Background: Systemic absorption of topical phenylephrine administered during mydriasis may potentially cause hemodynamic changes in patients. Objective: To compare the hemodynamic outcomes between patients given tropicamide+phenylephrine and those given tropicamide alone for mydriasis. Design: Randomized controlled trial. Setting: Ophthalmology Outpatient Clinic, Southern Philippines Medical Center, Davao City, from April to June 2017. Participants: 56 male and female patients aged ≥ 19 years and scheduled for mydriasis. Interventions: Random allocation to either one drop of 0.5% tropicamide plus 0.5% phenylephrine or one drop of 0.5% tropicamide for mydriasis of the examined eye. Main outcome measures: Mean systolic BP, mean diastolic BP, mean arterial pressure, mean heart rate, and at least one episode of tachycardia or bradycardia. Main results: Thirty (53.57%) patients received tropicamide drops, and the rest received tropicamide+phenylephrine drops. The demographic and clinical characteristics of the two intervention groups were comparable at baseline. The mean blood pressures and heart rates at 15, 30, 45, and 60 minutes postmydriasis did not significantly differ between the two groups. Four patients from the tropicamide group, and none from the phenylephrine+tropicamide group had tachycardia (p=0.1153). On the other hand, five patients from the tropicamide group, and four from the phenylephrine+tropicamide group had bradycardia (p=1.0000). Conclusion Hemodynamic outcomes did not significantly differ up to 60 minutes after mydriasis between patients who received tropicamide+phenylephrine drops and those who received tropicamide drops.
Blood Pressure ; Heart Rate ; Sympathomimetics ; Muscarinic Antagonists ; Parasympatholytics

PURPOSE: The aim of this study was to investigate the safety and the effects of elevated doses of solifenacin and trospium on cognitive function and health-related quality of life (HRQoL) in elderly women receiving treatment for urinary incontinence. METHODS: The study included 312 women aged 60–83 years (mean age, 69.4 years). All participants had scored at least 24 points on the Mini-Mental State Examination (MMSE) scale, and all of them had been diagnosed with urge urinary incontinence (UUI) or mixed urinary incontinence (MUI). The women were randomly assigned to 3 groups: group A, individuals who were simultaneously administered solifenacin at a high dosage of 20 mg per day and trospium at a high dosage of 60 mg per day; group B, persons taking solifenacin and trospium at the usual dosage of 10 and 30 mg per day, respectively; and group C, persons who received a placebo. Participants’ cognitive status was assessed by the MMSE, Controlled Oral Word Association Test, Wechsler Adult Intelligence Scale-Revised, Wechsler Memory Scale III, Colour Trails Test, and California Verbal Learning Test scales. The HRQoL assessment was performed using the Medical Outcomes Study 36-Item Health Survey. RESULTS: The cognitive function parameters did not differ at the start and end of the study across the groups (P>0.05). Additionally, the cognitive function parameters did not differ significantly within each group between the start and end of the study (P>0.05). The values of most HRQoL parameters regarding the functional state of the lower urinary tract (LUT) after the termination of treatment significantly improved in groups A and B (P < 0.05). A significant correlation between cognitive status and HRQoL or LUT parameters was absent (r < 0.3), while the correlations between HRQoL and LUT parameters were r=0.31–0.83, P < 0.05. CONCLUSIONS: The use of elevated doses of solifenacin and trospium did not increase the risk of cognitive impairment in women with UUI and MUI. The combination of solifenacin and trospium at a double dosage may be recommended to elderly women with treatment-resistant symptoms of UUI and MUI. However, the safety of combining antimuscarinic drugs in women with an increased volume of residual urine requires further study.
Adult ; Aged ; California ; Cognition Disorders ; Cognition* ; Female ; Health Surveys ; Humans ; Intelligence ; Memory ; Muscarinic Antagonists ; Quality of Life* ; Solifenacin Succinate* ; Urinary Incontinence* ; Urinary Tract ; Verbal Learning ; Weights and Measures ; Word Association Tests

