A comparison of citalopram and paroxetine in the treatment of panic disorder: a randomized, single-blind study. Postoperative nausea and vomiting: a comparison of anti-emetic drugs used alone or in combination. Intravesical instillation of oxybutynin in women with idiopathic detrusor instability: a randomised trial Anti-cholinergic load, health care utilization, and survival in people with advanced cancer: a pilot study. Posatirelin for the treatment of late‐onset Alzheimer's disease: a double‐blind multicentre study vs citicoline and ascorbic acid Modulation of Mood and Cognitive Performance Following Acute Administration of Single Doses of Melissa Officinalis (Lemon Balm) with Human CNS Nicotinic and Muscarinic Receptor-Binding Properties Can the pattern of neuropsychological improvement obtained with cholinergic drugs be used to infer a cholinergic mechanism in other nootropic drugs? Acetyl-L-carnitine: a drug able to slow the progress of Alzheimer's disease? Pharmacologic cholinesterase inhibition improves survival in experimental sepsis* Efficacy of cetirizine in cholinergic urticaria. Combination of a cholinergic drug and an alpha-blocker is more effective than monotherapy for the treatment of voiding difficulty in patients with underactive detrusor. Administration of clonazepam in the treatment of TMD and associated myofascial pain: a double-blind pilot study. Evaluation of Different Combined Regimens in the Treatment of Cholinergic Urticaria Rivastigmine in subcortical vascular dementia: An open 22-month study The Effects of Common Anti-Inflammatory Drugs on the Healing Rat Patellar Tendon
BACKGROUND Serotonin Selective Re-uptake Inhibitors ( SSRIs ) are the drugs of choice for treating panic disorder ( PD ) . In vitro studies have shown different pharmacodynamic profiles for SSRIs , but their clinical relevance is still unknown . Paroxetine , the SSRI with the strongest serotonergic effect , also shows significant cholinergic and noradrenergic activities . In this class of drugs , citalopram is the most selective for serotonin . We compared these two drugs and their effectiveness and tolerability in a sample of patients with PD in a two-month treatment course . METHOD Fifty-eight patients with PD were r and omly assigned to either the paroxetine or the citalopram treatment group in a single-blind , r and omized design . Each patient was assessed at days 0 , 7 and 60 by the Panic Associated Symptoms Scale ( PASS ) , the Sheehan Disability Scale ( SDS ) and the Fear Question naire ( FQ ) . Primary outcome measures were the percentage of patients free of panic attacks , anticipatory anxiety and phobic avoidance in the last week of the trial and the percentage of good responders , as defined by a reduction of at least 50 % from baseline of both PASS and SDS global scores at day 60 . RESULTS At day 60 , 86 % of patients receiving citalopram and 84 % of those receiving paroxetine responded well to treatment . No significant differences between the two drugs were found . Both were well tolerated , although sexual side effects and weight gain were frequent . Anticipatory anxiety decreased significantly after the first week of treatment , and no initial worsening in the panic attacks was observed . CONCLUSION Paroxetine and citalopram show similar anti-panic properties and a good tolerability profile . Our results support evidence that the serotonergic system plays a significant role in the anti-panic properties of these two SSRIs Drugs with anti-emetic properties can exert their actions at more than one receptor site , histamine H1 , muscarinic cholinergic or dopaminergic D2 receptors . This study was design ed to test the hypothesis that a combination of drugs acting at different receptor sites in lower than st and ard doses would be at least as effective as a st and ard therapeutic dose of a single anti-emetic agent . A combination of droperidol , hyoscine and metoclopramide in subtherapeutic doses has been shown to be at least as effective as droperidol ( 1.25 mg ) alone . In both groups there was a low incidence of emetic sequelae in the first 3 hours postoperatively Urinary incontinence is one of the most socially incapacitating problems affecting women .  Frequency , urgency and urge incontinence have been found to increase with age . Yet , no underlying cause has been established for the detrusor instability encountered in most patients .  