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The effect of prophylactic anti-asthma drugs on PAF-induced airway hyperreactivity.

Intravenous injection of platelet activating factor (PAF) in anesthetized guinea pigs induces non-selective airway hyperreactivity. This response to PAF was reduced in a dose-dependent manner by systemic administration of established prophylactic anti-asthma drugs (ketotifen, cromoglycate, aminophylline and glucocorticosteroids) and by competitive antagonists of PAF. These inhibitory effects could not be accounted for by antagonism of histamine (H1), serotonin or peptidoleukotrienes receptors; parasympatholytic activity; cyclo-oxygenase or lipoxygenase inhibition; mast cell stabilization; or bronchodilatation. Infusion or injection of PAF to induce airway hyperreactivity in the guinea pig may provide a prospective test for prophylactic anti-asthma drugs.

Animals↗

Incontinence surgery in female motor urge incontinence.

Conventional incontinence surgery was performed in 41 consecutive female patients despite the finding of motor urge incontinence. The patients were reinvestigated 6 months to more than 2 years after operation. Twenty-eight of the patients also had the symptom stress incontinence. Seventeen patients had coexisting symptomatic genital prolapse and were operated on without prior pharmacological treatment. The remaining 24 patients were all resistant to parasympatholytic treatment. The choice of operative procedure was based on vaginal examination as well as bladder suspension defect as demonstrated on voiding-colpo-cysto-urethrography. Subjective cure and improvement rate was 73%. At follow-up, 30% of the patients had normal detrusor reflex control, and a significant improvement in urge incontinence as well as frequency of micturition and nocturia was observed. Probably the primary treatment in females with motor urge incontinence should be pharmacological. However, in patients with symptomatic genital prolapse as well as in patients with ineffective medical treatment, conventional incontinence surgery seems to be well indicated in the absence of neurological disease-providing the patient has an associated bladder suspension defect.

Adult↗

Transdermal scopolamine in the treatment of asthma: a preliminary report.

The use of atropine has emerged over the past few years as a treatment for asthma. Scopolamine is pharmacologically similar to atropine and, as such, was used in a study of nine patients as a bronchodilator. These nine patients had diverse types of lung diseases. Two patients were intolerant to the medication and were not able to participate in the study. The other seven patients had variable responses with significant improvement in baseline pulmonary function testing occurring in four patients. Five of the seven patients had symptomatic relief and are now employing transdermal scopolamine on a once-every-3-days basis for the treatment of their bronchoconstriction. Baseline testing was performed to indicate response to parasympatholytic medications. Transdermal scopolamine appears to be a safe and effective means of achieving bronchodilation in some patients with asthma.

Administration, Cutaneous↗

Datura seed intoxication in two horses.

A sunflower-based feed supplement grossly contaminated with the seed of a Datura sp. resulted in severe signs of poisoning in 2 horses. One horse died peracutely of acute gastric dilatation and rupture following ingestion of the contaminated feed. The 2nd horse developed unresponsive paralytic ileus that led to euthanasia. Examination of the feed and gastrointestinal contents of both horses showed a high proportion of the characteristic Datura sp. seeds. The clinical signs and pathology in both cases were consistent with intoxication by the parasympatholytic alkaloid components of Datura sp.

Animal Feed↗

[Phacoemulsification without mydriasis before surgery: benefits to the patient].

PURPOSE: The aim of our study was to evaluate the frequency of side effects (ataxia, dizziness and dry mouth) due to systemic absorption of parasympatholytic eye-drops, before phacoemulsification. METHODS: This single surgeon, prospective, randomized and controlled study included 303 consecutive patients selected to undergo phacoemulsification with topical and intracameral anesthesia. Patients were distributed in two groups; those receiving no mydriatics before surgery (n=151) as control group and those dilated with cyclopentolate 1% and tropicamide 1% eye-drops (n=152) as the study group. Ataxia, dizziness and dry mouth were recorded in both groups by the same observer. Surgery time and changes in systolic and diastolic blood pressures were noted. Note was also taken of the cases where pupil widening maneuvers and a second intracameral instillation of lidocaine 1% plus epinephrine 1/200,000 were needed. RESULTS: Fifteen patients (9.9%) suffered ataxia in the study group vs. three patients (2%) in the control group. Twenty-three patients (15.1%) suffered dizziness in the study group vs. two patients (1.3%) in the control group. Thirty patients (19.7%) experienced dry mouth in the study group vs. ten patients (6.6%) in the control group. No significant changes in blood pressures, surgery time and pupil dilating maneuvers were noted between groups. The odds ratio for a second intracameral instillation was 2.0 in the control group vs. the study group. CONCLUSIONS: Lidocaine 1% plus epinephrine 1/200,000 as an adjunct to topical anesthesia during phacoemulsification showed to be an effective and safe alternative to abolish side effects caused by systemic absorption of mydriatics eye-drops before surgery.

Aged↗

Low-dose atropine in electroconvulsive therapy.

Anticholinergic medications such as atropine or glycopyrrolate have long been used in electroconvulsive therapy (ECT) to eliminate parasympathetically mediated dysrhythmias. However, such agents increase heart rate and myocardial workload and may increase risk of cardiac adverse events. What is needed is an intervention that is parasympatholytic without substantially increasing myocardial workload. In this study, a low dose of atropine was compared with placebo in ECT with attention to heart rate, blood pressure, cardiac rhythm, myocardial workload, and parasympathetic function. The dose of atropine that was used effectively blocked vagal tone with only a small and probably not clinically significant rise in myocardial workload for only a few minutes after the ECT seizure.

Adult↗

[Smokers with chronic bronchitis and emphysema. Utilize the entire therapy spectrum!].

In the majority of cases, chronic obstructive bronchitis is due to inhalative cigarette smoking. Not only does it cause high costs, but it also has a poor prognosis. The pathogenesis of the illness is now considered to be chronic, mainly neutrophilic, inflammation of the airways and the peripheral parts of the lungs--chronic hypersecretion is a common feature of the disease. Successful treatment requires the giving up of inhalative cigarette smoking. Pharmacological options include anticholinergics, beta sympathomimetics, theophylline and inhalative or systemic corticosteroids. Long-acting beta sympathomimetics such as formoterol, and salmeterol, and still experimental long-acting parasympatholytics, represent significant advances. Such additional measures as vaccination, long-term administration of oxygen and, more recently, surgical procedures such as lung volume reduction to treat severe pulmonary emphysema are described.

Bronchitis↗

Long-term results of sacral nerve stimulation (S3) for the treatment of neurogenic refractory urge incontinence related to detrusor hyperreflexia.

PURPOSE: We assess clinical and urodynamic results of sacral nerve stimulation for patients with neurogenic (spinal cord diseases) urge incontinence and detrusor hyperreflexia resistant to parasympatholytic drugs. MATERIALS AND METHODS: Since 1992, 9 women with a mean age of 42.6 years (range 26 to 53) were treated for refractory neurogenic urge incontinence with sacral nerve stimulation. Neurological spinal diseases included viral and vascular myelitis in 1 patient each, multiple sclerosis in 5 and traumatic spinal cord injury in 2. Mean time since neurological diagnosis was 12 years. All patients had incontinence with chronic pad use related to detrusor hyperreflexia. Intermittent self-catheterization for external detrusor-sphincter dyssynergia was used by 5 patients. Social life was impaired and these patients were candidates for bladder augmentation. A sacral (S3) lead was surgically implanted and connected to a subcutaneous neurostimulator after a positive test stimulation trial. RESULTS: Mean followup was 43.6 months (range 7 to 72). All patients had clinically significant improvement of incontinence, and 5 were completely dry. Average number of voids per day decreased from 16.1 to 8.2. Urodynamic parameters at 6 months after implant improved significantly from baseline, including maximum bladder capacity from 244 to 377 ml. and volume at first uninhibited contraction from 214 to 340 ml. Maximum detrusor pressure at first uninhibited contraction increased in 3, stabilized in 2 and decreased in 4 patients. Urodynamic results returned to baseline when stimulation was inactivated. All patients subjectively reported improved visual analog scale results by at least 75% at last followup. CONCLUSIONS: Sacral nerve stimulation can be used as a reversible treatment option for refractory urge incontinence related to detrusor hyperreflexia in select patients with spinal lesions.

Adult↗

Pharmacological properties of 2-(2-chloro-p-toluidino)-2-imidazoline-nitrate (tolonidine), a new antihypertensive agent. II. Action on cardiac contraction, circulatory parameters, autonomic receptors and diuresis.

Tolonidine, 2(2-chloro-p-toluidino)-2-imidazoline-nitrate, is a substance chemically related to clonidine. In the anesthetized dog, tolonidine administered i.v. decreased the amplitude of ventricular contractions, reduced aortic blood flow and increased peripheral vascular resistances. In the bivagotomized pithed rat, tolonidine induced a long-lasting increase in blood pressure with no secondary hypotension, thus suggesting peripheral sympathomimetic properties, however, contractions of seminal vesicles in vitro were not obtained. The product proved to have no peripheral sympatholytic or parasympatholytic properties. In the dog and the rat, diuresis was hardly changed. These properties are closely related to those of clonidine, which was studied comparatively. A general discussion is proposed at the end of a third article.

Animals↗

[Combined administration of ipratropium bromide (sch 1000) and fenoterol in patients with chronic obstructive airway disease (author's transl)].

40 outpatients with chronic obstructive airway disease received the parasympatholytic bronchodilator ipratropium bromide (Sch 1000) and the sympathomimetic bronchodilator fenoterol from a metered dose inhaler. After evaluation of the initial values, first Sch 1000 was administered and 20 min. later airway resistance was measured, then fenoterol was given and a measurement was taken again 20 min. later. On the following day the aerosol inhalants were given in the reverse sequence. After the first inhalation 0.08 mg Sch 1000 proved to be an equally strong bronchodilator as 0.4 mg fenoterol and airway resistance was decreased to 52% and 55%, respectively of the initial value (p less than 0.001). The additional inhalation of the other bronchodilator caused a further slight decrease in airway resistance to a minimum of 47%, but was statistically significant (p less than 0.001) only in the case of the fenoterol/Sch 1000 sequence. The importance of bronchiolar tonus in regard to fluctuation of airway resistance and the possibility of a specific additive bronchodilatory effect of adrenergics and vagolytics is discussed.

Adult↗

[Onset of action and maximum effect of bronchodilators administered by a metered dose inhaler. Clinical investigations with fenoterol, hexoprenaline, ipratropium bromide, isoprenaline, orciprenaline, salbutamol and terbutaline (author's transl)].

The acute effect of bronchodilatory metered dose inhalers was tested by whole-body plethysmography in patients with chronic obstructive airway disease. All patients had already used metered dose inhalers. The 18 patients of group A were successfully using the parasympatholytic drug ipratropium bromide. The onset of action of hexoprenaline, salbutamol and terbutaline was slightly quicker than that of ipratropium bromide but the maximum bronchodilation was similar. The 18 patients of group B considered adrenergics to be much more effective. Mean values showed that the onset of bronchodilation and maximum effect with fenoterol, isoprenaline, and orciprenaline was quicker and stronger than after ipratropium bromide over the first 20 minutes. Following ipratropium bromide the single resistance diagrams of group B, with the exception of 4 patients, showed bronchodilation equal to that of group A and also to that obtained following adrenergics in group B. The patients apparently judged bronchodilation on the basis of the adrenergic side effects rather than by improvement of dyspnoea. There were 3 patients, however, who repeatedly showed better bronchodilation in response to adrenergics than parasympholytic agents, not depending of the way of application.

Aerosols↗

[Drugs combined with neuroleptics in anesthesia].

The neuroleptics are characterised by the large number of pharmacological effects they develop. When they are associated with other substances, it is frequent for the latter to have with neuroleptics one or several common sites of action. At this level, they develop phenomena of drug interaction, for example, synergy with depressors of the central nervous system or, in the periphery, with alpha-adrenolytic or parasympatholytic drugs. This type of interaction is used in anesthesia to obtain more intense effects with lesser doses of each component and also avoid the toxic effects of efficacious doses of general anesthetics used alone. However, although certain interactions are useful, others may prove harmful. This is in particular the case where neuroleptic drugs are administered after ingestion of alcohol. Various mechanisms, central and peripheral, explain the marked depression of the central nervous system which results. Potentialisation of the effects of tricyclic antidepressor drugs by neuroleptics raises a difficult problem for the anesthetist, the elimination of tricyclic antidepressor drugs is slow and requires several weeks after stopping treatment. During this period, the tissue and plasma concentrations become reduced gradually. They are pharmacologically insufficient, but are potentialised by injection of neuroleptic drugs, and may become active again, and even toxic. It seems to us advisable to avoid the use of neuroleptic drugs in patients treated with tricyclic antidepressor drugs and, if necessary, to use another method of anesthesia.

Anesthesia↗

THE PHARMACOLOGY OF NEW ADRENERGIC NEURONE BLOCKING AGENTS, N-P-CYCLOHEXYLBENZYLTROPINIUM DERIVATIVES.

The three N-p-cyclohexylbenzyltropinium derivatives studied gave rise to lasting hypotension after transient stimulation and block of sympathetic ganglia in anaesthetized and conscious animals. The drugs inhibited the contractions of the nictitating membrane and spleen evoked by pre- or postganglionic nerve stimulation. In adrenalectomized animals the pressor effect of tetramethylammonium, the hypertensive response to carotid arterial occlusion and the effect of tyramine on the nictitating membrane were also reduced. The drugs have slight or no parasympathomimetic, parasympatholytic or curare-like side-effects. The bretylium-like action of the compounds is discussed.

Adrenergic Agents↗

Effects of remifentanil on human heart electrical system. A transesophageal pacing electrophysiological study.

AIM: Previous studies have shown that the administration of remifentanil (a micro-agonist opioid) is often accompanied by bradyarrhythmias preventable or manageable by parasympatholytic drugs. The aim of this paper is to evaluate if these negative chronotropic effects are exclusively due to an increased parasympathetic activity or to a direct action of remifentanil on heart conduction fibres. METHODS: A transesophageal pacing electrophysiological study on 40 healthy subjects scheduled for orthopaedic surgical treatment under general anaesthesia has been carried out. We determined either the correct sinus recovery time or the occurrence of Wencke-bach atrio-ventricular block in the awake state and, again, during remifentanil administration. RESULTS: In all patients either a significant depression of sino-atrial automatism or a decrease of atrio-ventricular node conduction reserve was noticed. In 2 cases, in particular, a sinus arrest and a junctional rhythm, respectively, both spontaneously recovered were observed. CONCLUSION. Atropine normalized all parameters, confirming that remifentanil-associated hypokinetic cardiac phenomena are exclusively vagally mediated.

Adult↗

[Causes of anaphylactoid reactions in cattle after administration of lipoid preparations].

In 1986-1988, adverse anaphylactoid reactions (AR) were observed in animals in Czechoslovakia after the administration of oil adjuvant-containing vaccines or other lipoid drugs. Treated animals showed signs resembling the classic anaphylactic reaction, i.e. restlessness, salivation, pruritus, oedema and cyanosis of udder and vulva, and eyelid oedema, developing within a few minutes. The reactions were not elicited by the antigen alone, but by the oil adjuvant. The aim of our experiments was to identify substances eliciting the reaction in susceptible animals and to investigate possible induction mechanisms. The emulsifier Tween 80 has been demonstrated to be an AR inducing component of vaccines and drugs (Tab. I and III). Weak or moderate reactions were observed in 33% of animals treated with 5% Tween and 66% of those treated with 10% Tween showed strong reactions. On the other hand, no reactions were elicited by treatment with several paraffin oils of different quality (Tab. I) nor with an oil-in-water emulsion containing Montanid as an emulsifier (Tab. II). The role of the vegetative nervous system in the rise of AR has been confirmed. AR were suppressed in animals pretreated with parasympatholytic atropine and enhanced in a part of those pretreated with parasympathomimetic pilocarpine (Tab. III). The percentage of animals affected and the intensity of AR were also lower in animals pretreated with complement inhibitor epsilon-aminocapronic acid (Tab. IV). A major role of complement activation is suggested in the discussion of possible mechanisms of AR induction. It is possible to draw a conclusion on the basis of the results presented here and of the analysis of individual cases that a certain degree of animal susceptibility, depending on the phase of reproductive cycle, metabolism level and neurovegetative balance is necessary besides the administration of an AR inducer (Tween 80 in our case). Hence it seems that the adverse anaphylactoid reactions results from interactions of the two factors, i.e. administration of an AR inducer to susceptible animals.

Adjuvants, Pharmaceutic↗

[Male contraception].

The only safe method of male contraception is vasectomy, with high reversibility secured by microsurgery. Italy, however, suffers from a lack of regulations on this subject. Hormonal treatment (testosterone plus progestational hormones) is far from providing reliability and safety, while some perspectives, theoretical only for the time being, are offered by studies on functional infertility induced by either speeding up (ganglioplegic, sympathomimetic, parasympatholytic, oxytocin, endothelin, angiotensin) or inhibiting (sympatholytic) the sperm transport through the epididymis, or altering the epididymal environment (alpha-chloridin, chlorodeoxyglucose).

Antispermatogenic Agents↗

[Colonic radiography by double-contrast enema in the elderly patient with the use of trimebutine maleate].

About 15% of hospitalizations of patients over 65 are due to disorders of the colon which means that accurate analysis of history and clinical and instrumental investigation are mandatory. Our attention has been focused on x-ray examination using a double-contrast enema which, together with endoscopy, permits to diagnose colonic disorders with significant reliability. Our aim was to adapt the method to the special needs of the patient over 65 by employing the active substance trimebutine maleate (M.T.) as a "contact" pressure-lowering agent. Thirty-five subjects aged 65-75 with pathologies implying a risk for the use of parasympatholytic agents were examined. None of these patients showed side effects. It can therefore be said that the use of M.T. as a hypotonic agent in double-contrast enemas is an indisputable diagnostic aid.

Aged↗

[The effects of medications on the eyes].

The visual system is very sensitive to side effects of medicines, either regarding systematic complications of eye drops or ocular complications following oral or intravenous treatments. For the latter, ophthalmologic regular monitoring is mostly the best preventive measure since most of iatrogenic abnormalities are reversible after ruling out the treatment. However, some ocular complications are poorly reversible, as for example with antimalarial drugs or vigabatrin. Concerning systemic complications of ocular treatments, their risk is often underestimated, while the passage of drugs in the blood can sometimes reach similar rates than those observed after an oral administration, as it is the case with some beta-blockers ophthalmic solutions. It is also advisable to distrust overdoses, or accidental oral ingestions, of parasympatholytic mydriatics which can induce neurological and cardiac complications in children or in elderly.

Drug-Related Side Effects and Adverse Reactions↗