Cholecystokinin-Induced Duodenogastric Bile Reflux Increases the Severity of Indomethacin-Induced Gastric Antral Ulcers in Re-fed Mice.

BACKGROUND/AIMS: We examined the involvement of cholecystokinin (CCK) in the exacerbation of indomethacin (IND)-induced gastric antral ulcers by gastroparesis caused by atropine or dopamine in mice. METHODS: Male mice were fed for 2 h (re-feeding) following a 22-h fast. Indomethacin (IND; 10 mg/kg, s.c.) was administered after re-feeding; gastric lesions were examined 24 h after IND treatment. In another experiment, mice were fed for 2 h after a 22-h fast, after which the stomachs were removed 1.5 h after the end of the feeding period. Antral lesions, the amount of gastric contents, and the gastric luminal bile acids concentration were measured with or without the administration of the pro- and antimotility drugs CCK-octapeptide (CCK-8), atropine, dopamine, SR57227 (5-HT3 receptor agonist), apomorphine, lorglumide (CCK1 receptor antagonist), ondansetron, and haloperidol alone and in combination. RESULTS: IND produced severe lesions only in the gastric antrum in re-fed mice. CCK-8, atropine, dopamine, SR57227 and apomorphine administered just after re-feeding increased bile reflux and worsened IND-induced antral lesions. These effects were significantly prevented by pretreatment with lorglumide. Although atropine and dopamine also increased the amount of gastric content, lorglumide had no effect on the delayed gastric emptying provoked by atropine and dopamine. Both ondansetron and haloperidol significantly inhibited the increase of bile reflux and the exacerbation of antral lesions induced by atropine and dopamine, respectively, but did not affect the effects of CCK-8. CONCLUSIONS: These results suggest that CCK-CCK1 receptor signal increases bile reflux during gastroparesis induced by atropine and dopamine, exacerbating IND-induced antral ulcers.

Central anticholinergic syndrome secondary to atropine eye drops: A case study.

Atropine eye drops are frequently used in the treatment of keratitis and during ophthalmic surgery. We described a rare complication of central anticholinergic syndrome secondary to atropine eye drops.

Gastroparesis Worsens Indomethacin-Induced Gastric Antral Ulcers by Bile Reflux via Activation of 5-HT3 and Dopamine D2 Receptors in Mice.

BACKGROUND/AIMS: We examined the contributions of gastric emptying and duodenogastric bile reflux in the formation of gastric antral ulcers induced by NSAIDs in mice. METHODS: We used the murine re-fed indomethacin (IND) experimental ulcer model. Outcome measures included the appearance of gastric lesions 24 h after IND treatment and the assessment of gastric contents and the concentration of bile acids 1.5 h after re-feeding. The effects of atropine, dopamine, SR57227 (5-HT3 receptor agonist), apomorphine, ondansetron, haloperidol, and dietary taurocholate and cholestyramine were also examined. RESULTS: IND (10 mg/kg, s.c.) induced severe lesions only in the gastric antrum in the re-fed model. The antral lesion index and the amount of food intake during the 2-h refeeding period were positively correlated. Atropine and dopamine delayed gastric emptying, increased bile reflux, and worsened IND-induced antral lesions. SR57227 and apomorphine worsened antral lesions with increased bile reflux. These effects were prevented by the anti-emetic drugs ondansetron and haloperidol, respectively. The anti-emetic drugs markedly decreased the severity of antral lesions and the increase of bile reflux induced by atropine or dopamine without affecting delayed gastric emptying. Antral lesions induced by IND were increased by dietary taurocholate but decreased by the addition of the bile acid sequestrant cholestyramine. CONCLUSIONS: These results suggest that gastroparesis induced by atropine or dopamine worsens NSAID-induced gastric antral ulcers by increasing duodenogastric bile reflux via activation of 5-HT3 and dopamine D2 receptors.

Effect of Low-Concentration Atropine Eyedrops vs Placebo on Myopia Incidence in Children: The LAMP2 Randomized Clinical Trial.

