DRUG-RELATED CHANGES TO SALIVARY GLANDS
Salivary fluid consists of approximately 99% water, with the remaining 1% representing a variety of electrolytes (sodium, potassium, calcium, chloride, magnesium, bicarbonate, and phosphate) and proteins (enzymes, immunoglobulins and other antimicrobial factors, glycoproteins, traces of albumin, etc.), in addition to glucose and nitrogenous products, such as urea and ammonia (de Almeida, Grégio, Machado, de Lima, & Azevedo, 2008; Pereira & van der Bilt, 2016). In a healthy state, mean daily saliva production ranges from 1 L to 1.5 L, with a normal stimulated salivary flow rate from 1 mL/minute to 3 mL/minute and an unstimulated flow rate from 0.25 mL/minute to 0.35 mL/ minute (Sharma, Somasundara, Prasanna Kumar, & Bhat, 2014). There is considerable intraindividual variation in salivary flow rate, and a normal or abnormal rate cannot be determined from one measurement alone. Xerostomia The functioning of the salivary glands can be influenced by drugs capable of producing reduced salivation (xerostomia) or excessive salivation (sialorrhea). Drugs influence salivation primarily by affecting the autonomic nervous system or hormone secretion (Proctor, 2016; Donaldson, & Goodchild, 2018). The subjective feeling of dryness in the oral cavity has been reported when the volume of saliva decreases by 50% to 70% (Singh & Papas, 2014). This reduction in saliva is an approximation, and a sensation of dryness in the oral cavity can be experienced with changes in the oral cavity that are greater or less than the previously mentioned values. Xerostomia has been associated with numerous medications, particularly antidepressants and antipsychotics, antihypertensives, antihistamines, and anticholinergics (NIH, 2014; Donaldson, & Goodchild, 2018). Polypharmacy – increasingly common in older adult patients – can result in synergistic effects of medications on salivary flow. Smoking and alcohol consumption may also contribute to oral dryness or the perception of dryness (Ongole & Praveen, 2013; Donaldson, & Goodchild, 2018). Additionally, xerostomia often is associated with Sjögren’s syndrome (Billings et al., 2016), an autoimmune condition that may be accompanied by rheumatoid arthritis or a related connective tissue disease (de Mendonça Invernici et al., 2014; Donaldson, Epstein, & Villines, 2014). Clinical manifestations of xerostomia include complaints of a dry mouth, oral burning or soreness, or a sensation of a loss of or altered taste. In more severe xerostomia, the tongue may appear erythematous, pebbled, cobblestoned, or fissured, with atrophy of the filiform papillae. The oral tissues may be erythematous and appear parched. Dental-related findings include increased Sialorrhea Increased salivary flow, called sialorrhea or ptyalism , is an uncommon condition, but it can result from physiological factors such as menstruation or early pregnancy, oral inflammatory lesions, food, local factors such as teething, or some medications (Miranda-Rius et al., 2015; Wolff et al., 2017). Classes of medications associated with sialorrhea include the typical antipsychotics, particularly clozapine, and cholinergic agonists used in Alzheimer-type dementia and myasthenia gravis. Certain heavy metal toxins (mercury and thallium) can also cause hypersalivation, as can exposure to irreversible acetylcholinesterase inhibitors (insecticides and nerve agents). Other causes may include sedatives, adrenergic antagonists, medications that irritate the esophagus, poisons or toxins, and specific herbal and fruit preparations (Miranda-Rius et al., 2015; Wolff et al., 2017). Physical complications of sialorrhea include perioral chapping, dehydration, and odor. Additionally, dermatitis, cheilitis, and fungal infection may accompany sialorrhea. Treatment options
During unstimulated salivary flow, the submandibular glands contribute 65% to 70% of salivary fluid, followed by the parotid glands (20%), sublingual glands (7% to 8%), and minor salivary glands (<10%). However, in stimulated salivary flow the parotids contribute more than 50% of the total salivary secretion (Miranda-Rius, Brunet-Llobet, Lahor-Soler, & Farré, 2015). Salivary secretions may be serous, mucous, or mixed. Serous secretions are produced mainly by the parotids, whereas mucous secretions are produced primarily by the smaller glands. The salivary content depends on the proportion between the serous and mucous cells in the mixed glands, such as the submandibular and sublingual glands.
cervical caries and denture discomfort. An expected oral manifestation in this patient population is fungal infections that can result from decreased salivary flow (Pinto, 2014; Donaldson & Goodchild, 2018). If xerostomia is determined to be caused by the patient’s medication, the healthcare team should consider modifying the medication. Palliative recommendations from the ADA include salivary flow stimulants such as sugarless chewing gum and avoiding the use of alcoholic beverages and mouth rinses (American Academy of Oral Medicine, 2015; American Dental Association, 2016; Donaldson, & Goodchild, 2018). Over-the- counter saliva substitutes and oral lubricants are available with carboxymethyl or hydroxymethyl cellulose plus electrolytes. These products are formulated as solutions, sprays, or gels. However, any relief the patient experiences will be temporary. There is limited evidence to indicate that topical products provide effective relief for dry mouth (Furness, Worthington, Bryan, Birchenough, & McMillan, 2011). The role of pilocarpine and cevimeline in treating xerostomia is limited because of significant adverse effects, but these medications have continued to find clinical application. Cholinergic drugs should be avoided in patients who have significant heart disease and are contraindicated for patients who have uncontrolled asthma or narrow-angle glaucoma (Pfizer Canada Inc., 2014; Than & Hardie, 2012). Ultimately, the practitioner and the patient decide whether pharmacological or nonpharmacological intervention is indicated (Gil-Montoya, Silvestre, Barrios, & Silvestre-Rangil, 2016). range from conservative to more aggressive intervention. Possible interventions include physiotherapy, oral motor therapy, behavioral modification through biofeedback, orofacial regulation therapy, pharmacological therapy, acupuncture, radiotherapy, photocoagulation of salivary ducts, neurectomy, and surgery (Miranda-Rius et al., 2015; Wolff et al., 2017). Glycopyrrolate and scopolamine – anticholinergic agents – effectively reduce drooling, but their use is limited by side effects. Injection of botulinum toxin type A into salivary glands is an off-label treatment option to control drooling, but the improvement is temporary and repeat injections are necessary (Sillanpaa, Sipila, Numminen, & Rautiainen, 2015; Jost, Steffen, & Berweck, 2021). Surgical intervention includes salivary gland excision, salivary duct ligation, and duct rerouting.
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