COURSE TITLE:
Commonly Prescribed Medications and
Managing the Oral Side Effects of Medication Use
COURSE INSTRUCTOR: Ann Eshenaur Spolarich, RDH, PhD
COURSE CREDITS:
3 Hours
COURSE DATE:
October 10, 2009
_____________________________________________________________________________
COURSE DESCRIPTION:
The purpose of this course is to review the 20 most commonly prescribed medications taken by
clients treated in the oral health care environment. In addition, drug interactions, popular drugs
in the media and new drugs in dentistry will be discussed. A comprehensive review of drugs and
dental care products used to manage the oral side effects of medications will be presented,
including an update on fluoride products and products for remineralization.
LEARNING OBJECTIVES:
Upon completion of this continuing education course, the participant will be able to:
1.
Identify and discuss commonly prescribed medications taken by clients treated in the oral
health care setting.
2.
Identify common drug interactions of significance to dental professionals.
3.
State the current American Heart Association guidelines for antibiotic premedication.
4.
Discuss new research findings that impact current recommendations for antibiotic
premedication.
5.
List several new dental drugs and discuss their indications for use in practice.
6.
Discuss the management of oral side effects caused by medications.
7.
Review common indications for fluoride therapy, and available fluoride products.
*This material may not be reproduced without the written permission of the author.
1
TOP 20 MOST COMMONLY PRESCRIBED MEDS
2008
(Total Prescriptions Dispensed)
1.
BRAND NAME: Co-Gesic, hycet, Lorcet, Lortab, Margesic, Maxidone, Norco, Stagesic, Vicodin,
Xodol, Zamicet, Zydone
GENERIC NAME: HYCD/APAP (hydrocodone with acetaminophen)
THERAPEUTIC CATEGORY: opioid analgesic
USE: post-operative pain control
ORAL COMPLICATIONS: xerostomia (rare)
DRUG INTERACTIONS: Concurrent use of hydrocodone with MAO inhibitors (Nardil, Parnate,
Marplan), tricyclic antidepressants (Elavil) and general anesthetics potentiates the effects of the
hydrocodone, and increases the risk for toxicity. Dextroamphetamine enhances the analgesic effect of
the hydrocodone. Additive CNS effects may occur when taking hydrocodone with other narcotics,
antipsychotics, antianxiety agents, general anesthetics and other CNS depressants (eg. alcohol).
Phenothiazines (eg. Thorazine) may decrease the analgesic effect of hydrocodone. Acetaminophen taken
with alcohol, barbituates or carbamazepine (Tegretol) increases the risk for liver toxicity. Chronic use of
acetaminophen may significantly enhance the anticoagulation effects of warfarin (Coumadin).
2.
BRAND NAME: Prinivil, Zestril
GENERIC NAME: lisinopril
THERAPEUTIC CATEGORY: ACE inhibitor
USE: hypertension, adjunctive therapy for congestive heart failure, post-MI if hemodynamically stable
ORAL COMPLICATIONS: xerostomia, dry cough, angioedema
DRUG INTERACTIONS: Increased risk for hypotension with alcohol, phenothiazines
(antipsychotics)and probenecid. ACE inhibitors increase serum concentrations of digoxin, lithium and
sulfonylureas (oral hypoglycemics). Increased risk for toxicity with potassium or potassium-sparing
diuretics. Diuretics have additive hypotensive effects when used with ACE inhibitors. Caution when
using NSAIDS in patients with compromised renal function who are taking ACE inhibitors. NSAIDS,
including high dose aspirin, may decrease the antihypertensive effects of ACE inhibitors. Antacids
decrease the bioavailability of ACE inhibitors.
3.
BRAND NAME: Zocor
GENERIC NAME: simvastatin
THERAPEUTIC CATEGORY: HMG-CoA reductase inhibitor
USE: hypercholesterolemia
ORAL COMPLICATIONS: taste alteration
DRUG INTERACTIONS: The risk for myopathy/rhabdomyolysis is increased with concurrent use of the
macrolide antibiotics clarithromycin and erythromycin, and the azole antifungal agents fluconazole,
itraconazole and ketoconazole. Risk for rhabdomyolysis also may be increased with concurrent use of
other lipid lowering agents, cyclosporoine, certain calcium channel blockers and protease inhibitors.
The anticoagulant effect of warfarin may be increased by simvastatin.
