I suffer from end stage lung disease (COPD) I am presently going through a flare up and my oxygen drops into the 80’s with minimum exertion. I am on 20 mg of prednisone (tapering off) and was on Factive. I take 20mg of Lexapro, Spiriva, Advair, Protonix, theophylline and 20 mg of Micardis. I put on weight (5′4, 236 lbs-female) but I had a very thorough exam for my heart- no sugar, cholesterol or triglyceride problem, no thyroid, stress test and echo perfect as well as blood pressure (it goes up a bit when I exert but usually is runs about 130/80 or bad is 140/90. Sometime it drops to 117/78. So, in that regard I am very lucky. My mouth became dry and I became very thirsty with this flare up (it has been going on now for about 3.5 weeks) I have a partial bridge and caps. I do not know what to make of it. I also noticed my skin getting very dry so I bought some Gatoraid and drank that and it helped for about 3 days. Seems like I’m dehydrated. I am constantly drinking water – maybe 10 glasses or so. Am constantly going to the bathroon to urinate and do have a yeast infection that will not go away. I also have been having headaches – mild and get dizzy- which I think is from the drop in oxygen. What do you suggest? Which doctor should I see- my primary, pulmonist, ENT, gynocologist or all? Sorry for the overload. I am 55 yrs. old if that makes any difference. I get hot flashes now and then but mostly in the extremities and do not sweat just get hot on the top of my head. (don’t laugh-is true) Thanks… Maria Published: July 23 ::
By Cathy L. Bartels, Pharm.D., assistant professor, pharmacy practice, School of Pharmacy and Allied Health Sciences, University of Montana
Introduction
Xerostomia is defined as dry mouth resulting from reduced or absent saliva flow. Xerostomia is not a disease, but it may be a symptom of various medical conditions, a side effect of a radiation to the head and neck, or a side effect of a wide variety of medications. It may or may not be associated with decreased salivary gland function.1,2 Xerostomia is a common complaint found often among older adults, affecting approximately 20 percent of the elderly.1,3-5 However, xerotomia does not appear to be related to age itself as much as to the potential for elderly to be taking medications that cause xerostomia as a side effect.
Normal salivary function is mediated by the muscarinic M3 receptor. Stimulation of this receptor results in increased watery flow of salivary secretions. When the oral mucosal surface is stimulated, afferent nerve signals travel to the salivatory nuclei in the medulla. The medullary signal may also be affected by cortical inputs resulting from stimuli such as taste, smell, anxiety or depression. Efferent nerve signals, mediated by acetylcholine, also stimulate salivary glandular epithelial cells and increase salivary secretions.7
Saliva components
Saliva is the viscous, clear, watery fluid secreted from the parotid, submaxillary, sublingual and smaller mucous glands of the mouth. Saliva contains two major types of protein secretions, a serous secretion containing the digestive enzyme ptyalin and a mucous secretion containing the lubricating aid mucin. The pH of saliva falls between 6 and 7.4. Saliva also contains large amounts of potassium and bicarbonate ions, and to a lesser extent sodium and chloride ions. In addition, saliva contains several antimicrobial constituents, including thiocyanate, lysozyme, immunoglobulins, lactoferrin and transferrin.8
Functions of saliva
Saliva possesses many important functions including antimicrobial activity, mechanical cleansing action, control of pH, removal of food debris from the oral cavity, lubrication of the oral cavity, remineralization and maintaining the integrity of the oral mucosa.2,8-10
Complications associated with xerostomia
Xerostomia is often a contributing factor for both minor and serious health problems. It can affect nutrition and dental, as well as psychological, health. Some common problems associated with xerostomia include a constant sore throat, burning sensation, difficulty speaking and swallowing, hoarseness and/or dry nasal passages.1 Xerostomia is an original hidden cause of gum disease and tooth loss in three out of every 10 adults.11 If left untreated, xerostomia decreases the oral pH and significantly increases the development of plaque and dental caries.1,2 Oral candidiasis is one of the most common oral infections seen in association with xerostomia.(2)
Signs and symptoms of xerostomia
Individuals with xerostomia often complain of problems with eating, speaking, swallowing and wearing dentures. Dry, crumbly foods, such as cereals and crackers, may be particularly difficult to chew and swallow. Denture wearers may have problems with denture retention, denture sores and the tongue sticking to the palate. Patients with xerostomia often complain of taste disorders (dysgeusia), a painful tongue (glossodynia) and an increased need to drink water, especially at night. Xerostomia can lead to markedly increased dental caries, parotid gland enlargement, inflammation and fissuring of the lips (cheilitis), inflammation or ulcers of the tongue and buccal mucosa, oral candidiasis, salivary gland infection (sialadenitis), halitosis and cracking and fissuring of the oral mucosa.(2,6,9,13)
Diagnosis and evaluation of xerostomia
Diagnosis of xerostomia may be based on evidence obtained from the patient’s history, an examination of the oral cavity and/or sialometry, a simple office procedure that measures the flow rate of saliva. Xerostomia should be considered if the patient complains of dry mouth, particularly at night, or of difficulty eating dry foods such as crackers.(2,5,7) When the mouth is examined, a tongue depressor may stick to the buccal mucosa.9 In women, the “lipstick sign,” where lipstick adheres to the front teeth, may be a useful indicator of xerostomia.7
The oral mucosa may be dry and sticky, or it may appear erythematous due to an overgrowth of Candida albicans. The red patches often affect the hard or soft palate and dorsal surface of the tongue. Occasionally, pseudomembranous candidiasis will be present, appearing as removable white plaques on any mucosal surface. There may be little or no pooled saliva in the floor of the mouth, and the tongue may appear dry with decreased numbers of papillae. The saliva may appear stringy, ropy or foamy. Dental caries may be found at the cervical margin or neck of the teeth, the incisal margins or the tips of the teeth.2
Several office tests and techniques can be utilized to ascertain the function of salivary glands. In sialometry, or salivary flow measurement, collection devices are placed over the parotid gland or the submandibular/
sublingual gland duct orifices, and saliva is stimulated with citric acid. The normal salivary flow rate for unstimulated saliva from the parotid gland is 0.4 to 1.5 mL/min/gland.2,3 The normal flow rate for unstimulated, “resting” whole saliva is 0.3 to 0.5 mL/min; for stimulated saliva, 1 to 2 mL/min. Values less than 0.1 mL/min are typically considered xerostomic, although reduced flow may not always be associated with complaints of dryness.2,5
Sialography is an imaging technique that may be useful in identifying salivary gland stones and masses. It involves the injection of radio-opaque media into the salivary glands.2,3 Salivary scintigraphy can be useful in assessing salivary gland function. Technetium-99m sodium pertechnate is intravenously injected to ascertain the rate and density of uptake and the time of excretion in the mouth.2,3 Minor salivary gland biopsy is often used in the diagnosis of Sjögren’s syndrome (SS), human immunodeficiency virus-salivary gland disease, sarcoidosis, amyloidosis and graft-vs.-host disease. Biopsy of major salivary glands is an option when malignancy is suspected.2
Common causes of xerostomia
Medications
Perhaps the most prevalent cause of xerostomia is medication. Xerogenic drugs can be found in 42 drug categories and 56 subcategories.14 More than 400 commonly used drugs can cause xerostomia.10,14 The main culprits are antihistamines, antidepressants, anticholinergics, anorexiants, antihypertensives, antipsychotics, anti-Parkinson agents, diuretics and sedatives. Other drug classes that commonly cause xerostomia include antiemetics, antianxiety agents, decongestants, analgesics, antidiarrheals, bronchodilators and skeletal muscle relaxants.2,6,10,14,15 It should be noted that, while there are many drugs that affect the quantity and/or quality of saliva, these effects are generally not permanent.
Patients complaining of xerostomia should be interviewed and their medications should be reviewed. It may be possible to change medications or dosages to provide increased salivary flow. Symptoms of xerostomia are often worse between meals, at night and in the morning. Therefore, consider modifying drug schedules to achieve maximum plasma levels when the patient is awake.9 Consider easy-to-take formulations, such as liquids, and avoid sublingual dosage forms if possible. Counsel your patients regarding which medications can and cannot be crushed. Also counsel them to first lubricate the mouth and throat with water prior to taking capsules and tablets and to follow this with a full glass of water. If possible, consider switching the patient from one medication to another with comparable efficacy but with less anticholinergic activity, for example, switching from the tricyclic antidepressant amoxapine to desipramine.
Diseases and other conditions
The most common disease causing xerostomia is Sjögren’s syndrome (SS), a chronic inflammatory autoimmune disease that occurs predominantly in postmenopausal women. It is estimated that as many as 3 percent of Americans suffer from Sjögren’s syndrome, with 90 percent of these patients being women with a mean age at diagnosis of 50 years. SS is characterized by lymphocytic infiltration of salivary and lacrimal glands, resulting in xerostomia and xerophthalmia. This combination is called the sicca complex. Enlargement of major salivary glands occurs in about one-third of patients with SS.9 There is no cure for the disease. The goal of therapy is to manage symptoms. Common symptoms associated with SS, in addition to xerostomia and xerophthalmia, include blurred vision, recurrent eye and mouth infections, dysphagia or difficulty swallowing, oral soreness, smell and taste alternations, fissures on the tongue and lips, fatigue, dry nasal passages and throat, constipation and vaginal dryness.(3)
Sarcoidosis and amyloidosis are other chronic inflammatory diseases that cause xerostomia. In sarcoidosis, noncaseating epithelioid granulomas in salivary glands result in reduced salivary flow. In amyloidosis, amyloid deposits in the salivary glands result in development of xerostomia.(2)
HIV-salivary gland disease occurs in some individuals infected with HIV, mainly in children. This disease results in enlargement of the parotid glands and, occasionally, the submandibular glands, resulting in xerostomia. The T-lymphocyte infiltrate is mainly comprised of CD8+ cells, as compared with SS where CD4+ cells predominate.(2)
Other systemic diseases that can cause xerostomia include rheumatoid arthritis, systemic lupus erythematosus, scleroderma, diabetes mellitus, hypertension, cystic fibrosis, bone marrow transplantation, endocrine disorders, nutritional deficiencies, nephritis, thyroid dysfunction and neurological diseases such as Bell’s palsy and cerebral palsy. Hyposecretory conditions, such as primary biliary cirrhosis, atrophic gastritis and pancreatic insufficiency, may also cause xerostomia. Dehydration resulting from impaired water intake, emesis, diarrhea or polyuria can result in xerostomia. Psychogenic causes, such as depression, anxiety, stress or fear, can also result in xerostomia. Alzheimer’s disease or stroke may alter the ability to perceive oral sensations. Dry mouth is often exacerbated by activities such as hyperventilation, breathing through the mouth, smoking or drinking alcohol. Trauma to the head and neck area can damage the nerves supplying sensation to the mouth, impairing the normal function of the salivary glands.2,6
Cancer therapy
Xerostomia is the most common toxicity associated with standard fractionated radiation therapy to the head and neck. Acute xerostomia from radiation is due to an inflammatory reaction, while late xerostomia, which can occur up to one year after radiation therapy, results from fibrosis of the salivary gland and is usually permanent.16 Radiation causes changes in the serous secretory cells, resulting in a reduction in salivary output and increased viscosity of the saliva. A common early complaint following radiation therapy is thick or sticky saliva. The degree of permanent xerostomia depends on the volume of salivary gland exposed to radiation and the radiation dose. When the total radiation dose exceeds 5,200 cGy, salivary flow is reduced, and little or no saliva is expressible from the salivary ducts. These changes are typically permanent.2
Certain cancer chemotherapeutic drugs can also change the composition and flow of saliva, resulting in xerostomia, but these changes are usually temporary. Xerostomia may also occur during graft-vs.-host disease. When donor lymphocytes proliferate and infiltrate the recipient’s salivary glands and other tissues, changes can occur in a clinical pattern resembling those seen in Sjögren’s syndrome.2
Patients experiencing xerostomia from radiation therapy or cancer chemotherapy are at particular risk of infections from normal oral flora. Oral ulcerations can become the nidus of invasive gram-positive and gram-negative infections, and opportunistic infections with fungal organisms such as Candida can occur.9
Practice scenario/case study
A 54-year-old woman complaining of a two-month history of fatigue and general trouble sleeping at night, stating that she wakes up often with a dry mouth and throat. She also states her eyes have been dry, tired and red lately, but she attributes this to her poor sleep patterns. She states she is currently consuming up to seven pints a day of liquids (coffee, tea, water, juice, milk, soda, etc.), and she is very distressed by her severe dry mouth. She wakes several times during the night and averages only four hours sleep. She drinks minimal alcohol and smokes approximately 15 cigarettes per day. She has no other complaints, and her past medical history is significant only for a history of allergic rhinitis for which she takes OTC antihistamines and decongestants.