Oxybutynin chloride is a tertiary amine with combined anti-cholinergic , muscle relaxant and local anaesthetic properties ( Diokno & Lapides 1972 ) . Oral oxybutynin chloride has a well documented therapeutic effect in patients with bladder instability . However , the high incidence of anti-cholinergic side effects ( 30 % to 80 % ) often requires dosage reduction or discontinuation of treatment ( Brendler et al. 1989 ) . Therefore , alternatives to conventional pharmacological treatment of detrusor instability have been the object of various studies ( Brendler et al. 1989 ; Greenfield & Fera 1991 ) . Intravesical drug instillation may be one such alternative . The aim of this study was to evaluate the benefits and side effects of intravesical oxybutynin application in women with idiopathic detrusor instability by means of a r and omised , placebo-controlled trial INTRODUCTION Anti-cholinergic medications have been associated with increased risks of cognitive impairment , premature mortality and increased risk of hospitalisation . Anti-cholinergic load associated with medication increases as death approaches in those with advanced cancer , yet little is known about associated adverse outcomes in this setting . METHODS A sub study of 112 participants in a r and omised control trial who had cancer and an Australia modified Karnofsky Performance Scale ( AKPS ) score ( AKPS ) of 60 or above , explored survival and health service utilisation ; with anti-cholinergic load calculated using the Clinician Rated Anti-cholinergic Scale ( modified version ) longitudinally to death . A st and ardised starting point for prospect ively calculating survival was an AKPS of 60 or above . RESULTS Baseline entry to the sub- study was a mean 62 + /- 81 days ( median 37 , range 1 - 588 ) days before death ( survival ) , with mean of 4.8 ( median 3 , SD 4.18 , range 1 - 24 ) study assessment s in this time period . Participants spent 22 % of time as an inpatient . There was no significant association between anti-cholinergic score and time spent as an inpatient ( adjusted for survival time ) ( p = 0.94 ) ; or survival time . DISCUSSION No association between anti-cholinergic load and survival or time spent as an inpatient was seen . Future studies need to include cognitively impaired population s where the risks of symptomatic deterioration may be more substantial Introduction ‐ Posatirelin ( L‐pyro‐2–aminoadipyl‐L‐leucil‐L‐prolinamide ) a new synthetic tripeptide with cholinergic , catecholaminergic and neurotrophic properties , was investigated in the treatment of Alzheimer 's disease . Material and methods ‐ A multicentre , double‐blind study vs citicoline ( reference drug ) and ascorbic acid ( inactive drug ) was carried out in elderly patients suffering from late‐onset Alzheimer 's disease . The once daily intramuscular treatment lasted for three months followed by one‐month oral treatment with a placebo . Subscales and factors of GBS ( Gottfries‐Bråne‐Steen ) Rating Scale were identified as primary measures for efficacy assessment . Results ‐ At the end of the treatment , GBS subscale and factor scores assessing intellectual and emotional impairments , orientation and memory , ability to perform activities of daily living , depression‐anxiety , attention and motivation were improved in the posatirelin group , showing significant differences with respect to the citicoline and /or ascorbic acid groups . Tolerability was good in all groups . Conclusions ‐ The improvement in the GBS Rating Scale scores observed in the posatirelin group is clinical ly relevant . It is worth verifying the drug‐induced functional improvements , in further studies with large sample Melissa officinalis ( Lemon balm ) is a herbal medicine that has traditionally been attributed with memory-enhancing properties , but which is currently more widely used as a mild sedative and sleep aid . In a previous study it was demonstrated that a commercial Melissa extract led to dose-specific increases in calmness , and dose-dependent decrements in timed memory task performance . However , the extract utilized in that study did not exhibit in vitro cholinergic receptor-binding properties . The current study involved an initial screening of sample s of M. officinalis for human acetylcholinesterase inhibition and cholinergic receptor-binding properties . The cognitive and mood effects of single doses of the most cholinergically active dried leaf were then assessed in a r and omized , placebo-controlled , double-blind , balanced crossover study . Following the in vitro analysis , 20 healthy , young participants received single doses of 600 , 1000 , and 1600 mg of encapsulated dried leaf , or a matching placebo , at 7-day intervals . Cognitive performance and mood were assessed predose and at 1 , 3 , and 6 h postdose using the Cognitive Drug Research computerized assessment battery and Bond – Lader visual analog scales , respectively . In vitro analysis