|Year : 2021 | Volume
| Issue : 6 | Page : 903-907
Artificial saliva for therapeutic management of xerostomia: A narrative review
Hajer Ayed Alhejoury1, Lina Fouad Mogharbel1, Mohammed Ahmed Al-Qadhi2, Suzan Sulaiman Shamlan3, Amal Fuad Alturki3, Wafaa Mohammed Babatin3, Renad Abdualrahman Mohammed Alaishan3, Fawaz Pullishery4
1 Dental Intern, Dentistry Program, Batterjee Medical College, Jeddah, Saudi Arabia
2 General Dentist, Ministry of Health, King Abdulaziz University, Jeddah, Saudi Arabia
3 Dental Intern, Batterjee Medical College, Jeddah, Saudi Arabia
4 Department of Community Dentistry, Dentistry Program, Batterjee Medical College, Jeddah, Saudi Arabia
|Date of Submission||24-Mar-2021|
|Date of Decision||04-Apr-2021|
|Date of Acceptance||12-Apr-2021|
|Date of Web Publication||10-Nov-2021|
Hajer Ayed Alhejoury
Dentistry Program, Batterjee Medical College, Jeddah-21442
Source of Support: None, Conflict of Interest: None
| Abstract|| |
In clinical practice, xerostomia or oral dryness is a chronic disease condition encountered by most dentists and dental hygienists, which often causes a negative impact on the oral health-related quality of life of the affected individual. Xerostomia is caused due to salivary gland dysfunction. It is related to reduced salivary secretion or the absence of saliva flow, more frequently, exhibits qualitative changes in saliva proteins and immunoglobulin concentrations that arise due to salivary gland dysfunction. This condition causes discomfort and interferes with normal oral activities, and affected individuals are at high caries risk. There are several options for treatment and symptom management: salivary stimulants, topical agents, saliva substitutes, and systemic sialogogues. This review explores the current status of therapeutic management of patients affected by xerostomia and hyposalivation using artificial saliva.
Keywords: Minimally invasive dentistry, rheology, saliva alternatives, xerostomia
|How to cite this article:|
Alhejoury HA, Mogharbel LF, Al-Qadhi MA, Shamlan SS, Alturki AF, Babatin WM, Mohammed Alaishan RA, Pullishery F. Artificial saliva for therapeutic management of xerostomia: A narrative review. J Pharm Bioall Sci 2021;13, Suppl S2:903-7
|How to cite this URL:|
Alhejoury HA, Mogharbel LF, Al-Qadhi MA, Shamlan SS, Alturki AF, Babatin WM, Mohammed Alaishan RA, Pullishery F. Artificial saliva for therapeutic management of xerostomia: A narrative review. J Pharm Bioall Sci [serial online] 2021 [cited 2022 Aug 11];13, Suppl S2:903-7. Available from: https://www.jpbsonline.org/text.asp?2021/13/6/903/330029
| Introduction|| |
Saliva is a watery liquid usually frothy seen in the oral cavity of animals and humans, secreted by the glands, which is a hydrous hypotonic solution that protects the whole of the oral cavity. Saliva has different actions such as lubrication for chewing and swallowing, helps in digestion, improves deglutition and talk, increases taste, moisturizes oral mucosa, and allows free movement of saliva in irrigation and cleansing action with damping capacity. It also plays a significant role in oral immunity as it contains many immunological components and has antimicrobial properties. Studies showed a reduced production or hypoptyalism is often related to many contingent outcomes, namely, retard actions to speak, chewing issues, block in deglutition, and flavor. Decreased saliva production is generally gone along with plaque-induced diseases such as cavities and inflammation of gums, which results in exodontia.
Xerostomia, usually called dry mouth, is a repeated problem and indication of salivary gland hypofunction (SGH). Elements that put up xerotes include blood-related diseases and treatment measures for cancer. While xerostomia often is a sign of damaged exocrine gland function, it may form with or without an observable decrease in saliva formation. Mainly, dry mouth is followed by SGH, which reflects a markable reduction in salivary production. Dry mouth manifestations may changes from minor oral irritation to a remarkable oral ailment that can affect patients' health, food consumption, and quality of life. Recognizing and managing the actual cause of this condition is necessary for delivering ideal dental care.