Importance: Early onset of myopia is associated with high myopia later in life, and myopia is irreversible once developed. Objective: To evaluate the efficacy of low-concentration atropine eyedrops at 0.05% and 0.01% concentration for delaying the onset of myopia. Design, Setting, and Participants: This randomized, placebo-controlled, double-masked trial conducted at the Chinese University of Hong Kong Eye Centre enrolled 474 nonmyopic children aged 4 through 9 years with cycloplegic spherical equivalent between +1.00 D to 0.00 D and astigmatism less than -1.00 D. The first recruited participant started treatment on July 11, 2017, and the last participant was enrolled on June 4, 2020; the date of the final follow-up session was June 4, 2022. Interventions: Participants were assigned at random to the 0.05% atropine (n = 160), 0.01% atropine (n = 159), and placebo (n = 155) groups and had eyedrops applied once nightly in both eyes over 2 years. Main Outcomes and Measures: The primary outcomes were the 2-year cumulative incidence rate of myopia (cycloplegic spherical equivalent of at least -0.50 D in either eye) and the percentage of participants with fast myopic shift (spherical equivalent myopic shift of at least 1.00 D). Results: Of the 474 randomized patients (mean age, 6.8 years; 50% female), 353 (74.5%) completed the trial. The 2-year cumulative incidence of myopia in the 0.05% atropine, 0.01% atropine, and placebo groups were 28.4% (33/116), 45.9% (56/122), and 53.0% (61/115), respectively, and the percentages of participants with fast myopic shift at 2 years were 25.0%, 45.1%, and 53.9%. Compared with the placebo group, the 0.05% atropine group had significantly lower 2-year cumulative myopia incidence (difference, 24.6% [95% CI, 12.0%-36.4%]) and percentage of patients with fast myopic shift (difference, 28.9% [95% CI, 16.5%-40.5%]). Compared with the 0.01% atropine group, the 0.05% atropine group had significantly lower 2-year cumulative myopia incidence (difference, 17.5% [95% CI, 5.2%-29.2%]) and percentage of patients with fast myopic shift (difference, 20.1% [95% CI, 8.0%-31.6%]). The 0.01% atropine and placebo groups were not significantly different in 2-year cumulative myopia incidence or percentage of patients with fast myopic shift. Photophobia was the most common adverse event and was reported by 12.9% of participants in the 0.05% atropine group, 18.9% in the 0.01% atropine group, and 12.2% in the placebo group in the second year. Conclusions and Relevance: Among children aged 4 to 9 years without myopia, nightly use of 0.05% atropine eyedrops compared with placebo resulted in a significantly lower incidence of myopia and lower percentage of participants with fast myopic shift at 2 years. There was no significant difference between 0.01% atropine and placebo. Further research is needed to replicate the findings, to understand whether this represents a delay or prevention of myopia, and to assess longer-term safety. Trial Registration: Chinese Clinical Trial Registry: ChiCTR-IPR-15006883.

[[A MULTICENTER SPANISH STUDY OF ATROPINE 0.01% IN CHILDHOOD MYOPIA PROGRESSION]].

Myopia, short-sightedness, is the most frequent cause of vision difficulty and its prevalence is expected to rise. Nowadays, the usage of atropine drops is effective for myopia progression control. Studies on the Asian population showed that atropine 0.01% is more efficient and safer than solutions that have a higher concentration. In this study, we report findings from a multicenter Spanish study that showed that atropine 0.01% decreases the progression of myopia in a pediatric population, with relatively few adverse effects. The results of this study may be relevant to doctors who treat children who have myopia, as well as to the children treated and their parents.

Anticholinergics and serious adverse events in pediatric procedural sedation: A report of the pediatric sedation research consortiums.

