Showing papers on "Atropine published in 2014"

Efficacy of antidotes (midazolam, atropine and HI-6) on nerve agent induced molecular and neuropathological changes

Abstract: Recent alleged attacks with nerve agent sarin on civilians in Syria indicate their potential threat to both civilian and military population. Acute nerve agent exposure can cause rapid death or leads to multiple and long term neurological effects. The biochemical changes that occur following nerve agent exposure needs to be elucidated to understand the mechanisms behind their long term neurological effects and to design better therapeutic drugs to block their multiple neurotoxic effects. In the present study, we intend to study the efficacy of antidotes comprising of HI-6 (1-[[[4-(aminocarbonyl)-pyridinio]-methoxy]-methyl]-2-[(hydroxyimino) methyl] pyridinium dichloride), atropine and midazolam on soman induced neurodegeneration and the expression of c-Fos, Calpain, and Bax levels in discrete rat brain areas. Therapeutic regime consisting of HI-6 (50 mg/kg, i.m), atropine (10 mg/kg, i.m) and midazolam (5 mg/kg, i.m) protected animals against soman (2 × LD50, s.c) lethality completely at 2 h and 80% at 24 h. HI-6 treatment reactivated soman inhibited plasma and RBC cholinesterase up to 40%. Fluoro-Jade B (FJ-B) staining of neurodegenerative neurons showed that soman induced significant necrotic neuronal cell death, which was reduced by this antidotal treatment. Soman increased the expression of neuronal proteins including c-Fos, Bax and Calpain levels in the hippocampus, cerebral cortex and cerebellum regions of the brain. This therapeutic regime also reduced the soman induced Bax, Calpain expression levels to near control levels in the different brain regions studied, except a mild induction of c-Fos expression in the hippocampus. Rats that received antidotal treatment after soman exposure were protected from mortality and showed reduction in the soman induced expression of c-Fos, Bax and Calpain and necrosis. Results highlight the need for timely administration of better antidotes than standard therapy in order to prevent the molecular and biochemical changes and subsequent long term neurological effects induced by nerve agents.

N-butylscopolammonium bromide causes fewer side effects than atropine when assessing bronchoconstriction reversibility in horses with heaves

Abstract: SummaryReasons for performing study Bronchospasm results in airway obstruction in horses with heaves. Atropine is the most potent bronchodilator drug currently available for horses, but is associated with side effects that limit its use. Like atropine, N-butylscopolammonium bromide (NBB) is an anticholinergic agent with bronchodilatory properties. Objectives To compare the bronchodilating effects and side effects of atropine and NBB in horses with heaves. Study design Cross-over experiment using horses with heaves. Methods Eight horses with heaves were administered atropine and NBB, using a cross-over design. Heart rate, pupillary dilatation, transrectal palpation, lung mechanics (maximal changes in transpulmonary pressure, pulmonary resistance and elastance) and arterial blood gases were assessed before and 10 and 30 min after drug administration. Results One horse treated with atropine developed colic. Significant pupillary dilatation was observed only with atropine. Tachycardia developed in all horses, but was more marked with atropine. Lung function improved with both drugs, but elastance values had returned to baseline at 30 min with NBB. There was no improvement in arterial hypoxaemia with either drug. Conclusions The study indicated that the bronchodilatory properties of NBB were not statistically different from those of atropine, but were of shorter duration. N-butylscopolammonium bromide was associated with fewer systemic side effects, and therefore NBB should be preferred over atropine when assessing the reversibility of airway obstruction in horses.