2
4.
BRAND NAME: Synthroid
GENERIC NAME: levothyroxine
THERAPEUTIC CATEGORY: hormone
USE: hypothyroidism
ORAL COMPLICATIONS: none
DRUG INTERACTIONS: Levothyroxine increases the effects of oral anticoagulants (Coumadin),
causing an increased risk of bleeding. When taken together, toxicity may occur for both levothyroxine
and tricyclic antidepressants (Elavil). Antacids containing aluminum and magnesium, iron, bile acid
sequestrants (colestipol, cholestyramine), and the ulcer medication sucralfate (Carafate) decrease the
absorption of levothyroxine. Certain seizure medications (phenytoin, phenobarbitol and carbamazepine)
and the TB medication rifampin (Rifadin) decrease levothyroxine levels. Levothyroxine may decrease
the effect of oral sulfonylureas.
5.
BRAND NAME: Amoxil, Moxatag
GENERIC NAME: amoxicillin
THERAPEUTIC CATEGORY: antibiotic
USE: infections of ear, skin, respiratory and urinary tracts; premedication
ORAL COMPLICATIONS: oral candidiasis and black hairy tongue
DRUG INTERACTIONS: Concomitant use of amoxicillin and erythromycin or amoxicillin and
tetracycline is contraindicated. Amoxicillin may decrease the efficacy of oral contraceptives; therefore,
patients should be instructed to use an alternative form of birth control while taking this antibiotic.
Disulfiram (Antabuse), used to treat alcoholism, and the uric acid lowering agent probenecid (Benemid)
cause increased levels of amoxicillin The effects of warfarin may be increased.
6.
BRAND NAME: AzaSite, Zithromax, Zmax
GENERIC NAME: azithromycin
THERAPEUTIC CATEGORY: macrolide antibiotic
USE: orofacial and respiratory tract infections; middle ear infections, pharyngitis, strep throat, tonsillitis,
pneumonia; premedication
ORAL COMPLICATIONS: none
DRUG INTERACTIONS: Antacids containing aluminum or magnesium (Maalox, Mylanta) should not
be taken with azithromycin, as antacids decrease serum levels of the drug. Two hours should lapse prior
to taking azithromycin following the use of an antacid. As with erythromycin, azithromycin interacts
with many drugs, and may increase the levels of some antihistamines (Hismanal), cyclosporine
(Sandimmune), carbamazepine (Tegretol), digoxin (Lanoxin), phenytoin (Dilantin), triazolam (Halcion),
warfarin (Coumadin) and antiasthmatic drugs containing theophylline. Concomitant use of the macrolide
antibiotics with the HMG Co-A reductase inhibitors increases the risk for rhabdomyolysis. Antibiotics
decrease the effectiveness of oral contraceptives.
3
7.
BRAND NAME: Lipitor
GENERIC NAME: atorvastatin
THERAPEUTIC CATEGORY: HMG-CoA reductase inhibitor
USE: hypercholesterolemia
ORAL COMPLICATIONS: none
DRUG INTERACTIONS: The risk for myopathy/rhabdomyolysis is increased with concurrent use of the
macrolide antibiotics clarithromycin and erythromycin, and the azole antifungal agents fluconazole
(Diflucan), itraconazole (Sporanox) and ketoconazole (Nizoral). Risk for rhabdomyolysis also may be
increased with concurrent use of other lipid lowering agents, cyclosporoine, certain calcium channel
blockers (diltiazem (Cardizem), verapamil (Calan)) and protease inhibitors. Atorvastatin may also
increase the effect of levothyroxine (Synthroid).
8.
BRAND NAME: Aquazide H, Microzide, Oretic
GENERIC NAME: hydrochlorothiazide
THERAPEUTIC CATEGORY: thiazide diuretic
USE: mild to moderate hypertension; edema with congestive heart failure and nephrotic syndrome
ORAL COMPLICATIONS: xerostomia, lichenoid reaction; photosensitivity
DRUG INTERACTIONS: NSAIDs decrease the antihypertensive effects of HCTZ. HCTZ may decrease
the effects of oral hypoglycemic agents. Absorption of HCTZ is decreased with the concurrent use of the
bile acid sequestrants (cholesterol lowering agents). Increased effect of HCTZ with concomitant use of
loop diuretics. Hypotension may occur when used with ACE inhibitors. Beta blockers increase
hyperglycemic effects of thiazides in Type 2 diabetics. Potential for toxicity reactions when HCTZ is
used with cyclosporine (renal toxicity), digoxin (digoxin toxicity) or lithium (lithium toxicity). Thiazides
prolong the duration of action of neuromuscular blocking agents.