BACKGROUND: Pediatric sedation is a clinical activity with potential for serious but rare airway adverse events, particularly laryngospasm. Anticholinergic drugs, atropine and glycopyrrolate, are frequently used with the intention to improve sedation safety by virtue of their antisialagogue effects. AIMS: The objective of this study is to describe the current practice of anticholinergic use in pediatric sedation and to compare the frequency of serious sedation-related adverse events in patients who received anticholinergics to those who did not. METHODS: We examined prospectively collected data from the Pediatric Sedation Research Consortium database. Patient characteristics, procedure type, sedation provider, sedatives, location of sedation, anticholinergic administered, adverse events, and airway interventions were reported. Propensity score matching and multivariable logistic regression were used to test whether any association exists between anticholinergic use and serious sedation-related adverse events. RESULTS: Anticholinergics were administered in 7.1% (n = 18 707) of all cases (n = 263 883) reported between November 2011 and October 2017. When anticholinergics were used, atropine was used in 22% (n = 4111) and glycopyrrolate in 78.1% (n = 14 601) of sedations. Use of anticholinergics was more common in patients with well-described risk factors for airway adverse events: active/history of upper respiratory infection, history of reactive airway disease/asthma, and exposure to smoke. However, infants and ASA 3 patients were not associated with higher rate of anticholinergic use. Anticholinergic use was independently associated with an increase in the odds of serious adverse events, OR 1.8 (95% CI 1.6-2.1), especially airway adverse events. CONCLUSIONS: In this large Pediatric Sedation Research Consortium study, we found the use of anticholinergic adjuvants independently associated with greater odds of serious adverse events, especially airway adverse events, after adjusting for well-known sedation risk factors using propensity score matching and multivariate analysis.

Atropine-induced toxicity after off-label sublingual administration of eyedrop for sialorrhoea treatment in neurological disabled patients.

Sialorrhea is a troublesome and disabling symptom defined by the unintentional loss of saliva from the mouth, usually associated with swallowing disorders. Today there is no consensus about the management of sialorrhoea, but off-label use of ophthalmic atropine eyedrop administered sublingually may offer benefits, despite limited safety data. We report 2 cases of atropine overdose after sublingual administration illustrating that atropine can expose to severe adverse effects when administered sublingually. The noncompartmental pharmacokinetic study of atropine performed in 1 patient highlighted that systemic absorption of sublingual atropine was effective (Cmax [1 h] = 2.2 ng mL-1 ; approximately) after a single dose of 1 mg.

[The safety of atropine for myopia prevention and control].

Atropine is a classical drug with a wide use in clinical practice. In ophthalmology, atropine can be used for cycloplegia before optometry, and the treatment of amblyopia, iridocyclitis, malignant glaucoma, etc. In recent years, the "old drugs with new application " research and application of atropine for myopia prevention and control has become a hotspot and the efficacy of atropine has been preliminarily recognized. However, before the widely used in clinical, the safety of atropine draws attention. Researches concerning side effects of atropine were searched. The most common problem is photophobia due to dilated pupils, followed by poor near visual acuity, allergy and inflammation, local irritation. Other side effects include withdraw rebound, dry eyes, elevation of intraocular pressure, system reactions, photic damage and toxicity. Among them, some side effects are theoretical yet, and the long-term effects of some side reactions are not clear. Further research and exploration is needed to serve clinical evidence. At present, investigational usage for myopia prevention and control in clinical trials of atropine can be beneficial. Safety observation and efficacy evaluation are equally important in the course of application. (Chin J Ophthalmol, 2021, 57: 299-304).

Efficacy and Safety of 1% Atropine on Retardation of Moderate Myopia Progression in Chinese School Children.

Background: To evaluate the long-term efficacy and safety of topical 1% atropine for retarding moderate myopia. Methods: A randomized, controlled study evaluating atropine and placebo in 660 Chinese children. Patients received drops q1month for 24 months, then q2month for 12 months, followed by no drops for 12 months. Spherical equivalent, axial length, intraocular pressure and atropine-related side effects were examined at 6, 12, 24, 36 and 48 months for all children. Results: Spherical equivalent, myopic progression, axial length augmentation, and progression rate were significantly reduced in the atropine group than those in the placebo group (all P<0.05), indicating that 1% atropine effectively retarded myopia. Moreover, myopic rebound and adverse effects of 1% atropine were eliminated by gradual withdrawal and elimination of 1% atropine. Furthermore, pupil size, near visual acuity, and amplitude of accommodation returned to pretreatment levels after withdrawal of atropine. Conclusion: Topical 1% atropine periodically and alternatively in phase I with gradual reduction in phase II and final withdrawal in phase III may effectively improve atropine efficacy, retard moderate myopia, reduce atropine side effects, minimize myopic rebound, and increase compliance of children simultaneously.

