-
Advances in Clinical and Experimental... 2016This paper presents the etiopathogenesis, symptomatology, evaluation and treatment of mouth dryness. Xerostomia affects 1-29% of the population, mostly women. It is... (Review)
Review
This paper presents the etiopathogenesis, symptomatology, evaluation and treatment of mouth dryness. Xerostomia affects 1-29% of the population, mostly women. It is observed in geriatric patients and in individuals using certain medications, those subjected to radiotherapy of the head and neck region or affected with autoimmune conditions. The main signs of xerostomia include the impression of a dry mouth, problems with food ingestion and dryness of the oral mucosa and skin. Evaluation is based on structured interviews (the Fox test) and determinations of unstimulated and stimulated salivary volume. The signs of xerostomia can be attenuated with saliva substitutes, cevimeline or malic acid. Only palliative treatment of this condition is available at present. Untreated xerostomia significantly impairs the quality of life, which can potentially lead to depression.
Topics: Humans; Palliative Care; Predictive Value of Tests; Quality of Life; Risk Factors; Salivary Glands; Salivation; Treatment Outcome; Xerostomia
PubMed: 26935515
DOI: 10.17219/acem/29375 -
RMD Open 2019To evaluate current evidence on the efficacy and safety of topical and systemic medications in patients with primary Sjögren syndrome (SjS) to inform European League... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate current evidence on the efficacy and safety of topical and systemic medications in patients with primary Sjögren syndrome (SjS) to inform European League Against Rheumatism treatment recommendations.
METHODS
The MEDLINE, EMBASE and Cochrane databases were searched for case-control/prospective cohort studies, randomised controlled trials (RCTs) and systematic reviews.
RESULTS
Current evidence in primary SjS patients fulfilling the 2002 criteria is based on the data from 9 RCTs, 18 prospective cohort studies and 5 case-control studies. Two Cochrane systematic literature reviews (SLRs) have reported that topical treatments for dry mouth and dry eye are safe and effective. Ocular cyclosporine A was safe and effective in two RCTs including 1039 patients with dry eye syndrome. Two Cochrane SLRs on serum tear drops and plugs showed inconsistency in possible benefits, both for symptoms and objective measures. Five RCTs reported significant improvements in oral dryness and salivary flow rates for pilocarpine and cevimeline. An RCT showed no significant placebo-differences for hydroxychloroquine 400 mg/day for the primary outcome (visual analogue scale (VAS) composite of dryness, fatigue and pain). We identified seven RCTs carried out in primary SjS patients. RCTs using infliximab, anakinra and baminercept found no placebo-differences for the primary outcomes. The two largest RCTs randomised 255 patients to receive rituximab or placebo and reported no significant results in the primary outcome (VAS composite), while prospective studies suggested efficacy in systemic disease.
CONCLUSION
The current evidence supporting the use of the main topical therapeutic options of primary SjS is solid, while limited data from RCTs are available to guide systemic therapies.
Topics: Clinical Trials as Topic; Combined Modality Therapy; Disease Management; Humans; Sjogren's Syndrome; Treatment Outcome
PubMed: 31749986
DOI: 10.1136/rmdopen-2019-001064 -
International Journal of Molecular... Aug 2021At present, Alzheimer's disease (AD) and related dementias cannot be cured. Therefore, scientists all over the world are trying to find a new approach to prolong an... (Review)
Review
At present, Alzheimer's disease (AD) and related dementias cannot be cured. Therefore, scientists all over the world are trying to find a new approach to prolong an active life of patients with initial dementia. Both pharmacological and non-pharmacological pathways are investigated to improve the key symptom of the disease, memory loss. In this respect, influencing the neuromodulator acetylcholine via muscarinic receptors, such as cevimeline, might be one of the therapeutic alternatives. The purpose of this study is to explore the potential of cevimeline on the cognitive functions of AD patients. The methodology is based on a systematic literature review of available studies found in Web of Science, PubMed, Springer, and Scopus on the research topic. The findings indicate that cevimeline has shown an improvement in experimentally induced cognitive deficits in animal models. Furthermore, it has demonstrated to positively influence tau pathology and reduce the levels of amyloid-β (Aβ) peptide in the cerebral spinal fluid of Alzheimer's patients. Although this drug has not been approved by the FDA for its use among AD patients and there is a lack of clinical studies confirming and extending this finding, cevimeline might represent a breakthrough in the treatment of AD.
