Pharmacologically-Mediated Salivary Dysfunction and the

Pharmacologic Management of Salivary Diseases

Biology of Salivary Glands

Domenica G. Sweier DDS

June 6, 2001

June 6, 2001 2

Pharmacologically-Mediated Salivary Gland Dysfunction

June 6, 2001 3

Oral Effects of Prescribed Drugs

RG Smith & AP Burtner, 1994RG Smith & AP Burtner, 1994

June 6, 2001 4

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 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

June 6, 2001 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

June 6, 2001 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

June 6, 2001 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

June 6, 2001 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

June 6, 2001 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

June 6, 2001 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

June 6, 2001 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

June 6, 2001 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

June 6, 2001 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

June 6, 2001 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• Akathisia-restlessness• Tardive dyskinesia-repetitive, involuntary

Examples include thorazine and levodopa

June 6, 2001 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

June 6, 2001 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

June 6, 2001 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

June 6, 2001 19

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 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

June 6, 2001 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

June 6, 2001 22

Pharmacologic Management of Salivary Diseases

June 6, 2001 23

Salivary Gland Diseases

Aging Medications Obstructions

• Neoplasms• Foreign body

Diseases• Local• Systemic

Head and Neck Radiation Chemotherapy

June 6, 2001 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

June 6, 2001 25

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

June 6, 2001 26

Treatment Modalities: Outline Medication-induced

xerostomia Pain/Inflammation

• Stomatitis• Mucositis

Infection• Bacterial• Fungal• Viral

Hyposalivation Caries Special Cases

• Head and Neck Radiation

• Chemotherapy

June 6, 2001 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

June 6, 2001 28

Pain and Inflammation

Rinses Coating Agents Analgesics

June 6, 2001 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

June 6, 2001 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

June 6, 2001 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

June 6, 2001 32

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 33

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

June 6, 2001 34

Hyposalivation: Substitutes

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

June 6, 2001 35

OTC Saliva SubstitutesCommon 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 36

Saliva Subs: Constituents

Proteins• Lactoferrin

Coating Agents• Carboxymethyl

cellulose

Preservatives• Preferably none

Enzymes• Lactoperoxidase

• Glucose Oxidase

• Lysozyme

Flavorings• Mint

• Citrus

• None

June 6, 2001 37

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

June 6, 2001 38

Special Cases

Head and Neck Radiation Chemotherapy

June 6, 2001 39

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 40

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 41

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

June 6, 2001 42

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

June 6, 2001 43

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 44

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 45

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

June 6, 2001 46

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 47

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