Artificial Saliva for Therapeutic Management of Xerostomia: A Narrative Review

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.

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.[1] 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.[2] 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).[3] 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.[4] 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.[5] 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.[6]

GENERAL PRINCIPLES TO FOLLOW IN XEROSTOMIA MANAGEMENT

The following primary principles of treatment are relevant in xerostomia:

1. 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

2. Maintenance of proper oral hygiene: Patients using dentures need to be encouraged to use fluoride toothpaste, preferably in conjugation with daily fluoride mouth rinse.[7] 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

3. Monitoring: Regular checkup combined with microbiological analysis is useful to find visible or hidden oral infections such as candida or Staphylococcus aureus species

4. 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:

1. Endogenous approach: Pharmaceutical treatment, mechanical stimulation, and genetic solutions and

2. 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.[8] It is reported that the use of chewing gum containing sorbitol after a sugary meal or snack is effective in normalizing plaque pH.[9] 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.[10]

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.[8] 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.[11] Many clinical studies have shown the beneficial use of acupuncture in treating xerostomia and hyposalivation associated with Sjögren's syndrome, radiotherapy, or idiopathic causes.[12,13,14]

Systemic therapies

The use of systemic agents has been found effective in producing salivary production and flow, of which pilocarpine HCl has made promising clinical results.[15]

Pilocarpine

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.[16] 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.[17] 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.

Cevimeline

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.[18,19] Cevimeline has a more selective affinity for M3 subtype muscarinic receptors, and this drug has been widely used in patients experiencing postradiation xerostomia.[20,21]

Anetholetrithione

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.[22] A dose of 25 mg is recommended three times daily to increase the salivary flow and reduce oral dryness.[23]

Yohimbine

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.[24] Animal studies have shown that yohimbine enhances salivary flow by inhibition of presynaptic α-2 adrenoceptors located on the chorda tympani.[25]

Interferon

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.[23,26,27] 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.[28] 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.[29]

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.[30] The spry dental defense system chewing gums incorporate xylitol, a sugar replacement with sweetness equal to sucrose.[31] 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.[32] 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.[33] 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.[34]

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.[35,36,37,38] A modern technique known as intensity-modulated radiotherapy has been found to be beneficial in minimizing the oral dryness in postradiation xerostomia.[39]

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.”

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.