Parasympathetic reflex vasodilation in the cerebral hemodynamics of rats

Abstract: We investigated the role of parasympathetic reflex vasodilation in the regulation of the cerebral hemodynamics, and whether GABAA receptors modulate the response. We examined the effects of activation of the parasympathetic fibers through trigeminal afferent inputs on blood flow in the internal carotid artery (ICABF) and the cerebral blood vessels (rCBF) in parietal cortex in urethane-anesthetized rats. Electrical stimulation of the central cut end of the lingual nerve (LN) elicited intensity- and frequency-dependent increases in ICABF that were independent of changes in external carotid artery blood flow. Increases in ICABF were elicited by LN stimulation regardless of the presence or absence of sympathetic innervation. The ICABF increases evoked by LN stimulation were almost abolished by the intravenous administration of hexamethonium (10 mg kg−1) and were reduced significantly by atropine administration (0.1 mg kg−1). Although the LN stimulation alone had no significant effect on rCBF, LN stimulation in combination with a blocker of the GABAA receptor pentylenetetrazole increased the rCBF markedly. This increase in rCBF was reduced significantly by the administration of hexamethonium and atropine. These observations indicate that the increases in both ICABF and rCBF are evoked by parasympathetic activation via the trigeminal-mediated reflex. The rCBF increase evoked by LN stimulation is thought to be limited by the GABAA receptors in the central nervous system. These results suggest that the parasympathetic reflex vasodilation and its modulation mediated by GABA receptors within synaptic transmission in the brainstem are involved in the regulation of the cerebral hemodynamics during trigeminal afferent inputs.

Investigation into the role of the cholinergic system in radiation-induced damage in the rat liver and ileum

Abstract: It has been previously shown that acetylcholine (ACh) may affect pro-inflammatory and anti-inflammatory cytokines. The role of the cholinergic system in radiation-induced inflammatory responses and tissue damage remains unclear. Therefore, the present study was designed to determine the radio-protective properties of the cholinergic system in the ileum and the liver of rats. Rats were exposed to 8-Gy single-fraction whole-abdominal irradiation and were then decapitated at either 36 h or 10 d post-irradiation. The rats were treated either with intraperitoneal physiological saline (1 ml/kg), physostigmine (80 µg/kg) or atropine (50 μg/kg) twice daily for 36 h or 10 d. Cardiac blood samples and liver and ileal tissues were obtained in which TNF-α, IL-1β and IL-10 levels were assayed using ELISA. In the liver and ileal homogenates, caspase-3 immunoblots were performed and myeloperoxidase (MPO) activity was analyzed. Plasma levels of IL-1β and TNF-α increased significantly following radiation (P < 0.01 and P < 0.001, respectively) as compared with non-irradiated controls, and physostigmine treatment prevented the increase in the pro-inflammatory cytokines (P < 0.01 and P < 0.001, respectively). Plasma IL-10 levels were not found to be significantly changed following radiation, whereas physostigmine augmented IL-10 levels during the late phase (P < 0.01). In the liver and ileum homogenates, IL-1β and TNF-α levels were also elevated following radiation, and this effect was inhibited by physostigmine treatment but not by atropine. Similarly, physostigmine also reversed the changes in MPO activity and in the caspase-3 levels in the liver and ileum. Histological examination revealed related changes. Physostigmine experiments suggested that ACh has a radio-protective effect not involving the muscarinic receptors.

Effect of atropine dose on heart rate during electroconvulsive therapy.

Abstract: Introduction Transient bradycardia during the stimulation phase of electroconvulsive therapy (ECT) is a well-known clinical observation. The optimal dose of atropine needed to prevent bradycardia has not been determined. This study was designed to investigate the effect of low doses of atropine on heart rate during ECT. Methods Patients who received at least 2 different doses of atropine over their series of right unilateral ECT were included in the analysis. The anesthetic consisted of 0, 0.2, 0.3, or 0.4 mg of atropine, methohexital, and succinylcholine. Heart rate was measured by the RR interval, the time between sequential R waves on the electrocardiogram. Analysis was performed using logistic multivariate regression and repeated-measures multivariate analysis of variance. Results One hundred eighteen ECT sessions were identified from 19 patients. Patients were grouped into 4 groups by atropine dose (0, 0.2, 0.3, or 0.4 mg) with 9, 33, 13, and 63 ECT sessions identified for each dose, respectively. Patients who received atropine had significantly less bradycardia after electrical stimulus and a faster heart rate through the seizure than patients who did not receive atropine. There was no significant difference in heart rate between patients receiving 0.2, 0.3, and 0.4 mg of atropine at any time point. There was no significant difference in heart rate at time points after the seizure conclusion in any group of patients. Conclusion Low-dose atropine results in significantly less bradycardia after electrical stimulus. There was no significant difference in heart rate across low doses of atropine.

Pharmacological characterization of muscarinic receptors in the contractions of isolated bronchi in the horse.

