摘要:

Summary—The effects of clonidine on adrenal medulla catecholamines levels were studied in normotensive rats. Intraperitoneal injections (50, 100 μ/kg) of clonidine caused a dose‐dependent decrease in adrenaline content of the gland. This effect was suppressed by denervation of the adrenal medulla,i.e.unilateral section of splanchnic fibers performed 5 days before. These results demonstrate that clonidine decreases the catecholamine content of the adrenal medulla only through a central action. They suggest that the adrenal medulla is involved in the hypotensive effect of cloni

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1987.tb00540.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Summary—Postjunctional renal alpha‐adrenoceptors were studied (1)in vivo, on the renal vasculature of the anaesthetized rat and compared with those in the femoral vasculature, and (2)in vitro, on the renal vascular bed of isolated perfused rat kidney.In vivo, renal and iliac blood flows were measured with an electromagnetic flow meter. The i.v. injection of (‐)‐phenylephrine (1–16 μ/kg) and B‐HT 920 (0.6–600 μ/kg) induced an increase in both renal and iliac vascular resistance, inhibited respectively with prazosin (300 μ/kg) or yohimbine (300 μ/kg). In the kidney, maximum response to B‐HT 920 was equivalent to 64% of that to (‐)‐phenylephrine; on the iliac vasculature, vasoconstrictor responses to both drugs were identical, but only corresponded to 50% of the maximum renal response to (‐)‐phenylephrine. This indicates the predominance of alpha1‐over alpha2‐adrenoceptors in the renal vascular bed.In vitro, on the isolated perfused rat kidney, vasoconstriction was induced by the preferential alpha1‐adrenoceptor agonists [(‐)‐phenylephrine, cirazoline and methoxamine] and the preferential alpha2‐adrenoceptor agonists (alpha‐methylnoradrenaline, dopamine and clonidine) at concentrations at which they lose their selectivity for the alpha2‐adrenoceptors; all responses were antagonised by prazosin but not by yohimbine. B‐HT 920, the selective alpha2‐adrenoceptor agonist, only induced renal vasoconstrictionin v

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1987.tb00541.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Summary—1The action of ergocristine at α‐adrenoceptors was studiedin vivoin the pithed rat, andin vitroon the rat isolated vas deferens.2In the pithed rat, the pressor response to ergocristine was reduced competitively by yohimbine, but not by prazosin.3Ergocristine decreased the tachycardia elicited by electrical stimulation of the cardioaccelerator sympathetic nerves, this effect being antagonized by yohimbine.4At postsynaptic α1‐adrenoceptors, on the vas deferens of the rat, ergocristine antagonized the contraction induced by phenylephrine in a competitive manner (pA2= 7.85).5These results show that vasoconstriction due to ergocristine is mediated by α2‐adrenoceptors and that, in the rat, ergocristine acts as an α2‐adrenoceptors agonist, and an α1‐adrenoce

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1987.tb00542.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Summary—1The effects of verapamil (120 mg orally) and a placebo on arterial pressure, heart rate, PR interval, arterial flows and diameters of the brachial and carotid arteries (pulsed Doppler technique), forearm vascular resistance, and venous diameter and compliance (cutaneous microstrain gauge and plethysmography) have been compared over a 10‐hr period in six healthy volunteers during a double‐blind and cross‐over study.2Verapamil reduced diastolic blood pressure by approximately 10 mm Hg, did not affect heart rate and increased PR interval by approximately 15%.3Verapamil significantly increased brachial and carotid arterial blood flows by 56% (P<0.01) and 16% (P<0.05), respectively, but the diameters of these vessels were not significantly modified (+ 7 and + 4%, respectively, NS). Forearm vascular resistance decreased by 40% (P<0.01), indicating that verapamil preferentially dilates small arteries. All these effects peaked at 2 h after drug intake and lasted for 6 h.4Verapamil increased hand dorsal vein diameter and flow by 95% (P<0.05) and 80% (P<0.05), respectively, from 2 to 4 h after drug intake but venous compliance, assessed by the venous diameter/venous flow ratio, was not significantly modified (from 0.71 to 0.69, NS), thus indicating that veins are not directly affected by th

