Sialogogues-Anti-sailogogues a detailed presentation

Sialogogues

1. Sialogogues & Anti-sialogogues Presented by: Dr. Tavleen Kaur PG I

2. Contents Causes of xerostomia Sialogogues Causes of sialorrhea Anti-sialogogues

3. Xerostomia Xerostomia is defined as subjective feeling of oral dryness resulting from decreased salivary flow - BURKET’S

4. Causes of Xerostomia 1. Iatrogenic causes Drugs: Anti-cholinergics (Atropine, Hyoscine) Anti-depressants (TCA’s, SSRI, Lithium) Anti-hypertensives Anti-histamines Anti-emetics Phenothiazines Proton pump inhibitors Cytotoxic drugs Opioids BZDs Diuretics Decongestants

5. 2. Salivary Gland Disorders A. Damage to salivary glands Auto immune diseases a. Sjögren's syndrome b. SLE c. Scleroderma d. Sarcoidosis B. Infections ( HIV, HCV, HTLV-1) C. Obstructive salivary gland diseases

6. 3. Therapeutic irradiation 4. Dehydration: - Decreased water intake - Water loss through skin (Burns) - Diarrhoea - Blood loss - Emesis 5. Ageing 6. Diabetes

7. 7. Vitamin deficiency 8. Interference with Neural transmission: - Psychological disorders - Alzheimer’s disease - Paralysis of facial nerve 9. Decrease in mastication 10. Depression

8. TREATMENT OPTIONS Preventive therapy Symptomatic treatment Salivary stimulation - Topical - Systemic 4. Treatment of underlying systemic disorders

9. 1. Preventive therapy: - Use of topical fluorides – to control dental caries Maintenance of optimal oral hygiene, Regular dental visits, noncariogenic diet For patients receiving radiation therapy - salivary gland exposure is limited by using Radiation stents, intensity-modulated radiotherapy (IMRT), image guided radiotherapy (IGRT), and use of amifostine. IMRT, IGRT shapes the radiation beams to closely fit the area where the cancer is, thereby reducing the exposure to adjacent important structures.

10. Amifostine is an sulfhydrol compound - act as oxygen scavenger that protect the salivary glands from free-radical damage during radiation therapy and promotes repair of damaged DNA. It has a broad spectrum of cyto -protective and radio-protective functions. It is reported to protect the salivary glands and reduce xerostomia during head and neck radiation therapy

11. Trade name – Ethyol Dosage: 200mg/m 2 administered daily as a 3 min IV infusion, starting 15-30 min prior to RT. 500mg with 2.5 mL normal saline administered subcutaneously in 1 or 2 injections once daily, 15 min prior to RT.

12. Side effects - Transient hypotension - nausea - vomiting - chills - fever - dizziness - hiccoughs Contraindications Sensitivity to aminothiol compounds Hypotension Dehydration

13. Mechanical stimulants - Eating foods which require mastication - Artificial Sweeteners Chemical stimulants - Mucopolysaccharide solutions containing Citric Acid Electrical stimulants (TENS) Artificial Salivary Substitutes a . Aqueous ionic solutions - Carboxymethyl cellulose - Mucin containing sol - Glycoprotein containing solutions b. Gel based substitutes Pharmacological stimulants

14. Symptomatic treatment - sipping water frequently – moisten, hydrate the oral mucosa, clear the debris from mouth - use of room humidifiers, - use of oral rinses, gels, mouth wash & artificial saliva, - a hydrating cream or ointment for dry lips, - saliva substitute placed in intraoral device. Artificial saliva mainly contains - carboxymethylcellulose - as lubricant - preservatives - chloride and flouride salts - variety of sweetners. Trade names: Wet mouth, GC dry mouth

15. Disadvantages : Their regular use is inconvenient to the patient More viscous than saliva Expensive Fail to provide antimicrobial and other protective functions of natural saliva.

16. 3. Salivary stimulation: Topical: – chewing sugar free gums and mints, citric acid containing lozenges – as chewing and taste will stimulate salivary flow effectively. Disadvantages: Effects are short lived Frequent application can be inconvenient Citric acid may irritate oral mucosa Continuous use may contribute to demineralization of teeth

17. Proposed systemic sialogogues Pilocarpine Cevimeline Bethanechol Anetholetrithione Guaifensin Bromhexine Neostigmine Yohimbine Potassium iodide Nicotinic acid Malic acid Vit A

18. Pilocarpine Hydrochloride Obtained from Pilocarpus Jaborandi plant Fox et al (1998), reported a clinical trial in primary Sjögren’s syndrome patients with pilocarpine - Subjective improvement of xerostomia - Improvement of parotid & submandibular flow rates First medication approved by FDA for the treatment of xerostomia in patients with SS

19. Parasympathetic agent Muscarinic agonist Causes pharmacological stimulation of exocrine glands Acts by stimulating functional salivary gland tissue Shown to be effective for patient’s with diminished salivation & who have some remaining secretory function Hence not much effective in patients with no remaining functional gland tissue

20. Indications: Mainly causes pupillary constriction & reduction of IOP Hence used in: Primary open angle glaucoma Angle closure glaucoma Oral dose: 5-10 mg 1 hr before eating T.I.D. or Q.I.D. Onset of action is 30 min Duration of action: 2-3 hrs

21. Contraindicated in patients: Gall bladder disease Narrow angle glaucoma Acute iritis Renal colic Risk to individuals with: Heart disease Asthma Angina pectoris Chronic bronchitis COPD History of MI