Abstract: We investigated the effects of nonselective muscarinic antagonist (atropine) and of selective muscarinic subtype 1 (M1), 2 (M2), 3 (M3) antagonists (VU0255035, methoctramine, pFHHSiD, respectively) on the contractions evoked by electrical field stimulation (EFS) or by exogenous ACh in isolated horse bronchial muscle. Atropine completely inhibited neurogenic contractions in a concentration-dependent fashion, whereas selective muscarinic antagonists induced relevant modifications only at the highest concentration tested. Experiments with selective muscarinic antagonists in combination showed that only the simultaneous blockade of M1 /M3 or M2 /M3 receptors was able to induce a nearly complete suppression of contractions. The contractions induced by exogenous ACh were competitively antagonized only by atropine (pA2 = 9.01 ± 0.05). M3 selective antagonist, up to 10(-6) m, caused a moderate concentration-dependent rightward shift of ACh curve (pA2 = 7.96 ± 0.10). These data show that M3 muscarinic receptors possess a central role in mediating cholinergic contraction of horse bronchi, while M1 and M2 receptors seem to have a cooperative role. Selective muscarinic antagonists seem unlikely to be useful against bronchoconstriction associated with airway diseases in horses. Conversely, compounds with selectivity for both M1 and M3 receptors could be as effective as traditional anticholinergics and induce fewer cardiac side effects.

Acetylcholine plays an antinociceptive role by modulating pain-induced discharges of pain-related neurons in the caudate putamen of rats.

Abstract: The caudate putamen (CPu) has been suggested to be involved in nociceptive modulation. Some neurotransmitters, including acetylcholine (ACh), participate in pain modulation in the central nervous system. However, the active mechanism of ACh on the pain-related neurons in the CPu remains unclear. This study aimed to investigate the effects of the cholinergic agonists ACh and pilocarpine and the muscarinic ACh receptor antagonist atropine on the pain-induced response of pain-related neurons in the CPu of Wistar rats. Trains of electrical impulses applied to the sciatic nerve of rat were used as the noxious stimulus. The electrical activities of pain-excited neurons (PENs) or pain-inhibited neurons (PINs) in the CPu were recorded by a glass microelectrode. Our results showed that an intra-CPu injection of 4 μg/2 μl ACh or pilocarpine decreased and increased the pain-induced discharge frequency in the PENs and PINs, respectively. Intra-CPu administration of 1 μg/2 μl atropine produced the opposite effect on these neurons. These findings indicate that ACh may play an analgesic role by affecting the electric activities of PENs and PINs, and the muscarinic pathway may be involved in the modulation of pain perception in the CPu.

A comparison of the combination of atropine and glycopyrrolate with atropine alone for the reversal of muscle relaxant.

Abstract: Background Muscle relaxant is commonly used in general anesthesia to facilitate surgery. When finishing the operation, anesthesiologists reverse the muscle relaxant with anticholinesterase, neostigmine, combined with anticholinergic for prevention of unwanted side effects from neostigmine. The only existed anticholinergic in Thailand is atropine, which has a more rapid onset than neostigmine resulting in initial tachycardia. Lately, we have glycopyrrolate that cause less increase in initial heart rate. Therefore, we would like to study the effect of heart rate of the combination between atropine and glycopyrrolate to counteract the effect of neostigmine. Objective Evaluate the different increase in heart rate after the reversal of muscle relaxant with neostigmine combined with atropine or glycopyrrolate plus atropine. Material and method The study was a randomized controlled trial study. Fifty-one, ASA I or II patients undergoing elective gynecological surgery under general anesthesia technique were enrolled in the present study. They were randomly assigned by computer-generated random sequence into two groups, control group and intervention group. Control group received neostigmine 2.5 mg and atropine 1.2 mg, intervention group received neostigmine 2.5 mg, glycopyrrolate 0.2 mg and atropine 0.6 mg for reversal of neuromuscular block after finishing the operation. Both groups received the same anesthetic agents including muscle relaxant. Heart rate was recorded before drugs administration and at 1, 3, 5, and 7 minutes after injection. We also recorded heart rate in the PA CU at 0, 15, 30, 45, and 60 minutes. Secondary outcome was incidence of arrhythmia during the observation in PACU. Results There was no difference in age and baseline heart rate between the two groups. There was no different increase in heart rate after administration of reversal agent between control group and intervention group at any time (p-value = 0.496). No incidence of significant arrhythmia in both groups. Conclusion There is no significant different increase in heart rate in 0.2 mg glycopyrrolate plus 0.6 mg atropine group compared to 1.2 mg atropine alone for antagonizing muscarinic effects of 2.5 mg neostigmine. Therefore, atropine 0.6 mg and glycopyrrolate 0.2 mg is an alternative to antagonize muscarinic effects of neostigmine.