The following are some examples of questions you might ask.
Do you need to moisten your mouth frequently or sip liquids often?
Does your mouth feel dry at mealtime?
Do you have less saliva than you used to?
Do you have trouble swallowing?
Is it difficult to eat dry foods such as crackers or toast?
Do you suffer from any chronic illness, such as diabetes or hypertension?
When was the last time you had a complete physical examination by your doctor?
What prescription and OTC medications are you currently taking?
What dietary supplements are you currently taking?
How often do you brush your teeth?
Do you wear dentures? If so, how often do you clean your dentures?
When was the last time you saw your dentist for a regular checkup?
Do you have toothaches or other dental pain?
Have you noticed any sores in your mouth or on your lips?
How much water do you drink throughout the day?
Management of xerostomia
Ideally, the management of xerostomia will include the identification of the underlying cause. In the event that steps can be taken to minimize the effect of the underlying cause, this should be done. For many patients, however, little can be done to alter the underlying cause. For those whose xerostomia is related to medication use, effective symptomatic treatment may be important to maintain compliance with their medication regime. Symptomatic treatment typically includes four areas: increasing existing saliva flow, replacing lost secretions, control of dental caries and specific measures such as treatment of infections.17,18
Self-care
Patients suffering from xerostomia should be encouraged to take an active role in management of their xerostomia with regard to both identifying products and practices that are most useful to them and in being vigilant to minimize the risks to dental health. Patients should be encouraged to conduct a daily mouth examination, checking for red, white or dark patches, ulcers or tooth decay. If anything unusual is found, it should be reported to their physician or dentist. Patients should be encouraged to practice regular preventive dentistry. Plaque removal and treatment of gingival infections or inflammation and dental caries are essential. Patients should also be counseled to brush and floss regularly and to use fluoride daily. The teeth should be cleansed at least twice daily using a soft bristled toothbrush and mildly flavored low-abrasive fluoride toothpaste.
Products containing sodium lauryl sulfate should be avoided as they may contribute to the formation of aphthous ulcers or canker sores. Sodium fluoride rinses should be held in the mouth for at least one minute before expectorating, while fluoride gels can be applied with a toothbrush and left in place for two to three minutes before expectorating. No food or beverage should be consumed for at least 30 minutes after fluoride application. Chlorhexidine rinses also may be useful in preventing caries by reducing lactobacillus counts in the mouth.
Dentures should not be worn during sleep and should be kept clean by overnight soaking. Acrylic appliances should be soaked in a sodium hypochlorite solution, and metal dentures should be soaked in chlorhexidine.2,3,6,9,10,17,18 Patient may want to consider visiting their dentist more frequently and should take advantage of the opportunity to discuss their xerostomia with their dental hygienist.
Because of their susceptibility to dental caries, patients with xerostomia should avoid sugary or acidic foods or beverages. These patients should also avoid irritating foods that are dry, spicy, astringent or excessively hot or cold. If possible, tobacco and alcohol intake should be eliminated to control dental caries.1-3,6,9,10,15,17-19 Lubricants such as Orajel® or Vaseline® and glycerin swabs on the lips and under dentures may relieve drying, cracking, soreness, and mucosal trauma.9,18 A cold air humidifier may aid mouth breathers who typically have their worst symptoms at night.2,3,6,9,10,17,18
Saliva stimulants or sialagogues, such as sugarless candies and chewing gum, may be used to stimulate saliva flow when functional salivary glands remain. Patients should be advised to take frequent sips of water throughout the day and to suck on ice chips. Eating foods such as carrots or celery may also help patients with residual salivary gland function. Addition of flavor enhancers such as herbs, condiments and fruit extracts may make food more palatable to patients complaining of their food tasting bland, papery, salty or otherwise unpleasant.1-3,6,9,10,15,17-19 Listed below are several additional self-care steps that patients can take to minimize the effects of their xerostomia.
Over-the-counter products
There are several over-the-counter products that are available to provide assistance in the management of xerostomia. These products range from saliva substitutes and stimulants to products designed to minimize dental problems.
Saliva substitutes:
Artificial saliva or saliva substitutes can be used to replace moisture and lubricate the mouth. These substitutes are available commercially, but they can also be compounded. Artificial salivas are formulated to mimic natural saliva, but they do not stimulate salivary gland production. Therefore, they must be considered as replacement therapy rather than a cure.1,13,15,17
Commercially available products come in a variety of formulations including solutions, sprays, gels and lozenges. In general, they contain an agent to increase viscosity, such as carboxymethylcellulose or hydroxyethylcellulose, minerals such as calcium and phosphate ions and fluoride, preservatives such as methyl- or propylparaben, and flavoring and related agents.15,20
Some commercially available saliva substitutes include:13,15,20,21
• Carboxymethyl, or hydroxyethylcellulose solutions:
Natrol Dry Mouth Relief, which has recently been developed, utilizes a patented pharmaceutical grade of anhydrous crystalline maltose (ACM) to stimulate saliva production. As its effect is to stimulate functional salivary glands, it would not be appropriate for patients whose salivary gland function has been lost through radiological treatment. However, in a clinical study of patients with Sjorgren’s Syndrome, ACM was shown to increase secretions and significantly improve patient’s subjective assessment of symptoms.34 Natrol Dry Mouth Relief is formulated as lozenges which are to be dissolve in the mouth three times daily.
Dentifrices:
Biotene® and Oralbalance® products are available over-the-counter from Laclede, Inc. (These are antixerostomia dentifrices that contain three salivary enzymes, lactoperoxidase, glucose oxidase and lysozyme, specifically formulated to activate intra-oral bacterial systems.9
Currently available formulations include:
• Biotene® Dry Mouth Toothpaste
• Biotene® Gentle Mouthwash
• Biotene® Dry Mouth Gum
• Oralbalance® Long-lasting Moisturizing Gel
• Biotene® Dry Mouth Kit
Prescription Products
Pilocarpine: Pilocarpine is a cholinergic parasympathomimetic agent with predominantly muscarinic M3 action that causes stimulation of residual-functioning exocrine glands. The tablets are indicated for the treatment of symptoms of dry mouth from salivary gland hypofunction caused by Sjögren’s syndrome or by radiotherapy for cancer of the head and neck. The time to reach peak concentrations following oral administration is approximately 1.25 hours. The duration of sialogogic effect is about two to three hours. In clinical studies, pilocarpine at dosages of 5 mg to 30 mg, divided into one to four oral daily doses, was shown to significantly decrease dryness of the mouth and eyes when compared to artificial saliva or placebo in patients with Sjögren’s syndrome and those who developed xerostomia following radiation therapy.2,3,17,18,22,24
Pilocarpine is contraindicated in patients with uncontrolled asthma, narrow-angle glaucoma or iritis. It is pregnancy category C. The most common side effects are increased sweating and gastrointestinal intolerance. Hypotension, rhinitis, diarrhea and visual disturbances can also occur. The recommended initial dose is one 5 mg tablet taken TID or QID; the usual dosage range is up to three to six tablets (15 to 30 mg) per day, not to exceed two tablets (10 mg) per dose. At least six to 12 weeks of uninterrupted therapy may be necessary before improvement in symptoms is seen. Pilocarpine is available in an ophthalmic solution and gel and also as an oral tablet (Salagen®). The tablet can also be compounded into an oral solution of varying concentrations.3,17,22,23 The 2001 AWP for 30 days of treatment with Salagen® 5 mg QID is $152.64.25
Cevimeline: Cevimeline is a cholinergic agonist with a high affinity for the muscarinic M3 receptors located on lacrimal and salivary gland epithelium, leading to an increase in exocrine gland secretions including saliva and sweat.7,26-28 It is indicated for the treatment of symptoms of dry mouth in patient’s with Sjögren’s syndrome.26 It is rapidly absorbed from the gastrointestinal tract, reaching peak concentrations in approximately 90 minutes without food. Its duration of sialogogic effect is unclear. Clinical trials have shown it to be more effective than placebo in relieving symptoms of dry mouth. No clinical trials are available comparing it to pilocarpine.
It is contraindicated in patients with uncontrolled asthma, narrow-angle glaucoma, or iritis. It is pregnancy category C. Excessive sweating and nausea are the most frequently reported adverse effects with cevimeline. Rhinitis, diarrhea and visual disturbances, especially at night, can also occur.26-28 The recommended oral dosage is 30 mg TID. The 2001 AWP for 30 days of treatment is $118. (13.29)
Other medications and preparations: Anethole trithione is a bile secretion-stimulating drug, or cholagogue. It stimulates the parasympathetic nervous system and increases the secretion of acetylcholine, resulting in the stimulation of salivation from serous acinic cells. Anethole trithione has been used for many years in the treatment of chronic xerostomia, but reports differ regarding its efficacy. While some studies report improvements in salivary flow rates in drug-induced xerostomia, trials in patients with Sjögren’s syndrome show conflicting results. Side effects reported include abdominal discomfort and flatulence. Dosages of 75 mg three times daily may be effective in treating patients with mild-to-moderate symptoms of xerostomia, but further research is needed to establish its safety and efficacy in this setting.2,3,8
Yohimbine is an alpha-2 adrenergic antagonist which indirectly results in an increase of cholinergic activity peripherally.3,30 In one small, randomized, double-blind, crossover study, the effect of yohimbine was compared to that of anethole trithione in 10 patients treated with psychotropic medications. Patients given yohimbine 6 mg three times daily for five days showed significantly increased saliva flow (p<0.01) when compared with anethole trithione 25 mg TID.31
Human interferon alfa (IFN-a) is currently undergoing clinical trials to determine the safety and efficacy of low-dose lozenges in the treatment of salivary gland dysfunction and xerostomia in patients with Sjögren’s syndrome. In one study, IFN-a lozenges at dosages of 150 IU given TID for 12 weeks resulted in a significant increase in stimulated whole saliva (p=0.04) when compared with placebo.3
Development of saliva substitutes based on novel thickening agents in hopes of providing longer retention on the mucosal surface is another area of current research. Substitutes based on linseed polysaccharide (Salinum®, Miwana AB, Gallivare, Sweden ) or xanthan gum polysaccharide (Xialine®, Lommerse Pharma BV, Oss, the Netherlands ) have been shown to be effective in patients with Sjögren’s syndrome.12
Another area of research includes the production of antimicrobial peptides originally derived by histatins, antifungal proteins naturally occurring in serous salivary glands.12 Prednisolone irrigation of parotid glands is being investigated as a potential treatment of xerostomia in patients with Sjögren’s syndrome.32 Slow-release delivery systems for pilocarpine are also being investigated.12 Vaccination with autoreactive T cells or with T cell receptor peptides is another area of research, as is the possibility of inserting water transporting proteins or aquaporins, in the cell membrane of the ductal cells.12
Practice scenario/case study
Now let’s return to our previous case: A 54-year-old woman complaining of a two-month history of fatigue and general trouble sleeping at night, stating that she wakes up often with a dry mouth and throat. After discussing her problem with you earlier, she made an appointment with her physician and has subsequently been diagnosed with Sjögren’s syndrome. She now returns to discuss management options for her xerostomia.