Bronchodilators provide improvements in lung function and reductions in symptoms and exacerbations, and are the mainstay of pharmacological management of chronic obstructive pulmonary disease (COPD). The Global Initiative for Chronic Obstructive Lung Disease strategy recommends the use of a combination of long-acting β₂-agonist/long-acting muscarinic antagonists (LABA/LAMA) as the first-line treatment option in the majority of symptomatic patients with COPD. This review provides an indirect comparison of available LABA/LAMA fixed-dose combinations (FDCs) through discussion of important efficacy and safety data from the key literature, with the objective of providing physicians with a framework for informed decision-making. LABA/LAMA FDCs provided greater benefits compared with placebo and similar or greater benefits compared with tiotropium and salmeterol/fluticasone in improving lung function, dyspnea, health-related quality of life, reducing rescue medication use and preventing exacerbations, although with some variability in efficacy between individual FDCs; further, tolerability profiles were comparable among LABA/LAMA FDCs. However, there is a disparity in the amount of evidence generated for different LABA/LAMA FDCs. Thus, this review shows that all LABA/LAMA FDCs may not be the same and that care should be taken when extrapolating individual treatment outcomes to the entire drug class. It is important that physicians consider the efficacy gradient that exists among LABA/LAMA FDCs, and factors such as inhaler devices and potential biomarkers, when choosing the optimal bronchodilator treatment for long-term management of patients with COPD.
Asian Continental Ancestry Group ; Biomarkers ; Bronchodilator Agents ; Disease Management ; Dyspnea ; Humans ; Korea ; Lung ; Muscarinic Antagonists* ; Nebulizers and Vaporizers ; Pulmonary Disease, Chronic Obstructive* ; Quality of Life ; Tiotropium Bromide

The autonomic nervous system contributes to prostate cancer proliferation and metastasis. However, the exact molecular mechanism remains unclear. In this study, muscarinic acetylcholine receptor M1 (CHRM1) expression was measured via immunohistochemical analysis in human prostate cancer tissue array slides. PC-3, LNCaP, and A549 cells were treated with pirenzepine or carbachol, and the cell migration and invasion abilities were evaluated. Western blotting and quantitative real-time PCR were performed to measure GLI family zinc finger 1 (GLI1), patched 1 (PTCH1), and sonic hedgehog (SHH) expression levels. High expression of CHRM1 was found in early-stage human prostate cancer tissues. In addition, the selective CHRM1 antagonist pirenzepine inhibited PC-3, LNCaP, and A549 cell migration and invasion, but the agonist carbachol promoted the migration and invasion of these three cell lines. Muscarinic signaling can be relayed by hedgehog signaling. These data show that CHRM1 is involved in the regulation of prostate cancer migration and invasion through the hedgehog signaling pathway.
Carbachol/pharmacology* ; Cell Movement/genetics* ; Cell Proliferation ; Hedgehog Proteins/genetics* ; Humans ; Male ; Muscarinic Agonists/pharmacology* ; Muscarinic Antagonists/pharmacology* ; Patched-1 Receptor/genetics* ; Pirenzepine/pharmacology* ; Prostatic Neoplasms/pathology* ; Receptor, Muscarinic M1/genetics* ; Zinc Finger Protein GLI1/genetics*

Despite a range of efficacious therapies for asthma, including inhaled corticosteroids (ICS) and long-acting β₂-agonists (LABA), a significant proportion of patients have poor asthma control and retain a risk of future worsening of their symptoms. Long-acting muscarinic antagonist (LAMA) bronchodilators offer a well-tolerated, efficacious, and cost-effective add-on to a patient's treatment. Of the LAMAs currently under investigation or available for the treatment of asthma, evidence from a comprehensive clinical trial program in adults and children shows that once-daily treatment with tiotropium provides benefits for patients with uncontrolled asthma despite the use of ICS and LABAs. Tiotropium is included in the Global Initiative for Asthma (GINA) strategy document as an add-on therapy option for patients at Step 4 or 5 with a history of asthma exacerbations. Tiotropium Respimat® has demonstrated safety and efficacy in patients with a range of disease severities, ages, and phenotypes. This review describes the evidence for the use of LAMA as add-on therapy for patients with asthma who remain uncontrolled despite the use of ICS and LABA treatments.
Adrenal Cortex Hormones ; Adult ; Asthma* ; Bronchodilator Agents ; Child ; Humans ; Muscarinic Antagonists* ; Phenotype ; Tiotropium Bromide

