Re-establishing a Normal Salivary Flow

Patients with diminished salivary flow have several options for treating salivary gland hypofunction (SGH), also known as xerostomia. Adequate salivary flow is so important because saliva is necessary in lubricating and moistening food for swallowing; solubilizing material for taste; initiating digestion; preventing dental caries; maintaining the pH of the upper gastrointestinal tract; maintaining the health of the oral mucosa and dentition; preventing opportunistic infection, such as candidiasis, by keeping the oral microflora balance; speaking; cleaning the mouth; and clearing the esophagus.

Adequate hydration is an important first step in treating SGH. Topical agents such as gels, sprays, and other saliva substitutes can be used for comfort. Salivary flow can be stimulated using topical or local approaches such as gustatory stimulation, masticatory stimulation, anhydrous crystalline maltose (ACM), acupuncture, and electrical stimulation.¹ Systemic prescription salivary gland stimulants include pilocarpine; cevimeline; bromhexine; anetholetrithione (Sialor); low dose alpha interferon; tumor necrosis factor-alpha blockers (infliximab); rituximab–monoclonal antibody; and yohimbine, an herbal a2 adrenoreceptor antagonist. Of the systemic agents, pilocarpine, anetholetrithione, and yohimbine are suggested for use in patients with medication-associated dry mouth.

The goals of treating SGH include: to relieve dryness symptoms (increase water and humidity); to prevent anticipated complications of SGH, including dental caries and oral candidiasis; to stimulate salivary gland function; to slow the loss of functional salivary gland tissue; and to promote repair of salivary gland tissue.² Currently, none of the topical or systemic options repair salivary gland tissue.

Gustatory stimulation includes acidic, bitter, or sour foods and beverages that are known to stimulate salivary flow. In general, these should be limited because low pH foods and beverages promote mucosal soreness, dental erosion, and dental caries. Masticatory stimulation includes using sugar free chewing gum to stimulate saliva. Lozenges of anhydrous crystalline maltose also stimulate saliva in dry mouth patients.³

Adequate water is important to saliva production. The commonly accepted general rule of eight to 10 8 oz glasses of water per day promotes adequate hydration. Patients with dry mouth are typically advised to sip water frequently to replace, at least in part, the missing saliva. There is no additional benefit to increasing daily water intake beyond this amount. Using a cool air humidifier during sleep, especially during winter months, can be helpful. The humidifier should be turned on approximately 1 hour prior to bedtime and left on all night. The humidifier should be cleaned frequently.

OVER-THE-COUNTER RELIEF

There are many topical products available over-the-counter to partially replace saliva and increase oral comfort levels. These products are available in pharmacies and other stores in the oral health section. Patients should try a variety of products until they find one they like. These over-the-counter products require frequent application, often one to two times per hour. Products that are free of sodium lauryl sulfate (SLS) are excellent for patients with dry mouth. Because they are SLS-free, these products can be used with prescription chlorhexidine mouthwash if needed.

Electrical stimulation can also increase salivary flow. Electrical stimulation with a TENS (transcutaneous electrical nerve stimulator) unit is used to stimulate salivary flow.^4,5,6 Acupuncture may stimulate saliva in patients with salivary gland hypofunction due to Sjogren’s syndrome and radiation. Acupuncture increases salivary flow, ability to eat and speak, and improved sleep in patients affected with Sjogren’s syndrome.^7-9 Acupuncture points on hands and ears are used to increase salivation.

PHARMACOLOGICAL OPTIONS

Currently, pharmacological options are the most reliable in stimulating salivation in patients with residual functional salivary gland tissue or “responders.” Responders are patients who have a low, unstimulated salivary flow rate, less than 0.1 ml per minute but the stimulated salivary flow rate is higher than 0.1 ml per minute. In the United States, two prescription products are available—pilocarpine and cevimeline. They are known as salivary stimulators, secretagogues, or sialogogues. Pilocarpine is a parasympathomimetic, muscarinic-cholinergic agonist that stimulates muscarinic-type ACH receptors in salivary glands. It received Food and Drug Administration (FDA) approval for radiation-associated xerostomia using 5 mg three times daily. In 1998, pilocarpine received approval for treating Sjogren’s syndrome 5 mg four times daily. Pilocarpine is safe and effective with minimal adverse effects, the most common of which are sweating and flushing. Pilocarpine’s onset of action is 20-30 minutes after ingestion by mouth with a duration of 3-5 hours and a half-life of 0.76 hours. Pilocarpine can be taken alone or with water and/or food, which will slow down the absorption and decrease sweating and flushing in affected patients. Patients need to be on the medication a minimum of 3 months prior to assessing the outcome of treatment because it takes time to achieve maximum subjective benefit in many patients.¹⁰ SGH is often progressive, especially in immune mediated disease, even with secretagogue medication. More Sjogren’s syndrome patients retained their salivary flow after 2 years of treatment with pilocarpine compared to a significant decrease in the untreated group.¹¹ Oral candidiasis is controlled in 2/3 of patients on long term pilocarpine.¹² It also improves mouth dryness, eye dryness, nasal dryness, dry skin, vaginal dryness, and the ability to expectorate.¹³ There are no reported drug interactions with pilocarpine. It is contraindicated in patients with uncontrolled asthma, known hypersensitivity, acute iritis, and narrow-angle glaucoma. Pilocarpine should be used with caution in patients with cardiovascular disease or a history of kidney or bile stones.