What specific treatment options and counseling tips should you offer her at this time?
• For her allergic rhinitis, suggest nonsedating antihistamines and avoidance of products containing decongestants.
• Go over the self-care measures covered earlier in this discussion (with emphasis on minimizing caffeine consumption and smoking).
• Give advice about good oral hygiene.
• Encourage adequate fluid intake, avoiding caffeine and sugar-containing products and alcohol.
• Encourage her to quit smoking.
• Consider the use of an artificial saliva and/or OTC saliva stimulant.
SUMMARY/CONCLUSIONS
Xerostomia is a common problem and if not recognized and treated, can have a significant effect on a patient’s quality of life. Through proper education, assessment, prevention, referral and appropriate treatment, patients with dentists help, can minimize xerostomia and its effect on dental health and quality of life.
REFERENCES:
1. American Dental Association. The public: Oral health topics: Dry mouth. [www document] (September 12, 2000). Available from URL: www.ada.org/public/topics/drymouth.html.
2. Greenspan D. Xerostomia: Diagnosis and management. Oncology 1996;10(Suppl):7-11.
3. Dyke S. Clinical management and review of Sjögren’s syndrome. Int J Pharm Compound 2000;4:338-341.
4. Pray WS. Consult your pharmacist. Help for patients with dry mouth. US Pharmacist 2000;25:16-22.
5. Sreebny LM, Valdini A. Xerostomia: A neglected symptom. Arch Intern Med 1987;147:1333-1337.
6. Astor FC, Hanft KL, Ciocon JO. Xerostomia: A prevalent condition in the elderly. Ear Nose Throat J 1999;78:476-479.
7. Fox RI. Sjögren syndrome: New approaches to treatment. [www document] (n.d. 2/1/01). Available from URL: www.medscape.com/Medscape/rheumatology/TreatmentUpdate/2000/tu01/pnt-tu01.html
8. Hamada T, Nakane T, Kimura T, Arisawa K, Yoneda K, Yamamoto T, Osaki T. Treatment of xerostomia with the bile secretion-stimulant drug anethole trithione: A clinical trial. Am J Med Sci 1999;318:146-151.
9. McDonald E, Marino C. Dry mouth: Diagnosing and treating its multiple causes. Geriatrics 1991;46:61-63.
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12. Van Der Reijden WA, Vissink A, Veerman ECI, Amerongen AVN. Treatment of oral dryness related complaints (xerostomia) in Sjögren’s syndrome. Ann Rheum Dis 1999;58:465-473.
13. Flynn AA. Counseling special populations on oral health care needs: Patients who are at increased risk for oral disease need to take special care of their teeth. Am Pharm 1993;33:33-39.
14. Sreebny LM, Schwartz SS. A reference guide to drugs and dry mouth – 2nd edition. Gerodontology 1997;14:33-47.
15. Anon. Treatment of xerostomia. Med Lett Drugs Ther 1988;30(771):74-76.
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18. Anon. Management of dry mouth and halitosis. Practitioner 1990;234:618-619.
19. Davies A. Clinically proved treatments for xerostomia were ignored. BMJ 1998;316:1247.
20. Burham TH, editor. Drug facts and comparisons. St. Louis (MO): Facts and ComparisonsÒ ;2000.
21. Evens RP, Ingalls K. Artificial saliva – availability (Drug Consult). In: Hutchison TA, Shahan DR, Anderson ML (Eds). DRUGDEXÒ System. MICROMEDEX, Inc., Englewood (CO), (edition expires 3/31/01.
22. Anon. Salagen. Med Lett Drugs Ther 1994;36:76.
24. Vivino FB, Al-Hashimi I, Khan Z, LeVeque FG, Salisburn PL, Tran-Johnson TK, 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.
25. Cardinale V, editor. 2000 Drug TopicsÒ Red BookÒ . Pharmacy’s Fundamental ReferenceTM. Montvale (NJ): Medical Economics Co.;2000.
27. Anon. Cevimeline (Evoxac) for dry mouth. Med Lett Drugs Ther 2000;42:70.
28. Kehoe WA. New drug: Evoxac (cevimeline). Pharmacist’s Letter 2000 May. Detail No.:160511.
29. Cardinale V, editor. 2000 Drug TopicsÒ Red BookÒ . Pharmacy’s Fundamental ReferenceTM. February 2001 Update. Montvale (NJ): Medical Economics Co.;2000.
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Dry mouth (xerostomia), is most commonly caused by radiation therapy directed at the head and neck region of the body. Radiation may irreversibly affect the production and quality of saliva in the salivary glands. A number of medications can also induce xerostomia. Dry mouth may affect the patients speech, taste sensation and ability to swallow.
Many patients complain of a sore or burning sensation, cracked lips, and fissures in the corners of the mouth. There is also an increased risk of cavities and mouth disease due to less saliva to cleanse the teeth and gums.
There are now some means of preventing xerostomia that were not available a few years ago. Amifostine, a radiation protector of normal tissues, has been shown to protect the salivary glands when given daily with radiation therapy. Also, a treatment known as Proton therapy may allow the radiation oncologist to spare the salivary glands from getting significant radiation doses. This may prevent dry mouth in the future. If you are getting radiation therapy to the head and neck region, you should discuss these options with your radiation oncologist. If you have developed xerostomia, there are management strategies that can effectively deal with your dry mouth and prevent cavities and periodontal disease.
Try to follow these simple guidelines:
Perform oral hygiene at least four times a day. (After each meal and before bedtime)
The oral cavity should be rinsed and wiped immediately after meals
Dentures need to be brushed and rinsed after meals
Only use toothpaste with fluoride when brushing
Keep water handy to keep the mouth moist at all times
Apply prescription strength fluoride gel at bedtime
Rinse with salt and baking soda solution 4-6 times a day
Avoid liquids and foods with high sugar content
Avoid rinses containing alcohol
Use moisturizer regularly on lips
Oral pilocarpine (Salagen) is the only drug approved by the FDA to stimulate saliva secretion from the remaining salivary glands.
Xerostomia is not a disease but can be a symptom of certain diseases. It can produce serious negative effects on the patients quality of life, affecting dietary habits, nutritional status, speech, taste, tolerance to dental prosthesis and increases susceptibility to dental caries. The increase in dental caries can be devastating in many patients and therefore special care must be made to control this condition.
Causes for Xerostomia include:
-Medications – Several hundred current medications can cause xerostomia. These include antihypertensives, antidepressants, analgesics, tranquilizers, diuretics and antihistamines c.
-Cancer Therapy – Chemotherapeutic drugs can change the flow and composition of the saliva. Radiation treatment that is focused on or near the salivary gland can temporarily or permanently damage the salivary glands.
-Sjogren’s syndrome – An autoimmune disease, causes xerostomia and dry eyes.
-Other conditions -such as bone marrow transplants, endocrine disorders, stress, anxiety, depression, and nutritional deficiencies may cause xerostomia.
-Nerve Damage – Trauma to the head and neck area from surgery or wounds can damage the nerves that supply sensation to the mouth. While the salivary glands may be left intact, they cannot function normally without the nerves that signal them to produce saliva.
Treatment:
1. Identify the xerostomic condition and the cause. Some of the causes may be ameliorated and this will aid therapy. But in many situations, it will be difficult to eliminate the causes. Thus, it will be necessary for the Dentist to control the results of xerostomia. This is especially true about the increase in dental caries.
2. Palliative treatment can be used but does not cure the condition:
-use of water and glycerin mixed in a small aerosol spray bottle.
3. Since a marked increase in dental caries is a common occurrence, it is important that this side effect is controlled. This will involve using the risk assessment and treatment strategies outlined in the cariology course.
-Establish if the patient is Xerostomic from symptoms and determine salivary flow rate.
-The xerostomic patient is classified into a risk assessment as outlined in the course material. However, this patient should be classified at high risk even if there are only several incipient lesions. This is done only in this type of patient because of the high caries risk.
-Determine if this patient is caries active or not active and follow the high risk protocol in the main outline in this course. When the ms infection is under control use a remineralization protocol along with the monitoring.
-Additional suggestions: -Both an ms and lactobacillus tests are indicated.
-Carefully observe color, texture and location of lesions.
-Seal pit and fissures and rough restorative margins with fluoride containing sealents.
-CHX treatment may have to be prolonged along with use of fluoride.
-Prolonged use of Xylitol gum is importance since its use enhances salivary flow and helps control mutans strep.
-Enhance use of hard cheese in diet. -Use sucralose in cooking.
By the late 1980s, NIDCR scientist Dr. Bruce Baum was frustrated. He had been searching for new drugs and other treatments that might help restore adequate salivary flow in people whose salivary glands had been damaged by radiation treatment for cancer. Yet, despite all of his hard work, Baum said he had not come close to solving the problem. That’s when he decided to turn to gene transfer, sometimes called gene therapy. If a fluid-transporting gene could be transferred into the damaged glands, he could potentially restore some degree of salivary flow and secretion into the mouth. According to Baum, the big question was: How would he deliver a gene into a salivary gland? The answer came to him several weeks later when he realized it might be possible to put a gene and its viral vector into a syringe and infuse them directly into the gland through its opening in the mouth. After more than a decade of systematically working out the science of gene transfer to the salivary glands, Baum and colleagues are ready to move the science into the clinic. The Inside Scoop recently met with Dr. Baum and talked to him about dry mouth in recovering cancer patients and the design of his upcoming clinical trial.
Nearly all patients with head and neck cancer have their tumors irradiated for several weeks. As I understand it, the problem is radiation doesn’t discriminate between tumor cells and healthy salivary glands. Is that correct?
That’s essentially right. The radiation kills the tumor cells but unfortunately also affects the nearby salivary glands. The damaged glands become less permeable to the water that naturally flows through them and either will yield less saliva or stop working altogether. If the damage is extensive, cancer patients will notice a persistent and irritating dryness in their mouths called radiation-induced xerostomia, or, more colloquially, dry mouth. It’s a very common problem. A survey of head and neck cancer patients comes to mind that was published a few years ago. It found that 65 percent of long-term survivors – defined as living three years post radiation therapy – had moderate to severe xerostomia. 1
Why is this parched sensation so irritating?
There’s an old Blues song titled, “You don’t miss your water til the well runs dry.” That’s certainly true with saliva. Most people don’t think of it until the moisture in their mouths runs dry, and that’s what makes xerostomia so irritating. Recovering cancer patients wonder, “Why is my mouth so dry?” But the dryness is more than an irritation. It can be a significant problem that impairs a person’s ability to chew, swallow, and even speak. In addition, dry mouth can lead to oral infections, such as tooth decay and Candidiasis.
Can anything be done to increase salivary flow?
For some people, yes. If tissue remains that is water permeable and capable of secretion, compounds such as pilocarpine can stimulate the glands to produce more saliva. The problem is most patients have salivary glands that have stopped working.
How so?
The radiation leaves the glands water impermeable. Let me explain. Salivary glands kind of look like a bunch of grapes attached to a stem. The grapes are called acinar cells. In people with working salivary glands, water enters the acinar cells, where myriad proteins are added, and the mixture then flows through the stems for further processing and ultimately exit into the mouth as saliva. In most head and neck cancer patients, the radiation has wiped out the acinar cells. They’re left with a network of water-impermeable stems that have no salivary flow. There is nothing left to stimulate.
