Trospium chloride for overactive bladder may induce central nervous system adverse events

BackgroundAnticholinergic drugs constitute the first-line pharmacologic treatment for overactive bladder (OAB). Of the various anticholinergic agents available, trospium chloride appears to have potentially favorable chemical and pharmacologic properties leading to reduce the incidence of central nervous system (CNS) adverse reactions, since their ability to cross the blood-brain barrier is reduced (relative to other drugs in this therapeutic class).ObjectiveThe objective of the present survey was to establish whether or not CNS adverse reactions may be associated with trospium exposure by evaluating spontaneous reports made to the French pharmacovigilance database (FPVD).MethodsAll serious adverse drug reactions, specifically confusion, hallucinations, agitation and cognitive impairment, associated with trospium (the immediate-release form only) recorded in the FPVD between September 2005 to September 2011 were identified and analyzed.ResultsWe identified 15 cases of CNS adverse events, according to at least one of the following terms: confusion (n = 9), hallucinations (n = 6), cognitive impairment (n = 4) and agitation (n = 2) and in which trospium chloride was suspected to have a causal link according to their imputability evaluation. The reports concerned 10 women and 5 men, with a mean age of 81 years (range: 62 to 96 years). The symptoms varied from relatively acute states of confusion and/or hallucinations to more progressive cognitive changes. In all these cases, CNS symptoms resolved rapidly after treatment discontinuation.ConclusionDespite the drug's favorable physiochemical properties, we have found pharmacovigilance data indicating that trospium chloride prescribed for OAB can induce CNS adverse reactions, such as confusion, hallucinations, agitation and/or cognitive impairment. Physicians should consider withdrawing trospium chloride if CNS symptoms suggestive of anticholinergic adverse effects occur in patients treated with this drug.     

Use of a Physostigmine Continuous Infusion for the Treatment of Severe and Recurrent Antimuscarinic Toxicity in a Mixed Drug Overdose

Introduction

Physostigmine was once a widely used antidote for the treatment of antimuscarinic toxicity. However, reports describing the association of physostigmine with asystole and seizures in severe tricyclic antidepressant poisoning resulted in a decrease in use. Recent literature has demonstrated that physostigmine is a safe and effective antidote for the treatment of antimuscarinic toxicity. There are only two previously published articles regarding the use of physostigmine administered as a continuous intravenous infusion for persistent antimuscarinic toxicity. We present a case of physostigmine continuous infusion for the treatment of antimuscarinic symptoms in a polydrug overdose due to the ingestion of diphenhydramine along with bupropion, citalopram, acetaminophen, and naproxen.

Case Presentation

A 13-year-old female presented with hyperthermia, myoclonus and rigidity, hallucinations, severe agitation, and antimuscarinic toxicity including inability to sweat after a polydrug overdose. Several doses of lorazepam were administered followed by physostigmine which produced resolution of hallucinations and attenuation of the antimuscarinic symptoms including perspiration, temperature improvement, and decreased agitation. After periods of improvement and recurrence of antimuscarinic effects, a continuous infusion of physostigmine was administered at 2 mg/h and continued for almost 8 h to maintain attenuation of symptoms. GABAergic agents including lorazepam and phenobarbital were used later in the hospital course for presumed symptoms of serotonergic and adrenergic toxicity after resolution of antimuscarinic effects. The patient did not experience any adverse effects of physostigmine administration.

Discussion

Physostigmine administered as a continuous infusion may be a reasonable treatment option for severe and recurrent symptoms related to antimuscarinic toxicity.     

Angel��s Trumpet (Datura stramonium) poisoning and delirium in adolescents in Winnipeg, Manitoba: Summer 2006

Over the course of the summer of 2006, four adolescent patients were hospitalized because of intentional Datura stramonium (Angel’s Trumpet) ingestion. Their records were reviewed for the presence of signs and symptoms of toxicity, clinical course, treatment and outcome. All four patients had a decreased level of consciousness measured by the Glasgow Coma Scale, visual hallucinations, dilated pupils and agitation. The changes in mental status are characteristic of delirium. All four patients were known to abuse substances. The average length of hospitalization was two days. No serious complications were encountered during hospitalization and a full recovery was noted in all patients. The use of sedation and restraints were sufficient treatment modalities. Health care workers should consider anticholinergic plant ingestion as a cause for abrupt onset of delirium.     