Objective: To study the dosage regimen of oral M-receptor blocker following transurethral resection of the prostate (TURP) for severe benign prostate hyperplasia (BPH) with predominant urine storage period symptoms (USPSs) and its clinical effect. METHODS: Severe BPH patients with predominant USPSs received oral tolterodine (2 mg q12d or 4 mg qd) 6 hours after TURP for 4 weeks. The medication continued for another 2 weeks in case of recurrence of USPSs or until the 12th week in case of repeated recurrence. Before and at 1, 4, 8 and 12 weeks after TURP, we analyzed the International Prostate Symptoms Score (IPSS), quality of life (QoL) score, maximum urinary flow rate (Qmax), and postvoid residual volume (PVR) of the patients. RESULTS: Complete clinical data were collected from 106 cases, of which 33 achieved successful drug withdrawal with no aggravation of USPSs at 4 weeks after TURP, 51 at 6－8 weeks, 13 at 10－12 weeks, and 9 needed medication after 12 weeks. Before and at 1, 4, 8 and 12 weeks after TURP, the total IPSSs were 25.33 ± 3.45, 19.33 ± 3.62, 11.56 ± 2.45, 8.38 ± 2.0 and 7.74 ± 1.87, those in the urine storage period were 11.97 ± 1.53, 10.76 ± 1.82, 6.16 ± 1.22, 4.08 ± 1.19 and 3.91 ± 1.15, those at urine voiding were 9.80 ± 1.60, 5.59 ± 1.45, 3.40 ± 0.92, 2.85 ± 0.71, and 2.61 ± 0.67, and the QoL scores were 4.70 ± 0.78, 3.92 ± 0.75, 2.55 ± 0.74, 1.83 ± 0.72 and 1.66 ± 0.75, respectively, with statistically significant differences between the baseline and the scores at 1 and 4 weeks (P <0.01) but not at 8 or 12 weeks (P >0.05). Qmax and PVR were improved progressively and significantly at 1 and 4 weeks (P <0.01) but not at 8 or 12 weeks (P >0.05). CONCLUSIONS Four to eight weeks of oral administration of M-receptor blocker may be an effective dosage regimen for severe BPH with predominant USPSs after TURP.
Administration, Oral ; Clinical Protocols ; Drug Administration Schedule ; Humans ; Male ; Muscarinic Antagonists ; administration & dosage ; Postoperative Care ; Prostatic Hyperplasia ; drug therapy ; surgery ; Quality of Life ; Recurrence ; Tolterodine Tartrate ; administration & dosage ; Transurethral Resection of Prostate ; Treatment Outcome ; Urination ; Urological Agents ; administration & dosage

Urinary incontinence (UI) has been a serious health problem which can significantly affect quality of life. UI may occur at any age but more common in the elderly population. Many conditions may leak to UI and differential diagnosis is critical to guide appropriate manage strategy. After a brief description of the pathophysiology, classification, and diagnostic evaluation of UI, this review highlights oral pharmacological therapy mainly in clinical point of view. For urge UI, antimuscarinic are the most commonly used medication supported with high level of evidence. Antimuscarinics competitively block muscarinic receptors with variations in selectivity for the different subtypes. Common adverse effects are dry mouth, constipation, and blurred vision. High caution for cognitive function should be applied in the use of antimuscarinics in the elderly. Mirabegron, a beta3-agonist, is a new class of drug targeting urge UI, which reported similar efficacy with antimuscarinics and favorable adverse effect profile. For stress UI, various type of medications have been clinically investigated but so far none showed satisfactory resolution of stress UI. Duloxetine is the only medication approved for stress UI in European countries but not in US Food and Drug Administration and Korean Food and Drug Administration due to low benefit-risk profile for UI. Conclusively, pharmacological therapy should be tailored to the type of UI. Recent options of medications may give further treatment possibilities for the optimal treatment for each patient.
Aged ; Classification ; Constipation ; Diagnosis, Differential ; Drug Delivery Systems ; Duloxetine Hydrochloride ; Humans ; Medication Therapy Management ; Mouth ; Muscarinic Antagonists ; Quality of Life ; Receptors, Muscarinic ; United States Food and Drug Administration ; Urinary Incontinence* ; Urinary Incontinence, Stress ; Urinary Incontinence, Urge

Administration, Inhalation ; Adrenal Cortex Hormones ; therapeutic use ; Adrenergic beta-Agonists ; therapeutic use ; Anti-Asthmatic Agents ; therapeutic use ; Antibodies, Monoclonal, Humanized ; therapeutic use ; Asthma ; prevention & control ; therapy ; Guideline Adherence ; Humans ; Molecular Targeted Therapy ; Muscarinic Antagonists ; therapeutic use ; Omalizumab ; therapeutic use ; Practice Guidelines as Topic ; Primary Prevention ; Quality Improvement ; Sublingual Immunotherapy