And that’s where salivary gene transfer is different than pilocarpine. It will for the first time help those with impermeable salivary glands.
That’s our hope. The gene transfer that we have developed builds on the fundamental fact that the stems, or ducts, are water impermeable in the irradiated glands. We think that with gene transfer, the ducts will have the potential to move fluid and secrete it into the mouth.
The answer, as I’ve heard you say, is osmosis.
Correct, it’s that concept everybody learns in junior high school. Water naturally follows an osmotic energy gradient, flowing from areas of low to high salt concentration. We believe the irradiated duct cells can generate such an osmotic gradient. Over the last decade or so, I’ve worked with scientists in our laboratory to determine whether transferring a gene into the cells that line the ducts can take advantage of the ability of these cells to generate an osmotic gradient and secrete saliva into the mouth. In August 2006, we received approval from the Food and Drug Administration to conduct the first gene-transfer study in people with radiation-induced xerostomia.
Which gene will be transferred?
The gene is Aquaporin-1. It encodes a large protein that transports fluid by forming pores, or water channels, in the cell membrane. Our hope is the transferred gene will produce reasonable levels of the aquaporin-1 protein in duct cells, setting in motion a therapeutic domino effect. That is, the aquaporin-1 protein will open up water channels in the duct cells. That will allow the very rapid movement of water through the duct in response to the osmotic gradient that we believe can be generated.
The gene is contained in a vector, which serves almost like a trojan horse to deliver aquaporin-1 to its target. Which vector will you use?
An adenovirus. It’s a common respiratory virus that has been used in gene transfer studies for many years. The virus has been modified and won’t make a person sick.
Will the first study be a Phase I investigation, meaning it will evaluate the safety and tolerability of the gene transfer in the participants?
It will be simultaneously a Phase I and II study, which is quite commonly done today. As part of the Phase II component, we will collect some efficacy data. By that, I mean we will measure whether salivary fluid output improves in the patients and, in turn, if they notice that their mouths feel moister and less dry.
How large will the study be?
The study will enroll 15 to 21 patients.
All local participants?
Well, in theory, they could live anywhere. But the patients will stay in the hospital here in Bethesda at least for the first three days. They must be back here on Day 7 and 14. If people were to come from the West Coast, they would probably have to stay in the area for an extended period. That could be a logistical problem. We will track the patients on Day 28, Day 42, and so on for a full year. If the FDA decides that they should be followed longer, we’ll do so.
Are there conceptual advantages to performing gene transfer in salivary glands as opposed to an internal organ?
Absolutely. First, unlike most internal organs, a salivary gland is not critical for life. Should a problem arise, people will continue to survive with low levels of saliva. Second, we have direct access to the gland. Its opening is right there in the mouth, and we can infuse the Aquaporin-1 gene directly into a major salivary gland. There is no need for anaesthesia or surgery.
Into which salivary gland will you deliver the vector?
We’ll use a single parotid gland. The parotid gland is the largest of the three major salivary glands. If you touch the side of your face, the parotid gland is located under the skin between the jawbone and the lobe of the ear.
A concern with gene transfer studies is the vector might accidently integrate into the DNA of cells elsewhere in the body and cause tumors and other problems. Is that a concern?
In theory, yes. Practically speaking, no. Adenoviruses are non-integrating viruses. Secondly, because a fibrous capsule surrounds the salivary gland, the vector is essentially walled off from the rest of the body. One of the things we did in our animal studies is look for the vector throughout the body. In rats, the glands aren’t as well encapsulated as they are in humans or primates. The animals eat hard chow, so you tend to see the virus in their mouth but it doesn’t spread throughout their body.
The rats had no tumors? Even salivary tumors?
That is correct. They had no tumors anywhere.
With the gene transfer, how much saliva might a patient produce?
We hope to restore 70 to 80 percent of normal salivary flow. Based on our earlier studies with miniature pigs, we saw significant increases in salivary flow on days 3 and 7. By day 14, it was, on average, a little above background. We had expected it to decrease by days 14 to 21. Then comes the obvious question: What next? You can’t give the virus again because the patients will have raised antibodies against it.
So, what next?
We have another vector called an adeno-associated virus, or AAV. In contrast to adenovirus, AAV lasts a very long time and provides quite stable gene transfer. In mice, it can last essentially as long as the animals are alive, which was up to two years.
Why not launch the study with the longer lasting vector?
To err on the side of caution. This study marks the first time that a viral vector will be delivered into a human salivary gland. Secondly, because our research to date has been conducted in animals, we have not yet demonstrated that radiation-damaged salivary duct cells in people can generate an osmotic gradient and support fluid flow. The adenovirus is essentially self limiting and will be removed from each patient by their immune system. If, by chance, the strategy doesn’t work, I didn’t want to have patients with a useless gene-transfer vector in their bodies indefinitely.
So, the goal would be to build on this study and move to Phase III. Is that right?
Well, no. It’s actually an interesting point. If this works, we could say that the Aquaporin-1 strategy works in humans. That is, the physiology of duct cells is such that they could generate an osmotic gradient. The strategy would be to go to an adeno-associated virus vector for long term expression as a Phase I/II study. If that works, the goal would be to advance to a Phase III clinical trial.
Good luck with the study.
Thanks. Let me just say, this study represents a start. It’s a very good start, though, based on solid science. I hope other research groups will take note of salivary gene transfer and continue to develop it even further. The salivary glands offer unique therapeutic possibilities that should be more intensively explored, not only by dental scientists but throughout medical research. More importantly, for all of the reasons that I’ve mentioned, it would be a big win for recovering cancer patients who are forced to battle radiation-induced xerostomia.
It prevents infection by controlling bacteria and fungi in the mouth
It makes it possible for you to chew and swallow
Without enough saliva you can develop tooth decay or other infections in the mouth. You also might not get the nutrients you need if you cannot chew and swallow certain foods.
People get dry mouth when the glands in the mouth that make saliva are not working properly. Because of this, there might not be enough saliva to keep your mouth wet. There are several reasons why these glands (called salivary glands) might not work right.
Side effects of some medicines. More than 400 medicines can cause the salivary glands to make less saliva. For example, medicines for high blood pressure and depression often cause dry mouth.
Disease. Some diseases affect the salivary glands. Sjögren’s syndrome, HIV/AIDS, and diabetes can all cause dry mouth.
Radiation therapy. The salivary glands can be damaged if they are exposed to radiation during cancer treatment.
Chemotherapy. Drugs used to treat cancer can make saliva thicker, causing the mouth to feel dry.
Nerve damage. Injury to the head or neck can damage the nerves that tell salivary glands to make saliva.
Dry mouth treatment will depend on what is causing the problem. If you think you have dry mouth, see your dentist or physician. He or she can try to determine what is causing your dry mouth.
If your dry mouth is caused by medicine, your physician might change your medicine or adjust the dosage.
If your salivary glands are not working right but can still produce some saliva, your physician or dentist might give you a medicine that helps the glands work better.
Your physician or dentist might suggest that you use artificial saliva to keep your mouth wet.
Xerostomia (ZEER-oh-STOH-mee-ah) is known as dry mouth. It is the condition of not having enough saliva, or spit, to keep the mouth wet. Dry mouth can happen to anyone occasionally when nervous or stressed. However, when dry mouth persists, it can make chewing, eating, swallowing and even talking difficult. Dry mouth also increases the risk for tooth decay because saliva helps keep harmful germs that cause cavities and other oral infections in check.
Causes
Dry mouth occurs when the salivary glands that make saliva don’t work properly. Many over-the-counter and prescription medicines, as well as diseases such as diabetes, Parkinson’s disease and Sjogren’s syndrome, can affect the salivary glands. Other causes of dry mouth include certain cancer treatments and damage to the glands’ nerve system. It’s important to see your dentist or physician to find out why your mouth is dry.
Treatment
Depending on the cause of your dry mouth, your health care provider can recommend appropriate treatment. There are also self-care steps you can take to help ease dry mouth, such as drinking plenty of water, chewing sugarless gum, and avoiding tobacco and alcohol. Good oral care at home and regular dental check-ups will help keep your mouth healthy.
How Common is Xerostomia?
Chronic dry mouth, or xerostomia, has long been considered a problem of aging. But how common is it? The medical literature contains just one study on the subject, and myriad questions remain about the risk factors, incidence, and natural history of the condition. Now, in the December issue of the journal Gerodontology, NIDCR grantees and colleagues have published a second longitudinal study. It tracked 1,205 dentate adults age 60 and older over several years, with 246 participants being followed for 11 years. The researchers found that the prevalence of xerostomia increased from 21.4 percent to 24.8 percent between the fifth and eleventh year of follow up. However, one quarter of those with xerostomia fluctuated over time in the severity, or status, of their condition. The researchers also carefully tracked the use of medications, a recognized but still nonspecific risk factor for xerostomia. Their use increased throughout the study, with nearly 95 percent taking at least one medication at the study’s 11-year mark. According to the authors, “While only two categories of medication being taken at 11 years were associated with the incidence of xerostomia between 5 and 11 years (antidepressants and daily aspirin), there were stronger associations when only those medications taken since the 5-year assessment were included in the analysis. In this exposure category, xerostomia incidence was greater among those taking diuretics, NSAIDs, antidepressants or daily aspirin.”
Your body uses a lot of energy to heal during radiation therapy. It is important that you eat enough calories and protein to keep your weight the same during this time. Ask your doctor or nurse if you need a special diet while you are getting radiation therapy. You might also find it helpful to speak with a dietitian.
Many people help with your radiation treatment and care. This group of health care providers is often called the “radiation therapy team.” They work together to provide care that is just right for you. Your radiation therapy team can include:
Radiation oncologist. This is a doctor who specializes in using radiation therapy to treat cancer. He or she prescribes how much radiation you will receive, plans how your treatment will be given, closely follows you during your course of treatment, and prescribes care you may need to help with side effects. He or she works closely with the other doctors, nurses, and health care providers on your team. After you are finished with radiation therapy, your radiation oncologist will see you for follow-up visits. During these visits, this doctor will check for late side effects and assess how well the radiation has worked.
Nurse practitioner. This is a nurse with advanced training. He or she can take your medical history, do physical exams, order tests, manage side effects, and closely watch your response to treatment. After you are finished with radiation therapy, your nurse practitioner may see you for follow-up visits to check for late side effects and assess how well the radiation has worked.
Radiation nurse. This person provides nursing care during radiation therapy, working with all the members of your radiation therapy team. He or she will talk with you about your radiation treatment and help you manage side effects.
Radiation therapist. This person works with you during each radiation therapy session. He or she positions you for treatment and runs the machines to make sure you get the dose of radiation prescribed by your radiation oncologist.
Other health care providers. Your team may also include a dietitian, physical therapist, social worker, and others.
You. You are also part of the radiation therapy team. Your role is to:
Arrive on time for all radiation therapy sessions
Ask questions and talk about your concerns
Let someone on your radiation therapy team know when you have side effects
Tell your doctor or nurse if you are in pain
Follow the advice of your doctors and nurses about how to care for yourself at home, such as:
Yes, radiation therapy is often used with other cancer treatments. Here are some examples:
Radiation therapy and surgery. Radiation may be given before, during, or after surgery. Doctors may use radiation to shrink the size of the cancer before surgery, or they may use radiation after surgery to kill any cancer cells that remain. Sometimes, radiation therapy is given during surgery so that it goes straight to the cancer without passing through the skin. This is called intraoperative radiation.
Radiation therapy and chemotherapy. Radiation may be given before, during, or after chemotherapy. Before or during chemotherapy, radiation therapy can shrink the cancer so that chemotherapy works better. Sometimes, chemotherapy is given to help radiation therapy work better. After chemotherapy, radiation therapy can be used to kill any cancer cells that remain.