The other prescription salivary stimulant medication available in the United States is cevimeline. Cevimeline is a cholinergic agonist that binds to muscarinic receptors. It binds to the M3 receptors of salivary glands with a greater specificity than pilocarpine and has a longer half life. After oral ingestion of a 30 mg capsule of cevimeline, the onset of action in 30-90 minutes with a duration of 6- hours, and a half-life of about 5 hours. It takes up to 3 months of 30 mg cevimeline taken three times daily to experience maximum subjective benefit. Japanese and American studies evaluating muscarinic agonists to treat xerostomia in Sjogren’s using 30 mg three times daily, found a moderate and lasting increase in salivary flow twice that of placebo with no evidence of tolerance or increased adverse effects in 12 weeks. Several weeks after stopping cevimeline, patients had a tendency to maintain salivary secretion at higher levels than pretreatment.¹⁴ Cevimeline is safe and efficacious in treating salivary gland hypofunction due to Sjogren’s syndrome.¹⁵ Contraindications include uncontrolled asthma, hypersensitivity, acute iritis, and narrow-angle glaucoma. Caution should be used when patients have chronic bronchitis, chronic obstructive pulmonary disease, emphysema, or a history of gall stones or kidney stones, and if patients are taking beta adrenegeric blockers. Caution should be advised while driving at night or while performing hazardous activities in reduced lighting.

LOZENGES AND LIQUID

There are two new topically acting prescription dry mouth products available in 2006—Numoisyn lozenges and liquid. Numoisyn lozenges contain sorbitol, polyethylene glycol, malic acid, sodium citrate, calcium phosphate dibasic, hydrogenated cottonseed oil, citric acid, magnesium stearate, and silicon dioxide. The lozenges are best suited for patients with some salivary gland function. Excessive consumption can cause digestive problems including diarrhea. There are no known drug interactions. The lozenges are recommended for use in dry mouth due to medications, chemotherapy, radiation, Sjogren’s, oral inflammation, or other conditions. The patient dissolves one lozenge in the mouth as needed for dry mouth, not to exceed six times daily. Numoisyn liquid contains water, sorbitol, linseed (flaxseed) extract, Chondrus crispus (Irish moss, carrageenan), methylparaben, sodium benzoate, potassium sorbate, dipotassium phosphate, and propylparaben. The liquid is best suited for patients with little or no salivary gland function. Use of the liquid can be irritating to patients with irritable bowel syndrome, diverticular disease, or those on high linseed oil diets. There are no known drug interactions. The recommended use for the liquid is in patients with dry mouth due to medications, chemotherapy, radiation, Sjogren’s, oral inflammation, or other conditions. The liquid forms a protective film that provides about 1 hour of comfort. The liquid is available by prescription only in a 300 ml bottle. The patient should use, 2 ml (1/2 teaspoon, swish around mouth then swallow) as needed for dry mouth.

To summarize, the patient with dry mouth requires adequate water; often a secretagogues medication—either pilocarpine or cevimeline—to re-establish a normal salivary flow rate; and over-the-counter products for comfort.

REFERENCES

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13. Vivino FB, Al-Hashimi I, Khan Z, et al. Pilocarpine tablets for the treatment of dry mouth and dry eye symptoms in patients With Sjögren syndrome a randomized, placebo-controlled, fixed-dose, multicenter trial. Arch Intern Med. 1999;159:174-181.
14. Yasuda H, Niki H. Review of the pharmacological properties and clinical usefulness of muscarinic agonists for xerostomia in patients with Sjogren’s syndrome. Clin Drug Invest. 2002;22:67-73.
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From Dimensions of Dental Hygiene. May 2006;4(5): 30, 32.