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Xerostomia: pharmacological treatments

Francesco Spadari1*
  • 1 Università degli studi di Milano Bicocca, Department of Biomedical, Surgical and Dental Sciences, Italy

There is confusion about the definition of dry mouth because the terms xerostomia and salivary gland hypofunction have been used interchangeably in relation to the subjective complaints or objective aspects of dry-mouth (Guggenheimer and Moore, 2003). When we observe a clinical dry mouth condition with real and documented hyposalivation, we can confirm an actual secretory hypofunction of the salivary glands. Instead, xerostomia is the subjective symptom of dry mouth and occurs in 5.5-46% of the population (Navazesh and Kumar, 2009). Xerostomia is also more common in women and is often observed in older adults (Saleh et al., 2015). Dry mouth is often a consequence of acute or chronic salivary gland hypofunction or inadequate salivary secretion (Table 1). This functional condition is categorized as “true” xerostomia. Typically, patients complain of oral dryness only when the salivary secretion is reduced >50%. Xerostomia also occurs in patients with no measurable decrease in saliva production, without local signs of hyposalivation. In this clinical condition, we can define the presence of a “pseudo”-xerostomia (Astor et al., 1999). Causes of this subjective symptom include modifications of saliva composition, atypical oral and facial symptoms, burning mouth syndrome, oral dysesthesia and mental, psychological and psychiatric disorders (Bergdahl and Bergdahl, 2000). The production of salivary fluids occurs through complex processes, controlled by the autonomic nervous system. Sympathetic stimulation mainly affects protein content and composition, whereas parasympathetic cholinergic neurotransmission mediated through the muscarinic M3 receptor stimulation acts to increase the volume of secreted saliva (Humphrey and Williamson, 2001). Saliva has many protective functions, including cleansing the oral cavity, facilitating oral processing and swallowing of food, protecting oral tissues against physical and microbial assaults, maintaining a neutral pH and preventing tooth demineralization. Symptoms of dry mouth may range from mild oral discomfort to significant oral disease (Table 2). Patients with “true” xerostomia and salivary gland hypofunction can have difficulty in swallowing, chewing, and/or speaking, burning mouth sensation, halitosis, altered taste perception, dry buccal mucosa, chronic oral candidiasis and glossitis, periodontal and dental degenerations. As a result, xerostomia can lead to a poor quality of life for the affected individuals (Lenander-Lumikari and Loimaranta, 2000). The underlying aetiology of xerostomia may be divided into two categories: systemic diseases and local factors. The former includes and advancing age, immune disorders, endocrine, infectious and granulomatous diseases (Gupta et al., 2006). The latter encompasses head and neck radiation therapy, and lifestyle factors (Dirix et al., 2006). Systemic drug therapies are also considered important etiological factors of dry mouth (Table 3). The pharmacological molecules able to inhibit the saliva production would be considered as a systemic cause of hyposalivation (Leal et al., 2010). Drugs which are implicated in xerostomia are: anticholinergics, antidepressants and antipsychotics, antihypertensive agents, diuretic, sedative and anxiolytic agents, opioids, non-steroidal anti-inflammatory drugs, and antihistamines (Villa et al., 2015). Suffering of the salivary glands is a frequent adverse effect of radiation therapies as effect of the local treatments of head and neck neoplasms and oral cancer. Indeed, the salivary parenchyma and secretory tissues are very sensitive to radiation. Therefore, the severity of xerostomia depends on the degree of radiation exposure. Management of oral cancer requires administration of 60-70 Gy of radiation dose, which causes acute decrease in salivary flow in the 1st week, with a gradual reduction to 95% and by the 5th week the salivary flow can stop with a low probability of functional recovery (Radvansky et al., 2013). The diagnosis of xerostomia begins with a thorough and detailed medical history. Patients should be asked about difficulty swallowing, chewing, speaking, and altered taste. Patients with salivary gland hypofunctions may report difficulty wearing partial or total dentures, in addition to difficulty in eating crunchy, hard, acidic, or spicy foods. A review of the patient’s medications and medical history, along with social history are all needed factors in order to determine the underlying causes of dry mouth (Atkinson et al., 2005). Many questionnaires have been devised to evaluate the severity of xerostomia. It is necessary to perform a careful oral clinical examination after a complete medical history and verbal evaluations through specific questionnaires (Cassolato and Turnbull, 2003). Signs of hyposalivation include glassy oral mucosa, smoothed gingiva, loss of papillae of the dorsal tongue, fissured/lobulated dorsum of the tongue, foamy saliva, none/minimal salivary accumulation in the floor of the mouth, multiple cervical caries and mucosal debris on the oral palate, gums and upper and lower vestibules (Kruszka and O'Brian, 2009). Salivary flow rates can also be counted for an objective diagnosis of hyposalivation. Sialometric tests include the measurements of the stimulated and unstimulated salivary low rate. Normal stimulated salivary flow rate is 1.5-2.0 mL/min and when unstimulated the flow rate is reduced to 0.3-0.4 mL/min. Hyposalivation refers to unstimulated salivary flow rate is ≤0.1 mL/min and stimulated salivary flow rate of ≤0.5-0.7 mL/min (Navazesh, 1993). A diagnosis of