of the chosen extract established IC50 concentrations of 0.18 and 3.47 mg ml−1 , respectively , for the displacement of [3H]-(N)-nicotine and [3H]-(N)-scopolamine from nicotinic and muscarinic receptors in the human cerebral cortex tissue . However , no cholinesterase inhibitory properties were detected . The most notable cognitive and mood effects were improved memory performance and increased ‘ calmness ’ at all postdose time points for the highest ( 1600 mg ) dose . However , while the profile of results was overwhelmingly favorable for the highest dose , decrements in the speed of timed memory task performance and on a rapid visual information-processing task increased with decreasing dose . These results suggest that doses of Melissa officinalis at or above the maximum employed here can improve cognitive performance and mood and may therefore be a valuable adjunct in the treatment of Alzheimer 's disease . The results also suggest that different preparations derived from the same plant species may exhibit different properties depending on the process used for the sample preparation 1 . Enhancement of episodic memory and reduction of intrusion errors are considered as the most characteristic outcome of cholinergic drugs administration in AD patients . 2 . Since the nootropic drugs Piracetam and Oxiracetam are deemed to act through a cholinergic mechanism , we checked whether AD patients treated with these drugs would show the same pattern of neuropsychological improvement . 3 . Results were negative , since ( a ) episodic memory showed a similar degree of improvement both in patients treated with these drugs and in patients treated with placebo ; ( b ) the number of intrusions tended to increase , rather than to decrease , after the treatment period Defects in cholinergic neurotransmission do not , by themselves , constitute the sole pathophysiologic concomitants of Alzheimer 's disease ( AD ) . Recent findings point out that abnormalities in membrane phospholipid turnover and in brain energy metabolism may also characterize AD . Acetyl-L-carnitine ( ALC ) is an endogenous substance that , acting as an energy carrier at the mitochondrial level , controls the availability of acetyl-L-CoA. ALC has a variety of pharmacologic properties that exhibit restorative or even protective actions against aging processes and neurodegeneration . A review of a series of controlled clinical studies suggests that ALC may also slow the natural course of AD Objective : Lethal sepsis occurs when an excessive inflammatory response evolves that can not be controlled by physiologic anti-inflammatory mechanisms , such as the recently described cholinergic anti-inflammatory pathway . Here we studied whether the cholinergic anti-inflammatory pathway can be activated by pharmacologic cholinesterase inhibition in vivo . Design : Prospect i ve , r and omized laboratory investigation that used an established murine sepsis model . Setting : Research laboratory in a university hospital . Subjects : Female C57BL/6 mice . Interventions : Sepsis in mice was induced by cecal ligation and puncture . Animals were treated immediately with intraperitoneal injections of nicotine ( 400 & mgr;g/kg ) , physostigmine ( 80 & mgr;g/kg ) , neostigmine ( 80 & mgr;g/kg ) , or solvent three times daily for 3 days . Measurements and Main Results : Treatment with physostigmine  significantly reduced lethality ( p ≤ .01 ) as efficiently as direct stimulation of the cholinergic anti-inflammatory pathway with nicotine ( p ≤ .05 ) . Administration of cholinesterase inhibitors significantly down-regulated the binding activity of nuclear factor-&kgr;B ( p ≤ .05 ) and significantly reduced the concentration of circulating proinflammatory cytokines tumor necrosis factor-&agr ; , interleukin-1&bgr ; , and interleukin-6 ( p ≤ .001 ) , and pulmonary neutrophil invasion ( p ≤ .05 ) . Animals treated with the peripheral cholinesterase inhibitor neostigmine showed no difference compared with physostigmine-treated animals . Conclusions : Our results demonstrate that cholinesterase inhibitors can be used successfully in the treatment of sepsis in a murine model and may be of interest for clinical use In order to examine the efficacy of cetirizine in cholinergic urticaria , we studied 24 patients in a double-blind crossover design during 3-week treatment periods , with either 10 or 20 mg/d cetirizine or placebo . The placebo period was always placed in between the two verum treatments to allow for a washout of the drug . Evaluation of the patients ' daily symptom scores based on itching , erythema and whealing showed a highly significant improvement ( p < 0.01 ) . The percentage of days