| Artificial Saliva|| |
Saliva alternatives, otherwise called artificial saliva, basically proceeds by moisturizing the desiccate oral tissue. The biological and physical characteristics of artificial saliva must be similar as viable to normal human saliva. Artificial saliva is usually a mix of buffering agents, cellulose derivatives, and flavoring agents. Saliva replacements are accessible as different agents such as liquids, sprays, gels, oils, mouthwash, chewing gums, and toothpaste. It permits to give of wetting features that are important in safeguarding oral tissues, appropriate speech functioning, and eating purpose. Moreover, it acts to minimize the irritation in the oral cavity caused by liquid nature differently from natural saliva. The sticky consistency of the normal saliva shows that it is a nonNewtonian fluid. When the flow rate is in the range of 0.1–1 liter/s, residual saliva's sticky consistency is much greater than the sticky consistency during chewing and talking when the shown rate is about 60 and 160 liter/s. This reliance of density on the rate of alteration is called pseudoplasticity and is essential for its normal functioning. Saliva alternate using Newtonian fluids such as carboxymethylcellulose or glycerol are done, which has a greater viscosity (sticky consistency) than normal human saliva. Closer physiochemical properties to normal human saliva have alternates that contain mucin with xanthan guar gum or just mucin alone. Another important physiochemical property of saliva is its viscoelasticity that displays indirect behavior between a viscous solution and an elastic solid. Viscoelasticity is assessed in vitro with rheometers under creep/recovery or dynamic tests.
| General Principles to Follow in Xerostomia Management|| |
The following primary principles of treatment are relevant in xerostomia:
- Patient education: The affected individual has to be entrusted with a qualified clinician to discuss the issues, concerns about the condition for clarity. The etiology, diagnosis, prognosis, and prospective management should be discussed with the patients to follow the recommended treatment with regular appointments
- Maintenance of proper oral hygiene: Patients using dentures need to be encouraged to use fluoride toothpaste, preferably in conjugation with daily fluoride mouth rinse. The intake of refined carbohydrates should be minimized or discouraged, and the application of chlorhexidine mouthwash should also be advised. Denture patients should be educated with denture cleaning techniques, especially to remove the appliance before sleeping
- Monitoring: Regular checkup combined with microbiological analysis is useful to find visible or hidden oral infections such as candida or Staphylococcus aureus species
- SGH: A sensible decision has to be made on the dry mouth's appropriate treatment options with artificial saliva or combination therapy, where the ultimate aim should be the stimulation of normal salivary flow.
| Therapeutic Option for Salivary Dysfunction|| |
SGH is managed mainly with two approaches that can be followed:
- Endogenous approach: Pharmaceutical treatment, mechanical stimulation, and genetic solutions and
- Exogenous approach: Drinking water frequently, moisturizing, and saliva substitutes.
The stimulants for SGH are classified as topical and systemic agents. In the case of topical agents, the act of chewing itself enhances salivary production and could be supplemented with flavored chewing gums, sorbitol, or xylitol. It is reported that the use of chewing gum containing sorbitol after a sugary meal or snack is effective in normalizing plaque pH. Citric acid is also suggested to be a good and useful salivary stimulant. The use of citric acid enriched foods or sweets may contribute to symptomatic comfort from xerostomia but have to consider the cariogenicity in dentate patients as citrate chelates calcium ions, which may increase the caries activity.
The systemically delivered medicaments for SGH have mainly been used in patients with Sjogren syndrome. Several medicaments have been suggested as systemic medicaments that comprise bethanechol chloride, pyridostigmine, pilocarpine hydrochloride, bromhexine trithioparamethoxy phenylpropene, nicotinic acid, and Vitamin A.
| Salivary Enhancement Therapies|| |
Topical and local therapies
Salivation is a response to taste, mainly sour and bitter, and salivary production can be enhanced by increasing oral activities. Flavored gums and lozenges will improve salivation and act as a pillar for xerostomia treatment. The combined gustatory and masticatory functions could temporarily produce more saliva and reduce oral dryness. It is also advised to use sugar-free gums, lozenges, candies, or mints for relief from oral dryness. It is often recommended to use sugar-free gums to minimize caries activity among these individuals. Even though not an ideal medical therapy, acupuncture has been found to be useful in enhancing salivary production. Many clinical studies have shown the beneficial use of acupuncture in treating xerostomia and hyposalivation associated with Sjögren's syndrome, radiotherapy, or idiopathic causes.,,
The use of systemic agents has been found effective in producing salivary production and flow, of which pilocarpine HCl has made promising clinical results.