氯氮平引起流涎的治疗

流涎是氯氮平的主要不良反应,发生率约为1/3,一般认为该不良反应与阻断M4受体和/或α2受体,以及吞咽反射紊乱有关.本文就使用抗胆碱药、抗肾上腺素药等对其治疗的情况作一综述.     

Reduced growth hormone secretion improves insulin sensitivity in adolescent girls with type 1 diabetes

The aims of the present study were to compare nocturnal growth hormone (GH) secretion, insulin requirements and insulin sensitivity on two occasions in six adolescent girls with type 1 diabetes when the GH secretion was reduced one night by an oral dose of 100 mg of pirenzepine at bedtime. The mean nocturnal intravenous insulin infusion required to maintain a normal constant blood glucose concentration between 24:00 and 07:00 was 53% higher during the night on placebo ( p = 0.0212). During the night on pirenzepine, the serum GH area under the curve (AUC) was reduced in all patients to a mean concentration which was 50.1% (15-78%) of that during the night without pirenzepine ( p = 0.0036). The nocturnal urinary GH excretion was also reduced in all of the investigated patients ( p = 0.0229). Insulin sensitivity in the morning, measured by the euglycaemic hyperinsulinaemic glucose clamp, increased significantly from 115±51mg m^-2 min^-1 after the night on placebo to 205±67 mg m^-2 min^-1 after the night on pirenzepine ( p = 0.0161). No side-effects were observed during the pirenzepine night. Negative correlations were found between the nocturnal serum GH AUC and the insulin-stimulated glucose metabolism ( r = 0.65, p = 0.0241) and between the nocturnal urinary GH excretion and the insulin-stimulated glucose metabolism ( r = -0.77, p = 0.0054). In conclusion, the present study shows a relation between GH secretion and insulin resistance in adolescent girls with type I diabetes. The administration of pirenzepine acutely reduces GH secretion and improves insulin sensitivity.     

Qualitative analysis of scopolamine-induced amnesia

The neurochemistry of memory remains to be determined. Acetylcholine may be one of the neuotransmitters which mediates memory function, since the anticholinergic drug scopolamine produces amnesia in man. This study of scopolamine-induced memory deficits further defines those cognitive processes which are disrupted. The drug does not diminish attention, as assessed with an auditory vigilance task, or initial signal detection. More complex auditory decoding is affected, however. Scopolamine impairs aspects of initial memory acquisition (e. g., encoding and consolidation) and spontaneous memory retrieval. Retention is unaffected. Precise delineation of the neurochemistry of human memory will require comparative studies of amnesia-producing compounds, systematically examining the neuropsychological processes impaired by each.     

Acetylcholine and choline levels in rabbit fetuses exposed to anticholinergics

It has been hypothesized that acetylcholine, choline acetylase and acetylcholinesterase may have an ontogenic and trophic influence in the embryo, and that therefore certain drugs may produce malformations via their effect on the acetylcholine and choline levels in the fetus. Thalidomide and the anticholinergics, scopolamine hydrobromide and orphenadrine hydrochloride, and doxylamine succinate, an antihistamine with secondary anticholinergic action, were administered to pregnant New Zealand White rabbit does from day 8 to day 15 of gestation. Cesarean sections were performed on gestational day 16, the fetuses removed and the acetylcholine and choline contents of the fetuses and placentas were estimated by organic extraction and derivation for injection into a GCMS. These acetylcholine and choline levels were compared with those of the fetuses and placentas of the control animals mated with the same buck on the same day as the treated animals. Thalidomide (50 mg/kg) did not affect acetylcholine or choline levels in the fetuses or the placentas obtained from the treated animal. Scopolamine (approximately 100 micrograms/kg) reduced the choline level in the placenta and fetus but not the acetylcholine levels. Orphenadrine (approximately 24 mg/kg) reduced acetylcholine and choline levels in the fetus and choline levels in the placenta. Doxylamine succinate (10 mg/kg) reduced the acetylcholine levels in the fetus and the choline levels in the placenta. The placenta is a fetal organ and the significance of acetylcholine production by the placenta is as yet unknown. The reduction in acetylcholine levels in the fetus exposed to drugs with an anticholinergic action may be of significance in the production of malformations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Amitriptyline,clovoxamine and cognitive function: a placebo-controlled comparison in depressed outpatients