Pulmonary effects of intravenous atropine induce ventilation perfusion mismatch.

Abstract: Atropine is used for a number of medical conditions, predominantly for its cardiovascular effects. Cholinergic nerves that innervate pulmonary smooth muscle, glands, and vasculature may be affected by anticholinergic medications. We hypothesized that atropine causes alterations in pulmonary gas exchange. We conducted a prospective interventional study with detailed physiologic recordings in anesthetized, spontaneously breathing rats (n = 8). Animals breathing a normoxic gas mixture titrated to a partial arterial pressure of oxygen of 110-120 were exposed to an escalating dose of intravenous atropine (0.001, 0.01, 0.1, 5.0, and 20.0 mg/kg body mass). Arterial blood gas measurements were recorded every 2 min (×5) at baseline, and following each of the 5 doses of atropine. In addition, the animals regional pulmonary blood flow was measured using neutron-activated microspheres. Oxygenation decreased immediately following intravenous administration of atropine, despite a small increase in the volume of inspired air with no change in respiratory rate. Arterial blood gas analysis showed an increase in pulmonary dysfunction, characterized by a widening of the alveolar-arteriole gradient (p < 0.003 all groups except for the lowest dose of atropine). The microsphere data demonstrates an abrupt and marked heterogeneity of pulmonary blood flow following atropine treatment. In conclusion, atropine was found to decrease pulmonary gas exchange in a dose-dependent fashion in this rat model.

Uterine Relaxation Potential of Ethanol Leaf Extract of Moringa oleifera Lam. VIA the Muscarinic Receptor Pathway

Abstract: Aim: The effect of Ethanol Leaf Extract of Moringa oleifera (ELMO) on uterine smooth muscles of nonpregnant female rats was studied in vitro with a view to finding out the mechanism(s) for observed effects. Original Research Article British Journal of Pharmaceutical Research, 4(20): 2455-2462, 2014 2456 Experiential Design: In vitro studies using isolated rat’s uteri. Methods: Female albino rats (140-180g) pretreated 24 hours before experiments with diethylstilbestrol were sacrificed and the uterine horns carefully harvested into a beaker of De Jalon solution bubbled with 95% oxygen and 5% carbon dioxide. Each horn was mounted in an organ bath and allowed to equilibrate for 30 minutes, then the effects of graded doses of Acetylcholine, oxytocin and ELMO were established, using a physiograph and its accessories. The drugs were re-administered in the presence of their respective antagonists (Atropine for Acetylcholine and Atosiban for Oxytocin) and also in the presence of ELMO. Results: Results obtained showed that while Acetylcholine and oxytocin induced uterine contractions, ELMO caused relaxation. ELMO significantly (P<0.05) blocked the uterine contractile effect of Acetylcholine but had no effect on Oxytocin induced uterine contractions. The experiments therefore indicate that ELMO contain active ingredients capable of inducing uterine relaxation via the muscarinic receptor pathway. Conclusion: The extract therefore, may not be a valuable tocolytic agent in cases of Oxytocin induced uterine contractions, particularly in pregnancy but its observed strong anticholinergic activity may be exploited in the treatment of diseases associated with hyper activity of the parasympathetic arm of the autonomic nervous system.

Dose dependent effects of intramuscular administered atropine on heart rate in Trachemys scripta (879.16)

Abstract: Atropine sulfate is a common anticholingeric drug that is used in human medicine and veterinary medicine, as well as in scientific research. At doses less than 0.1mg/kg, it is used to treat bradyca...

