonist, was injected intravenously to eight men with normotension. There was a transient small increase in blood pressure and a decrease in heart rate within 20 min of injection, with a slight increase in plasma norepinephrine levels. These effects are consistent with antagonism of prejunctional alpha 2-adrenoceptors. In response to infusions of the relatively selective alpha 2-adrenoceptor agonist alpha-methylnorepinephrine, the pressor dose-response curve shifted to the right with idazoxan. These data provide evidence for receptors with alpha 2-adrenoceptor characteristics on resistance vessels in man. In vitro platelet aggregation studies provide further evidence of selective alpha 2-adrenoceptor antagonism by idazoxan, with greater potency and affinity than alpha-yohimbine. These observations are consistent with both pre- and postjunctional peripheral alpha 2-adrenoceptors in man and provide further support that idazoxan is a selective alpha 2-adrenoceptor antagonist.
Adrenergic alpha-Antagonists↗
Trimazosin in normotensive subjects.
Oral and intravenous trimazosin, a quinazoline derivative, resulted in a significant reduction in blood pressure of normal subjects, particularly when the subjects rose from a supine position to standing. This hypotensive effect was maximal between 4 and 6 hr after dosing and was accompanied by a significant increase in heart rate. The responses to intravenous infusions of phenylephrine indicated that trimazosin had significant, selective, peripheral alpha 1-antagonist properties. Kinetic analysis showed oral bioavailability of 63%, a clearance rate of 66 ml/min, and a terminal elimination t1/2 of approximately 3 hr. The correlation between drug levels and hypotensive effect was significantly improved by inclusion of the concentrations of trimazosin's major metabolite, 1-hydroxy-trimazosin (CP 23445), particularly for the period of maximum effect. Our data show that acute administration of trimazosin is associated with a fall in blood pressure, an increase in heart rate, and a significant degree of alpha 1-antagonism and that the overall hypotensive effect may in part be mediated by an active metabolite. It seems 1-hydroxy-trimazosin is a likely candidate for this role, but it is not clear whether this metabolite also has significant alpha-adrenoceptor antagonist properties.
Absorption↗
False aneurysm of a left ventricular stab wound for left vent during extracorporeal circulation--case report.
The left ventricular apical stab wound had been used for instrumentation and venting since 1923. Despite the frequent use of this myotomy, only a few complications and even fewer operative corrections have been reported. One of these complications is a false aneurysm, its reported etiology being infection or suture failure. In this case we describe a case of left ventricular false aneurysm formation most likely due to suddenly increased intrathoracic pressure, 6 months after coronary artery bypass grafting. Evidence for likely causes, such as infection, suture failure or poor myocardial quality, was not found. As etiology we suspect an acute elevation of ventricular pressure superimposed upon poorly regenerated myocardium.
Coronary Artery Bypass↗
[Intrarenal localized renorenal collaterals in dogs after ligation of the principal arterial branch].
In 7 kidneys of 6 dogs one of the main stem of the renal artery was ligated. The development of the renorenal collaterals could be followed in 5, as two dogs died after the operation. In all cases intrarenal collaterals could be demonstrated, even in the postoperative dead dogs. The vessels responsible for the collateral circulation are performed interarterial anastomoses, belonging to the extra-glomerular arterial system. From the results of these and former experimental studies it can be concluded, that the renal artery of the dog when entering the renal sinus cannot be regarded as an anatomic, but at most as a functional end artery.
Animals↗
Influence of selenium sulphide on hair lipids in seborrhoea oleosa.
Explore the source record for details and available documents.
Dermatitis, Seborrheic↗
New group of prostaglandin-like compounds in P. acnes.
Explore the source record for details and available documents.
Humans↗