BACKGROUND/AIMS: The internal anal sphincter (IAS) plays an important role in maintaining continence and a number of neurotransmitters are known to regulate IAS tone. The aim of this study was to determine the relative importance of the neurotransmitters involved in the relaxant and contractile responses of the porcine IAS. METHODS: Responses of isolated strips of IAS to electrical field stimulation (EFS) were obtained in the absence and presence of inhibitors of neurotransmitter systems. RESULTS: Contractile responses of the sphincter to EFS were unaffected by the muscarinic receptor antagonist, atropine (1 muM), but were almost completely abolished by the adrenergic neuron blocker guanethidine (10 muM). Contractile responses were also reduced (by 45% at 5 Hz, P < 0.01) following desensitisation of purinergic receptors with alpha,beta-methylene-ATP (10 muM). In the presence of guanethidine, atropine, and alpha,beta-methylene-ATP, the remaining relaxatory responses to EFS were examined. These responses were not altered by the cyclooxygenase inhibitor, indomethacin (5 muM), the vasoactive intestinal polypeptide receptor antagonist, [D-p-Cl-Phe6,Leu17]-vasoactive intestinal peptide (PheLeu-VIP; 100 nM), or the purinoceptor antagonists, 8-phenyltheophyline (P1 receptors) or suramin (P2 receptors). However, relaxation responses were reduced by Nomega-nitro-L-arginine (L-NNA; 100 muM), an inhibitor of nitric oxide synthesis (40-50% reduction), zinc protoprophyrin IX (10 muM), an inhibitor of carbon monoxide synthesis (20-40% reduction), and also propargylglycine (30 muM) and aminooxyacetic acid (30 muM), inhibitors of hydrogen sulphide synthesis (15-20% reduction). CONCLUSIONS: Stimulation of IAS efferent nerves releases excitatory and inhibitory neurotransmitters: noradrenaline is the predominant contractile transmitter with a smaller component from ATP, whilst 3 gases mediate relaxation responses to EFS, with the combined contributions being nitric oxide > carbon monoxide > hydrogen sulfide.
Adenosine Triphosphate ; Adrenergic Neurons ; Aminooxyacetic Acid ; Anal Canal* ; Atropine ; Autonomic Pathways ; Carbon Monoxide* ; Carbon* ; Gases ; Guanethidine ; Hydrogen Sulfide* ; Hydrogen* ; Indomethacin ; Neurotransmitter Agents* ; Nitric Oxide* ; Norepinephrine ; Prostaglandin-Endoperoxide Synthases ; Purinergic Antagonists ; Receptors, Muscarinic ; Receptors, Purinergic ; Relaxation* ; Suramin ; Vasoactive Intestinal Peptide ; Zinc

PURPOSE: The prevalence of hyperactive-type lower urinary tract symptoms is 45.2%, with shares of overactive bladder (OAB) and urge incontinence (UI) symptoms of 10.7% and 8.2%, respectively. We investigated the possible impact of a wide range of social, economic, and medical factors on compliance with solifenacin treatment in the working population. METHODS: Social, economic, and medical factors as well as the Overactive Bladder questionnaire – the OAB-q Short Form (OAB-q SF), bladder diaries, and uroflowmetry of 1,038 people who were administered solifenacin for a year were gathered from employer documentation. RESULTS: Among the subjects, 32% maintained their compliance with solifenacin treatment throughout the year. Only 65% of the patients had compliance exceeding 80%, and 17% of patients had compliance of ≥50%, yet less than 80% were still taking solifenacin 12 months after the beginning of this experiment. Working people whose compliance level was, at least, 80% had reliably higher (P≤0.01) average age, annual salary, and treatment efficacy, and a greater treatment satisfaction level, as well as a lack of satisfaction with other antimuscarinic treatments and higher rate of urge UI diagnosis. The same cohort also featured a lower level (P≤0.01) of caffeine abuse and lower share of salary spent purchasing solifenacin. CONCLUSIONS: This study has shown that compliance with solifenacin treatment is associated with a number of significant medical, social, and economic factors. The medical factors included the type of urination disorder, severity of incontinence symptoms, presence of side effects, treatment efficacy and patients’ satisfaction with it, and experience using other antimuscarinic treatments. Among the social and economic factors, those with the strongest correlation to compliance were patient age, employment in medicine and education, annual income level, percentage of solifenacin purchase expenditures, and caffeine abuse. Factors with a weaker, but still significant, association were gender, employment in the transportation industry, and monthly income level.
Caffeine ; Cohort Studies ; Compliance* ; Diagnosis ; Education ; Employment ; Health Expenditures ; Humans ; Lower Urinary Tract Symptoms* ; Muscarinic Antagonists ; Prevalence ; Salaries and Fringe Benefits ; Solifenacin Succinate* ; Transportation ; Treatment Outcome ; Urinary Bladder ; Urinary Bladder, Overactive ; Urinary Incontinence, Urge ; Urination Disorders