Pharmacological evidence of hypotensive activity of Somina (herbal drug) in normotensive rats

Abstract: Purpose: To evaluate the effects of somina (herbal drug) on the arterial blood pressure. Methods: Hypotensive activity was studied in pentothal sodium-anesthetized normotensive albino rats at various doses of somina (5, 10, 15, 20 and 35 mg/kg). The drugs were administered intravenously and changes in arterial blood pressure (systolic, diastolic and mean arterial blood pressure) were registered directly from the carotid artery. Acetylcholine (Ach, 10 -4 M) was used as positive control for comparison while the receptor activity of Ach and somina was assessed using atropine (muscarinic receptor antagonist) on rat heart. Results: Somina caused dose-dependent significant (p 0.05) in rats that were pretreated with atropine. Conclusion: Somina possesses potent hypotensive effect at different doses in normal rats by stimulating non-selective muscarinic receptors.

Effect of progesterone-carbachol derivative on perfusion pressure and coronary resistance in isolated rat heart: via activation of the M2 muscarinic receptor.

Abstract: Aim. The present study was designed to investigate the effects of progesterone-carbachol derivative on perfusion pressure and coronary resistance in rats. An additional aim was to identify the molecular mechanisms involved. Methods. The Langendorff model was used to measure perfusion pressure and coronary resistance changes in isolated rat heart after progesterone-carbachol derivative alone and after the following compounds; mifepristone (progesterone receptor blocker), yohimbine (α 2 adreno-receptor antagonist), ICI 118,551 (selective β 2 receptor blocker), atropine (non-selective muscarinic receptor antagonist), methoctramine (antagonist of M 2 receptor) and L-NAME (inhibitor of nitric oxide synthase). Results. The results show that progesterone-carbachol derivative [10 -9 mM] significantly decreased perfusion pressure (P=0.005) and coronary resistance (P=0.006) in isolated rat heart. Additionally, the effect of progesterone-carbachol on perfusion pressure [10 -9 to 10 -4 mM] was only blocked in the presence of methoctramine and L-NAME. Conclusions. These data suggest that progesterone derivative exert its effect on perfusion pressure via activation of the M 2 muscarinic. In addition, this phenomenon involves stimulation of nitric oxide synthase (NOS).

Anticholinergics Syndrome Related to Plants and Herbs

Abstract: Anticholinergic poisoning is one of the typical toxidromes. Plant tropane alkaloids – atropine, scopolamine and hyoscyamine – are the common causes of this toxidrome when they enter the human body through GI absorption and/or skin contact. Because the toxins mimic to the essential neurotransmitter acetylcholine, they cause antagonist effects on the parasympathetic nerves with specific receptors that control mucous secretion, sweating, and heart rate. The plants that containing tropane alkaloids are Solanaceae, such as Atropa, Datura, andMandragora, with the distribution to the individual plant and the ratio of toxins different from species to species. Although the clinical presentations may be slightly different, the antidotes of all the intoxications are physostigmine. Decontamination and supportive care may be required.

Comparison between different atropine doses as an antisialagogue for patients receiving ketamine-midazolam undergoing gamma knife radiosurgery

Abstract: Objectives Comparing different atropine doses to detect the least effective dose as an antisialagogue, in patients receiving ketamine-midazolam sedation for gamma knife radiosurgery. Patients and methods The study included 120 American Society of Anesthesiologists Physical Status I, II patients (age range 1860 years) undergoing gamma knife radiosurgery. The patients were randomly divided into three equal groups. Patients in group A received atropine 0.5 mg intravenously, atropine 0.3 mg intravenously in group B, whereas patients in group C received 0.1 mg atropine intravenously. All patients received intravenous ketamine 0.5 mg/kg, plus intravenous midazolam 1 mg. Baseline heart rate and blood pressure, change in heart rate, and occurrence of increased secretions were recorded. Results A total of 120 patients undergoing gamma knife radiosurgery were included in the study. Only one patient in group A and two patients in group B showed increased secretions (2.5 and 5%, respectively), whereas in group C 15 patients experienced increased secretions (37.5%). None of the patients who experienced increased secretions required suctioning of secretions. With regard to the change in heart rate, group A patients had significant increase in heart rate, whereas the changes in heart rate in group B and C were not significant. Conclusion The dose of 0.3 mg atropine used in group B showed the same efficacy as an antisialagogue as the dose of 0.5 mg atropine that was used in group A, and was significantly more efficient than the dose of 0.1 mg atropine used in group C patients, who experienced significant increase of secretions. In addition, group B patients did not experience the significant increase in heart rate that was experienced by group A patients.