9.
BRAND NAME: Alprazolam Intensol, Xanax
GENERIC NAME: alprazolam
THERAPEUTIC CATEGORY: benzodiazepine
USE: anxiety disorder, panic disorder, anxiety associated with depression
ORAL COMPLICATIONS: xerostomia
DRUG INTERACTIONS: Increased sedative effects seen with other CNS depressants, including
narcotics, barbiturates, phenothiazines (antipsychotics), antihistamines, MAO inhibitors, sedativehypnotic drugs, cyclic antidepressants and alcohol. Increased serum levels of alprazolam occur with
ciprofloxacin, macrolide antibiotics (eg. erythromycin), cimetidine (Tagamet), disulfiram, digoxin,
ethanol, systemic azole antifungal agents (eg. ketoconazole), metronidazole, miconazole, antiviral agents
(protease inhibitors) for HIV. Decreased effects seen with carbamazepine (Tegretol), rifampin, cigarette
smoking and phenobarbital. Contraindicated with ketoconazole, itraconazole, ritonavir, indinavir. Avoid
drinking alcohol with benzodiazepines.
4
10.
BRAND NAME: Tenormin
GENERIC NAME: atenolol
THERAPEUTIC CATEGORY: cardioselective beta blocker; antianginal
USE: hypertension, angina, post-myocardial infarction; unlabeled use: acute alcohol withdrawal,
ventricular arrhythmias, migraine headache prophylaxis
ORAL COMPLICATIONS: xerostomia
DRUG INTERACTIONS: NSAIDS reduce the hypotensive effects of beta blockers when used for
greater than 3 weeks. The penicillins (ampicillin), salicylates, barbiturates, bile acid sequestrants,
rifampin, and aluminum and calcium salts decrease the effects of atenolol. Beta blockers may increase
the effects of ethanol, which increases the risk for hypotension and/or dizziness. Atenolol may mask the
tachycardia from hypoglycemia caused by insulin or oral hypoglycemics. When receiving concurrent
therapy, the risk of hypertensive crisis increases when either clonidine (used to manage diabetesassociated diarrhea) or the beta blocker is withdrawn. Beta blockers decrease the effect of sulfonylureas.
Beta blockers increase the effects of other drugs that slow AV conduction (digoxin, verapamil,
diltiazem), alpha-blockers, and alpha adrenergic stimulants (eg. epinephrine). Epinephrine can be used
safely (lowest dose, least concentration).
11.
BRAND NAME: Fortamet, Glucophage, Glucophage XR, Riomet
GENERIC NAME: metformin
THERAPEUTIC CATEGORY: oral hypoglycemic, biguanide
USE: management of non-insulin dependent diabetes mellitus (type II)
ORAL COMPLICATIONS: vomiting, taste alteration
DRUG INTERACTIONS: Multiple drug interactions: drugs that decrease the effects of metformin
include diuretics, corticosteroids, phenothiazines, thyroid medications, estrogens, oral contraceptives,
phenytoin (Dilantin), nicotinic acid, sympathomimetics, calcium channel blockers and isoniazid
(antitubercular agent); these drugs produce hyperglycemia and lead to loss of glucose control.
Furosemide (Lasix) and cimetidine (Tagamet) increase metformin serum concentrations. Increased
metformin levels are seen with the diuretics amiloride (Midamor) and triamterene (Dyrenium); digoxin
(Lanoxin), morphine, the antiarrhythmics procainamide (Procanbid) and quinidine (Cardioquin); the
muscle relaxant quinine (Legatrin); ranitidine (Zantac), and the antibiotics trimethoprim (Trimpex) and
vancomycin. Avoid or limit alcohol.
5
12.
