Pharmacologically-Mediated Salivary Dysfunction and the Pharmacologic Management of Salivary Diseases

1. Pharmacologically-Mediated Salivary Dysfunction and the Pharmacologic Management of Salivary Diseases Biology of Salivary Glands Domenica G. Sweier DDS June 9, 2003

2. Pharmacologically-Mediated Salivary Gland Dysfunction

3. Oral Effects of Prescribed Drugs RG Smith & AP Burtner, 1994

4. Abnormal hemostasis Altered host resistance Angioedema Coated (black hairy) tongue Dry socket Dysgeusia Erythema multiforme Gingival enlargement Leukopenia and neutropenia Lichenoid lesions Movement disorders Soft-tissue reactions Salivary gland enlargement Sialorrhea Xerostomia Oral Manifestations of Systemic Agents ADA Guide to Dental Therapeutics, 1998

5. Abnormal Hemostasis • Interfere with platelet function • Decrease prothrombin synthesis in the liver • Require bleeding profile prior to dental procedures • Oral cavity very vascular, need to be sure bleeding profile is conducive to invasive treatment • Examples include coumadin and aspirin

6. Altered Host Resistance • Results from alteration in normal oral microflora leading to an overgrowth of organisms found as normal oral flora • Eliminate or replace drug, if possible, and administer antifungal agents if candidiasis has developed • Caused by broad-spectrum antibiotics, corticosteroids, cancer chemotherapeutics, among others

7. Angioedema • Drug induced hypersensitivity involving mucosal and submucosal layers of upper GI tract • Mild cases treated with antihistamines • Severe cases may be life threatening when the airway is compromised; emergency treatment to restore airway • Has been reported with use of ACE inhibitors, midazolam, ketoconazole

8. Coated Tongue • The most common is Black Hairy Tongue • Usually black, may be shades of brown • Hypertrophy of filiform papillae • Mechanism unknown • Asymptomatic • No treatment indicated • Examples include clonazepam, ketoprofen, tetracycline

9. Dry Socket • Alveolar Osteitis • Lysis of blood clot prior to it being replaced by granulation tissue • Higher incidence in those who smoke and females using BCPs • Preventative and palliative treatment • Do surgery in days 23-28 of BCP cycle

10. Dysgeusia • Taste alteration, medication or metallic taste, changes and distate for food • Exact mechanism unknown; however, may be interaction of medication with trace metal ions which interact with cell membranes of taste pores • May have other causes, imperative to confirm it is drug induced • No treatment • Examples include iron, metronidazole

11. Erythema Multiforme • May be immunologic reaction mediated by deposition of An-Ab complexes in tissues • Symmetrical mucocutaneous lesions with a predilection for oral mucosa, hands and feet • Tongue and lips most involved • Initial presentation as erythema with vesicles and erosions developing within hours. • Normally self-limiting • Oral lesions heal without scars • Examples include clindamycin and pentobarbital

12. Gingival Enlargement • Clinically appears as a diffuse swelling of interdental papillae which coalesces into a nodular topography • Theory of direct affect of drug or metabolite on fibroblast which produces proteins and collagen • Oral hygiene, mouth breathing, and crowded teeth may exacerbate condition • Examples include dilantin, cyclosporin

13. Leukopenia and Neutropenia • Alteration of a person’s hematopoietic status • Manifested by increased infections, ulcerations, nonspecific inflammation, bleeding gingiva and increased bleeding after a dental procedure • Replace or remove drug if possible • Examples include chloramphenicol and quinine

14. Lichenoid Lesions • Buccal mucosa and lateral border of tongue most often • Wickham’s striae • Pain after ulcerations develop • Differ from Lichen Planus in that the drug induced lesions disappear after the drug is removed • Examples include furosemide and methyldopa

15. Movement Disorders • Neuroleptic drugs affect muscles of facial expression and mastication • Once developed, hard to control and is irreversible • Difficult to eat, communicate, and wear prostheses • Movements include: • Pseudoparkinsonism-rigidity, tremor • Akathesia-restlessness • Tardive dyskinesia-repetitive, involuntary • Examples include thorazine and levodopa

16. Soft Tissue Reactions • Include discoloration, ulcerations, stomatitis, glossitis, and pigmentation • A variety of mechanisms • Examples include • Coumadin-ulcerations • Accutane-glossitis • Meprobamate-stomatitis • Minocycline-discoloration • Mercury-pigmentation