Dry Mouth – Real Cases
I suffer from end stage lung disease (COPD) I am presently going through a flare up and my oxygen drops into the 80’s with minimum exertion. I am on 20 mg of prednisone (tapering off) and was on Factive. I take 20mg of Lexapro, Spiriva, Advair, Protonix, theophylline and 20 mg of Micardis. I put on weight (5′4, 236 lbs-female) but I had a very thorough exam for my heart- no sugar, cholesterol or triglyceride problem, no thyroid, stress test and echo perfect as well as blood pressure (it goes up a bit when I exert but usually is runs about 130/80 or bad is 140/90. Sometime it drops to 117/78. So, in that regard I am very lucky. My mouth became dry and I became very thirsty with this flare up (it has been going on now for about 3.5 weeks) I have a partial bridge and caps. I do not know what to make of it. I also noticed my skin getting very dry so I bought some Gatoraid and drank that and it helped for about 3 days. Seems like I’m dehydrated. I am constantly drinking water – maybe 10 glasses or so. Am constantly going to the bathroon to urinate and do have a yeast infection that will not go away. I also have been having headaches – mild and get dizzy- which I think is from the drop in oxygen. What do you suggest? Which doctor should I see- my primary, pulmonist, ENT, gynocologist or all? Sorry for the overload. I am 55 yrs. old if that makes any difference. I get hot flashes now and then but mostly in the extremities and do not sweat just get hot on the top of my head. (don’t laugh-is true) Thanks… Maria Published: July 23 ::
Helping Patients with Dry Mouth
Helping patients with dry mouth
By Cathy L. Bartels, Pharm.D., assistant professor, pharmacy practice, School of Pharmacy and Allied Health Sciences, University of Montana
Introduction
Xerostomia is defined as dry mouth resulting from reduced or absent saliva flow. Xerostomia is not a disease, but it may be a symptom of various medical conditions, a side effect of a radiation to the head and neck, or a side effect of a wide variety of medications. It may or may not be associated with decreased salivary gland function.1,2 Xerostomia is a common complaint found often among older adults, affecting approximately 20 percent of the elderly.1,3-5 However, xerotomia does not appear to be related to age itself as much as to the potential for elderly to be taking medications that cause xerostomia as a side effect.
Normal salivary function is mediated by the muscarinic M3 receptor. Stimulation of this receptor results in increased watery flow of salivary secretions. When the oral mucosal surface is stimulated, afferent nerve signals travel to the salivatory nuclei in the medulla. The medullary signal may also be affected by cortical inputs resulting from stimuli such as taste, smell, anxiety or depression. Efferent nerve signals, mediated by acetylcholine, also stimulate salivary glandular epithelial cells and increase salivary secretions.7
Saliva components
Saliva is the viscous, clear, watery fluid secreted from the parotid, submaxillary, sublingual and smaller mucous glands of the mouth. Saliva contains two major types of protein secretions, a serous secretion containing the digestive enzyme ptyalin and a mucous secretion containing the lubricating aid mucin. The pH of saliva falls between 6 and 7.4. Saliva also contains large amounts of potassium and bicarbonate ions, and to a lesser extent sodium and chloride ions. In addition, saliva contains several antimicrobial constituents, including thiocyanate, lysozyme, immunoglobulins, lactoferrin and transferrin.8
Functions of saliva
Saliva possesses many important functions including antimicrobial activity, mechanical cleansing action, control of pH, removal of food debris from the oral cavity, lubrication of the oral cavity, remineralization and maintaining the integrity of the oral mucosa.2,8-10
Complications associated with xerostomia
Xerostomia is often a contributing factor for both minor and serious health problems. It can affect nutrition and dental, as well as psychological, health. Some common problems associated with xerostomia include a constant sore throat, burning sensation, difficulty speaking and swallowing, hoarseness and/or dry nasal passages.1 Xerostomia is an original hidden cause of gum disease and tooth loss in three out of every 10 adults.11 If left untreated, xerostomia decreases the oral pH and significantly increases the development of plaque and dental caries.1,2 Oral candidiasis is one of the most common oral infections seen in association with xerostomia.(2)
Signs and symptoms of xerostomia
Individuals with xerostomia often complain of problems with eating, speaking, swallowing and wearing dentures. Dry, crumbly foods, such as cereals and crackers, may be particularly difficult to chew and swallow. Denture wearers may have problems with denture retention, denture sores and the tongue sticking to the palate. Patients with xerostomia often complain of taste disorders (dysgeusia), a painful tongue (glossodynia) and an increased need to drink water, especially at night. Xerostomia can lead to markedly increased dental caries, parotid gland enlargement, inflammation and fissuring of the lips (cheilitis), inflammation or ulcers of the tongue and buccal mucosa, oral candidiasis, salivary gland infection (sialadenitis), halitosis and cracking and fissuring of the oral mucosa.(2,6,9,13)
Diagnosis and evaluation of xerostomia
Diagnosis of xerostomia may be based on evidence obtained from the patient’s history, an examination of the oral cavity and/or sialometry, a simple office procedure that measures the flow rate of saliva. Xerostomia should be considered if the patient complains of dry mouth, particularly at night, or of difficulty eating dry foods such as crackers.(2,5,7) When the mouth is examined, a tongue depressor may stick to the buccal mucosa.9 In women, the “lipstick sign,” where lipstick adheres to the front teeth, may be a useful indicator of xerostomia.7
The oral mucosa may be dry and sticky, or it may appear erythematous due to an overgrowth of Candida albicans. The red patches often affect the hard or soft palate and dorsal surface of the tongue. Occasionally, pseudomembranous candidiasis will be present, appearing as removable white plaques on any mucosal surface. There may be little or no pooled saliva in the floor of the mouth, and the tongue may appear dry with decreased numbers of papillae. The saliva may appear stringy, ropy or foamy. Dental caries may be found at the cervical margin or neck of the teeth, the incisal margins or the tips of the teeth.2
Several office tests and techniques can be utilized to ascertain the function of salivary glands. In sialometry, or salivary flow measurement, collection devices are placed over the parotid gland or the submandibular/
sublingual gland duct orifices, and saliva is stimulated with citric acid. The normal salivary flow rate for unstimulated saliva from the parotid gland is 0.4 to 1.5 mL/min/gland.2,3 The normal flow rate for unstimulated, “resting” whole saliva is 0.3 to 0.5 mL/min; for stimulated saliva, 1 to 2 mL/min. Values less than 0.1 mL/min are typically considered xerostomic, although reduced flow may not always be associated with complaints of dryness.2,5
Sialography is an imaging technique that may be useful in identifying salivary gland stones and masses. It involves the injection of radio-opaque media into the salivary glands.2,3 Salivary scintigraphy can be useful in assessing salivary gland function. Technetium-99m sodium pertechnate is intravenously injected to ascertain the rate and density of uptake and the time of excretion in the mouth.2,3 Minor salivary gland biopsy is often used in the diagnosis of Sjögren’s syndrome (SS), human immunodeficiency virus-salivary gland disease, sarcoidosis, amyloidosis and graft-vs.-host disease. Biopsy of major salivary glands is an option when malignancy is suspected.2
Common causes of xerostomia
Medications
Perhaps the most prevalent cause of xerostomia is medication. Xerogenic drugs can be found in 42 drug categories and 56 subcategories.14 More than 400 commonly used drugs can cause xerostomia.10,14 The main culprits are antihistamines, antidepressants, anticholinergics, anorexiants, antihypertensives, antipsychotics, anti-Parkinson agents, diuretics and sedatives. Other drug classes that commonly cause xerostomia include antiemetics, antianxiety agents, decongestants, analgesics, antidiarrheals, bronchodilators and skeletal muscle relaxants.2,6,10,14,15 It should be noted that, while there are many drugs that affect the quantity and/or quality of saliva, these effects are generally not permanent.
Patients complaining of xerostomia should be interviewed and their medications should be reviewed. It may be possible to change medications or dosages to provide increased salivary flow. Symptoms of xerostomia are often worse between meals, at night and in the morning. Therefore, consider modifying drug schedules to achieve maximum plasma levels when the patient is awake.9 Consider easy-to-take formulations, such as liquids, and avoid sublingual dosage forms if possible. Counsel your patients regarding which medications can and cannot be crushed. Also counsel them to first lubricate the mouth and throat with water prior to taking capsules and tablets and to follow this with a full glass of water. If possible, consider switching the patient from one medication to another with comparable efficacy but with less anticholinergic activity, for example, switching from the tricyclic antidepressant amoxapine to desipramine.
Diseases and other conditions
The most common disease causing xerostomia is Sjögren’s syndrome (SS), a chronic inflammatory autoimmune disease that occurs predominantly in postmenopausal women. It is estimated that as many as 3 percent of Americans suffer from Sjögren’s syndrome, with 90 percent of these patients being women with a mean age at diagnosis of 50 years. SS is characterized by lymphocytic infiltration of salivary and lacrimal glands, resulting in xerostomia and xerophthalmia. This combination is called the sicca complex. Enlargement of major salivary glands occurs in about one-third of patients with SS.9 There is no cure for the disease. The goal of therapy is to manage symptoms. Common symptoms associated with SS, in addition to xerostomia and xerophthalmia, include blurred vision, recurrent eye and mouth infections, dysphagia or difficulty swallowing, oral soreness, smell and taste alternations, fissures on the tongue and lips, fatigue, dry nasal passages and throat, constipation and vaginal dryness.(3)
Sarcoidosis and amyloidosis are other chronic inflammatory diseases that cause xerostomia. In sarcoidosis, noncaseating epithelioid granulomas in salivary glands result in reduced salivary flow. In amyloidosis, amyloid deposits in the salivary glands result in development of xerostomia.(2)
HIV-salivary gland disease occurs in some individuals infected with HIV, mainly in children. This disease results in enlargement of the parotid glands and, occasionally, the submandibular glands, resulting in xerostomia. The T-lymphocyte infiltrate is mainly comprised of CD8+ cells, as compared with SS where CD4+ cells predominate.(2)
Other systemic diseases that can cause xerostomia include rheumatoid arthritis, systemic lupus erythematosus, scleroderma, diabetes mellitus, hypertension, cystic fibrosis, bone marrow transplantation, endocrine disorders, nutritional deficiencies, nephritis, thyroid dysfunction and neurological diseases such as Bell’s palsy and cerebral palsy. Hyposecretory conditions, such as primary biliary cirrhosis, atrophic gastritis and pancreatic insufficiency, may also cause xerostomia. Dehydration resulting from impaired water intake, emesis, diarrhea or polyuria can result in xerostomia. Psychogenic causes, such as depression, anxiety, stress or fear, can also result in xerostomia. Alzheimer’s disease or stroke may alter the ability to perceive oral sensations. Dry mouth is often exacerbated by activities such as hyperventilation, breathing through the mouth, smoking or drinking alcohol. Trauma to the head and neck area can damage the nerves supplying sensation to the mouth, impairing the normal function of the salivary glands.2,6
Cancer therapy
Xerostomia is the most common toxicity associated with standard fractionated radiation therapy to the head and neck. Acute xerostomia from radiation is due to an inflammatory reaction, while late xerostomia, which can occur up to one year after radiation therapy, results from fibrosis of the salivary gland and is usually permanent.16 Radiation causes changes in the serous secretory cells, resulting in a reduction in salivary output and increased viscosity of the saliva. A common early complaint following radiation therapy is thick or sticky saliva. The degree of permanent xerostomia depends on the volume of salivary gland exposed to radiation and the radiation dose. When the total radiation dose exceeds 5,200 cGy, salivary flow is reduced, and little or no saliva is expressible from the salivary ducts. These changes are typically permanent.2
Certain cancer chemotherapeutic drugs can also change the composition and flow of saliva, resulting in xerostomia, but these changes are usually temporary. Xerostomia may also occur during graft-vs.-host disease. When donor lymphocytes proliferate and infiltrate the recipient’s salivary glands and other tissues, changes can occur in a clinical pattern resembling those seen in Sjögren’s syndrome.2
Patients experiencing xerostomia from radiation therapy or cancer chemotherapy are at particular risk of infections from normal oral flora. Oral ulcerations can become the nidus of invasive gram-positive and gram-negative infections, and opportunistic infections with fungal organisms such as Candida can occur.9
Practice scenario/case study
A 54-year-old woman complaining of a two-month history of fatigue and general trouble sleeping at night, stating that she wakes up often with a dry mouth and throat. She also states her eyes have been dry, tired and red lately, but she attributes this to her poor sleep patterns. She states she is currently consuming up to seven pints a day of liquids (coffee, tea, water, juice, milk, soda, etc.), and she is very distressed by her severe dry mouth. She wakes several times during the night and averages only four hours sleep. She drinks minimal alcohol and smokes approximately 15 cigarettes per day. She has no other complaints, and her past medical history is significant only for a history of allergic rhinitis for which she takes OTC antihistamines and decongestants.