BRAND NAME: Toprol-XL
GENERIC NAME: metoprolol succinate
THERAPEUTIC CATEGORY: cardioselective beta blocker
USE: hypertension, angina, prevention of MI, atrial fibrillation; investigational for ventricular
arrhythmias, migraines, essential tremors, aggressive behavior
ORAL COMPLICATIONS: xerostomia
DRUG INTERACTIONS: Metoprolol may increase the effects of other drugs that slow AV conduction,
alpha-blockers and alpha-adrenergic stimulants (eg. epinephrine). Epinephrine is safe to use in patients
taking cardioselective beta blockers (lowest dose, least concentration). NSAIDS (ibuprofen,
indomethacin) used for greater than 3 weeks can decrease the antihypertensive effects of the drug. The
effects of beta blockers are decreased with aluminum salts, calcium salts, barbituates, bile acid
sequestrants (cholesterol-lowering drugs), NSAIDS, penicillins, rifampin and salicylates. Beta blockers
may decrease the effects of sulfonylureas (oral hypoglycemics), and may slow the metabolism of
lidocaine. Increased hypotension and bradycardia may be observed with concurrent use of inhaled
anesthetics and fentanyl derivatives.
13.
BRAND NAME: Lasix
GENERIC NAME: furosemide
THERAPEUTIC CATEGORY: loop diuretic
USE: management of edema associated with congestive heart failure and/or hepatic/renal disease,
hypertension
ORAL COMPLICATIONS: vomiting, oral irritation, xerostomia, lichenoid drug reaction
DRUG INTERACTIONS: Avoid use in patients with hypersensitivity to sulfonamides. Ototoxicity is
associated with rapid IV administration, renal impairment, excessive doses and concurrent use of other
ototoxins (aminoglycosides, cis-platinum). Concurrent use of corticosteroids may increase electrolyte
imbalance. Hypotensive effects and adverse renal effects of ACE inhibitors and NSAIDS are potentiated
by furosemide-induced hypovolemia. Increased risk for arrhythmias with some quinolone antibiotics.
Furosemide increases the risk of toxicity from lithium and high dose salicylates. NSAIDS, aspirin,
phenobarbital, phenytoin, bile acid sequestrants and sucralfate reduce the effects of furosemide. Glucose
tolerance may be decreased by furosemide. Metformin decreases furosemide concentrations.
14.
BRAND NAME: Lopressor, Toprol
GENERIC NAME: metoprolol
THERAPEUTIC CATEGORY: cardioselective beta blocker
USE: hypertension, angina, prevention of MI, atrial fibrillation; investigational for ventricular
arrhythmias, migraines, essential tremors, aggressive behavior
ORAL COMPLICATIONS: xerostomia
DRUG INTERACTIONS: Metoprolol may increase the effects of other drugs that slow AV conduction,
alpha-blockers and alpha-adrenergic stimulants (eg. epinephrine). Epinephrine is safe to use in patients
taking cardioselective beta blockers (lowest dose, least concentration). NSAIDS (ibuprofen,
indomethacin) used for greater than 3 weeks can decrease the antihypertensive effects of the drug. The
effects of beta blockers are decreased with aluminum salts, calcium salts, barbituates, bile acid
sequestrants (cholesterol-lowering drugs), NSAIDS, penicillins, rifampin and salicylates. Beta blockers
may decrease the effects of sulfonylureas (oral hypoglycemics), and may slow the metabolism of
lidocaine. Increased hypotension and bradycardia may be observed with concurrent use of inhaled
anesthetics and fentanyl derivatives.
6
15.
BRAND NAME: Zoloft
GENERIC NAME: sertraline
THERAPEUTIC CATEGORY: selective serotonin reuptake inhibitors
USE: antidepressant; obsessive-compulsive disorder, panic attacks, post-traumatic stress
syndrome
ORAL COMPLICATIONS: xerostomia, taste alteration, bruxism
DRUG INTERACTIONS: SSRIs decrease the liver metabolism of many drugs due to their inhibition of
the cytochrome P450 enzyme system. Sertraline is contraindicated with MAO inhibitors (Marplan,
Nardil, Parnate). Risk for serotonin syndrome increases when SSRIs are combined with many drugs,
including amphetamines, serotonin agonists, sympathomimetics, meperidine (Demerol) and other SSRIs.
Sertraline may increase the serum concentrations of benzodiazepines, cabamazepine, clozapine,
cyclosporine, digoxin, haloperidol, HMG-CoA reductase inhibitors, phenytoin, trazodone, tricyclic
antidepressants and valproic acid. Concurrent use with lithium increases the risk for nephrotoxicity.
