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Transcript
Pharmacologically-Mediated
Salivary Dysfunction and the
Pharmacologic Management of
Salivary Diseases
Biology of Salivary Glands
Domenica G. Sweier DDS
June 6, 2001
Pharmacologically-Mediated
Salivary Gland Dysfunction
June 6, 2001
2
Oral Effects of Prescribed Drugs
RG Smith & AP Burtner, 1994
June 6, 2001
3
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
June 6, 2001
4
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
June 6, 2001
5
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
June 6, 2001
6
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
June 6, 2001
7
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
June 6, 2001
8
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
June 6, 2001
9
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
June 6, 2001
10
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
June 6, 2001
11
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
June 6, 2001
12
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
June 6, 2001
13
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
June 6, 2001
14
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
June 6, 2001
15
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
June 6, 2001
16
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
June 6, 2001
17
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
June 6, 2001
18
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
June 6, 2001
19
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
June 6, 2001
20
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
June 6, 2001
21
Pharmacologic Management of
Salivary Diseases
June 6, 2001
22
Salivary Gland Diseases
 Aging
 Medications
 Obstructions
• Neoplasms
• Foreign body
 Diseases
• Local
• Systemic
 Head and Neck Radiation
 Chemotherapy
June 6, 2001
23
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
June 6, 2001
24
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
June 6, 2001
 Mechanical plaque
removal
• Soft toothbrushes
• Moist gauze
• Toothettes good for
soft tissue cleansing
• Use mild toothpaste
and avoid alcoholcontaining products
 Interdental Aids
• Floss
• Proxy brush
25
Treatment Modalities: Outline
 Medication-induced
xerostomia
 Pain/Inflammation
• Stomatitis
• Mucositis
 Infection
• Bacterial
• Fungal
• Viral
June 6, 2001
 Hyposalivation
 Caries
 Special Cases
• Head and Neck
Radiation
• Chemotherapy
26
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
June 6, 2001
27
Pain and Inflammation
 Rinses
 Coating Agents
 Analgesics
June 6, 2001
28
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
June 6, 2001
29
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
June 6, 2001
30
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
June 6, 2001
31
Infection
 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
 Steroids
• Kenalog in Orabase
0.5%
• Temovate 0.05%
 Antibiotics
• Penicillin,
clindamycin,
amoxicillin,
cephalosporins
 Culture resistant
organisms
• Chlorhexidine
gluconate 0.12%
June 6, 2001
32
Caries
 Amputation 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
June 6, 2001
• 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
33
Hyposalivation: Substitutes
 Large Selection
• Mouthwashes,
toothpastes,
moisturizers, gums
 Poor patient
acceptance
• Feels like someone
else’s saliva
June 6, 2001
 “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
34
OTC Saliva Substitutes
Common OTC Saliva Substitutes
Product
Comments
Entertainer’s 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
June 6, 2001
35
Saliva Subs: Constituents
 Proteins
• Lactoferrin
 Coating Agents
• Carboxymethyl
cellulose
 Preservatives
• Preferably none
June 6, 2001
 Enzymes
• Lactoperoxidase
• Glucose Oxidase
• Lysozyme
 Flavorings
• Mint
• Citrus
• None
36
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
June 6, 2001
 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
37
Special Cases
 Head and Neck Radiation
 Chemotherapy
June 6, 2001
38
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
June 6, 2001
39
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
June 6, 2001
40
Radiation: During
 Weekly checks
 Monitor oral hygiene
• Reinforce techniques
 Monitor muscle
trismus
 Monitor salivary flow
• Salivary substitutes
• Salivary stimulation
June 6, 2001
 Address problems at
first sign
•
•
•
•
Mucositis/stomatitis
Candidiases
Cheilosis/cheilitis
Caries
 Supportive
• Encouragement
41
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
June 6, 2001
 Continue
• Fluoride trays
• Supportive salivary
therapy
• Monitor for fungal
infections
• Monitor for bacterial
infections
42
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
June 6, 2001
43
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
June 6, 2001
44
Chemotherapy: During
 Weekly checks
 Monitor oral hygiene
• Reinforce techniques
 Monitor
myelosuppresion
 Monitor salivary flow
• Salivary substitutes
• Salivary stimulation
June 6, 2001
 Address problems at
first sign
•
•
•
•
Mucositis/stomatitis
Candidiases
Cheilosis/cheilitis
Caries
 Supportive
• Encouragement
45
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
June 6, 2001
46
Summary
 PharmacologicallyMediated Salivary
Dysfunction
• Many medications
affect the oral cavity,
salivary function
specifically
• Xerostomia
• Seen mostly in elderly
June 6, 2001
 Pharmacologic
Management of
Salivary Disease
• Much morbidity
affecting quality of life
seen in salivary
dysfunction/disease
• Review techniques to
manage the morbidity
47