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At least 1,495 records · Page 83Linked to original sources
PubMed1996

Block of the endplate acetylcholine receptor channel by the sympathomimetic agents ephedrine, pseudoephedrine, and albuterol.

Recent observations suggest that some patients with congenital myasthenic syndromes respond favorably to ephedrine, pseudoephedrine, or albuterol. Conventional microelectrode studies, however, provide no clear explanation for a beneficial effect of ephedrine in endplate diseases. To gain further insight into how these drugs affect neuromuscular transmission, we investigated their effects on the kinetic properties of the acetylcholine (ACh) receptor. Single channel currents were recorded from rat lumbrical muscles endplates using low concentrations of ACh and 2.5-100 microM of drugs. Between 10-100 microM, each drug progressively increased the rate of channel closure in a concentration dependent manner, consistent with an open-channel block. Albuterol acted as a sequential fast-acting channel blocker, increasing the mean burst duration in a concentration dependent manner without altering the total open time per burst or the duration of intraburst blockages. Increasing concentrations of ephedrine and pseudoephedrine also increased the number of intraburst closures but decreased the total open time per burst. None of the drugs altered single channel conductance. The channel blocking effects of ephedrine and pseudoephedrine might reduce the synaptic overactivity that occurs in the slow-channel myasthenic syndromes or in endplate ACh esterase deficiency, but these effects occur at concentrations not attainable in clinical practice.

Albuterol↗
PubMed1995

Avoiding unsuspected respiratory side-effects of topical timolol with cardioselective or sympathomimetic agents.

Topical timolol given for the treatment or chronic simple glaucoma may cause unrecognised bronchospasm among elderly people. We recruited 80 patients aged over 60 years, who were without a history of airways disease and already used timolol, into a randomised crossover study comparing the effects on spirometry and exercise tolerance of changing to betaxolol or dipivefrine therapy. Results showed an increase of 13% and 8% in mean peak flow rate and forced expiratory volume in 1 s (FEV1), respectively, when using betaxolol; and of 14% and 11% when using dipivefrine. There was also improved exercise tolerance with both agents. More than a quarter of the patients showed at least a 15% improvement in FEV1 when changed from timolol. Analysis of enrolment symptoms and response to nebulised salbutamol failed to produce a method of identifying these patients. Timolol may impair respiratory function and exercise tolerance of elderly patients even if they have no history of reversible airways disease.

Aged↗
PubMed1994

Determination of beta-sympathomimetics in liver and urine by immunoaffinity chromatography and gas chromatography-mass-selective detection.

A specific and sensitive method for the determination of several beta-agonistic drugs in liver and urine is described. Following clean-up by immunoaffinity chromatography and two different derivatizations, gas chromatography-mass spectrometry with electron-impact ionization is performed. The immunoaffinity chromatography columns were packed with Sepharose-immobilized polyclonal antibodies raised against the beta-agonist clenbuterol. Owing to the high clean-up efficiency of the immunoaffinity column large sample volumes can be used (up to 100 ml urine or 25 gram liver). The immunoaffinity sample pretreatment is highly specific and no further sample pretreatment was necessary. Due to the combination of two different derivatizations only GC-MS with electron-impact ionization is necessary to fulfil legal requirements. The first confirmation step consists of a derivatization reaction between the hydroxyl group of the parent compound and trimethylsilane. The second confirmation method is a derivatization to a cyclic derivative with the hydroxyl group and the aliphatic nitrogen group. Limits of determination in liver as well in urine are at the 10 ng/kg or ng/l (ppt) level with acceptable signal-to-noise ratio. The method is suitable for identification and quantification of trace amounts of several similar beta-agonistic drugs either used separately or in combination and can be used also for quantification of clenbuterol in liver with regard to levels exceeding the maximum residue limit (MRL) of 1 microgram/kg (ppb).

Adrenergic beta-Agonists↗
PubMed1998

[Nebulization in acute asthma. Association of an atropine and a beta2-sympathomimetic].

Nebulization is a basic treatment for the management of severe acute asthma. Three mechanisms are involved in bronchial obstruction: bronchospasms, inflammation and an increase in bronchial secretions. Combination therapy including beta 2-sympatheticomimetic and synthetic atropinic drugs is strongly synergistic. In a French multicenter trial including 45 adult patients presenting with asthma, combination of nebulized Berotec and Atrovent was studied. It proved to be efficacious in two thirds of the patients. Results were even better for younger patients whose initial peak flow rate was high. Tolerance to this combination therapy was as good as that to beta 2-sympatheticomimetic monotherapy.

Acute Disease↗
PubMed1989

Synthesis and evaluation of the pharmacological activity of rigid analogues of sympathomimetic catecholamines derived from bicyclo[2.2.1]heptane.

endo-3-Amino-exo-2-(3,4-dihydroxyphenyl)-2-hydroxybicyclo[2.2.1]he ptane (4a) and its N-isopropyl derivative (4b) were synthesized and assayed for their adrenergic activity on various isolated preparations. Compounds 4a and 4b, tested up to a dose of 10(-4) M, did not reveal any activity, either stimulant or blocking, on the alpha- and beta-adrenoceptors. Possible rationalizations of the results obtained, however, are suggested.

Animals↗
PubMed2001

Child development after maternal tocolysis with beta-sympathomimetic drugs.