with mild or no symptoms was also increased significantly with the drug ( p < 0.05 ) . Except for whealing ( p < 0.05 ) , no significant differences between the two dosages of cetirizine could be determined . Since antihistamines have previously been shown to be frequently unsatisfactory in the treatment of cholinergic urticaria , the present data are encouraging regarding the control of symptoms in this condition AIM The aim of the present study was to compare the effectiveness of a cholinergic drug , an alpha-blocker and combinations of the two for the treatment of underactive detrusor . METHODS One hundred and nineteen patients with underactive bladder were assigned to three groups : the cholinergic group , consisting of 40 patients taking bethanechol chloride ( 60 mg/day ) or distigmine bromide ( 15 mg/day ) ; the alpha-blocker group , consisting of 38 patients taking urapidil ( 60 mg/day ) ; and the combination group , consisting of 41 patients taking both a cholinergic drug and an alpha-blocker . The effectiveness of each therapy was assessed 4 weeks after initialization of the therapy . RESULTS Total urinary symptom scores ( International Prostate Symptom Score , IPSS ) remained unchanged after the cholinergic therapy , but were significantly lower after the alpha-blocker treatment ( P = 0.0001 ) and the combination therapy ( P = 0.0001 ) . With regard to the total IPSS , there were significant differences between the cholinergic and the alpha-blocker groups ( P = 0.0008 ) , and also between the cholinergic and combination groups ( P = 0.0033 ) , in favor of the latter . The average and maximum flow rates did not increase significantly after monotherapy with either the cholinergic drug or the alpha-blocker , but they significantly increased after combination therapy compared to baseline values ( P = 0.0033 and P= 0.0004 , respectively ) . Postvoid residual volume did not decrease significantly after the cholinergic drug therapy , but decreased significantly after the alpha-blocker ( P = 0.0043 ) and the combination therapies ( P = 0.0008 ) . The percentage of residual urine decreased significantly after therapy in all groups ( P = 0.0005 , P= 0.0176 and P= 0.0001 , respectively ) . CONCLUSION Combination therapy with a cholinergic drug and an alpha-blocker appears to be more useful than monotherapy for the treatment of underactive detrusor A double-blind pilot study was undertaken to test the administration of low doses of the long-acting benzodiazepine drug clonazepam in the management of chronic intractable temporom and ibular disorder/myofascial pain patients who were not responsive to occlusal splint , behavioral , and physical therapy .  Clonazepam was selected for its long duration and its cholinergic/GABA-ergic/serotonergic , anxiolytic , muscle relaxant , and sedative properties .  Clonazepam appears to be effective when compared to a placebo . However , caution must be observed with long-term administration of clonazepam because of potential side effects such as depression and liver dysfunction . Indiscriminate administration of clonazepam may be harmful to the patient Background Cholinergic urticaria is uncommon and accounts for 10 % of all young adults . To date , there is no effective therapy for cholinergic urticaria . Objective To determine the therapeutic efficacy of different drug combinations in the treatment of cholinergic urticaria . Patients and Methods The participants included in the study are in the age range of 16 to 29 years , with cholinergic urticaria of any duration as diagnosed by physicians . Patients were recruited from Asthma and Allergy Centers in Baghdad and Tikrit . The selected patients were divided r and omly into 3 groups according to the treatment protocol . All patients completed screening before treatment . Results The study indicated that cholinergic urticaria was completely controlled in 30.4 % of patients ( group A ) receiving 4 mg of chlorpheniramine maleate , half hour before the exercise , plus chlordiazopoxide ( 5 mg ) and clindium bromide ( 2.5 mg ) tablets , 3 times daily . However , cure rate was higher ( 83.1 % ) in patients ( group B ) receiving 4 mg of chlorpheniramine maleate ( histadine ) , 3 times daily , plus 25 mg of maprotiline HCl ( ludiomil ) , once daily at night . Furthermore , the complete cure rate was 85.4 % in patients ( group C ) receiving 4 mg of chlorpheniramine maleate (histadine)3 times daily , plus 200 mg of cimetidine ( tagadine ) , 3 times daily . The frequency of relapse was higher in group A ( 89 % ) as compared with group B ( 68.4 % ) and group C ( 23.5 % ) ( P < 0.0001 ) . Conclusions Combination of H1 and H2 antagonists was more