17. Salivary Gland Involvement • Appear as salivary gland swelling and pain, may mimic mumps • Differential diagnosis includes more serious conditions, accurate diagnosis important • Mechanism unknown • Treat by removing or replacing drug, if possible • Examples include methyldopa and lithium

18. Sialorrhea • An increase in salivation • An increase in cholinergic stimulation by direct stimulation of parasympathetic receptors • Example: pilocarpine HCl • An inhibition of cholinesterase • Example: neostigmine

19. May be a result of another condition, must determine cause Often reported side effect of many drugs Increased reported effect with prolonged use of drugs and when multiple drugs are used Most often in elderly where there is an increase in drug use Xerostomia

20. Xerostomic Medications • Anticholinergics • Antihistamines • Antidepressants, antipsychotics • Sedative and hypnotic agents • Antihypertensives • Antiparkinson agents • Problem: • While xerostomia is often listed as a side effect, few clinical trials and studies have definitively established this relationship and/or investigated the mechanisms Sreebny and Schwartz, Gerodontology 1997

21. Given the many drugs that can induce salivary gland hypofunction, manifested as xerostomia, and the variety of other causes for this condition, it is imperative that a differential diagnosis be formulated and an accurate cause be determined

22. Pharmacologic Management of Salivary Diseases

23. Salivary Gland Diseases • Aging • Medications • Obstructions • Neoplasms • Foreign body • Diseases • Local • Systemic • Head and Neck Radiation • Chemotherapy

24. In General • Encourage patient to visit the dentist regularly • Address problems when they first appear • Encourage meticulous oral hygiene • Encourage the patient to stay well-nourished and well-hydrated • Keep an updated list of all medications the patient is taking (Rx, OTC, regularly or not) • Update the medical history often • Keep in communication with physicians and other health care providers, consult when needed

25. Rinse/wipe oral cavity and associated structures after every meal Rinse/wipe any removable prosthesis Denture brush Remove at night and between meals Anti-fungal soak Mechanical plaque removal Soft toothbrushes Moist gauze Toothettes good for soft tissue cleansing Use mild toothpaste and avoid alcohol-containing products Interdental Aids Floss Proxy brush Oral Hygiene

26. Medication-induced xerostomia Pain/Inflammation Stomatitis Mucositis Infection Bacterial Fungal Viral Hyposalivation Caries Special Cases Head and Neck Radiation Chemotherapy Treatment Modalities: Outline

27. Medication-Induced Xerostomia • Associated more with certain types of medications • Incidence increases with prolonged use and polypharmacy • Increased incidence among elderly • Use of medications and more of them simultaneously: prescription and OTC • Treatment • Replace medication • Alter dose • Alter administration times • Treat xerostomia and associated symptoms

28. Pain and Inflammation • Rinses • Coating Agents • Analgesics

29. Pain/Inflammation: Rinses • Goals • Cleanse • Moisturize • Lubricate • Preparations • Salt and soda (1/2 tsp each in 8 oz warm water) every 2 hours • Salt or soda (1 tsp one or other in 8 oz warm water) every 2 hours • Hydrogen peroxide diluted 1:1 in water or saline; 1-2 days maximum • Particularly useful to debride ulcerated/crusted area

30. Pain/Inflammation: Coating Agents • Goals • Sustained moisturizing and lubricating • Water soluble lubricating jelly • Diclonine hydrochloride 0.5-1.0% • Carbamide peroxide 10% • Home preps • Milk of magnesia • Kaolin with pectin suspension • Avoid preparations containing glycerin • Hygroscopic

31. Pain/Inflammation: Analgesics • Topical Analgesics • Lidocaine 2% viscous • Benadryl 12.5mg/5ml kaopectate • Capsiacin* • Systemic Analgesics • Ibuprofen • Opioids • Be aware of agents that cause GI distress and alter hemostasis

32. Antifungals Nystatin 100,000 units/ml Clotrimazole troches 10mg When a removable prosthesis is worn, be sure to treat is as well: dilute bleach solution works well Steroids Kenalog in Orabase 0.5% Temovate 0.05% Antibiotics Penicillin, clindamycin, amoxicillin, cephalosporins Culture resistant organisms Chlorhexidine gluconate 0.12% Infection