Risk for hyponatremia increases with concurrent use of loop diuretics (eg. furosemide). Sertraline
increases the effects of warfarin (Coumadin). Sertraline inhibits the metabolism of the phenothiazines,
resulting in increased plasma concentration and increased risk for prolonged QT interval, leading to
serious arrhythmias. Combined use of SSRIs with sumatriptan (Imitrex) or other serotonin agonists may
result in toxicity.
16.
BRAND NAME: Prilosec (OTC), Prilosec
GENERIC NAME: omeprazole
THERAPEUTIC CATEGORY: proton pump inhibitor
USE: short-term treatment of active duodenal ulcer disease; treatment of heartburn and GERD; shortterm treatment and maintenance healing of erosive esophagitis; long-term treatment of pathological
hypersecretory conditions
ORAL COMPLICATIONS: xerostomia, taste alteration, esophageal candidiasis, mucosal atrophy of the
tongue
DRUG INTERACTIONS: Omeprazole may increase the levels of some benzodiazepines (diazepam,
midazolam, triazolam). The level of omeprazole may be increased by concurrent use with systemic azole
antifungals (ketoconazole, fluconazole). Omeprazole may decrease the levels of clopidogrel (Plavix),
itraconazole, and ketoconazole. Drug absorption is significantly decreased by food – take on an empty
stomach before breakfast; avoid the use of alcohol, as it may cause gastric mucosal irritation.
17.
BRAND NAME: Ambien. Edluar, Zolpimist
GENERIC NAME: zolpidem
THERAPEUTIC CATEGORY: hypnotic, nonbenzodiazepine
USE: short-term treatment of insomnia
ORAL COMPLICATIONS: xerostomia
DRUG INTERACTIONS: Concurrent use with other centrally-acting drugs may produce an additive
CNS depression, including alcohol. Increased drug effects seen with azole antifungals, ciprofloxacin,
clarithromycin, diclofenac, doxycycline, erythromycin, imatinib (antineoplastic agent), isoniazid,
nefazadone (Serzone), nicardipine, propofol (general anesthetic), protease inhibitors, quinidine,
verapamil. Decreased drug effect seen with aminoglutethimide (anti-adrenal), carbamazepine, nafcillin,
nevirapine (antiretroviral), phenobarbital, phenytoin.
7
18.
BRAND NAME: Nexium
GENERIC NAME: esomeprazole
THERAPEUTIC CATEGORY: proton pump inhibitor
USE: short-term treatment of erosive esophagitis; symptomatic gastroesophageal reflux disease (GERD)
ORAL COMPLICATIONS: xerostomia
DRUG INTERACTIONS: Esomeprazole may increase the levels of carbamazepine, statin drugs, and
some benzodiazepines (diazepam, midazolam, triazolam). Drugs in this class may decrease the
absorption of antiretroviral medications, iron, and systemic antifungal medications (itraconazole,
ketoconazole). Esomeprazole may decrease the levels of phenytoin. Drug absorption is significantly
decreased (43%-53%) when taken with food; take at least 1 hour before meals.
19.
BRAND NAME: Lexapro
GENERIC NAME: escitalopram
THERAPEUTIC CATEGORY: selective serotonin reuptake inhibitor
USE: major depressive disorder; generalized anxiety disorders (GAD)
ORAL COMPLICATIONS: xerostomia, toothache, vomiting
DRUG INTERACTIONS: Do not take this drug with MAOIs: fatal reactions have been reported.
Combined use of this drug with other SSRIs and/or other classes of antidepressants increases risk for
serotonin syndrome. Use of this drug with aspirin, NSAIDS and other drugs that alter coagulation
increases risk for bleeding. Systemic azole antifungals, ciprofloxacin, clarithromycin, diclofenac,
doxycycline, erythromycin, and other CYP3A4 inhibitors may increase the levels and/or effects of
escitalopram. Avoid drinking alcohol with this medication. Combined use of SSRIs with sumatriptan
(Imitrex) or other serotonin agonists may result in toxicity. CYP3A4 inducers may decrease the
levels/effects of escitalopram, including cabamazepine nafcillin, phenobarbital and phenytoin.
20.