The following are some examples of questions you might ask.
Management of xerostomia
Ideally, the management of xerostomia will include the identification of the underlying cause. In the event that steps can be taken to minimize the effect of the underlying cause, this should be done. For many patients, however, little can be done to alter the underlying cause. For those whose xerostomia is related to medication use, effective symptomatic treatment may be important to maintain compliance with their medication regime. Symptomatic treatment typically includes four areas: increasing existing saliva flow, replacing lost secretions, control of dental caries and specific measures such as treatment of infections.17,18
Self-care
Patients suffering from xerostomia should be encouraged to take an active role in management of their xerostomia with regard to both identifying products and practices that are most useful to them and in being vigilant to minimize the risks to dental health. Patients should be encouraged to conduct a daily mouth examination, checking for red, white or dark patches, ulcers or tooth decay. If anything unusual is found, it should be reported to their physician or dentist. Patients should be encouraged to practice regular preventive dentistry. Plaque removal and treatment of gingival infections or inflammation and dental caries are essential. Patients should also be counseled to brush and floss regularly and to use fluoride daily. The teeth should be cleansed at least twice daily using a soft bristled toothbrush and mildly flavored low-abrasive fluoride toothpaste.
Products containing sodium lauryl sulfate should be avoided as they may contribute to the formation of aphthous ulcers or canker sores. Sodium fluoride rinses should be held in the mouth for at least one minute before expectorating, while fluoride gels can be applied with a toothbrush and left in place for two to three minutes before expectorating. No food or beverage should be consumed for at least 30 minutes after fluoride application. Chlorhexidine rinses also may be useful in preventing caries by reducing lactobacillus counts in the mouth.
Dentures should not be worn during sleep and should be kept clean by overnight soaking. Acrylic appliances should be soaked in a sodium hypochlorite solution, and metal dentures should be soaked in chlorhexidine.2,3,6,9,10,17,18 Patient may want to consider visiting their dentist more frequently and should take advantage of the opportunity to discuss their xerostomia with their dental hygienist.
Because of their susceptibility to dental caries, patients with xerostomia should avoid sugary or acidic foods or beverages. These patients should also avoid irritating foods that are dry, spicy, astringent or excessively hot or cold. If possible, tobacco and alcohol intake should be eliminated to control dental caries.1-3,6,9,10,15,17-19 Lubricants such as Orajel® or Vaseline® and glycerin swabs on the lips and under dentures may relieve drying, cracking, soreness, and mucosal trauma.9,18 A cold air humidifier may aid mouth breathers who typically have their worst symptoms at night.2,3,6,9,10,17,18
Saliva stimulants or sialagogues, such as sugarless candies and chewing gum, may be used to stimulate saliva flow when functional salivary glands remain. Patients should be advised to take frequent sips of water throughout the day and to suck on ice chips. Eating foods such as carrots or celery may also help patients with residual salivary gland function. Addition of flavor enhancers such as herbs, condiments and fruit extracts may make food more palatable to patients complaining of their food tasting bland, papery, salty or otherwise unpleasant.1-3,6,9,10,15,17-19 Listed below are several additional self-care steps that patients can take to minimize the effects of their xerostomia.
Over-the-counter products
There are several over-the-counter products that are available to provide assistance in the management of xerostomia. These products range from saliva substitutes and stimulants to products designed to minimize dental problems.
Saliva substitutes:
Artificial saliva or saliva substitutes can be used to replace moisture and lubricate the mouth. These substitutes are available commercially, but they can also be compounded. Artificial salivas are formulated to mimic natural saliva, but they do not stimulate salivary gland production. Therefore, they must be considered as replacement therapy rather than a cure.1,13,15,17
Commercially available products come in a variety of formulations including solutions, sprays, gels and lozenges. In general, they contain an agent to increase viscosity, such as carboxymethylcellulose or hydroxyethylcellulose, minerals such as calcium and phosphate ions and fluoride, preservatives such as methyl- or propylparaben, and flavoring and related agents.15,20
Some commercially available saliva substitutes include:13,15,20,21
• Carboxymethyl, or hydroxyethylcellulose solutions:
• Entertainer’s Secret® (KLI Corp) , spray
• Glandosane® (Kenwood/Bradley) spray
• Moi-Stir® (Kingswood Labs) spray
• Moi-Stir® Oral Swabsticks (Kingswood Labs) swabs
• Optimoist® (Colgate-Palmolive) spray
• Saliva Substitute® (Roxane Labs) liquid
• Salivart® (Gebauer) preservative-free aerosol
• Salix® (Scandinavian Natural Health & Beauty) tablets
• V. A. Oralube® (Oral Dis. Res. Lab) sodium-free; liquid
• Xero-Lube® Artificial Saliva (Scherer) sodium-free; spray
• Mucopolysaccharide Solutions:
• MouthKote® (Parnell) , spray
Saliva stimulants:
Natrol Dry Mouth Relief, which has recently been developed, utilizes a patented pharmaceutical grade of anhydrous crystalline maltose (ACM) to stimulate saliva production. As its effect is to stimulate functional salivary glands, it would not be appropriate for patients whose salivary gland function has been lost through radiological treatment. However, in a clinical study of patients with Sjorgren’s Syndrome, ACM was shown to increase secretions and significantly improve patient’s subjective assessment of symptoms.34 Natrol Dry Mouth Relief is formulated as lozenges which are to be dissolve in the mouth three times daily.
Dentifrices:
Biotene® and Oralbalance® products are available over-the-counter from Laclede, Inc. (These are antixerostomia dentifrices that contain three salivary enzymes, lactoperoxidase, glucose oxidase and lysozyme, specifically formulated to activate intra-oral bacterial systems.9
Currently available formulations include:
• Biotene® Dry Mouth Toothpaste
• Biotene® Gentle Mouthwash
• Biotene® Dry Mouth Gum
• Oralbalance® Long-lasting Moisturizing Gel
• Biotene® Dry Mouth Kit
Prescription Products
Pilocarpine: Pilocarpine is a cholinergic parasympathomimetic agent with predominantly muscarinic M3 action that causes stimulation of residual-functioning exocrine glands. The tablets are indicated for the treatment of symptoms of dry mouth from salivary gland hypofunction caused by Sjögren’s syndrome or by radiotherapy for cancer of the head and neck. The time to reach peak concentrations following oral administration is approximately 1.25 hours. The duration of sialogogic effect is about two to three hours. In clinical studies, pilocarpine at dosages of 5 mg to 30 mg, divided into one to four oral daily doses, was shown to significantly decrease dryness of the mouth and eyes when compared to artificial saliva or placebo in patients with Sjögren’s syndrome and those who developed xerostomia following radiation therapy.2,3,17,18,22,24
Pilocarpine is contraindicated in patients with uncontrolled asthma, narrow-angle glaucoma or iritis. It is pregnancy category C. The most common side effects are increased sweating and gastrointestinal intolerance. Hypotension, rhinitis, diarrhea and visual disturbances can also occur. The recommended initial dose is one 5 mg tablet taken TID or QID; the usual dosage range is up to three to six tablets (15 to 30 mg) per day, not to exceed two tablets (10 mg) per dose. At least six to 12 weeks of uninterrupted therapy may be necessary before improvement in symptoms is seen. Pilocarpine is available in an ophthalmic solution and gel and also as an oral tablet (Salagen®). The tablet can also be compounded into an oral solution of varying concentrations.3,17,22,23 The 2001 AWP for 30 days of treatment with Salagen® 5 mg QID is $152.64.25
Cevimeline: Cevimeline is a cholinergic agonist with a high affinity for the muscarinic M3 receptors located on lacrimal and salivary gland epithelium, leading to an increase in exocrine gland secretions including saliva and sweat.7,26-28 It is indicated for the treatment of symptoms of dry mouth in patient’s with Sjögren’s syndrome.26 It is rapidly absorbed from the gastrointestinal tract, reaching peak concentrations in approximately 90 minutes without food. Its duration of sialogogic effect is unclear. Clinical trials have shown it to be more effective than placebo in relieving symptoms of dry mouth. No clinical trials are available comparing it to pilocarpine.
It is contraindicated in patients with uncontrolled asthma, narrow-angle glaucoma, or iritis. It is pregnancy category C. Excessive sweating and nausea are the most frequently reported adverse effects with cevimeline. Rhinitis, diarrhea and visual disturbances, especially at night, can also occur.26-28 The recommended oral dosage is 30 mg TID. The 2001 AWP for 30 days of treatment is $118. (13.29)
Other medications and preparations: Anethole trithione is a bile secretion-stimulating drug, or cholagogue. It stimulates the parasympathetic nervous system and increases the secretion of acetylcholine, resulting in the stimulation of salivation from serous acinic cells. Anethole trithione has been used for many years in the treatment of chronic xerostomia, but reports differ regarding its efficacy. While some studies report improvements in salivary flow rates in drug-induced xerostomia, trials in patients with Sjögren’s syndrome show conflicting results. Side effects reported include abdominal discomfort and flatulence. Dosages of 75 mg three times daily may be effective in treating patients with mild-to-moderate symptoms of xerostomia, but further research is needed to establish its safety and efficacy in this setting.2,3,8
Yohimbine is an alpha-2 adrenergic antagonist which indirectly results in an increase of cholinergic activity peripherally.3,30 In one small, randomized, double-blind, crossover study, the effect of yohimbine was compared to that of anethole trithione in 10 patients treated with psychotropic medications. Patients given yohimbine 6 mg three times daily for five days showed significantly increased saliva flow (p<0.01) when compared with anethole trithione 25 mg TID.31
Human interferon alfa (IFN-a) is currently undergoing clinical trials to determine the safety and efficacy of low-dose lozenges in the treatment of salivary gland dysfunction and xerostomia in patients with Sjögren’s syndrome. In one study, IFN-a lozenges at dosages of 150 IU given TID for 12 weeks resulted in a significant increase in stimulated whole saliva (p=0.04) when compared with placebo.3
Development of saliva substitutes based on novel thickening agents in hopes of providing longer retention on the mucosal surface is another area of current research. Substitutes based on linseed polysaccharide (Salinum®, Miwana AB, Gallivare, Sweden ) or xanthan gum polysaccharide (Xialine®, Lommerse Pharma BV, Oss, the Netherlands ) have been shown to be effective in patients with Sjögren’s syndrome.12
Another area of research includes the production of antimicrobial peptides originally derived by histatins, antifungal proteins naturally occurring in serous salivary glands.12 Prednisolone irrigation of parotid glands is being investigated as a potential treatment of xerostomia in patients with Sjögren’s syndrome.32 Slow-release delivery systems for pilocarpine are also being investigated.12 Vaccination with autoreactive T cells or with T cell receptor peptides is another area of research, as is the possibility of inserting water transporting proteins or aquaporins, in the cell membrane of the ductal cells.12
Practice scenario/case study
Now let’s return to our previous case: A 54-year-old woman complaining of a two-month history of fatigue and general trouble sleeping at night, stating that she wakes up often with a dry mouth and throat. After discussing her problem with you earlier, she made an appointment with her physician and has subsequently been diagnosed with Sjögren’s syndrome. She now returns to discuss management options for her xerostomia.
