piperidines and Deglutition-Disorders

Oropharyngeal dysphagia (OD) is a major gastrointestinal motility disorder that causes severe nutritional and respiratory complications in elderly and neurological patients. In an earlier study, we found that stimulation of pharyngeal sensory neurons by capsaicinoids acting on transient receptor potential vanilloid 1 (TRPV1) improved the swallow response of dysphagic patients. The aim of this study was to explore the effect of piperine, a dual TRPV1/TRPA1 agonist, on the swallow response of dysphagic patients.. A videofluoroscopic study was performed to assess the signs of impaired safety and efficacy of swallow and the swallow response of 40 dysphagic patients while swallowing one series of nectar control boluses and two series of nectar boluses supplemented with piperine. Patients were randomized into two groups: one group received 150 μM piperine and the other group received 1 mM.. Piperine improved the safety of swallow by: (a) reducing the prevalence of unsafe swallows by -34.48% (P = 0.004) at 150 μM and -57.19% (P < 0.001) at 1 mM, and the severity score of the penetration-aspiration scale from 3.25 ± 0.51 to 1.85 ± 0.27 (P = 0.003, 1 mM); and (b) shortening the time to laryngeal vestibule closure from 0.366 ± 0.024 to 0.270 ± 0.022 s with 150 μM piperine (P < 0.001) and from 0.380 ± 0.032 to 0.306 ± 0.028 s with 1 mM piperine (P < 0.05).. Supplementing the alimentary bolus with piperine speeds swallow response and strongly improves safety of swallow in patients with OD, with a maximal therapeutic effect at 1 mM. Our results suggest that activation of TRPV1/A1 in oropharyngeal sensory neurons is a very promising neurostimulation strategy for dysphagic patients.

Topics: Administration, Oral; Aged; Alkaloids; Benzodioxoles; Calcium Channels; Deglutition; Deglutition Disorders; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluoroscopy; Humans; Male; Nerve Tissue Proteins; Piperidines; Polyunsaturated Alkamides; Sensory Receptor Cells; Transient Receptor Potential Channels; TRPA1 Cation Channel; TRPV Cation Channels; Video Recording

Fluid thickening is the main compensatory strategy for patients with oropharyngeal dysphagia (OD) associated with aging or neurological diseases, and there is still no pharmacological treatment. We aimed to compare the effects of increasing bolus viscosity with that of acute stimulation with TRPV1, TRPA1 or TRPM8 agonists on the biomechanics and neurophysiology of swallow response in patients with OD. We retrospectively analyzed seven studies from our laboratory on 329 patients with OD. The effect of increasing shear viscosity up to 3682 mPa·s was compared by videofluoroscopy and pharyngeal sensory evoked potentials (pSEP) with that of adding to the bolus: capsaicin (TRPV1, 150 μM/10 μM), piperine (TRPA1/V1, 1 mM/150 μM), menthol (TRPM8, 1 mM/10 mM), cinnamaldehyde-zinc (TRPA1, 100 ppm−70 mM), citral (TRPA1, 250 ppm) or citral-isopulegol (TRPA1-TRPM8, 250 ppm−200 ppm). Fluid thickening improved the safety of swallow by 80% (p < 0.0001) by delaying bolus velocity by 20.7 ± 7.0% and time to laryngeal vestibule closure (LVC) by 23.1 ± 3.7%. Capsaicin 150μM or piperine 1 mM significantly improved safety of swallow by 50% (p < 0.01) and 57.1% (p < 0.01) by speeding time to LVC by 27.6% (p < 0.001) and 19.5% (p < 0.01) and bolus velocity by 24.8% (p < 0.01) and 16.9% (p < 0.05), respectively. Cinnamaldehyde-zinc shortened the P2 latency of pSEPs by 11.0% (p < 0.01) and reduced N2-P2 amplitude by 35% (p < 0.01). In conclusion, TRPV1 and TRPV1/A1 agonists are optimal candidates to develop new pharmacological strategies to promote the recovery of brain and swallow function in patients with chronic OD.

Topics: Acrolein; Acyclic Monoterpenes; Alkaloids; Benzodioxoles; Biomechanical Phenomena; Capsaicin; Deglutition; Deglutition Disorders; Humans; Menthol; Piperidines; Polyunsaturated Alkamides; Retrospective Studies; Zinc