Organophosphorus compounds and oximes: a critical review.

Organophosphorus (OP) pesticides and nerve agents still pose a threat to the population. Treatment of OP poisoning is an ongoing challenge and burden for medical services. Standard drug treatment consists of atropine and an oxime as reactivator of OP-inhibited acetylcholinesterase and is virtually unchanged since more than six decades. Established oximes, i.e. pralidoxime, obidoxime, TMB-4, HI-6 and MMB-4, are of insufficient effectiveness in some poisonings and often cover only a limited spectrum of the different nerve agents and pesticides. Moreover, the value of oximes in human OP pesticide poisoning is still disputed. Long-lasting research efforts resulted in the preparation of countless experimental oximes, and more recently non-oxime reactivators, intended to replace or supplement the established and licensed oximes. The progress of this development is slow and none of the novel compounds appears to be suitable for transfer into advanced development or into clinical use. This situation calls for a critical analysis of the value of oximes as mainstay of treatment as well as the potential and limitations of established and novel reactivators. Requirements for a straightforward identification of superior reactivators and their development to licensed drugs need to be addressed as well as options for interim solutions as a chance to improve the therapy of OP poisoning in a foreseeable time frame.

Atropine Eye Drops Inappropriately Used for Diplopia Following Cosmetic Botulinum A Toxin Injections.

This is a first case report of atropine eye drops used inappropriately to treat diplopia that followed botulinum A toxin injections for a cosmetic indication. Also presented is a review of precautions on use of atropine eye drops by non-ophthalmic physicians.

Comparative pharmacokinetics of (S)-MP3950, a novel 5-HT4 receptor agonist, in normal and atropine-induced gastrointestinal motility disorders rats.

1. (S)-MP3950 is the (S)-enantiomer of active metabolite of mosapride, which exhibits higher 5-HT4 receptor agonistic effect than mosapride. It shows promise to become a novel drug candidate for the treatment of gastrointestinal motility disorders (GMDs). However, the pharmacokinetic behavior of (S)-MP3950 in the pathological state of GMDs remains unclear. Herein, we investigated the comparative pharmacokinetics of (S)-MP3950 in normal and GMDs rats. 2. The comparative pharmacokinetics of (S)-MP3950 in normal and atropine-induced GMD rats were studied by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The validated UPLC-MS/MS method was successfully applied to investigate the pharmacokinetic profiles of (S)-MP3950 in normal and atropine-induced GMDs rats. Results showed that comparing to normal rats, Cmax reduced by 73.8%, AUC0-t decreased by 57.6% and AUC0-∞ declined by 56.8% in model rats. Additionally, the elimination half-life (t1/2) and Tmax were prolonged slightly. 3. The pharmacokinetic results demonstrated that the atropine-induced GMDs reduced the absorption of (S)-MP3950. The pharmacokinetics research in the pathological state might provide more useful information for further study of novel gastric motility candidates.

Physostigmine Reversal of Dysarthria and Delirium After Iatrogenic Atropine Overdose From a Dental Procedure.

BACKGROUND: Sublingual atropine, dosed at 0.4-0.8 mg, is used by dentists as an antisialogogue to facilitate and increase the speed of procedures. Concentrated ophthalmic atropine drops (10 mg/mL) are commonly used off-label for this purpose. These highly concentrated drops may result in medication errors, atropine toxicity, and the antimuscarinic toxidrome. We report a case of a man who suffered acute delirium and dysarthria (from dry mouth) after an iatrogenic overdose from a dental procedure. His symptoms were initially interpreted as a stroke, but they completely resolved with physostigmine. CASE REPORT: A 57-year-old man presented with acute dysarthria and delirium after a dental procedure; 4 hours earlier he was fitted for a temporary replacement of some premolar/molar teeth. He received sublingual atropine to assist in gingival drying for molding of his prosthesis, but a calculation error resulted in the administration of approximately 113 mg. A stroke evaluation was initially planned; however, 2.5 mg of intravenous physostigmine completely reversed his symptoms. His symptoms reoccurred and were successfully treated twice more with physostigmine; the patient was observed overnight with no additional symptoms and safely discharged the next morning. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Ophthalmic atropine drops are highly concentrated and may cause an overdose after ingestion of small amounts. This novel case highlights the importance of considering antimuscarinic poisoning in cases of acute delirium or dysarthria after dental procedures and stands as a reminder to inquire about the use of atropine drops in such cases. Timely recognition of the antimuscarinic toxidrome and appropriate use of physostigmine may prevent unnecessary testing while providing an effective therapy. This case also highlights the need for observation after resolution of delirium treated with physostigmine.

