**5. Consequences of xerostomia**

**4.2. Drugs**

**4.3. Systemic conditions**

**Medicine group Examples**

20 Salivary Glands - New Approaches in Diagnostics and Treatment

Anorectic Fenfluramine Anticonvulsants Gabapentin

Antiemetics Meclizine Antihistaminics Loratadine

Muscle relaxants Baclofen

Sedatives Flurazepam

Antiarthritic Piroxicam

**Table 3.** Medicines and drugs with side effects on salivary secretion.

Anxiolytics Lorazepam, diazepam

Antidepressants—tricyclic Amitriptyline, imipramine Antidepressants—SSRI Sertraline, fluoxetine

Antiparkinsonian Biperidene, selegiline Antipsychotics Clozapine, chlorpromazine Bronchodilators Ipratropium, albuterol Decongestants Pseudoephedrine

Diuretics Spironolactone, furosemide

Narcotic analgesics Meperidine, morphine

Antihyperptensive Prazosin hydrochloride

The most common cause of xerostomia is the use of some systemic medications [43]. Several drugs are able to induce hyposalivation and xerostomia, but they rarely cause irreversible damage to the salivary glands. Over 400 medicines, many of them in common use, induce salivary gland hypofunction [44]. Some examples are: anxiolytics, anticonvulsants, antidepressants, antiemetics, antihistamines, antiparkinsonian, antipsychotics, bronchodilators, decongestants, diuretics, muscle relaxants, analgesics, sedatives and anti-hypertensives, and others (**Table 3**) [29]. The exact mechanisms whereby some drugs determine xerostomia or hyposalivation are still unknown. Salivary dysfunction associated to drugs may occur through anticholinergic, cytotoxic action, sympathomimetic, or by damaged ion transport pathways in the acinar cells [39, 45, 46]. Patients who consume a higher number of daily medications have been associated with complaints of xerostomia [47, 48]. The therapeutic and controlled doses of medications do not damage the salivary gland structure. For that reason, drug-induced xerostomia is reversible. The discontinued use of these drugs can restore salivary flow [49].

Xerostomia or hyposalivation may be caused by local factors, including salivary gland disease (sialadenitis) or salivary gland destruction associated with head and neck irradiation for the

> Patients with xerostomia may have oral and dental consequences. Xerostomia can seriously impact quality of life and may alter speech, eating, and swallowing [13]. The most common complaints of patients with xerostomia include oral discomfort, difficulty speaking, dysphagia, dysgeusia (decreased taste), feeling of thick saliva, and generally, chewing issues, dental caries, dental demineralization, periodontal disease, salivary gland infection (sialodenitis), oral microflora alterations, burning sensation, mucosal inflammation, sore throats, hoarseness, ulcerations, halitosis, mucosal dehydration, reduced lubrication, painful tongue (glossodynia), enlarged parotid gland, oral mucosal fracture, inflammation and fissures of the lips (cheilitis). The reduction of rates of elimination of substances can affect the palate and be associated with changes in the mouth microbiota. The reduction of rates of elimination of substances can affect the palate and be associated with changes in the mouth microbiota. From the mouth, alterations of taste and intolerance to acidic or spicy foods, dry foodstuffs like biscuits can be very uncomfortable for them, and oral cavity examination may exhibit signs such as fissures on the tongue and

lips, angular cheilitis, and dry mucosa. Also, caries, candidiasis, halitosis, or loss of appetite and weight could be observed [25, 57, 58]. This collection of clinical parameters has been indicated as simply estimated for recognizing most patients with xerostomia [38, 47].

**6.2. Preventive therapies**

standard radiation therapy [68].

**6.3. Symptomatic treatment**

neoplasias of the pharynx and larynx [70].