Pilocarpine is a cholinomimetic drug with mild ß-adrenergic actions. It has been considered as a medicament of choice for xerostomia over the years. The clinical experiments have constantly demonstrated that Pilocarpne in doses of 5–10 mg 3–4 times daily could minimize the signs of xerostomia and produce more saliva. Even though pilocarpine is a well-tolerated drug, some adverse effects have been reported, including diaphoresis, flushing, and polyuria, which are of mild or moderate intensity and although the effects are of short duration. It is contraindicated in patients with uncontrolled asthma, narrow-angle glaucoma, or acute iritis. Precautionary measures need to be followed in patients with blood disorders and cardiovascular diseases.
The use of cholinomimetic drugs such as cevimeline HCl has been tested for its effectiveness, and daily intake of 30 mg of cevimeline has shown remarkable clinical results in improving the salivary flow and production in patients with Sjögren's syndrome., Cevimeline has a more selective affinity for M3 subtype muscarinic receptors, and this drug has been widely used in patients experiencing postradiation xerostomia.,
This agent, which was first used to increase the bile output, has been shown to improve salivation in patients experiencing minor salivary dysfunctioning, such as senile hypofunction. A dose of 25 mg is recommended three times daily to increase the salivary flow and reduce oral dryness.
There is a lack of supportive studies for the use of an alpha-receptor antagonist such as yohimbine to treat xerostomia. Yohimbine has been found to effective in increasing salivary flow compared to anetholtrithione in patients using psychotropic drugs. Animal studies have shown that yohimbine enhances salivary flow by inhibition of presynaptic α-2 adrenoceptors located on the chorda tympani.
Many of the clinical studies have used interferon (IFN) in injectable form in high doses for the management of dry mouth, especially in patients with Sjögren's syndrome.,, The injectable IFN is a genetically modified protein, and the lozenge is a natural IFN. The small dosage lozenge formulae, at 150 IU three times a day, have decreased xerostomia and added salivary flow. A recent meta-analysis has confirmed that INF-α at a dose of 150 IU three times daily is effective in increasing salivary production and flow rate and modifies the immunomodulatory action in SS patients with minimal side effects.
| Saliva Stimulants|| |
Saliva stimulants are successful methods of improving salivation in patients with SGH. No saliva supplement has been identified yet that exactly reproduces all necessary standard human saliva character, and trials should be done to increase saliva's natural production, however, achievable. Saliva production may be through local activity, through physical action, or systemically through medicines. Recaldent Gum (GC Corporation) supplemented the saliva's innate capacity to remineralize tooth structure by releasing both calcium and phosphate in casein phosphopeptide amorphous calcium phosphate 13. Saliva stimulants with antiseptic features were also used and found to be beneficial in managing xerostomia. The spry dental defense system chewing gums incorporate xylitol, a sugar replacement with sweetness equal to sucrose. Use of xylitol for a more extended period has proved to reduce Streptococcus mutans and in turn, decrease the susceptibility to caries. Biotene and BioXtra have chewing gums with protein enzyme systems in their oral hygiene and oral lubrication products. While chewing gums can increase salivary production and replace saliva with cariostatic and remineralizing agents, gums are restricted in changing the salivary content.
| Recent Advances|| |
Several advanced therapies for SGH and xerostomia have been explored. One is acupuncture, which is a holistic approach that enhances saliva production by improving blood circulation over the parotid gland. Subsequently, intraoral electro-stimulators produce salivation by putting reduced electronic flow levels to the oral mucosa. Electrostimulators could make a 3–4 folds increase in salivary flow and provide considerable relief in patients with severe SGH. Continuous use also boosts the efficiency of neural stimulations. They can either be a replaceable mouthguard-like device or fixed to a dental implant. Baum et al. have demonstrated a gene therapy approach using aquaporin-1 cDNA in increasing salivary flow in patients with postradiation gland hypofunction that incorporated this particular therapeutic gene to the target cells of the patient through a carrier molecule. A more commonly used vector is a genetically modified virus that can carry normal human DNA. This virus delivers the therapeutic gene to the damaged saliva-producing cells.