[Atropine for the Prevention of Progression in Myopia - Data, Side Effects, Practical Guidelines]. / Atropin zur Prävention der Myopieprogression ­ Datenlage, Nebenwirkungen, praktische Empfehlungen.

The prevalence of myopia has increased worldwide in recent decades. In East Asia's metropolises ≥ 80% of young adults are affected. This dramatic increase is mainly caused by changes in lifestyle and behaviour. Atropine has been used for more than 100 years to arrest myopia progression. It has become an evidence-based treatment regimen in the last decade, although the exact mechanism of the effect of treatment is still unknown. Atropine eye drops can slow myopia progression by an average of - 0.54 dioptres (D)/year in Asian children and - 0.35 D/year in Caucasian children. However, a non-response rate of about 10% has been found. Treatment should be established in schoolchildren only (age ≥ 6 years) with myopia ≤ - 2 D (spherical equivalent, cycoplegic refraction) and with documented myopic progression of - 0.5 D in the preceding year. 0.01% eyedrops should be instilled into the lower fornix at bedtime. Atropine 0.01% therapy is well tolerated. Atropine is usually administered for 2 years since efficacy is somewhat better in the second year. During treatment, a 6-month follow-up with cycoplegic refraction and axial length measurement is recommended. After the 2-year period, atropine withdrawal is justified if progression is less than - 0.25 D/year in the second year. Even after atropine has been stopped, follow-up examinations are needed to detect any rebound. Atropine-therapy is resumed if progression is again higher than - 0.5 D/year. Topical atropine is used off-label.

Hypoxemia after single-shot anesthesia in common marmosets.

BACKGROUND: It remains unknown how single-shot anesthesia influences physical parameters, especially respiratory function and blood oxygen level of common marmosets (Callithrix jacchus) which came to be used for laboratory research. METHODS: We measured blood oxygen levels, both before and after oxygenation, in 13 common marmosets under two single-shot anesthesia conditions: ketamine/xylazine/atropine and alphaxalone. RESULTS AND CONCLUSIONS: We found that SpO2 values decreased to about 80% in the ketamine/xylazine/atropine protocol and fell just below 90% in the alphaxalone protocol. We observed a clear decrease in PaO2 values under the anesthetized condition compared to the awake condition. Our data indicate that single-shot anesthesia may cause hypoxemia in marmosets. Previous studies on other non-human primate have reported no SpO2 decrease and hypoxemia; thus, our experiment suggests that marmosets may have a more fragile respiratory system and require intensive veterinary care during anesthesia.

Transient symptomatic worsening by atropine in opsoclonus-myoclonus syndrome.

Opsoclonus-myoclonus syndrome (OMS) is characterized by abnormal eye and systemic involuntary movements, as well as cerebellar ataxia. Some sedatives and anesthetics worsen movements associated with OMS, while there is no known report of a negative effect of atropine. We report on sedation in two patients with OMS. Involuntary movements were transiently worsened after using atropine with midazolam or thiamylal in both, but were not seen when atropine was not used. We speculated that atropine has the potential to exacerbate involuntary movements in OMS due to vulnerability to this agent via unknown mechanisms.

Central anticholinergic syndrome vs. idiosyncratic reaction triggered by a small IV dose of atropine.