Ibrutinib is a small molecule inhibitor of Bruton's tyrosine kinase indicated for the treatment of a variety of B-cell malignancies including chronic lymphocytic leukemia, mantle cell lymphoma, marginal zone lymphoma, and Waldenstrom's macroglobulinemia. These indolent hematologic malignancies are considered diseases of the elderly, a population that may have dysphagia leading to difficulty swallowing tablets and capsules. Ibrutinib is currently not available in a liquid oral dosage form. We report the utilization and clinical outcomes associated with alternative administration of ibrutinib capsules in a patient with chronic lymphocytic leukemia and significant dysphagia.. An 86-year old female requiring chronic lymphocytic leukemia-directed therapy due to a rising absolute lymphocyte count and worsening, transfusion-dependent anemia with a past medical history of dementia and dysphagia, was initiated on ibrutinib.. Due to the patient's significant inability to swallow, ibrutinib capsules were administered via an alternative method by opening them and sprinkling onto soft food or applesauce. With ibrutinib therapy, the patient has had a significant clinical response in her chronic lymphocytic leukemia as evidenced by her decreased absolute lymphocyte count and achieving transfusion independence with improvements in hemoglobin.. Ibrutinib administration via this alternative method resulted in an initial clinical response in the treatment of our patient's chronic lymphocytic leukemia as evidenced by a decreasing absolute lymphocyte count and improved anemia that achieved transfusion independence. The patient has maintained this response to therapy after approximately 1 year at the time of manuscript preparation.

Topics: Adenine; Agammaglobulinaemia Tyrosine Kinase; Aged, 80 and over; Deglutition Disorders; Female; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Piperidines; Protein Kinase Inhibitors

Topics: Carbazoles; Carcinoma, Non-Small-Cell Lung; Deglutition Disorders; Diet; Humans; Lung Neoplasms; Piperidines; Protein Kinase Inhibitors

Diphtheria toxin-mediated, acute ablation of hypothalamic neurons expressing agouti-related protein (AgRP) in adult mice leads to anorexia and starvation within 7 d that is caused by hyperactivity of neurons within the parabrachial nucleus (PBN). Because NMDA glutamate receptors are involved in various synaptic plasticity-based behavioral modifications, we hypothesized that modulation of the NR2A and NR2B subunits of the NMDA receptor in PBN neurons could contribute to the anorexia phenotype. We observed by Western blot analyses that ablation of AgRP neurons results in enhanced expression of NR2B along with a modest suppression of NR2A. Interestingly, systemic administration of LiCl in a critical time window before AgRP neuron ablation abolished the anorectic response. LiCl treatment suppressed NR2B levels in the PBN and ameliorated the local Fos induction that is associated with anorexia. This protective role of LiCl on feeding was blunted in vagotomized mice. Chronic infusion of RO25-6981, a selective NR2B inhibitor, into the PBN recapitulated the role of LiCl in maintaining feeding after AgRP neuron ablation. We suggest that the accumulation of NR2B subunits in the PBN contributes to aphagia in response to AgRP neuron ablation and may be involved in other forms of anorexia.

Topics: Adjuvants, Immunologic; Agouti-Related Protein; Animals; Anorexia; Appetite; Blotting, Western; Body Weight; Deglutition Disorders; Eating; Lithium Chloride; Male; Mice; Mice, Knockout; Neurons; Phenols; Piperidines; Pons; Receptors, N-Methyl-D-Aspartate; Rhombencephalon; Time Factors; Vagotomy

(1) Sialorrhoea is the production of saliva that patients perceive as excessive; (2) Saliva accumulation is either due to a reduction in swallowing frequency or to an increase in saliva production; (3) Patients who drool may be ostracized, and there is also an increased risk of aspiration pneumonia; (4) Sialorrhoea can be caused by buccal, gastrointestinal or neurological disorders, or by drugs; (5) Sedatives such as benzodiazepines, neuroleptics, cholinesterase inhibitors and pilocarpine carry a dose-dependent risk of sialorrhoea; (6) In practice, the role of a drug should be borne in mind when a patient presents with sialorrhoea or excessive saliva accumulation. The parents of children treated with sedative drugs should be informed of this risk.

Topics: Antipsychotic Agents; Benzodiazepines; Cholinesterase Inhibitors; Clozapine; Deglutition Disorders; Donepezil; Galantamine; Humans; Hypnotics and Sedatives; Indans; Phenylcarbamates; Pilocarpine; Piperidines; Quality of Life; Risperidone; Rivastigmine; Sialorrhea

Although oesophagitis is the most common diagnosis made at upper gastrointestinal endoscopy, data on the longterm outcome of affected patients are sparse.. This study assessed the level of reflux symptoms, quality of life, drug consumption, and complications in patients at least 10 years after diagnosis of oesophagitis at one centre.. One hundred and fifty two patients with typical reflux symptoms and a first time diagnosis by endoscopy of grade I-III oesophagitis between 1981 and 1984, were followed up using a postal questionnaire and telephone interview.. Eighteen of 152 patients had died, 33 failed to respond, and 101 replied (mean follow up 11 years, range 121-160 months). Over 70% of patients still had heartburn at least daily (32%) or weekly (19%) or required daily acid suppression treatment (20%). Two patients (2%) had developed oesophageal strictures and one had Barrett's oesophagus. Two of eight quality of life scores (physical function and social function) measured by the Short Form-36 were significantly lower than Northern Ireland population scores.. Nearly three quarters of patients previously diagnosed as having oesophagitis still had significant morbidity related to gastro-oesophageal reflux disease more than 10 years after diagnosis. Some quality of life scores were significantly lower than those of the general population.