Salivary pacemakers have been recently tried to improve salivation and indirectly minimize the long-term effects of oral dryness. Devices such as the Salitron system (Biosonics Inc, USA), GenNarino, SaliPen, and Saliwell Crown (implant-supported device) have shown effectiveness in increasing salivation in xerostomia patients.,,, A modern technique known as intensity-modulated radiotherapy has been found to be beneficial in minimizing the oral dryness in postradiation xerostomia.
| Conclusion|| |
Xerostomia is a significant oral health problem that increases caries activity, salivary gland enlargement, oral malodor, sialadenitis, infections such as candidiasis, and inflammation of various oral structures, which causes a profound impact on not only the oral-health related quality of life but also on general health quality of life. Dentists play a crucial role in easing xerostomia symptoms and improving the quality of life in these patients. Artificial salivary agents or saliva stimulating agents have been found to be beneficial in reducing the subjective symptoms associated with xerostomia. More than this, most of the methods discussed above envisages the new oral health promotion concept “Minimally Invasive Dentistry.”
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Boyce HW, Bakheet MR. Sialorrhea: A review of a vexing, often unrecognized sign of oropharyngeal and esophageal disease. J Clin Gastroenterol 2005;39:89-97.
Pedersen A, Sørensen CE, Proctor GB, Carpenter GH. Salivary functions in mastication, taste and textural perception, swallowing and initial digestion. Oral Dis 2018;24:1399-416.
Alsakran Altamimi M. Update knowledge of dry mouth – A guideline for dentists. Afr Health Sci 2014;14:736-42.
Łysik D, Niemirowicz-Laskowska K, Bucki R, Tokajuk G, Mystkowska J. Artificial saliva: Challenges and future perspectives for the treatment of xerostomia. Int J Mol Sci 2019;20:3199.
Marcinkowska-Gapińska A, Linkowska-Świdzińska K, Świdziński T, Surdacka A. Rheological parameters of saliva in comparison with taste examination. Biorheology 2018;55:51-60.
Vissink A, Waterman HA, S-Gravenmade EJ, Panders AK, Vermey A. Rheological properties of saliva substitutes containing mucin, carboxymethylcellulose or polyethylenoxide. J Oral Pathol 1984;13:22-8.
Horst JA, Tanzer JM, Milgrom PM. Fluorides and other preventive strategies for tooth decay. Dent Clin North Am 2018;62:207-34.
Karami-Nogourani M, Kowsari-Isfahan R, Hosseini-Beheshti M. The effect of chewing gum's flavor on salivary flow rate and pH. Dent Res J (Isfahan) 2011;8:S71-5.
Rafeek R, Carrington CV, Gomez A, Harkins D, Torralba M, Kuelbs C, et al
. Xylitol and sorbitol effects on the microbiome of saliva and plaque. J Oral Microbiol 2019;11:1536181.
Gardner A, So PW, Carpenter G. Endogenous salivary citrate is associated with enhanced rheological properties following oral capsaicin stimulation. Exp Physiol 2020;105:96-107.
Gupta D, Dalai DR, Swapnadeep, Mehta P, Indra BN, Rastogi S, et al
. Acupuncture (zhēn jiŭ) – An emerging adjunct in routine oral care. J Tradit Complement Med 2014;4:218-23.
] [Full text]
Assy Z, Brand HS. A systematic review of the effects of acupuncture on xerostomia and hyposalivation. BMC Complement Altern Med 2018;18:57.
Li LX, Tian G, He J. The standardization of acupuncture treatment for radiation-induced xerostomia: A literature review. Chin J Integr Med 2016;22:549-54.
Zhuang L, Yang Z, Zeng X, Zhua X, Chen Z, Liu L, et al
. The preventive and therapeutic effect of acupuncture for radiation-induced xerostomia in patients with head and neck cancer: A systematic review. Integr Cancer Ther 2013;12:197-205.
Wu CH, Hsieh SC, Lee KL, Li KJ, Lu MC, Yu CL. Pilocarpine hydrochloride for the treatment of xerostomia in patients with Sjögren's syndrome in Taiwan – A double-blind, placebo-controlled trial. J Formos Med Assoc 2006;105:796-803.
Muthumariappan S, Ng WC, Adine C, Ng KK, Davoodi P, Wang CH, et al
. Localized delivery of pilocarpine to hypofunctional salivary glands through electrospun nanofiber mats: An ex vivo
and in vivo
study. Int J Mol Sci 2019;20:541.
Nusair S, Rubinow A. The use of oral pilocarpine in xerostomia and Sjögren's syndrome. Semin Arthritis Rheum 1999;28:360-7.
Leung KC, McMillan AS, Wong MC, Leung WK, Mok MY, Lau CS. The efficacy of cevimeline hydrochloride in the treatment of xerostomia in Sjögren's syndrome in southern Chinese patients: A randomised double-blind, placebo-controlled crossover study. Clin Rheumatol 2008;27:429-36.