Topics: Animals; Cognition Disorders; Humans; Muscarinic Agonists; Neurodegenerative Diseases; Neuropharmacology; Pharmaceutical Preparations; Quinuclidines; Thiophenes
PubMed: 34445613
DOI: 10.3390/ijms22168908 -
Systematic Reviews May 2022Dry eye disease (DED) is a condition that compromises the ocular surface and affects millions of people around the world. In recent years, a scheme has been proposed for...
BACKGROUND
Dry eye disease (DED) is a condition that compromises the ocular surface and affects millions of people around the world. In recent years, a scheme has been proposed for the treatment of DED, with the use of artificial tear being the mainstay of treatment. In this scheme, the use of secretagogues is suggested as part of the treatment for patients with moderate to severe affectation. With this systematic review, we aim to evaluate the effectiveness and safety of secretagogues for DED.
METHODS
Electronic databases will be searched; we will include randomized controlled trials that compare secretagogues and artificial tears. Study inclusion will not be restricted on the basis of language or publication status. We will use Google Translate to assess studies written in languages other than English and Spanish. Identification, evaluation, data extraction, and assessment of risk of bias will be conducted by two authors of the review, a third review author will resolve any disagreement. The outcomes will be the ocular surface disease index score, tear film break-up time, Schirmer test score, VRQoL Score, and tear film osmolarity. We will use the Cochrane Collaboration Risk of Bias 2 (RoB 2) tool for assessing the risk of bias of the included studies. Based on the heterogeneity of the included studies, we will combine the findings in a meta-analysis using a fixed effect model if heterogeneity ≤ 50% or a random effect model if heterogeneity > 50%. If we deem meta-analysis as inappropriate, we will document the reasons and report findings from the individual studies narratively.
DISCUSSION
Based on the evidence obtained, we will evaluate the effect of pilocarpine, cevimeline, and diquafosol and compare it to artificial tears on multiple outcome measures. This systematic review aims to determine the efficacy and safety of the secretagogues pilocarpine, cevimeline, and diquafosol to help clinicians in the decision-making process.
TRIAL REGISTRATION
PROSPERO CRD42020218407 .
Topics: Dry Eye Syndromes; Humans; Lubricant Eye Drops; Meta-Analysis as Topic; Pilocarpine; Polyphosphates; Quinuclidines; Secretagogues; Systematic Reviews as Topic; Thiophenes; Uracil Nucleotides
PubMed: 35643581
DOI: 10.1186/s13643-022-01979-4 -
Science Advances Dec 2022Salivary gland acinar cells are severely depleted after radiotherapy for head and neck cancer, leading to loss of saliva and extensive oro-digestive complications. With...
Salivary gland acinar cells are severely depleted after radiotherapy for head and neck cancer, leading to loss of saliva and extensive oro-digestive complications. With no regenerative therapies available, organ dysfunction is irreversible. Here, using the adult murine system, we demonstrate that radiation-damaged salivary glands can be functionally regenerated via sustained delivery of the neurogenic muscarinic receptor agonist cevimeline. We show that endogenous gland repair coincides with increased nerve activity and acinar cell division that is limited to the first week after radiation, with extensive acinar cell degeneration, dysfunction, and cholinergic denervation occurring thereafter. However, we found that mimicking cholinergic muscarinic input via sustained local delivery of a cevimeline-alginate hydrogel was sufficient to regenerate innervated acini and retain physiological saliva secretion at nonirradiated levels over the long term (>3 months). Thus, we reveal a previously unknown regenerative approach for restoring epithelial organ structure and function that has extensive implications for human patients.
PubMed: 36542703
DOI: 10.1126/sciadv.adc8753 -
The Kurume Medical Journal 2013Cevimeline is a muscarinic agonist that promotes saliva secretion and is used to treat Sjögren's syndrome (SS), an autoimmune disorder in which the exocrine glands that...
An immunohistochemistry-based study on aquaporin (AQP)-1, 3, 4, 5 and 8 in the parotid glands, submandibular glands and sublingual glands of Sjögren's syndrome mouse models chronically administered cevimeline.
Cevimeline is a muscarinic agonist that promotes saliva secretion and is used to treat Sjögren's syndrome (SS), an autoimmune disorder in which the exocrine glands that produce saliva are destroyed. Cevimeline is thought to affect the composition of saliva in part by regulating the localization of aquaporins (AQPs). In this study, we investigated the effects of chronic Cevimeline administration in the salivary glands of SS mice on the immunohistochemical localization of aquaporin (AQP)-1, 3, 4, 5 and 8. We used Cevimeline-untreated SS mice, treated SS mice, discontinued SS mice and untreated normal mice. AQP-5 was found in the apical and lateral membranes of acinar cells in the parotid and submandibular glands of cevimeline-treated SS mice and untreated normal mice. Saliva secretion and AQP-5 localization were sustained in SS mice who were chronically administered Cevimeline and at four weeks after discontinuation. Unlike AQP-5, the localization of AQP-1, 3, 4 and 8 were not affected by Cevimeline administration. Our findings demonstrated that administration of Cevimeline maintains the proper localization of AQP-5 in the acinar cells of the salivary gland, which may promote salivation in chronically treated SS mice. Clinically, this suggests that chronic Cevimeline administration may be useful therapeutically for SS patients suffering from a decrease in saliva secretion by improving the disordered AQP-5 localization.