Topics: Adult; Aged; Aged, 80 and over; Antacids; Barrett Esophagus; Cisapride; Deglutition Disorders; Disease Progression; Esophagitis, Peptic; Female; Follow-Up Studies; Humans; Male; Metoclopramide; Middle Aged; Omeprazole; Piperidines; Quality of Life

A rare case of dysphagia caused by leiomyomatosis of the esophagus is presented. Esophageal leiomyomatosis is triggered by diffuse proliferation of smooth muscle cells in the wall of the entire esophagus. Only 1.0% of all tumors of the esophagus are benign lesions; 0.4% of all esophageal neoplasms are leiomyomas. Only a few cases of leiomyomatosis-a special form of diffuse leiomyomas-have been described so far in the literature. Modern diagnostic imaging techniques such as CT and MR are described in esophageal leiomyomatosis.

Topics: Anti-Ulcer Agents; Biopsy; Cisapride; Combined Modality Therapy; Deglutition Disorders; Esophageal Neoplasms; Esophagus; Follow-Up Studies; Humans; Leiomyomatosis; Magnetic Resonance Imaging; Male; Middle Aged; Nifedipine; Omeprazole; Pathology; Piperidines; Tomography, X-Ray Computed

The risk of aspiration during tube feedings has been reduced but not abolished by percutaneous endoscopic gastrostomy (PEG). This open study was planned to evaluate whether cisapride may play some role in preventing aspiration in long-term enteral feeding via PEG. A group of 29 patients, unable to swallow because of head and neck cancer (14 cases) or neurological disorders (15 cases) entered the study; 7 neurological patients, fed via nasogastric tube before PEG placement, had suffered from aspiration pneumonia during nasogastric feeding. All patients underwent PEG, and 10 mg cisapride was routinely given via PEG before each administration of enteral feeding and 6 h after its initiation when the feeding was continued for 12 h or more. Only 1 minor complication was observed during the acute hospital setting (ileus, spontaneously resolving after 36 h). After hospital discharge, the patients were followed for a total of 4935 days of feeding (range 47-508 days, mean time per patient: 170 days) and assessed weekly for the development of complications. No episode of probable/possible aspiration pneumonia was observed during the follow-up. Two neurological patients with involuntary movements had rupture of the feeding tube, which was replaced without complications. These results support the hypothesis that cisapride might play some role in the prevention of aspiration in patients fed via PEG, and justify the planning of some controlled, double-blind trials to verify such a hypothesis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cisapride; Deglutition Disorders; Enteral Nutrition; Female; Follow-Up Studies; Gastroscopy; Gastrostomy; Head and Neck Neoplasms; Humans; Intubation, Gastrointestinal; Male; Middle Aged; Nervous System Diseases; Pilot Projects; Piperidines; Pneumonia, Aspiration; Serotonin Antagonists; Survival Rate

Topics: Aged; Aged, 80 and over; Cisapride; Deglutition Disorders; Humans; Male; Piperidines; Serotonin Antagonists

An intraluminal balloon was used to study the peristaltic reflex, which is mediated by the intrinsic nerves of the oesophagus. Serial balloon distension was performed in nine asymptomatic volunteers and 133 patients with oesophageal symptoms. Eight of the volunteers had a normal response with proximal stimulation and distal inhibition of motility. Only 42 patients (31.6 per cent) had a normal response. The commonest abnormal response (39.1 per cent) was some form of failure of the distal inhibitory reflex. Other patterns of abnormality were an unresponsive oesophagus (15.8 per cent) with no motility change during balloon inflation, or spasm (13.5 per cent) proximal to the balloon. These alterations of secondary peristaltic activity suggest that there are abnormalities of the intrinsic (enteric) nerves of the oesophagus. Different abnormalities were found in patients with similar symptoms. Awareness of this difference might allow a more rational approach to treatment. This hypothesis was tested in a small pilot study treating functional dysphagia with cisapride. Three of nine patients had marked symptomatic improvement within 4 weeks and all three had an unresponsive oesophagus. The remaining six patients, who had failure of distal inhibition or a normal response, did not improve.

Topics: Adult; Aged; Catheterization; Cisapride; Deglutition Disorders; Esophageal Diseases; Esophagus; Female; Humans; Hydrogen-Ion Concentration; Male; Manometry; Middle Aged; Peristalsis; Piperidines; Reflex, Abnormal; Serotonin Receptor Agonists

Topics: Adolescent; Adult; Aged; Biliary Tract Diseases; Deglutition Disorders; Esophageal Diseases; Female; Humans; Male; Middle Aged; Muscles; Piperidines