What are sialagogues

What Are Sialogogues?

Sialogogues are pharmacological agents that stimulate saliva production by increasing salivary gland secretion, primarily used to treat dry mouth (xerostomia) and salivary gland hypofunction. 1

Mechanism and Classification

Sialogogues work by stimulating the flow of saliva from functional salivary gland tissue. 2 They are classified into two main categories:

Systemic (Pharmacological) Sialogogues

• Muscarinic agonists are the primary systemic agents, including pilocarpine and cevimeline 1
• These medications require sufficient responsive exocrine tissue to be effective 3
• Pilocarpine has been used extensively for over a century, with typical dosing ranging from 1 to 15 mg four times daily 3
• Cevimeline has a similar mechanism to pilocarpine but may have a better tolerance profile 2

Non-Pharmacological Sialogogues

• Gustatory stimulants such as sugar-free acidic candies, lozenges, and xylitol 2
• Mechanical stimulants including sugar-free chewing gum 1, 2
• These are recommended as first-line therapy for mild salivary gland dysfunction 2

Clinical Applications

Sialogogues are indicated for:

• Dry mouth (sicca syndrome) from various causes including Sjögren's syndrome, medications, and radiation therapy 1
• Moderate to severe xerostomia when topical measures alone are insufficient 1
• Immunotherapy-related salivary dysfunction, where they are used alongside supportive care measures 1

Treatment Algorithm

For mild glandular dysfunction: Begin with non-pharmacological stimulation using sugar-free gum or candies 2

For moderate dysfunction: Consider systemic sialogogues (pilocarpine 5 mg orally four times daily or cevimeline) 2

For severe dysfunction with no salivary output: Sialogogues are ineffective; use saliva substitutes instead 2

Important Side Effects and Monitoring

The most common adverse effects of systemic sialogogues include:

• Excessive sweating (18.7% with cevimeline) 4
• Nausea (13.8% with cevimeline) 4
• Rhinitis (11.2% with cevimeline) 4
• Diarrhea (10.3% with cevimeline) 4
• Other cholinergic effects including excessive salivation, urinary frequency, and flushing 4

Pilocarpine causes more sweating compared to bethanechol or cevimeline, which is an important consideration for patient tolerance 5

Clinical Pitfalls

• Sialogogues require functional salivary gland tissue to work - they are not effective in severe cases where salivary parenchyma is lost 6
• Individual variation in response is considerable, so dose titration is necessary to achieve therapeutic benefit without significant side effects 3
• A carryover effect beyond washout periods has been observed, suggesting intermittent treatment may be an alternative to continuous therapy 5
• Baseline salivary gland function should be measured before initiating treatment, as subjective feelings of dryness may not match objective measurements 2

Adjunctive Measures

When using sialogogues, concurrent interventions should include:

• Hydration optimization and limiting caffeine intake 2
• Saliva substitutes with neutral pH containing fluoride and electrolytes 2
• Dietary modifications avoiding crunchy, spicy, acidic, or hot foods 1, 2
• Dental referral for patients at risk of dental caries from chronic dry mouth 1, 2