22. Side effects: Sweating Hot flushes Urinary frequency Diarrhea & Blurred vision

23. Cevimeline hydrochloride Cholinergic agonist Binds to Muscarinic receptors Stimulates remaining functional salivary gland tissue Binds more specifically to M 1 & M 3 receptors of salivary & lacrimal glands Because it specifically targets the salivary glands, side effects are less severe Hence better tolerated than Pilocarpine Approved by FDA for treatment of xerostomia in SS patients

24. Duration of secretogogue activity is longer than pilocarpine; but onset is slower It is under clinical trails for postradiotherapy xerostomia Dose: 30 mg t.i.d Reported peak blood conc. is 1.5-2 hrs Contraindications: Uncontrolled Asthma Narrow angle glaucoma Cardiac diseases ( alters cardiac conduction & heart rate)

25. Bethanechol chloride Cholinergic drug Used for: Urinary retention Neurogenic atony of bladder Stimulates Parasympathetic nervous system Dose: 10-25 mg 3-4 times daily Onset of action of GI effects is 30 min Duration of action is 1hr Tab. Urotone – 25mg Tab. Urotonin - 25mg

26. Contraindications: Bronchial asthma Hyperthyroidism Peptic ulcer disease Bradycardia Hypotension Mechanical obstruction of GI / Urinary tract Common cholinergic side effects: Sweating, GI upset, Miosis Decreased BP & reflex tachycardia Bronchial obstruction & Asthmatic attacks

27. Bromhexine Alkaloid derived from Adhatoda vasica Mucolytic agent Used for treatment of chronic bronchitis & COPD Acts by increasing quantity of secretions while decreasing their viscosity Does not appear to be an effective treatment for xerostomia (In clinical trials)

28. Mucolytic Agents Guaifensin & Potassium iodide: Used to treat respiratory infections Decrease the viscosity of saliva Improve the symptoms of oral dryness by improving flow through salivary ducts No controlled clinical trials have been demonstrated

29. DISEASE MODIFYING AGENTS Alpha Interferon Hydroxychloroquine NSAIDs Corticosteroids Methotrexate ALTERNATIVE MEDICINES Herbal medications Acupuncture therapy

30. Alpha interferon Alteration in salivary cytokines are seen in SS These abnormal salivary cytokine levels may contribute to progressive destruction of salivary gland tissue in SS Recombinant human alpha interferon may function as a biological response modifier Improves salivary gland function in autoimmune related xerostomia Clinical trials with weekly IM injections of alpha interferon demonstrated

31. Sialorrhea Sialorrhea is defined as an excessive secretion of saliva - BURKET’S

32. Causes for sialorrhea Medication Infant teething Secretory phase of menstruation Heavy metal poisoning Oraganophosphorous poisoning Nausea Gastro Esophageal Reflux Disease Obstructive esophagitis Neurologic & neuromuscular diseases Down syndrome

33. Management Depending upon etiology of sialorrhea 3 treatment modalities are present; Physical therapy Medications Surgical intervention

34. Physical therapy It can be used to improve neuromuscular control. Speech & swallowing therapy should be attempted prior to medical & surgical intervention. Patient cooperation is essential, so this therapy reported very low success rate.

35. Medications If patient is experienced sialorrhea secondary to pharmaceutical treatment, alternative medications should be evaluated, If therapeutic regimen cannot be altered, compatible xerostomic agents should be considered. Cholinergic muscarinic receptor antagonists can be used. Atropine sulfate can be advised.

36. Atropine: It is competitive antagonist of muscarinic agonist of Ach. - it does not prevent release of Ach, but antagonize effects on cells - this action results in drying of mouth through reduction of salivary gland secretion Shown to reduce amount of resting secretion, accumulation of pharyngeal-laryngeal pooling of saliva in 50% of pts. Onset of action: 30 – 60 mints; peaks in within 2hours can persists for 4hours. Dosage: o.4mg every 4-6hrs; children 0.01µg / kg body wt dose should exceeds 0.4mg / day

37. These drugs are contraindicated: - H/o cardiac problem, - closure glaucoma, - prostate hypertrophy, - asthma, - paralytic ileus / pyloric obstruction. Sublingual administered atropine reduces hypersalivation Other drugs: Scopolamine – 0.4 –0.6mg Methantheline – 50 – 100mg Propantheline – 15 – 30mg

38. Scopolamine - 3X more potent than atropine - Agent of choice when ANTISECRETORY EFFECT + SEDATION is required. Glycopyrrolate - 2X more potent than atropine - Agent of choice when ANTISECRETORY EFFECT without SEDATION is required.

39. Minimally invasive methods Injection of botulinum toxin A: BTX/A (7.5-15 units) is injected in the salivary gland it inhibit acetylcholine release mainly at neurosecretory junctions. It binds SNAP-25 protein forming a complex that impairs neuronal exocytosis by inhibiting fusion of the presynaptic vesicles containing the neurotransmitter. BTX / B displays better pharmacological properties than type A; documented success in Parkinson’s disease

40. References Burket's Oral Medicine 11 th Edition Salivary gland dysfunction: A review of systemic therapies - OOOE 2001;92:56-62. An update of etiology and management of xerostomia - OOOE 2004;97:28-46. Drooling of saliva: A review of etiology and management options - OOOE 2006;101:48-57.