Pharmacological interventions for the prevention of radiation-induced salivary gland dysfunction have been studied. The use of chemical radioprotectors represents an obvious strategy to improve the therapeutic index in radiotherapy. However, the vast majority of these are either too weak in terms of radioprotection, too toxic, or without any apparent mechanisms to ensure selective normal tissue protection [62]. The sulfhydryl compound amifostine (WR-2721; 2-[(3-aminopropyl) amino] ethylphosphorothioic acid), is an oxygen scavenger that may protect salivary glands from free-radical damage during radiation therapy without attenuation of the anti-tumor effects in many experiments performed [63]. Amifostine has been approved for prevention of xerostomia, in head and neck squamous cell carcinoma patients undergoing radiotherapy [64]. A recent systematic review that included randomized controlled trials suggested that the drug amifostine prevents the feeling of dry mouth in people receiving radiotherapy to head and neck (with or without chemotherapy) in the short- (end of radiotherapy) to medium-term (3 months after radiotherapy) [65]. However, amifostine has adverse effects such as nausea, vomiting, hypotension, transient, hypocalcemia, and allergic reactions [66]. Then, the benefits of amifostine should be weighed against its high cost and side effects. Another cytoprotective compound described in literature is the bioactive factor Keratinocyte growth factor-1 (KGF-1, also known as FGF-7) [67]. In a phase II Study, recombinant KGF (Palifermin) appeared to reduce mucositis, dysphagia, and xerostomia during hyperfractionated radiotherapy but not

Xerostomia: An Update of Causes and Treatments http://dx.doi.org/10.5772/intechopen.72307 23

Current preventative therapies also include surgical salivary glands relocation outside the radiation field [69]. Jha et al. described a surgical transfer of a submandibular salivary gland to the submental space in order to prevent radiation-induced xerostomia in patients with

Saliva substitutes can provide some relief since provide higher viscosity and protection to the oral mucosa [39]. An ideal saliva substitute must simulate natural human saliva, providing long lasting and intense hydration of the oral mucosa, be inexpensive, edible, easy-to-swallow but retainable in the mouth and should allow a minimal number of applications [71]. Saliva substitutes are available in various formulations, e.g., lozenges, sprays, mouth rinses, gels, oils, chewing gums, or toothpastes. Most available in the market contain carboxymethylcellulose (CMC), mucins, xanthan gum, hydroxyethylcellulose, linseed oil, or polyethylene oxide [72]. Subjective impressions of patients suffering from severe xerostomia showed that artificial saliva containing mucins and xanthan gum are better in their rheological and moisturizing properties than those with CMC [73], because mucin-based substitutes had viscosities that were more similar to natural saliva. Recently, it was reported that a polysaccharide-based oral rinse was effective in symptom control in patients with xerostomia and may lead to an increase in saliva production [74]. Other studies include the use of natural products, in this line, a recent doubleblinded, placebo-controlled clinical trial, evaluated the efficacy of topical lycopene-enriched virgin olive oil. It showed an improvement of oral quality of life and reduction of xerostomia symptoms [75]. Also, gelatinous substitutes of saliva showed a significant reduction of the

The side effects associated with xerostomia are microbial colonization and proliferation in the oral cavity, dental or decreased demineralization, accumulation of stones in the teeth, dehydration of the mucosa, reduction of rates of elimination of substances from the mouth and lubrication of the oral mucosa reduced [13]. When the production of saliva decreases, the buffering capacity of the saliva is reduced, and thus the environment of the oral cavity is vulnerable to acidification, which in addition to determining changes in the normal flora (ecological imbalance) has contributed to the increase in the number of some microorganisms such as *Candida albicans* (a salivary flow less than 0.1 mL/min may cause an increase in the incidence of this fungus) and *Streptococcus mutans* (Gram-negative bacteria). A higher proportion of these microorganisms results in greater acidification of the oral cavity environment, and thus contribute to the enamel demineralization and caries progression. There is a study related to it in which subjects with low salivary flow rate also had significantly more dental caries compared to those with a higher saliva flow rate [58]. In addition, high caries prevalence has been reported to be associated with significantly poorer quality of life compared to low caries prevalence [13].

The infection of the oral mucosa with *C. albicans* affects the lubrication of oral tissues, favoring an increase in the risk of caries and severity of periodontal disease. Candidiasis can also cause burning sensation, glossodynia, glossitis, and angular cheilitis (in areas where the lips are dry or cracked). Patients with prostheses may have reduced retention of the prostheses, pain, and ulcers [59]. The prevalence of oral Candida in the normal population has been estimated to range from 23 to 68% and 68 to 100% among SS patients. Studies have attributed the higher prevalence of oral Candida carriage in this disease to xerostomia [60].