Voskoboynik B, Babu K, Hack JB. Cevimeline (Evoxac ®) overdose. J Med Toxicol 2011;7:57-9.
Petrone D, Condemi JJ, Fife R, Gluck O, Cohen S, Dalgin P. A double-blind, randomized, placebo-controlled study of cevimeline in Sjögren's syndrome patients with xerostomia and keratoconjunctivitis sicca. Arthritis Rheum 2002;46:748-54.
Chambers MS, Posner M, Jones CU, Biel MA, Hodge KM, Vitti R, et al
. Cevimeline for the treatment of postirradiation xerostomia in patients with head and neck cancer. Int J Radiat Oncol Biol Phys 2007;68:1102-9.
Hamada T, Nakane T, Kimura T, Arisawa K, Yoneda K, Yamamoto T, et al
. Treatment of xerostomia with the bile secretion-stimulating drug anethole trithione: A clinical trial. Am J Med Sci 1999;318:146-51.
Fox PC. Salivary enhancement therapies. Caries Res 2004;38:241-6.
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;52:339-42.
Montastruc P, Berlan M, Montastruc JL. Effect of yohimbine on submaxillary salivation in dogs. Br J Pharmacol 1989;98:101:4.
Shiozawa S, Tanaka Y, Shiozawa K. Single-blinded controlled trial of low-dose oral IFN-alpha for the treatment of xerostomia in patients with Sjögren's syndrome. J Interferon Cytokine Res 1998;18:255-62.
Mamber SW, Lins J, Gurel V, Hutcheson DP, Pinedo P, Bechtol D, et al
. Low-dose oral interferon modulates expression of inflammatory and autoimmune genes in cattle. Vet Immunol Immunopathol 2016;172:64-71.
Ship JA, Fox PC, Michalek JE, Cummins MJ, Richards AB. Treatment of primary Sjögren's syndrome with low-dose natural human interferon-alpha administered by the oral mucosal route: A phase II clinical trial. IFN Protocol Study Group. J Interferon Cytokine Res 1999;19:943-51.
Garlapati K, Kammari A, Badam RK, Surekha BE, Boringi M, Soni P. Meta-analysis on pharmacological therapies in the management of xerostomia in patients with Sjogren's syndrome. Immunopharmacol Immunotoxicol 2019;41:312-8.
Gil-Montoya JA, Silvestre FJ, Barrios R, Silvestre-Rangil J. Treatment of xerostomia and hyposalivation in the elderly: A systematic review. Med Oral Patol Oral Cir Bucal 2016;21:e355-66.
Turska-Szybka A, Pasternok P, Olczak-Kowalczyk D. Xylitol Content in dental care and food products available on the polish market and their significance in caries prevention. Dent Med Probl 2016;53:542-50.
Dost F, Farah CS. Stimulating the discussion on saliva substitutes: A clinical perspective. Aust Dent J 2013;58:11-7.
Baum BJ, Zheng C, Alevizos I, Cotrim AP, Liu S, McCullagh L, et al
. Development of a gene transfer-based treatment for radiation-induced salivary hypofunction. Oral Oncol 2010;46:4-8.
Baum BJ, Alevizos I, Chiorini JA, Cotrim AP, Zheng C. Advances in salivary gland gene therapy – Oral and systemic implications. Expert Opin Biol Ther 2015;15:1443-54.
Talal N, Quinn JH, Daniels TE. The clinical effects of electrostimulation on salivary function of Sjögren's syndrome patients. A placebo controlled study. Rheumatol Int 1992;12:43-5.
Gil-Montoya JA, Barrios R, Sánchez-Lara I, Carnero-Pardo C, Fornieles-Rubio F, Montes J, et al
. Prevalence of drug-induced xerostomia in older adults with cognitive impairment or dementia: An observational study. Drugs Aging 2016;33:611-8.
Ara SA, Patil A, Patil BM. Current trends in the management of xerostomia: A review. Arch Dent Med Res 2016;2:15-21.
Lafaurie G, Fedele S, López RM, Wolff A, Strietzel F, Porter SR, et al
. Biotechnological advances in neuro-electro-stimulation for the treatment of hyposalivation and xerostomia. Med Oral Patol Oral Cir Bucal 2009;14:E76-80.
Tariq A, Jamshaid M, Majeed I. Xerostomia: Post radiation management strategies. Int J Pharmac Res Allied Sci 2015;4:35-47.