No longer prescribed only for vegetative signs of depression, tricyclic antidepressants also lessen depressive cognitive distortions. Less clear is whether they ameliorate depressed patients' other cognitive deficits in memory, information processing speed, and psychomotor performance. We tested the alternative hypothesis that amitriptyline, because of its anticholinergic and sedative properties, would exacerbate depressed patients' cognitive disturbances. Depressed outpatients received double-blind placebo (n=15), amitriptyline (n=10), or clovoxamine fumarate (n=10), a serotonin reuptake inhibitor relatively lacking in anticholinergic properties. Depression, memory, and psychomotor performance were assessed at baseline and after 7 and 28 days of drug treatment. Depression was alleviated after all treatments, including placebo. Only amitriptyline impaired performance on tests of memory, producing a significant decrement, relative to placebo, after 4 weeks of treatment. None of the treatments adversely affected performance on psychomotor tasks. These findings add to the evidence that antidepressant drugs with high anticholinergic activity can impair memory, despite alleviation of depression.     

The wet patient: understanding patients with overactive bladder and incontinence

SUMMARY

Overactive bladder (OAB) is a constellation of lower urinary tract symptoms, including urinary frequency and urgency, which can occur with or without urinary incontinence. Incontinence is present in over half of female patients with OAB. This condition affects more than 33 million Americans and imposes considerable economic, social, and psychological burdens. Although continued improvements in the pharmacologic management of lower urinary tract disorders have led to the availability of well-tolerated, effective treatment options, the symptoms of OAB are generally underreported by patients and under- treated by healthcare professionals. Heightened awareness of the multifaceted disease burden imposed by OAB and increased understanding of the characteristics of patients who are likely to be most severely affected, in particular those who suffer from incontinence, may improve the timely identification, diagnosis, and clinical management of the syndrome, enhancing both the health and quality of life of these patients. This review will summarize the characteristic features, prevalence and epidemiology, clinical consequences, and management of OAB, with particular focus on the incontinent patient.     

Feasibility and baseline findings of an educational intervention in a randomized trial to optimize drug treatment among residents in assisted living facilities

PurposeTo describe the baseline findings and feasibility of a cluster randomized controlled trial of staff training to optimize the use of drugs among older residents in assisted living facilities.MethodsParticipants (n = 227) were recruited from assisted living facilities in Helsinki, Finland. Their wards were randomized into two arms: 1) intervention wards in which staff received training (2 × 4 hours) to identify prescribing of harmful drugs; 2) control wards in which staff received training after completion of the intervention. Cognition, health-related quality-of life (HRQoL) by 15D and psychological well-being (PWB) were assessed of all participants. Demographics, diagnoses and drug use were verified from medical records. Drugs were categorized using anatomical therapeutic chemical (ATC) codes. The prevalence of anticholinergic, multiple psychotropic and Beers Criteria drugs was computed.ResultsThe mean age of participants was 83 years, 71% were females and 93% had dementia. The intervention and comparison groups did not differ with respect to cognition or PWB. However, the proportion of females and HRQoL was lower, and the Charlson comorbidity index higher in the intervention than in the control group. In addition, the prevalence of pro re nata (PRN) drugs, and the proportion using any harmful drug was higher in the intervention than in the control group. Staff training was received favourably by staff participants in the intervention wards. However, not all nurses participated in the training sessions, and there was some resistance to change working habits.ConclusionsWe have successfully randomized wards of assisted living facilities and trained staff in the intervention arm.