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 6, 2001

2
Pharmacologically-Mediated Salivary Gland
Dysfunction
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Oral Effects of Prescribed Drugs
RG Smith AP Burtner, 1994
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Oral Manifestations of Systemic Agents

• 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

ADA Guide to Dental Therapeutics, 1998
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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

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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

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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

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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

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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

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Leukopenia and Neutropenia

• Alteration of a persons 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

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Lichenoid Lesions

• Buccal mucosa and lateral border of tongue most
  often
• Wickhams 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

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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
• Akathisia-restlessness
• Tardive dyskinesia-repetitive, involuntary
• Examples include thorazine and levodopa

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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

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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

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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

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Xerostomia

• 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

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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
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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
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Pharmacologic Management of Salivary Diseases
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Salivary Gland Diseases

• Aging
• Medications
• Obstructions
• Neoplasms
• Foreign body
• Diseases
• Local
• Systemic
• Head and Neck Radiation
• Chemotherapy

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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

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Oral Hygiene

• 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

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Treatment Modalities Outline

• Medication-induced xerostomia
• Pain/Inflammation
• Stomatitis
• Mucositis
• Infection
• Bacterial
• Fungal
• Viral

• Hyposalivation
• Caries
• Special Cases
• Head and Neck Radiation
• Chemotherapy

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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

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Pain and Inflammation

• Rinses
• Coating Agents
• Analgesics

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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 11 in water or saline
  1-2 days maximum
• Particularly useful to debride ulcerated/crusted
  area

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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

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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

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Infection

• Steroids
• Kenalog in Orabase 0.5
• Temovate 0.05
• Antibiotics
• Penicillin, clindamycin, amoxicillin,
  cephalosporins
• Culture resistant organisms
• Chlorhexidine gluconate 0.12

• Antifungals
• Nystatin 100,000 units/ml
• Clotrimazole troches 10mg
• When a removable prosthesis is worn, be sure to
  treat is as well diulte bleach solution works
  well

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Caries

• 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

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Hyposalivation Substitutes

• Large Selection
• Mouthwashes, toothpastes, moisturizers, gums
• Poor patient acceptance
• Feels like someone elses 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

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OTC Saliva Substitutes
Common OTC Saliva Substitutes Common OTC Saliva Substitutes
Product Comments
Entertainers Secret 60 ml spray
Glandosane Preservative- free? 50 ml spray Unflavored, lemon, mint
Moi-Stir Swabsticks Packets of three
Mouthkote 5, 60, 240 ml solution Citrus flavor
Optimoist 60, 355 ml spray Fluoride
Oralbalance, biotène Preservative-free? Gel Unflavored
Salive Substitute (Roxane) Preservative-free 5, 120 ml vials
Salivart Preservative-free 25, 75 ml spray Unflavored
Salix 100 count lozenges
Sodium carboxymethyl cellulose 0.5 solution, 8 oz rinse
Sterile Water Sip as needed
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Saliva Subs Constituents

• Proteins
• Lactoferrin
• Coating Agents
• Carboxymethyl cellulose
• Preservatives
• Preferably none

• Enzymes
• Lactoperoxidase
• Glucose Oxidase
• Lysozyme
• Flavorings
• Mint
• Citrus
• None

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Hyposalivation Stimulation

• Gustatory
• Sugarless hard candies
• Avoid citric candies since they may irritate
  mucositis and promote acidic destruction of tooth
  structure
• Mechanical
• Sugarless chewing gums

• Pharmacological
• Pilocarpine HCl, marketed under the brand name
  Salagen
• 5mg tablets, one three to four times daily
• Titrate up to two tablets per dose, not to exceed
  30mg daily dose
• Lowest dose effective and tolerated is recommended

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Special Cases

• Head and Neck Radiation
• Chemotherapy

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Radiation Pre-Therapy

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

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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 blades
• Educate on signs/symptoms of disease

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Radiation During

• Weekly checks
• Monitor oral hygiene
• Reinforce techniques
• Monitor muscle trismus
• Monitor salivary flow
• Salivary substitutes
• Salivary stimulation

• Address problems at first sign
• Mucositis/stomatitis
• Candidiases
• Cheilosis/cheilitis
• Caries
• Supportive
• Encouragement

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Radiation After

• 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

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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

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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

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Chemotherapy During

• 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

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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

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Summary

• 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