The psycho-social development of both preterm and term children whose mothers reported tocolytic treatment was assessed at the ages of 2, 4.5, and 8 years. Term children exposed to tocolysis showed a higher rate of psychiatric disorders as well as poorer cognitive and motor performance than controls. In the preterm children no adverse impact of tocolysis could be found. The results are discussed concerning possible ways in which tocolytic treatment may influence child development. Restrictions because of the preliminary character of this study and the need of further prospective studies to clarify the developmental impact of tocolysis are also considered.

Adrenergic beta-Agonists↗
PubMed1986

[Treatment of urinary urgency symptoms in the female with the beta-2-sympathomimetic clenbuterol].

Aside from parasympatheticolytis, calcium antagonists, musculotropic relaxants and tricyclic antidepressants, beta 2-sympatheticomimetics are also used in the treatment of urgency. The beta 2-sympatheticomimetic Clenbuterol, which has relatively slight cardiological side effects, was administered per os to 30 women. Prior to and six weeks after the commencement of daily medication with 2 x 20 micrograms of Clenbuterol, the therapeutic effect of the drug was tested by means of a urogynecological examination (history, gynecological findings, cystometrography, urethrocystometrography, uroflowmetry and pretherapeutic urethrocystometrography). An improvement rate of 65% was found. The parameters of urethrocystometrography and uroflowmetry were not altered under medication with Clenbuterol. Cystometrographic parameters, on the other hand, improved (minimal desire to urinate, maximal desire to urinate, compliance). The results of this study are discussed with reference to the literature. For the beta 2-sympatheticomimetic Clenbuterol, a good level of efficacy can be established in women patients on whom parasympatheticolytics alone failed to have a satisfactory effect.

Clenbuterol↗
PubMed1983

[Tocolysis with beta sympathomimetics alone or combined with the calcium antagonist verapamil? I. Effect of verapamil on maternal cardiovascular parameters and the course of pregnancy].

In a retrospective study covering 471 cases the influence of the calcium antagonist Verapamil on tocolytic therapy with beta-mimetics was examined. 308 patients received Fenoterol therapy (group A) and 163 were treated with a combination of Fenoterol and Verapamil in a dosage-relation 1/20 (group B). There was no significant difference between group A and B in respect of age, parity, week of gestational age at the beginning of therapy and at delivery, and mode of delivery. The cardiovascular parameters demonstrated alterations as described in literature. The heart frequencies increased significantly in all patients while the systolic and the diastolic blood pressures decreased significantly in hypertonic patients only. These alterations of the cardiovascular parameters were the same in both groups. The efficiency of the tocolytic therapy was tested by comparing the prolongation index (Richter) and the frequency of uterine contractions measured by external cardiotocography. There was no significant difference between groups A and B. Severe complications occurred in 6 patients so that the therapy had to be discontinued (3 women suffered from pulmonary oedemas). These complications were also seen under additional Verapamil application during tocolytic treatment. The side effects as far as reported by the patients were restricted to a significantly lower rate of obstipation in the Fenoterol/Verapamil treated group B. We conclude that administration of the calcium antagonist Verapamil is of no additional value in tocolytic treatment with beta-mimetics.

Adult↗
PubMed1983

[Tocolysis with beta sympathomimetics alone or combined with the calcium antagonist verapamil? Influence of verapamil on the fetus].

In a retrospective study, patients who underwent tocolytic therapy by beta-mimetics were investigated. 308 received Fenoterol monotherapy (group A) and 163 a combination of Fenoterol with the calcium-antagonist Verapamil in a dosage-relation of 1/20 (group B). The review of 287 cardiotocograms showed a significant increase in the foetal heart rate in both groups by about 13% after 114 minutes (A) and 146 minutes (B). Although the diaplacental transfer of Fenoterol to the foetus is very small, a high percentage of foetuses showed an increase in heart rate (84.7% in A, 86% in B). There was a significantly longer duration of foetal tachycardia in group B. Both groups were not different in respect of perinatal mortality (5.4% in A, 5.2% in B), birth weight, APGAR score, and the reasons for paediatric care. The great difference in placental permeability for Fenoterol and Verapamil may cause a danger for the foetus. Since no reasonable improvements are seen, additional Verapamil therapy is not recommended.

Apgar Score↗
PubMed1985

External Ca-independent release of norepinephrine by sympathomimetics and its role in negative feedback modulation.

The release of [3H]norepinephrine from isolated mouse vas deferens has been measured. 1-Phenylephrine and 1-norepinephrine significantly enhanced the spontaneous release of radioactivity. As shown by a combination of HPLC and scintillation spectrometry, the release of total radioactivity in response to 1-phenylephrine or 1-norepinephrine consisted mainly of [3H]norepinephrine. Evidence has been obtained that the release of endogenous norepinephrine by exogenous norepinephrine and 1-phenylephrine is independent of the external Ca2+ concentration. The released endogenous norepinephrine in turn inhibits the release of norepinephrine in response to electrical field stimulation. In the presence of yohimbine, the enhancement of spontaneous release due to 1-phenylephrine (or to 1-norepinephrine) was not affected, whereas there was a significant superimposed release of [3H]norepinephrine in response to field stimulation, indicating that the inhibition of stimulation-induced norepinephrine release is an alpha 2-adrenoceptor-mediated process. An important consequence of these findings is to question previous interpretations that the effects of administration of 1-norepinephrine or 1-phenylephrine are due exclusively to their direct effects on the effector cells. The Ca-independent release of endogenous norepinephrine might partly initiate their pharmacological responses. It is concluded that this Ca-independent release is of functional importance, since norepinephrine may accumulate in a concentration sufficient to modulate the release of norepinephrine from varicosities in response to electrical stimulation.

Adrenergic alpha-Agonists↗