What specific treatment options and counseling tips should you offer her at this time?
• For her allergic rhinitis, suggest nonsedating antihistamines and avoidance of products containing decongestants.
• Go over the self-care measures covered earlier in this discussion (with emphasis on minimizing caffeine consumption and smoking).
• Give advice about good oral hygiene.
• Encourage adequate fluid intake, avoiding caffeine and sugar-containing products and alcohol.
• Encourage her to quit smoking.
• Consider the use of an artificial saliva and/or OTC saliva stimulant.
SUMMARY/CONCLUSIONS
Xerostomia is a common problem and if not recognized and treated, can have a significant effect on a patient’s quality of life. Through proper education, assessment, prevention, referral and appropriate treatment, patients with dentists help, can minimize xerostomia and its effect on dental health and quality of life.
REFERENCES:
1. American Dental Association. The public: Oral health topics: Dry mouth. [www document] (September 12, 2000). Available from URL: www.ada.org/public/topics/drymouth.html.
2. Greenspan D. Xerostomia: Diagnosis and management. Oncology 1996;10(Suppl):7-11.
3. Dyke S. Clinical management and review of Sjögren’s syndrome. Int J Pharm Compound 2000;4:338-341.
4. Pray WS. Consult your pharmacist. Help for patients with dry mouth. US Pharmacist 2000;25:16-22.
5. Sreebny LM, Valdini A. Xerostomia: A neglected symptom. Arch Intern Med 1987;147:1333-1337.
6. Astor FC, Hanft KL, Ciocon JO. Xerostomia: A prevalent condition in the elderly. Ear Nose Throat J 1999;78:476-479.
7. Fox RI. Sjögren syndrome: New approaches to treatment. [www document] (n.d. 2/1/01). Available from URL: www.medscape.com/Medscape/rheumatology/TreatmentUpdate/2000/tu01/pnt-tu01.html
8. Hamada T, Nakane T, Kimura T, Arisawa K, Yoneda K, Yamamoto T, Osaki T. Treatment of xerostomia with the bile secretion-stimulant drug anethole trithione: A clinical trial. Am J Med Sci 1999;318:146-151.
9. McDonald E, Marino C. Dry mouth: Diagnosing and treating its multiple causes. Geriatrics 1991;46:61-63.
10. National Institute of Dental and Craniofacial Research (NIDCR), National Institutes of Health (NIH). Dry mouth. Bethesda, MD: National Oral Health Information Clearinghouse (NOHIC). 1999.
11. California Dental Hygienists’ Association. Xerostomia: Dry mouth. [www document] (October 25, 2000). Available from URL: www.cdha.org/articles/drymouth.htm.
12. Van Der Reijden WA, Vissink A, Veerman ECI, Amerongen AVN. Treatment of oral dryness related complaints (xerostomia) in Sjögren’s syndrome. Ann Rheum Dis 1999;58:465-473.
13. Flynn AA. Counseling special populations on oral health care needs: Patients who are at increased risk for oral disease need to take special care of their teeth. Am Pharm 1993;33:33-39.
14. Sreebny LM, Schwartz SS. A reference guide to drugs and dry mouth – 2nd edition. Gerodontology 1997;14:33-47.
15. Anon. Treatment of xerostomia. Med Lett Drugs Ther 1988;30(771):74-76.
16. Hensley ML, Schuchter LM, Lindley C, Meropol NJ, Cohen GI, Broder G, et al. American society of clinical oncology clinical practice guidelines for the use of chemotherapy and radiotherapy protectants. J Clin Oncol 1999;17:3333-3355.
17. Kuntz R, Allen M, Osburn J. Xerostomia. Int J Pharm Compound 2000;4:1176-177.
18. Anon. Management of dry mouth and halitosis. Practitioner 1990;234:618-619.
19. Davies A. Clinically proved treatments for xerostomia were ignored. BMJ 1998;316:1247.
20. Burham TH, editor. Drug facts and comparisons. St. Louis (MO): Facts and ComparisonsÒ ;2000.
21. Evens RP, Ingalls K. Artificial saliva – availability (Drug Consult). In: Hutchison TA, Shahan DR, Anderson ML (Eds). DRUGDEXÒ System. MICROMEDEX, Inc., Englewood (CO), (edition expires 3/31/01.
22. Anon. Salagen. Med Lett Drugs Ther 1994;36:76.
23. MGI Pharma Inc. SalagenÒ Tablets prescription information. Minnetonka, MN:1998 April.
24. Vivino FB, Al-Hashimi I, Khan Z, LeVeque FG, Salisburn PL, Tran-Johnson TK, 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.
25. Cardinale V, editor. 2000 Drug TopicsÒ Red BookÒ . Pharmacy’s Fundamental ReferenceTM. Montvale (NJ): Medical Economics Co.;2000.
26. SnowBrand Pharmaceuticals Inc. EvoxacÒ Capsules package insert. Rockville, MD: 2000 Feb.
27. Anon. Cevimeline (Evoxac) for dry mouth. Med Lett Drugs Ther 2000;42:70.
28. Kehoe WA. New drug: Evoxac (cevimeline). Pharmacist’s Letter 2000 May. Detail No.:160511.
29. Cardinale V, editor. 2000 Drug TopicsÒ Red BookÒ . Pharmacy’s Fundamental ReferenceTM. February 2001 Update. Montvale (NJ): Medical Economics Co.;2000.
30. DRUGDEXÒ Editorial Staff. Yohimbine therapy of xerostomia (Drug Consult). In: Hutchison TA, Shahan DR, Anderson ML (Eds). DRUGDEXÒ System. MICROMEDEX, Inc., Englewood (CO), edition expires 3/31/01.
31. Bagheri H, Schmitt L, Berlan M, Montastruc JL. A comparative study of the effects of yohimbine and anetholtrithione on salivary secretion in depressed patients treated with psychotropic drugs. Eur J Clin Pharmacol 1997;52:339-342.
32. Izumi M, Eguchi K, Nakamura H, Takagi Y, Kawabe Y, Nakamura T. Corticosteroid irrigation of parotid gland for treatment of xerostomia in patients with Sjögren’s syndrome. Ann Rheum Dis 1998;57:464-469.
33. Jessin JM, Batz F, Hitchens K. Pharmacist’s Letter/Prescriber’s Letter Natural Medicines Comprehensive Database. Stockton, CA: Therapeutic Research Faculty; 1999.
34. Fox PC, Cummins MJ, Cummins JM. Use of orally administered anhydrous crystalline maltose for relief of dry mouth. Journal of Alternative and Complementary Medicine 2001; 7: 33-43.
source: http://www.oralcancerfoundation.org/dental/xerostomia.htm
Dry Mouth Caused by Radiation Therapy
Dry mouth (xerostomia), is most commonly caused by radiation therapy directed at the head and neck region of the body. Radiation may irreversibly affect the production and quality of saliva in the salivary glands. A number of medications can also induce xerostomia. Dry mouth may affect the patients speech, taste sensation and ability to swallow.
Many patients complain of a sore or burning sensation, cracked lips, and fissures in the corners of the mouth. There is also an increased risk of cavities and mouth disease due to less saliva to cleanse the teeth and gums.
There are now some means of preventing xerostomia that were not available a few years ago. Amifostine, a radiation protector of normal tissues, has been shown to protect the salivary glands when given daily with radiation therapy. Also, a treatment known as Proton therapy may allow the radiation oncologist to spare the salivary glands from getting significant radiation doses. This may prevent dry mouth in the future. If you are getting radiation therapy to the head and neck region, you should discuss these options with your radiation oncologist. If you have developed xerostomia, there are management strategies that can effectively deal with your dry mouth and prevent cavities and periodontal disease.
Try to follow these simple guidelines:
source: http://www.thecancerblog.com/2007/02/13/radiation-tips-for-dealing-with-dry-mouth/
Xerostomia (Dry Mouth)
Xerostomia (Dry Mouth)
Xerostomia is not a disease but can be a symptom of certain diseases. It can produce serious negative effects on the patients quality of life, affecting dietary habits, nutritional status, speech, taste, tolerance to dental prosthesis and increases susceptibility to dental caries. The increase in dental caries can be devastating in many patients and therefore special care must be made to control this condition.
Causes for Xerostomia include:
Treatment:
1. Identify the xerostomic condition and the cause. Some of the causes may be ameliorated and this will aid therapy. But in many situations, it will be difficult to eliminate the causes. Thus, it will be necessary for the Dentist to control the results of xerostomia. This is especially true about the increase in dental caries.
2. Palliative treatment can be used but does not cure the condition:
-The xerostomic patient is classified into a risk assessment as outlined in the course material. However, this patient should be classified at high risk even if there are only several incipient lesions. This is done only in this type of patient because of the high caries risk.
-Determine if this patient is caries active or not active and follow the high risk protocol in the main outline in this course. When the ms infection is under control use a remineralization protocol along with the monitoring.
-Both an ms and lactobacillus tests are indicated.
-Carefully observe color, texture and location of lesions.
-CHX treatment may have to be prolonged along with use of fluoride.
-Prolonged use of Xylitol gum is importance since its use enhances salivary flow and helps control mutans strep.
-Enhance use of hard cheese in diet.
-Use sucralose in cooking.
Study May Help Head and Neck Cancer Patients Find Relief From Dry Mouth
March 2007
Nearly all patients with head and neck cancer have their tumors irradiated for several weeks. As I understand it, the problem is radiation doesn’t discriminate between tumor cells and healthy salivary glands. Is that correct?
That’s essentially right. The radiation kills the tumor cells but unfortunately also affects the nearby salivary glands. The damaged glands become less permeable to the water that naturally flows through them and either will yield less saliva or stop working altogether. If the damage is extensive, cancer patients will notice a persistent and irritating dryness in their mouths called radiation-induced xerostomia, or, more colloquially, dry mouth. It’s a very common problem. A survey of head and neck cancer patients comes to mind that was published a few years ago. It found that 65 percent of long-term survivors – defined as living three years post radiation therapy – had moderate to severe xerostomia. 1
Why is this parched sensation so irritating?
There’s an old Blues song titled, “You don’t miss your water til the well runs dry.” That’s certainly true with saliva. Most people don’t think of it until the moisture in their mouths runs dry, and that’s what makes xerostomia so irritating. Recovering cancer patients wonder, “Why is my mouth so dry?” But the dryness is more than an irritation. It can be a significant problem that impairs a person’s ability to chew, swallow, and even speak. In addition, dry mouth can lead to oral infections, such as tooth decay and Candidiasis.
Can anything be done to increase salivary flow?
For some people, yes. If tissue remains that is water permeable and capable of secretion, compounds such as pilocarpine can stimulate the glands to produce more saliva. The problem is most patients have salivary glands that have stopped working.
How so?