33. Prevention Chlorhexidine gluconate 0.12% Fluorides as rinse or applied via custom trays Stannous fluoride gel 0.4% Sodium fluoride gel 1.0%, 1.1% Act, Fluorigard rinse OTC fluoride Amputation Caries Circumferential decay at or below the CEJ compromising the integrity of the tooth Treatment Restore with amalgam or fluoride-containing and -leaching glass ionomers and other restoratives Caries

34. Large Selection Mouthwashes, toothpastes, moisturizers, gums Poor patient acceptance Feels like someone else’s saliva “Home” Remedy Best Tolerated Frequents sips of water Ice Chips Avoid larger ice cubes since the larger surface may actually stick to the dry mucosa Hyposalivation: Substitutes

35. OTC Saliva Substitutes

36. Proteins Lactoferrin Coating Agents Carboxymethyl cellulose Preservatives Preferably none Enzymes Lactoperoxidase Glucose Oxidase Lysozyme Flavorings Mint Citrus None Saliva Subs: Constituents

37. Gustatory Sugarless hard candies Avoid citric candies since they may irritate mucositis and promote acidic destruction of tooth structure Mechanical Sugarless chewing gums Hyposalivation: Stimulation

38. Salagen® Pilocarpine HCl 5mg tablets, one three to four times daily Titrate up to two tablets per dose, not to exceed 30mg daily dose Muscarinic agonist Targeted for Sjögren’s Syndrome EvoxacTM Cevimeline HCL 30mg taken three times per day Insufficient evidence for higher or more frequent dosing Muscarinic agonist Targeted for Sjögren’s Syndrome Hyposalivation: Pharmacologic Stimulation

39. Special Cases • Head and Neck Radiation • Chemotherapy

40. Radiation: Pre-Therapy • Referral from Physician for consult • Thorough Medical history including medications • Obtain plan of (surgery and) radiation including field(s), amount, duration • Complete dental exam, x-rays, and treatment planning

41. Radiation: Dental Treatment • Complete all invasive treatment 10-14 days prior to radiation • When in doubt  extract • Fabricate fluoride trays, provide Rx • Use cotton-tipped applicators if needed • Instruction on diet, hydration, oral hygiene • Instruct on exercises using tongue depressors • Educate on signs/symptoms of disease

42. Weekly checks Monitor oral hygiene Reinforce techniques Monitor muscle trismus Monitor salivary flow Salivary substitutes Salivary stimulation Address problems at first sign Mucositis/stomatitis Candidiasis Cheilosis/cheilitis Caries Supportive Encouragement Radiation: During

43. Place Patient on 3 month recall or less Avoid any invasive therapy if at all possible Tissues will not heal as quickly Wait at least 6 mos prior to construction removable prosthesis Continue Fluoride trays Supportive salivary therapy Monitor for fungal infections Monitor for bacterial infections Radiation: After

44. Chemotherapy: Pre-Therapy • Referral from Physician for consult • Thorough Medical history including medications • Obtain plan of therapy, which drugs, amount, duration • Determine timing of myelosuppresion • Complete dental exam, x-rays, and treatment planning

45. Chemotherapy: Dental Treatment • Complete all invasive treatment 10-14 days prior to chemotherapy • Avoid periodontal and endodontic surgery • Any surgery with active soft tissue disease--extract • Fabricate fluoride trays, provide Rx • Instruction on diet, hydration, oral hygiene • Educate on signs/symptoms of disease

46. Weekly checks Monitor oral hygiene Reinforce techniques Monitor myelosuppresion Monitor salivary flow Salivary substitutes Salivary stimulation Address problems at first sign Mucositis/stomatitis Candidiases Cheilosis/cheilitis Caries Supportive Encouragement Chemotherapy: During

47. Chemotherapy: After • Allow tissues to heal when chemotherapy completed • This varies with the drug(s) used • May return to pre-chemotherapy recall interval • Treatment plan and provide dental treatment per pre-chemotherapy

48. Pharmacologically-Mediated Salivary Dysfunction Many medications affect the oral cavity, salivary function specifically Xerostomia Seen mostly in elderly Pharmacologic Management of Salivary Disease Much morbidity affecting quality of life seen in salivary dysfunction/disease Review techniques to manage the morbidity Summary