A 58-year-old male was scheduled to undergo radical gastrectomy for cancer under general anesthesia. The patient developed agitation and irregular breathing after receiving a single dose of atropine (0.5 mg) to treat bradycardia immediately prior to induction of anesthesia. Within 5 min after the atropine injection, the patient became unresponsive with facial flushing and diaphoresis. When a drop in oxygen saturation was observed, a laryngeal mask airway was inserted after administering a small bolus dose of propofol (80 mg) and the patient was ventilated with 100% oxygen. Physostigmine was not administered because of the relatively low dose of atropine and the fact that his symptoms were not totally consistent with central anticholinergic syndrome (CAS). The differential diagnosis at the time also included an acute cardiovascular event and an idiosyncratic reaction to atropine. The patient fully recovered within 80 min from this highly unusual reaction to a single 0.5 mg IV dose of atropine.

To Pretreat or Not to Pretreat: Prophylactic Anticholinergic Administration Before Dexmedetomidine in Pediatric Imaging.

BACKGROUND: Dexmedetomidine (Dex) appears to be very effective as a sole sedative for pediatric imaging when used at high doses, but at an increased risk of transient hypertension, hypotension, and bradycardia. There are no clinical evidence/guidelines to guide anesthesia providers as to whether patients should be pretreated with an anticholinergic. The aim of this study was to demonstrate the changes in hemodynamic parameters after Dex sedation attributed to receiving or not receiving an anticholinergic pretreatment and compare for any differences or similarities. A subgroups analysis was performed in children with Down syndrome (DS). METHODS: In this retrospective descriptive study, we reviewed the records of 163 children receiving Dex anesthesia during MRI studies. Data analyzed included demographics, history of DS, and hemodynamics (heart rate [HR], systolic blood pressure [SBP], and diastolic blood pressure [DBP]) following Dex loading and infusion and the administration of an anticholinergic (atropine or glycopyrrolate). RESULTS: The mean age was 94.5 months, and 52 (32%) patients had DS. The generalized linear mixed-effects regression model showed a significant reduction in HR and SBP in all patients when no anticholinergic was administered compared with when it was administered. There was no significant change with DBP. During the scan period, the HR of the no-anticholinergic group decreased 26.6%, whereas that of the anticholinergic group decreased by only 16.7% from baseline (P < 0.01). The maximal SBP increased by a significantly greater percentage, compared with baseline, in the anticholinergic group in comparison with the no-anticholinergic group (20.2% vs 10.4%, respectively; P = 0.02). In the DS group, the difference in the maximal SBP change during the scan period was exaggerated, with a percentage increase that was 36 times larger in the anticholinergic group compared with the no-anticholinergic group (22% vs 0.6%, respectively; P< 0.01). CONCLUSIONS: Administration of a prophylactic anticholinergic with Dex shows no advantage other than a transient clinically insignificant increase in HR and SBP, and it may precipitate transient exaggerated SBP in more patients compared with not using a prophylactic anticholinergic.

The effect of topical ophthalmic 1% atropine on heart rate and rhythm in normal dogs.

OBJECTIVE: To determine if topically administered ophthalmic atropine affects heart rate or rhythm in clinically normal dogs. METHODS: Two groups of 15 healthy dogs were evaluated, one consisting of dogs weighing <15 kg, the other consisting of dogs weighing >15 kg. Each dog was suited with a Holter monitor. At start time 0, dogs received one drop of ophthalmic 1% atropine solution, or one drop of sterile saline solution as a control in each eye, via random assignment. Each dog served as their own control. This procedure was repeated two more times, at 6-h intervals, for a total of three treatments over a 12-h period. Holter monitors recorded heart rate and rhythm for 24 h. Statistical analysis was performed to compare values between the groups. Dose dependent changes in cardiac parameters were evaluated. RESULTS: The mean heart rate and average minimum heart rate was significantly higher during the treatment period compared to the control period (8% and 13%, respectively). The mean number of hours with a heart rate <50 bpm decreased by 47% in the treatment vs. the control period. The mean maximum heart rate and number of h with a heart rate > 180 bpm did not differ significantly between the two groups. There was no evidence of dose dependence on heart rate when comparing small and large dogs. No significant differences in heart rhythm were noted between groups for measurable parameters. CONCLUSIONS: Topically administered atropine causes a small but significant increase in heart rate in healthy dogs.