effective based on complete control of cholinergic urticaria with lower relapsing rate . However , a future placebo-controlled clinical trial taking in consideration higher H1 antagonists than we used is warranted Further to recent data indicating that patients with vascular dementia ( VaD ) show a cholinergic deficit , we aim ed to determine whether rivastigmine , a dual inhibitor of acetylcholinesterase ( AChE ) and butyrylcholinesterase ( BuChE ) , has any effects on the symptoms of VaD. Patients aged 65 - 80 , with a diagnosis of dementia and probable VaD , received rivastigmine 3 - 6 mg/day ( n=8 ) or cardioaspirin ( n=8 ) in an open study for 22 months . At 22 months , patients treated with rivastigmine showed significant improvements in executive function and behavioural symptoms ( both p<0.05 vs. both baseline and control group ) , which were reflected in reduced caregiver stress ( p<0.05 vs. baseline and controls ) . Baseline scores of global response , cognition , word fluency and activities of daily living were maintained in patients receiving rivastigmine , and there was no increase in benzodiazepine or neuroleptic intake . In contrast , the control group showed no improvements in any domain , and significant deterioration in global response and executive function ( both p<0.05 vs. baseline and rivastigmine group ) . Side effects in both groups were tolerable and there were no study withdrawals . Long-term rivastigmine treatment appeared to be safe and effective in this patient population . In particular , improvements in domains particularly relevant to this condition were observed . These benefits may reflect the drug 's dual inhibitory effects on the cholinergic system , and its particular activity in frontal areas of the brain . A large , double-blind study of rivastigmine in patients with VaD would be worthwhile Background Tendon injuries that occur at the osteotendinous junction are commonly seen in clinical practice and range from acute strain to rupture . Nonsteroidal anti-inflammatory drugs are often prescribed in the treatment of these conditions , but the effect that these agents may have on the healing response at the bone-tendon junction is unclear . Hypothesis In response to an acute injury at the osteotendinous junction , the healing patellar tendon will have inferior biomechanical properties with administration of anti-inflammatory drugs as compared with acetaminophen and control . Study Design Controlled laboratory study . Methods A total of 215 Sprague-Dawley rats underwent transection of the patellar tendon at the inferior pole of the patella , which was subsequently stabilized with a cerclage suture .  The animals were then r and omized into 7 groups and administered 1 of the following analgesics for 14 days ibuprofen , acetaminophen , naproxen , piroxicam , celecoxib , valdecoxib , or control . At 14 days , all animals were sacrificed , and the extensor mechanism was isolated and loaded to failure . Biochemical analysis of the repair site tissue was performed . Animal activity throughout the study was monitored using a photoelectric sensor system . Results The control group demonstrated greater maximum load compared with the celecoxib , valdecoxib , and piroxicam groups ( P < .05 ) . The acetaminophen and ibuprofen groups were also significantly stronger than the celecoxib group ( P < .05 ) but not statistically different than the control group . A total of 23 specimens had failure of the cerclage suture with the following distribution control ( 0/23 ) , ibuprofen ( 0/23 ) , acetaminophen ( 0/24 ) , naproxen ( 3/24 ) , piroxicam ( 4/24 ) , celecoxib ( 6/22 ) , and valdecoxib ( 10/24 ) . The difference in distribution of the failures was significant ( P < .001 ) . Conclusions Anti-inflammatory drugs , with the exception of ibuprofen , had a detrimental effect on healing strength at the bone-tendon junction as demonstrated by decreased failure loads and increased failures of the cerclage suture . Acetaminophen had no effect on healing strength . The biomechanical properties paralleled closely with the total collagen content at the injury site , suggesting that these agents may alter healing strength by decreasing collagen content . Clinical Relevance Selective and nonselective cyclooxygenase ( COX ) inhibitors should be used judiciously in the acute period after injury or surgical repair at the bone-tendon junction
medicines with anti-cholinergic properties have a significant adverse effect on cognitive and physical function , but limited evidence exists for delirium or mortality outcomes
OBJECTIVES to determine the effect of drugs with anti-cholinergic properties on relevant health outcomes .