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1987.tb00543.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Summary—The relationships between plasma mexiletine levels and the presence of ventricular arrhythmias and side effects were studied on patients from IMPACT (International Mexiletine and Placebo Antiarrhythmic Coronary Trial). 630 patients who had suffered a myocardial infarction were randomized between placebo and mexiletine.Plasma levels were measured 1 month after the beginning of treatment. Arrhythmia findings (presence or absence of premature ventricular contractions (PVCs), couplets, runs, bigeminy, trigeminy, multiformity and various combinations) were assessed from 24‐h ambulatory ECG recordings. The empirical logistic transform was used for modeling the relationships. For all these variables, except the presence of PVCs, trigeminy and runs, the association with plasma level was significant: the higher the plasma level, the lower the rate of occurrence of the particular arrhythmia. This was true whether or not the patient had the arrhythmia at baseline. Analyses based on the same model showed a significant correlation between plasma level and tremor, constipation, sexual problems and the presence of at least one side effect.As the levels of mexiletine at which side effects become frequent are in the same range as those necessary to suppress arrhythmias, the therapeutic range is narrow and individual dose adjustment should preferably be m

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1987.tb00544.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Summary—The effect of atropine (1–10 μ‐kg‐1) on neuromuscular transmission in humans was studied by analysing its effects on the amplitude of indirectly‐elicited twitch (0.2 Hz) and tetanic (50 and 100 Hz for 1 s duration) contractions. Six patients, free from any neuromuscular disorders, undergoing orthopaedic surgery, were included in the present study. The patients received either no premedication or the oral benzodiazepine, temazepam, 30 mg 1–2 h pre‐operatively. Anaesthesia was induced with propofol (1–2 mg‐kg‐1, i.v., over 20 s). The patients breathed no less than 30% oxygen in nitrous oxide, halothane (1%) or enflurane (1–2%). Incremental doses of fentanyl (50–100 μ) were given to provide additional analgesia.The ulnar nerve was stimulated, supramaximally, at the wrist, and control mechanical responses of the adductor pollicis muscle, to nerve stimulation at 50 and 100 Hz for 1 s duration, were recorded. Theses responses were repeated at 2, 5 and 10 min intervals, after injection of atropine (1–10 μ‐kg‐1). At the same time, heart rate and blood pressures (systolic and diastolic) were recorded.The results showed that atropine enhanced the tetanic contractions, elicited at 50 and 100 Hz for 1 s duration, by 27 ± 1.2% (50 Hz and atropine, control 220 ± 13 g tension), and by 43 ± 7% (100 Hz and atropine, control 333 ± 26 g tension) at the 5 min intervals (mean ± S.E.,n= 6). The heart rate and blood pressures were also increased, by 24 ± 2.5% (heart rate control 110±3.5 beats/min), 16±1.0% (systolic control 138±2.2 mm Hg), and 13±1.1% (diastolic control 76±1.5 mm Hg), and this precluded the use of higher doses of atropine (e.g.1.2 mg, i.e. 20 μ‐kg‐1) in our study.The results and mechanism of action of atropine, at the neuromuscular junction, are discussed with reference to animal work, in which atropine has been shown to enhance neuromuscular transmission and/or transmitter (ACh) release, possibly by acting on muscarinic presynaptic inhibitory receptors, which are involved

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1987.tb00545.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Summary—In angina pectoris, diltiazem is usually prescribed as two 60 mg tablets in the morning and two 60 mg tablets in the evening. In the course of the pharmaceutical development of this drug, it was therefore planned to study an experimental formulation containing 120 mg of diltiazem. On the basis of dissolution testsin vitro, a bioavailability study was initiated to compare the 120 mg experimental formulation to the standard 60 mg tablet. The study was conducted in 12 healthy volunteers who received the 2 treatments (one 120 mg tablet bid for 7 daysversustwo 60 mg standard tablets bid for 7 days) according to a cross‐over design. Blood and urine samples were analysed by HPLC method with a UV spec‐trophotometric detection (sensitivity: 5 ng/ml). Analysis of variance did not show any significant difference between the two formulations for the following parameters: maximum plasma levels observed at steady‐state, area under the curves and unchanged urinary diltiazem. From these results the extent of absorption of the 120 mg experimental formulation can be considered as bioequivalent to the administration of 2 tablets of the 60 mg commercialy available diltiazem formulation. The time to peak, however, was delayed in 75% of the subjects with the 120 mg diltiazem tablet, showing that the surface area of the pharmaceutical preparation is of primary importance for drug dissolution and rate of abs

ISSN:0767-3981    

DOI:10.1111/j.1472-8206.1987.tb00546.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY