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PubMed1983

[Vesicourethral physiology during continence and urination in cats. In vivo and in vitro studies].

The mechanisms implicated in the opening of the bladder neck during voiding are still controversial. We present a study of the reflexes of bladder, urethra and periurethral striated muscles in the cat. The study in vivo shows that a passive muscle tonus of the urethra is able to maintain the continence. During voiding, opening of the bladder outlet is done actively: contraction of the longitudinal and relaxation of the circular muscle layers of the urethra associated with detrusor contraction. There is a local reflex between the urethra, bladder and periurethral striated muscles that completes emptying of the bladder with an interrupted stream. The study in vitro confirms that the 2 muscle layers of the urethra have different innervation: the parasympathomimetic agents act on the longitudinal layer and very weakly on the circular. Both layers react to adrenergic stimulation.

Animals↗

PubMed1980

A simple animal test system to predict the likelihood of a drug causing human physical dependence.

The test system utilizes adult, male, Sprague-Dawley rats to consume their entire daily water intake in a single 60 minute session. The results of administering various doses of more than 70 therapeutic agents 15 minutes prior to the test session permit the classification of drugs into two categories. Group I drugs cause only a dose-dependent reduction in water intake, beginning at a threshold value below which no effect is seen. Group II drugs, upon reaching a threshold value, cause first a dose-dependent increase in water intake to a maximum; additional dosage increments produce a dose-dependent decrease. Group I agents include: amphetamines, antidepressants, antihistamines, antipsychotics, narcotic antagonists, parasympathomimetics, and parasympatholytics. Group II includes agents known to induce human physical dependence, namely anxiolytics, barbiturates, sedative/hypnotics, and narcotic agonists. Double-blind testing has confirmed the value of this test system as a predictive screen for identifying drugs capable of causing physical dependence.

Animals↗

PubMed1982

[On the use of physostigmine in anesthesia and intensive care].

Physostigmine is an antidote in cases of overdosage with intravenous anaesthetics such as dehydrobenzperidol, benzodiazepines and ketamine. It is also useful in antagonizing drug induced comas of different origin particularly in cases of acute intoxication with tricyclic antidepressants and alcohol. We discuss our therapeutic observations in anaesthesiological and intensive care patients. We have not seen any side effects after physostigmine administration, but the possibility of undesired parasympathomimetic activity demands correct indication, well calculated dosage and continuous surveillance of the patient.

Aged↗

PubMed1982

[Cardiac electrophysiologic effect of various catecholamines and parasympatholytic agents].

Using His-bundle-electrography and programmed atrial stimulation the effects of different catecholamines (dopamine, dobutamine, orciprenaline), parasympatholytics like atropine, ipratropiumbromide and the xanthine derivative aminophylline have been studied on the conduction system of the human heart in 119 patients with and without different disturbances of rhythm. In contrast to dopamine a moderate effect was found by dobutamine (3 or 6 micrograms/kg/min) in patients with sinus node dysfunction and delayed AV-conduction. In comparison it must by pointed out, that orciprenaline has the greatest positive dromotropic and chronotropic effect on sinus and AV-node. No effect was seen by these catecholamines on electrophysiological properties of the atrium and the intraventricular conduction (HPS). Particularly the fatigue-phenomenon of the Tawara-fibers were not influenced. 0,24 g aminophylline has only a minimal electrophysiological effect, only the sino-atrial conduction time was shortened significantly. The parasympathomimetic agents atropine (1,0; 2 mg i.v.) and ipratropiumbromide (0,5; 1 mg i.v.) are able to improve the sinuatrial and AV-dysfunction. In some patients, however, paradoxical effects were seen in patients with sick sinus syndrome. The refractory periods of the HPS were not influenced - otherwise a secondary impulse - generator was accelerated, which seems to indicate that the AV-node is localized in the NH-region.

Adolescent↗

PubMed1980

The separate uterotonic and prostaglandin-releasing actions of oxytocin. Evidence and comparison with angiotensin and methacholine in the isolated rat uterus.

Both oxytocin (OT) and prostaglandin (PG) possess potent uterotonic activity. It has been suggested that the uterotonic action of OT may be mediated by PG release. We investigated the uterotonic and PG-releasing actions of OT, angiotensin II (AT) and methacholine (MC) in isolated pregnant rat uteri. Our findings indicate that the OT-induced PG release is a direct effect of OT and not a secondary response to myometrial contractions and that the uterotonic action of OT is not dependent on PG participation. This is shown by: 1) equipotent uterotonic doses of OT, AT and MC had different effects on uterine PG release. OT and AT caused uterine contractions and PG release, whereas MC caused contractions but no PG release. 2) OT produced a dose-dependent uterotonic responses. However, there was no proportional relationship and the rate of PG release. 3) In uterine homogenates, which lack the functional integrity for mechanical contractions, OT also caused an increase in PG biosynthesis. Indomethacin suppressed both the spontaneous and the OT-stimulated PG synthesis in the uterine homogenates. 4) In isolated uterine horns, the contractile response to OT was only slightly attenuated in the presence of indomethacin sufficient to inhibit completely the OT-stimulated PG synthesis. We concluded that OT has a dual action in the uterus and may act on two different receptors, one leading to myometrial contractions and the other leading to PG release. AT, an octapeptide like OT, may also have a dual action, whereas the parasympathomimetic, MC, has predominately a direct uterotonic action.

Angiotensin II↗

PubMed1978

[Urination disorders following general surgery].

The disturbance of miction after general surgical operations has three causes. They exist individually and combined. The first cause is a relative trauma of anaesthesiological remedies. They have a central site of action in the brain stem and a peripheral one in the parasympathetic and sympathetic ganglian of the urinary bladder. The second cause is an operative trauma of the abdomino-pelvic initial reflex of the miction. The two traumata, the vegetative and the mechanical one, decompensate an imminent neuropathic or obstructive reduction of the urinary bladder. The two traumata are prolonged by abdominal, pulmonary and cerebral insufficiency. The third cause is a direct lesion of the sacral plexus pelvicus. - The postoperative disturbance of miction concerns about 25% of all operated persons. Children are specifically rarely concerned. Operations on the lower half of the body cause the disturbance of miction by far more frequently than operations on the upper half of the body or on extremities. The therapy consists of a rational, liberal and differentiated use of the catheter, further in parasympathomimetic and sympatholytic medication, in the obstructively or neuropathically decompensated cases in transurethral operative correction of the outlet of the urinary bladder.

Anesthesia, General↗

PubMed1978

The inhibitory effect induced by delta9-tetrahydrocannabinol on the contractions of the isolated rat vas deferens.

To analyse the influence of delta9-Tetrahydrocannabinol (THC) on the effects induced by sympathomimetic, parasympathomimetic and direct spasmogenic drugs, the isolated rat vas deferens preparation was chosen. Instead of the usual emulsifying agents, we have used 1% ethanol (ET-OH) to keep the cannabinoids in homogeneous dispersion in the bath. THC exerted a non-competitive inhibition of noradrenaline and of acetylcholine responses but no synergistic action nor competitive antagonism was seen on the dose range used. BaCl2 was potentiated by ethanol and this effect was abolished by THC. The water soluble derivative SP 111 showed actions similar to those of THC on noradrenaline and acetylcholine responses. It did not affect BaCl2 contractions, indicating that the cannabinoid might act by depressing early events of membrane activation.

Acetylcholine↗

PubMed1994

[The risk of anesthesia in bronchopulmonary diseases].

Surgery and anaesthesia, including positioning and mechanical ventilation, encompass alterations in respiratory mechanics and gas exchange persisting through the postoperative period and may cause respiratory complications. The closer the anatomical ties between the surgical site and the respiratory system, the higher the pulmonary risks. Pre-existing respiratory and pulmonary diseases further increase the patient's risk. In addition to the numerous patients suffering from chronic obstructive pulmonary disease, patients with restrictive disorders, e.g. obesity, are concerned as well. Arterial oxygen saturation tracked by pulse oximetry is recommended for screening the respiratory system. Patients at an increased risk of respiratory complications should be scheduled individually for preoperative preparation, anaesthesia requirements, and postoperative management. When anaesthetizing patients with coexisting pulmonary disease, regional anaesthesia is preferred unless limited by the surgical procedure or for obvious technical reasons. Pasch provides recommendations for the management of anesthesia: Acute respiratory obstruction should be prevented by personal attention and pharmacological protection. Anaesthetics and relaxants with parasympathomimetic and histamine liberating effects should be avoided. Attention should be paid to hazardous pharmacological interactions with existing respiratory therapy. Bronchospasm should be avoided by deep anaesthesia and by smooth intubation and extubation. Pain therapy is an essential requirement for respiratory therapy in the postoperative period to maintain or to restore pulmonary function with improved performance.

Anesthesia, Conduction↗

PubMed1977

Atropine-induced bradycardia in the guinea pig: dose-response.

The effect of atropine sulfate on the heart rate of the unanesthetized guinea pig was studied using a wide range of doses injected via a chronic jugular cannula; dose-response data are presented for the range of 5 mg/kg to 50 mg/kg. A long-lasting dose-dependent bradycardia was produced. This finding is in contrast to the clasically reported effect of atropine in man and dog: tachycardia sometimes preceded by a transient bradycardia. Thus, the guinea pig may be an excellent model for the study of parasympathomimetic, bradycardia-producing effects of atropine.

Animals↗

PubMedDate not supplied

[The therapeutic prospects in glaucoma treatment].

The appearance of new drugs in glaucoma's treatment has the aim to reduce the ocular hypertonia and to preserve the visual field maintaining the integrity of visual fibres which form the optic nerve. The authors review the drugs which have action on the trabeculum, such as parasympathomimetics, adrenalin, glicocorticoid antihormones and colchicine, also influencing the ciliary processes as inhibitors of carbonic anhydrase, and the drugs which have an action on the uveoscleral paths such as prostaglandines.

Chronic Disease↗

PubMed1995

Reversal of tropicamide mydriasis with single instillations of pilocarpine can induce substantial pseudo-myopia in young adults.

Pupillary dilation for diagnostic purpose has become an increasingly common procedure in UK optometry in recent years and the consensus seems currently to militate against the routine use of miotics; an eye that is judged safe to dilate is thought to be at minimal risk during the natural recovery phase to normal pupil size. Nevertheless, the optometrist does, on occasion, need to consider whether there might be some advantage in minimising the sometimes debilitating effects of cycloplegia and mydriasis produced in young adults by tropicamide. In this context we compare the effects of single instillations of two miotic agents: the alpha-adrenoceptor antagonist thymoxamine HCl (0.5%), and the parasympathomimetic pilocarpine HCl (1 and 2%). Tropicamide was used to induce mydriasis in a group of 12 volunteer student subjects aged 20-26 years (7 males, 5 female; mean 21.67 years) selected to provide low (L; n = 4), medium (M; n = 4) and high (H; n = 4) iris pigment levels. Measurements of pupil diameter (Brocca pupillometer), Snellen visual acuity and accommodative amplitude (near point rule) were made every 3 min over a 90 min recording period for 4 trials: (1) a control condition whereby a miotic was not employed; (2) thymoxamine HCl 0.5% was instilled after 30 min; (3) and (4) pilocarpine 1% and 2% was instilled after 30 min, respectively. Tropicamide induced a mean increase in pupil area from 25 to 50 mm2 after 22 min which was generally sustained over the 90 min period and was enhanced for the lower pigment groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Accommodation, Ocular↗

PubMed1996

Characterization of chronotropic and dysrhythmogenic effects of atropine in dogs with bradycardia.

OBJECTIVE: To characterize the magnitude, character, and time course of chronotropic and dysrhythmogenic responses of dogs with vagally mediated bradycardia to atropine sulfate. DESIGN: Latin square design. ANIMALS: Seven clinically normal adult mixed-breed dogs. PROCEDURE: Vagally mediated bradycardia was induced with morphine and fentanyl citrate. Atropine (0.02 mg/kg of body weight) was administered i.v., s.c., or i.m.. Electrocardiograms were recorded continuously for 5 minutes before and for 35 minutes after atropine administration or until a sustained parasympatholytic response was observed. Data were digitized, analyzed independently for changes in atrial and ventricular rate, and compared between different routes of administration. RESULTS: All dogs developed second-degree atrioventricular (AV) block after i.v. administration of atropine, and 71% of dogs developed AV block after s.c. or i.m. administration. The AV block arose and resolved more rapidly with i.v. administration than with s.c. or i.m. administration. The AV block was principally attributable to an increase in the atrial rate prior to increases in the ventricular rate. Atropine, regardless of route of administration, potentiated baseline ventricular bradycardia in 62% of the experiments (mean heart rate decrease of 16 beats/min; decreased to < 20 beats/min in 2 dogs for < or = 10 seconds). Duration of the bradycardic potentiation was longer with s.c. administration (9.1 minutes, s.c., vs 1.4 minutes, i.v., and 4.6 minutes, i.m.). Parasympatholytic rate was higher for i.v. than s.c. or i.m. administration (128 beats/min vs 92 beats/min and 101 beats/min). Two dogs given atropine s.c. failed to resolve the AV block and attain sinus rhythm. CONCLUSIONS: Administration of 0.02 mg of atropine/kg by i.v., i.m., and s.c. routes for vagally mediated bradycardia in dogs consistently induces AV block and occasional brief potentiation of ventricular bradycardia. CLINICAL RELEVANCE: Parasympathomimetic effects occur and resolve most rapidly and consistently, and the stable parasympatholytic effect is of greatest magnitude after i.v. administration. Thus, vagally mediated bradycardia in clinically normal dogs appears to be best abolished by i.v. administration of atropine.

Analysis of Variance↗

PubMed1977

Cardiovascular effects of atropine on acupuncture, needling with electrostimulation, at Tsu San Li (St-36) in dogs.

Acupuncture, needling with electrostimulation, at Tsu San Li (St-36) produced (1) significant decrease in cardiac output, (2) decrease in stroke volume, (3) increase in total peripheral resistance, and (4) minimal changes in heart rate, mean arterial pressure, pulse pressure, and central venous pressure in dogs under halothane anesthesia. Atropine given alone and given before acupuncture at Tsu San Li (St-36) produced (1) early significant increase in cardiac output, (2) early significant increase in heart rate, (3) increase in mean arterial pressure, (4) decrease in total peripheral resistance, and (5) minimal changes in stroke volume, pulse pressure, and central venous pressure in anesthetized dogs. It was concluded that the effects of acupuncture at Tsu San Li (St-36) were parasympathomimetic-like and that these effects could be blocked by atropine, a parasympatholytic drug.

Acupuncture Therapy↗

PubMed1996

What can be expected for the management of heart failure in the near future?

Further reduction in the morbidity and mortality from diseases associated with heart failure is to be expected by the early introduction of strategies aimed at preventing cardiac damage. In the future, ACE inhibitors, beta-adrenergic blocking agents and type III antiarrhythmic agents, as well as pacemakers, will be used judiciously and in combination following better risk profiling using non-invasive techniques. Cardiac transplantation could be a more widely used treatment for end-stage cardiac disease. Ongoing randomized studies are revealing the usefulness of various pharmaceutical products as well as implanted defibrillators. In the more distant future, anti-endothelin therapy, cardiac autoantibody immunotherapy, cardiac-specific inhibition of angiotensin-converting enzyme and/or normalization of autonomic parasympathetic activity by parasympathomimetic agents may prove to be additional tools for reducing the complications from cardiac disease.

Adrenergic beta-Antagonists↗

PubMedDate not supplied

[The clinico-physiological characteristics of biologically active points].

Biological active acupoints (BAAp) are peculiar markers of the reflector and general vegetative reaction. Their particular structure, relation to neuro-humoral regulation in the organism are still disputable. The experimental study confirms the availability of BAAp morphological subject. The BAAp stimulation causes parasympathomimetic or sympathomimetic reactions in the efferent organs. Changes in the biochemical indicators caused by BAAp stimulation are of a special neurochemical type under definite functional conditions.

Acupuncture Points↗

PubMed1977

Studies on the neurophysiology of the vas deferens.

In order to investigate the mechanism of sperm transport along the genital ducts, intraluminal pressure of isolated segments of the vas deferens was recorded in vivo. Responses to filling and mechanical as well as pharmacologic and electric stimulation of the autonomic nervous system were monitored. Contraction waves were initated in response to the stretch of filling and from mechanical stimulation. Pharmacologic response was variable. Low doses of alpha-adrenergic stimulant produced an increase in frequency of the contraction wave. Large doses of the same drug induced stroking contraction of the entire vas. alpha-Blocking drugs did not alter the rhythmic activity of the vas. beta-Adrenergic stimulation blocked peristaltic activity while administration of parasympathomimetic drugs increased the force of contraction. Electric stimulation of the hypogastric nerve produced strong sustained contractions. These data suggest that, whenever stretched, the vas deferens responds by regular peristaltic waves of low amplitude. These peristaltic waves can be enhanced by sympathomimetics or electric stimulation of the sympathetic system. The contents of the vas are propulsed into the urethra through strong rhythmic contractions of the entire vas.

Animals↗

PubMed1997

Pharmacology of butylthio[2.2.2] (LY297802/NNC11-1053): a novel analgesic with mixed muscarinic receptor agonist and antagonist activity.

Butylthio[2.2.2], ((+)-(S)-3-(4-butylthio-1,2,5-thiadiazol-3-yl)-1-azabicyclo[2.2.2] octane; LY297802/NNC11-1053) is a muscarinic receptor ligand which is equiefficacious to morphine in producing antinociception. In vitro, butylthio[2.2.2] had high affinity for muscarinic receptors in brain homogenates, but had substantially less or no affinity for several other neurotransmiter receptors and uptake sites. In isolated tissues, butylthio[2.2.2] was an agonist with high affinity for M1 receptors in the rabbit vas deferens (IC50 = 0.33 nM), but it was an antagonist at M2 receptors in guinea pig atria (pA2 = 6.9) and at M3 receptors in guinea pig urinary bladder (pA2 = 7.4) and a weak partial agonist in guinea pig ileum, which contains a heterogeneous population of muscarinic receptors. In vivo, butylthio[2.2.2] was without effect on acetylcholine, dopamine and serotonin levels in rat brain. Moreover, butylthio[2.2.2] did not decrease charcoal meal transit in mice, nor did it significantly alter heart rate in rats. Further, butylthio[2.2.2] did not produce parasympathomimetic effects such as salivation or tremor in mice, but it antagonized salivation and tremor produced by the nonselective muscarinic agonist oxotremorine. The present data demonstrate that butylthio[2.2.2] is a novel muscarinic receptor mixed agonist/antagonist and its pharmacological profile suggests that it may have clinical utility in the management of pain as an alternative to opioids.

Analgesics↗

PubMed1997

Recognizing and Managing the Oral Clues That Point to Sjögren's Syndrome.

Sjögren's syndrome (SS), a chronic autoimmune exocrinopathy, occurs mainly after age 40. Most SS patients--80% to 90%--are women. SS is characterized by dry eyes and mouth due to lacrimal and salivary gland lymphocytic infiltration. It may be primary or secondary in association with a connective tissue disease, usually rheumatoid arthritis. Lymphoproliferation may produce extraglandular manifestations in pulmonary, cardiac, genitourinary, vascular, and/or nervous systems. The risk of lymphoma is increased 40-fold among SS patients. Dry mouth, or xerostomia, hinders eating, speaking, and swallowing. A thorough patient history, serum analysis, and salivary function tests are essential to determine the genesis of the xerostomia. Insufficient salivary protection can cause rampant dental destruction and soft-tissue mycosis in the mouth. A biopsy of the minor salivary gland from the lower lip is used to detect hallmark inflammatory changes that confirm the diagnosis of SS. Therapy is symptomatic. Regardless of the cause of xerostomia, therapy has 3 fundamental aspects: preventive dental care, dietary counseling (reduction of sugar intake to avoid caries), and moisture replacement (including artificial salivas, frequent sips of water, and room humidifiers). Women taking xerostomic medications may need to lower the dose or substitute them with less xerogenic drugs if possible. Salivation can be stimulated by chewing gum, mints, or paraffin. Cracked lips are treated with petroleum. Dental flossing, supplemental fluoride, and dental appointments every 3 to 4 months are essential to control caries. Pilocarpine, a parasympathomimetic drug that increases salivation, has been found to reduce the severity of xerostomia from radiotherapy; multicenter trials in SS patients are ongoing.

Journal Article↗