The radiation leaves the glands water impermeable. Let me explain. Salivary glands kind of look like a bunch of grapes attached to a stem. The grapes are called acinar cells. In people with working salivary glands, water enters the acinar cells, where myriad proteins are added, and the mixture then flows through the stems for further processing and ultimately exit into the mouth as saliva. In most head and neck cancer patients, the radiation has wiped out the acinar cells. They’re left with a network of water-impermeable stems that have no salivary flow. There is nothing left to stimulate.
And that’s where salivary gene transfer is different than pilocarpine. It will for the first time help those with impermeable salivary glands.
That’s our hope. The gene transfer that we have developed builds on the fundamental fact that the stems, or ducts, are water impermeable in the irradiated glands. We think that with gene transfer, the ducts will have the potential to move fluid and secrete it into the mouth.
The answer, as I’ve heard you say, is osmosis.
Correct, it’s that concept everybody learns in junior high school. Water naturally follows an osmotic energy gradient, flowing from areas of low to high salt concentration. We believe the irradiated duct cells can generate such an osmotic gradient. Over the last decade or so, I’ve worked with scientists in our laboratory to determine whether transferring a gene into the cells that line the ducts can take advantage of the ability of these cells to generate an osmotic gradient and secrete saliva into the mouth. In August 2006, we received approval from the Food and Drug Administration to conduct the first gene-transfer study in people with radiation-induced xerostomia.
Which gene will be transferred?
The gene is Aquaporin-1. It encodes a large protein that transports fluid by forming pores, or water channels, in the cell membrane. Our hope is the transferred gene will produce reasonable levels of the aquaporin-1 protein in duct cells, setting in motion a therapeutic domino effect. That is, the aquaporin-1 protein will open up water channels in the duct cells. That will allow the very rapid movement of water through the duct in response to the osmotic gradient that we believe can be generated.
The gene is contained in a vector, which serves almost like a trojan horse to deliver aquaporin-1 to its target. Which vector will you use?
An adenovirus. It’s a common respiratory virus that has been used in gene transfer studies for many years. The virus has been modified and won’t make a person sick.
Will the first study be a Phase I investigation, meaning it will evaluate the safety and tolerability of the gene transfer in the participants?
It will be simultaneously a Phase I and II study, which is quite commonly done today. As part of the Phase II component, we will collect some efficacy data. By that, I mean we will measure whether salivary fluid output improves in the patients and, in turn, if they notice that their mouths feel moister and less dry.
How large will the study be?
The study will enroll 15 to 21 patients.
All local participants?
Well, in theory, they could live anywhere. But the patients will stay in the hospital here in Bethesda at least for the first three days. They must be back here on Day 7 and 14. If people were to come from the West Coast, they would probably have to stay in the area for an extended period. That could be a logistical problem. We will track the patients on Day 28, Day 42, and so on for a full year. If the FDA decides that they should be followed longer, we’ll do so.
Are there conceptual advantages to performing gene transfer in salivary glands as opposed to an internal organ?
Absolutely. First, unlike most internal organs, a salivary gland is not critical for life. Should a problem arise, people will continue to survive with low levels of saliva. Second, we have direct access to the gland. Its opening is right there in the mouth, and we can infuse the Aquaporin-1 gene directly into a major salivary gland. There is no need for anaesthesia or surgery.
Into which salivary gland will you deliver the vector?
We’ll use a single parotid gland. The parotid gland is the largest of the three major salivary glands. If you touch the side of your face, the parotid gland is located under the skin between the jawbone and the lobe of the ear.
A concern with gene transfer studies is the vector might accidently integrate into the DNA of cells elsewhere in the body and cause tumors and other problems. Is that a concern?
In theory, yes. Practically speaking, no. Adenoviruses are non-integrating viruses. Secondly, because a fibrous capsule surrounds the salivary gland, the vector is essentially walled off from the rest of the body. One of the things we did in our animal studies is look for the vector throughout the body. In rats, the glands aren’t as well encapsulated as they are in humans or primates. The animals eat hard chow, so you tend to see the virus in their mouth but it doesn’t spread throughout their body.
The rats had no tumors? Even salivary tumors?
That is correct. They had no tumors anywhere.
With the gene transfer, how much saliva might a patient produce?
We hope to restore 70 to 80 percent of normal salivary flow. Based on our earlier studies with miniature pigs, we saw significant increases in salivary flow on days 3 and 7. By day 14, it was, on average, a little above background. We had expected it to decrease by days 14 to 21. Then comes the obvious question: What next? You can’t give the virus again because the patients will have raised antibodies against it.
So, what next?
We have another vector called an adeno-associated virus, or AAV. In contrast to adenovirus, AAV lasts a very long time and provides quite stable gene transfer. In mice, it can last essentially as long as the animals are alive, which was up to two years.
Why not launch the study with the longer lasting vector?
To err on the side of caution. This study marks the first time that a viral vector will be delivered into a human salivary gland. Secondly, because our research to date has been conducted in animals, we have not yet demonstrated that radiation-damaged salivary duct cells in people can generate an osmotic gradient and support fluid flow. The adenovirus is essentially self limiting and will be removed from each patient by their immune system. If, by chance, the strategy doesn’t work, I didn’t want to have patients with a useless gene-transfer vector in their bodies indefinitely.
So, the goal would be to build on this study and move to Phase III. Is that right?
Well, no. It’s actually an interesting point. If this works, we could say that the Aquaporin-1 strategy works in humans. That is, the physiology of duct cells is such that they could generate an osmotic gradient. The strategy would be to go to an adeno-associated virus vector for long term expression as a Phase I/II study. If that works, the goal would be to advance to a Phase III clinical trial.
Good luck with the study.
Thanks. Let me just say, this study represents a start. It’s a very good start, though, based on solid science. I hope other research groups will take note of salivary gene transfer and continue to develop it even further. The salivary glands offer unique therapeutic possibilities that should be more intensively explored, not only by dental scientists but throughout medical research. More importantly, for all of the reasons that I’ve mentioned, it would be a big win for recovering cancer patients who are forced to battle radiation-induced xerostomia.
source: http://www.nidcr.nih.gov/Research/ResearchResults/InterviewsOHR/TIS032007.htm
What You Should Know About Dry Mouth
Symptoms of Dry Mouth
Why is saliva so important?
Saliva does more than keep the mouth wet.
Without enough saliva you can develop tooth decay or other infections in the mouth. You also might not get the nutrients you need if you cannot chew and swallow certain foods.
What causes dry mouth?
People get dry mouth when the glands in the mouth that make saliva are not working properly. Because of this, there might not be enough saliva to keep your mouth wet. There are several reasons why these glands (called salivary glands) might not work right.
What can be done about dry mouth?
Dry mouth treatment will depend on what is causing the problem. If you think you have dry mouth, see your dentist or physician. He or she can try to determine what is causing your dry mouth.
What can I do?
What is xerostomia?
What is xerostomia?
Xerostomia (ZEER-oh-STOH-mee-ah) is known as dry mouth. It is the condition of not having enough saliva, or spit, to keep the mouth wet. Dry mouth can happen to anyone occasionally when nervous or stressed. However, when dry mouth persists, it can make chewing, eating, swallowing and even talking difficult. Dry mouth also increases the risk for tooth decay because saliva helps keep harmful germs that cause cavities and other oral infections in check.
Causes
Dry mouth occurs when the salivary glands that make saliva don’t work properly. Many over-the-counter and prescription medicines, as well as diseases such as diabetes, Parkinson’s disease and Sjogren’s syndrome, can affect the salivary glands. Other causes of dry mouth include certain cancer treatments and damage to the glands’ nerve system. It’s important to see your dentist or physician to find out why your mouth is dry.
Treatment
Depending on the cause of your dry mouth, your health care provider can recommend appropriate treatment. There are also self-care steps you can take to help ease dry mouth, such as drinking plenty of water, chewing sugarless gum, and avoiding tobacco and alcohol. Good oral care at home and regular dental check-ups will help keep your mouth healthy.
How Common is Xerostomia?
Chronic dry mouth, or xerostomia, has long been considered a problem of aging. But how common is it? The medical literature contains just one study on the subject, and myriad questions remain about the risk factors, incidence, and natural history of the condition. Now, in the December issue of the journal Gerodontology, NIDCR grantees and colleagues have published a second longitudinal study. It tracked 1,205 dentate adults age 60 and older over several years, with 246 participants being followed for 11 years. The researchers found that the prevalence of xerostomia increased from 21.4 percent to 24.8 percent between the fifth and eleventh year of follow up. However, one quarter of those with xerostomia fluctuated over time in the severity, or status, of their condition. The researchers also carefully tracked the use of medications, a recognized but still nonspecific risk factor for xerostomia. Their use increased throughout the study, with nearly 95 percent taking at least one medication at the study’s 11-year mark. According to the authors, “While only two categories of medication being taken at 11 years were associated with the incidence of xerostomia between 5 and 11 years (antidepressants and daily aspirin), there were stronger associations when only those medications taken since the 5-year assessment were included in the analysis. In this exposure category, xerostomia incidence was greater among those taking diuretics, NSAIDs, antidepressants or daily aspirin.”
Should I follow a special diet while I am getting radiation therapy?
Your body uses a lot of energy to heal during radiation therapy. It is important that you eat enough calories and protein to keep your weight the same during this time. Ask your doctor or nurse if you need a special diet while you are getting radiation therapy. You might also find it helpful to speak with a dietitian.
Who is on my radiation therapy team?
Many people help with your radiation treatment and care. This group of health care providers is often called the “radiation therapy team.” They work together to provide care that is just right for you. Your radiation therapy team can include:
Radiation oncologist. This is a doctor who specializes in using radiation therapy to treat cancer. He or she prescribes how much radiation you will receive, plans how your treatment will be given, closely follows you during your course of treatment, and prescribes care you may need to help with side effects. He or she works closely with the other doctors, nurses, and health care providers on your team. After you are finished with radiation therapy, your radiation oncologist will see you for follow-up visits. During these visits, this doctor will check for late side effects and assess how well the radiation has worked.
Nurse practitioner. This is a nurse with advanced training. He or she can take your medical history, do physical exams, order tests, manage side effects, and closely watch your response to treatment. After you are finished with radiation therapy, your nurse practitioner may see you for follow-up visits to check for late side effects and assess how well the radiation has worked.
Radiation nurse. This person provides nursing care during radiation therapy, working with all the members of your radiation therapy team. He or she will talk with you about your radiation treatment and help you manage side effects.
Radiation therapist. This person works with you during each radiation therapy session. He or she positions you for treatment and runs the machines to make sure you get the dose of radiation prescribed by your radiation oncologist.
Other health care providers. Your team may also include a dietitian, physical therapist, social worker, and others.
You. You are also part of the radiation therapy team. Your role is to:
Arrive on time for all radiation therapy sessions
Ask questions and talk about your concerns
Let someone on your radiation therapy team know when you have side effects
Tell your doctor or nurse if you are in pain
Follow the advice of your doctors and nurses about how to care for yourself at home, such as:
Taking care of your skin
Drinking liquids
Eating foods that they suggest
Keeping your weight the same
Is radiation therapy used with other types of cancer treatment?
Yes, radiation therapy is often used with other cancer treatments. Here are some examples:
Radiation therapy and surgery. Radiation may be given before, during, or after surgery. Doctors may use radiation to shrink the size of the cancer before surgery, or they may use radiation after surgery to kill any cancer cells that remain. Sometimes, radiation therapy is given during surgery so that it goes straight to the cancer without passing through the skin. This is called intraoperative radiation.
Radiation therapy and chemotherapy. Radiation may be given before, during, or after chemotherapy. Before or during chemotherapy, radiation therapy can shrink the cancer so that chemotherapy works better. Sometimes, chemotherapy is given to help radiation therapy work better. After chemotherapy, radiation therapy can be used to kill any cancer cells that remain.