salivary gland dysfunction can also be made through imaging, including sialography, scintigraphy with technetium-99m, and CT or MRI of the salivary glands. Laboratory tests can be obtained in order to determine if the underlying cause is related to a systemic disease, such as anti-Ro and anti-La antibodies for Sjögren syndrome (Fox et al., 2000). A minor salivary gland biopsy, obtained from lower lip, and histopathological examination can also be performed, particularly in patients of suspected Sjögren syndrome (van der Reijden et al., 1999). Treatment of the real absence or decrease of salivary fluids can be divided in systemic sialogogues and topical agents. The two systemic drugs are pilocarpine and cevimeline (Smith et al., 2013). Pilocarpine is a non-selective muscarinic agonist and parasympathetic agent. The recommended starting dose range from 5 to 30 mg daily. Patients are typically instructed to take 5 mg three times daily for at least three months (Aframian et al., 2007). Pilocarpine can diminish dry mouth in patients after head and neck radiation therapy. Positive pharmacological effects with increase of salivary fluids in patients with head and neck radiation occur between two and three months after initiating the medication with systemic pilocarpine. The main side effects include bradycardia, hypotension, bronchoconstriction, nausea, vomiting, diarrhoea, and increase of daily diuresis. Moreover, pilocarpine therapy should be prescribed with caution in patients with cardiovascular and pulmonary diseases, and it should be contraindicated in patients with iritis and narrow-angle glaucoma (Aframian et al., 2007). Cevimeline, a M1- and M3-selective muscarinic agonist, shows fewer side effects than pilocarpine, because it does not affect M2 receptors. Standard dosing is 30 mg three times daily for at least 3 months. Its most common side effect is dyspepsia (Weber and Keating, 2008). However, cevimeline is contraindicated in patients with hypertension, chronic pulmonary disease, and active gastric ulcers (Braga et al., 2009). Other systemic sialogogues include bethanechol, anethole trithione, and yohimbine. Bethanechol is a carbamic ester of β-methylcholine resistant to cholinesterase, affecting M3 receptors. It is beneficial in patients with xerostomia after head and neck radiation therapy as it increases their salivary flow rate. The recommended systemic dose is 25 mg three times daily. Side effects include diarrhoea and nausea (Jham et al., 2007). Anethole trithione, a bile secretion-stimulating medication, can improve dry mouth sensations and increase the salivary flow. Yohimbine, an α2-adrenoceptor antagonist, may be effective for hyposalivation in patients taking psychotropic medications (Bagheri et al., 1997). Topical therapies are the first-line treatments recommended for xerostomia and salivary hypofunction (Furness et al., 2011). The more commonly used medications and agents can be categorized into salivary stimulants and saliva substitutes, and chewing gums or candies (van der Reijden et al., 1999). Chewing gums and candies should be sugar-free in order to prevent dental caries. They can often stimulate saliva secretion and reduce friction of the oral mucosa. Salivary stimulants and substitutes include mouthwashes, sprays, oral gels and toothpastes as they can improve salivary gland function (Furness et al., 2011). Saliva substitutes resemble natural saliva and increase the salivary viscosity. Saliva substitutes commonly contain carboxymethyl-cellulose, xanthan gum, mucins, salivary proteins and enzymes, hydroxyl-ethyl-cellulose, polyethylene oxide, or linseed oil (Hahnel et al., 2009). Sprays have been used for the treatment of xerostomia (Furness et al., 2011). A sialagogue spray, composed of 1% of malic acid, has produced benefit in antihypertensive and antidepressant-induced xerostomia (Gomez-Moreno et al., 2013). An intraoral lubricant spray, oxygenated glycerol triester, has showed increased efficacy for xerostomia compared with a commercially available saliva substitute (Furness et al., 2011). Other topical products, containing xylitol, vitamins and natural pharmaceutical products have also been effective against medication-induced dry mouth. Other reported treatments for xerostomia include acupuncture and intraoral electrostimulation (Furness et al., 2013). It has been acknowledged that hyperbaric oxygen in patients who have undergone radiation has increased their salivary function (Teguh et al., 2009). It has been noted that after head and neck radiotherapy salivation improvements can be achieved with systemic amifostine, a cytoprotective agent (Gu et al., 2014). A greater understanding of xerostomia and an evolution of salivary gland hypofunction therapies would represent an important goal, and future discoveries in gene therapies, stem cell therapies and tissue bioengineering could provide great promise for future treatments.

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Keywords: dry mouth, Xerostomia, salivary gland hypofunction, Sjogren׳s syndrome (SS), Sialogogues

Conference: 5th National and 1st International Symposium of Italian Society of Oral Pathology and Medicine., Ancona, Italy, 19 Oct - 20 Oct, 2018.

Presentation Type: oral presentation

Topic: Salivary Research

Citation: Spadari F (2019). Xerostomia: pharmacological treatments. Front. Physiol. Conference Abstract: 5th National and 1st International Symposium of Italian Society of Oral Pathology and Medicine.. doi: 10.3389/conf.fphys.2019.27.00074

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Received: 28 Nov 2018; Published Online: 09 Dec 2019.

* Correspondence: Prof. Francesco Spadari, Università degli studi di Milano Bicocca, Department of Biomedical, Surgical and Dental Sciences, Milan, Italy, marcomascitti86@hotmail.it