Topics: Animals; Aquaporin 1; Aquaporin 3; Aquaporin 4; Aquaporin 5; Aquaporins; Disease Models, Animal; Immunohistochemistry; Mice; Muscarinic Agonists; Parotid Gland; Quinuclidines; Salivation; Sjogren's Syndrome; Sublingual Gland; Submandibular Gland; Thiophenes; Time Factors
PubMed: 23925155
DOI: 10.2739/kurumemedj.ms60227 -
World Journal of Clinical Oncology Jan 2019Xerostomia, or dry mouth, is a significant problem affecting quality of life in patients treated with radiation therapy for head and neck cancer. Strategies for... (Review)
Review
Xerostomia, or dry mouth, is a significant problem affecting quality of life in patients treated with radiation therapy for head and neck cancer. Strategies for reduction of xerostomia burden vary widely, with options including: sialagogue medications, saliva substitutes, acupuncture, vitamins, hyperbaric oxygen, submandibular gland transfer, and acupuncture or associated treatments. In this review, we sought to evaluate long-term outcomes of patients treated with various interventions for radiation-induced xerostomia. A literature search was performed using the terms "xerostomia" and "radiation" or "radiotherapy"; all prospective clinical trials were evaluated, and only studies that reported 1 year follow up were included. The search results yielded 2193 studies, 1977 of which were in English. Of those, 304 were clinical trials or clinical studies. After abstract review, 23 trials were included in the review evaluating the following treatment modalities: pilocarpine (three); cevimeline (one); amifostine (eleven); submandibular gland transfer (five); acupuncture like transcutaneous electrical nerve stimulation (ALTENS) (one); hyperbaric oxygen (one); and acupuncture (one). Pilocarpine, cevimeline, and amifostine have been shown in some studies to improve xerostomia outcomes, at the cost of toxicity. ALTENS has similar efficacy with fewer side effects. Submandibular gland transfer is effective but requires an elective surgery, and thus may not always be appropriate or practical. The use of intensity-modulated radiation therapy, in addition to dose de-escalation in select patients, may result in fewer patients with late xerostomia, reducing the need for additional interventions.
PubMed: 30627521
DOI: 10.5306/wjco.v10.i1.1 -
Caries Research 2004When salivary output is reduced chronically to a significant extent, there is a marked increase in dental caries. As the role of saliva in protection of the oral hard... (Review)
Review
When salivary output is reduced chronically to a significant extent, there is a marked increase in dental caries. As the role of saliva in protection of the oral hard tissue is well recognized, there have long been efforts to enhance salivary function in conditions with associated secretory hypofunction. The rationale is that by stimulating salivary output, caries and other oral complications will be reduced or eliminated. The most widely used method for increasing salivary function is a combination of masticatory and gustatory stimulation. A large number of systemic agents have also been proposed as secretagogues, but only a few have shown consistent salivary enhancing properties in well-designed, controlled trials. Pilocarpine has been shown to improve symptoms of oral dryness and to increase salivary output in patients with Sjögren's syndrome and postradiation xerostomia. Recently, cevimeline has shown significant salivary enhancement in Sjögren's syndrome. Pilocarpine and cevimeline have a similar mechanism of action, side effect profile and duration of activity. No secretagogues have been linked directly in clinical trials to either caries prevention or a reduction in the existing caries rate of salivary dysfunction patients. Improved secretagogues are needed, with fewer side effects, increased duration of activity and greater potency. Future research directions include gene therapeutic approaches to direct salivary growth and differentiation or modify remaining tissues to promote secretion, creation of a biocompatible artificial salivary gland and salivary transplantation. With improved secretagogues, the effects of conditions that result in reduced salivary function and increased caries will be ameliorated.
Topics: Acupuncture Therapy; Humans; Muscarinic Agonists; Physical Stimulation; Saliva; Salivation; Stimulation, Chemical; Xerostomia
PubMed: 15153695
DOI: 10.1159/000077761