Prophylactic Altropine administration should be considered during laparoscopic surgery

Abstract: Background: Routine use of vagotonic drugs during general anaesthesia with mechanical ventilation and carboperitoneum creation during laparoscopic surgery may lead to severe bradycardia and even asystole, which can be countered by prophylactic use of Atropine sulphate. Objective: To study whether Atropine sulphate administered one minute after endotracheal intubation will be effective in preventing bradycardia induced by vagotonic anaesthetics and carboperitoneum during laparoscopic surgery. Methods: Ninety two patients of American Society of Anaesthesiologist Physical Status I were included in the study. These patients were randomly divided into two groups (Control group and Atropine group) of 46 each by envelope method. Control group received one mL of saline and Atropine group received 0.6 mg (one mL) Atropine one minute after endotracheal intubation. Heart rate, systolic, diastolic and mean arterial pressures were monitored before intubation; one, three and fi ve minutes after intubation; fi ve, 15 and 30 minutes after carboperitoneum creation and before and after extubation. Atropine 0.6 mg was given intravenously if any of patients developed heart rate less than 50 beats per minute. Results: Demographic characteristics were similar in both groups. Thirty percent (14 out of 46) of patients in control group developed bradycardia immediately after carboperitoneum creation and no patients developed bradycardia in atropine group. Haemodynamic parameters after intubation, during intraoperative period and after extubation were similar in both groups. Conclusion: Vagolytic drug (Atropine sulphate) should be considered if vagotonic anaesthetic drugs are used along with carboperitoneum creation during laparoscopic surgery.DOI: http://dx.doi.org/10.3126/jkmc.v2i2.10622Journal of Kathmandu Medical College, Vol. 2, No. 2, Issue 4, Apr.-Jun., 2013, Page : 45-50

Evaluation of oculocardiac reflex in non- atropinized patients during cataract surgery under local anaesthesia

Abstract: Oculocardiac reflex (OCR) is an event seen during the cataract operation revealed as bradycardia. The situation is triggered by pulling or stitching of external ocular muscles. Anesthesiologists used atropine for controlling this reflex if ensues. This study aimed to estimate the incidence of the oculocardiac reflex during cataract surgery under local anesthesia (LA) and to assess the need for atropine to avoid this event. This study included eighty patients aged 45-80 years with class I or II ASA physical status listed for elective cataract extraction and intraocular lens (IOL) implantation under peribulbar block. The past medical history, drugs history, investigations and baseline vital signs were all observed and recorded. The observer continuously monitors heart rate readings. Oxygen was given to all patients through nasal cannula while spontaneously breathing. The results showed a significant drop in the heart rate following superior rectus muscle grasp and stitching (5.69%). This finding was observed following sedation (6.19%) and after removing of the stitch (6.22%), which indicates triggering of OCR. This slowing in heart rate did not require the use of atropine as bradycardia did not reach a serious level. In conclusion, the alterations in heart rate during cataract surgery observed mainly at handling of the extra-ocular muscles and following sedation. Atropine is not essential as a routine premedication in cataract surgery, particularly in geriatric populations in order to avoid the major side effects of atropine such as: tachyarrhythmias, central nervous system toxicity and urine retention, however, it should be accessible for administration if bradycardia ensues.

Регуляция мускариновыми рецепторами кальциевого транзиента и синаптической передачи в нервно-мышечном соединении лягушки

Abstract: In frog neuromuscular junction, muscarine, exogeneous acetylcholine and acetylcholinesterase inhibitor proserine reduced the intensity of calcium-sensitive dye fluorescence (calcium transient) at low frequency of nerve stimulation, suggesting that calcium ions entry into nerve ending was decreased. M2 muscarinic receptor blocker methoctramine prevented the action of muscarine. The amplitude of endplate currents was reduced in presence of muscarine at low frequency nerve stimulation, and atropine abolished this effect. Amplitudes of endplate currents evoked by high frequency stimulation were enhanced in presence of methoctramine, and synaptic depression was less pronounced, probably due to elevated calcium concentration in nerve ending. Thus, activation of presynaptic muscarinic receptors predominantly of M2 subtype reduces the intensity of quantal acetylcholine release in frog neuromuscular synapses that may be associated with decreased level of calcium ions in the nerve ending to provide the modulation of postsynaptic currents amplitude at high frequency firing.