BRAND NAME: Endocet, Magnacet, Percocet, Primalev, Roxicet, Tylox
GENERIC NAME: oxycodone and acetaminophen
THERAPEUTIC CATEGORY: analgesic, opioid
USE: management of moderate to severe pain; treatment of postoperative dental pain
ORAL COMPLICATIONS: xerostomia, vomiting
DRUG INTERACTIONS: Concurrent use of this drug may increase the levels of alcohol, CNS
depressants, selective serotonin reuptake inhibitors. Drug level may be increased by amphetamines and
antipsychotic agents. Drug level may be decreased by some anticonvulsants (hydantoin, barbiturates,
carbamazepine) and cholestyramine resin (Prevalite, Questran). Alcohol may have additive CNS
depressant effects, and excessive intake increases risk for acetaminophen-induced hepatotoxicity = avoid
alcohol and/or limit to < 3 drinks per day.
8
CARDIAC CONDITIONS ASSOCIATED WITH HIGHEST RISK: ANTIBIOTIC PREMEDICATION
RECOMMENDED
Prosthetic cardiac valve or prosthetic material used for cardiac valve repair
Previous history of infective endocarditis
Congenital heart disease (CHD)
-Unrepaired cyanotic CHD, including palliative shunts and conduits
-Completely repaired congenital heart defect with prosthetic material or device, whether placed by
surgery or by catheter intervention, during the first six months after the procedure
-Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or
prosthetic device (which inhibit endothelialization)
Cardiac transplantation recipients who develop cardiac valvulopathy
2007 AHA Guidelines for the Prevention of Bacterial Endocarditis
STANDARD GENERAL PROPHYLAXIS:
amoxicillin
Adults: 2 gm orally 1 hr before procedure
Children: 50 mg/kg orally 1 hr before procedure
UNABLE TO TAKE ORAL MEDICATIONS:
ampicillin
Adults: 2 gm IM or IV within 30 min before procedure
Children: 50 mg/kg IM or IV within 30 min before procedure
ALLERGIC TO PENICILLIN:
clindamycin
Adults: 600 mg orally 1 hr before procedure
(Cleocin)
Children: 20 mg/kg orally 1 hr before procedure
___________________________________________________________________
cephalexin
Adults: 2 gm orally 1 hr before procedure
(Keflex)
Children: 50 mg/kg orally 1 hr before procedure
___________________________________________________________________
azithromycin
Adults: 500 mg orally 1 hr before procedure
9
(Zithromax)
Children: 15 mg/kg orally 1 hr before procedure
clarithromycin
(Biaxin)
ALLERGIC TO PENICILLIN AND UNABLE TO TAKE ORAL MEDICATIONS:
clindamycin
Adults: 600 mg IV within 30 min before procedure
Children: 20 mg/kg IV within 30 min before procedure
cefazolin or
Adults: 1 gm IM or IV within 30 min before procedure
ceftriaxone
Children: 50 mg/kg IM or IV within 30 min before procedure
JADA vol 138, June 2007 http://jada.ada.org
THOSE PATIENTS WITH PROSTHETIC JOINT
WITH POTENTIAL ELEVATED RISK OF JOINT INFECTION
Immunocompromised/Immunosuppressed Patients:
Inflammatory arthropathies: rheumatoid arthritis, systemic lupus
erythematosus
Drug- or radiation-induced immunosuppression
Other Patients:
Previous prosthetic joint infections
Malnourishment
Hemophilia
HIV infection
Insulin-dependent (Type I) diabetes
10
Malignancy
ANTIBIOTIC REGIMENS FOR PATIENTS
WITH PROSTHETIC IMPLANTS
Patients not allergic to penicillin:
Cephalexin, cephradine, or
2 g orally 1 hour prior to the
amoxicillin
procedure
and unable to take oral
Cefazolin
1 g I.M. or I.V. 1 hour prior to the
medications:
or
procedure
Patients not allergic to penicillin
Ampicillin
2 g I.M. or I.V. 1 hour prior to
the procedure
Patients allergic to penicillin:
Clindamycin
Patients allergic to penicillin and
600 mg orally 1 hour prior to
dental procedure
unable to take oral medications:
Clindamycin
600 mg I.V. 1 hour prior to the
procedure
American Dental Association, American Academy of Orthopaedic Surgeons. “Advisory Statement: Antibiotic
Prophylaxis for Dental Patients with Total Joint Replacements.” JADA, July 2003, 134:895-899.
American Academy of Orthopedic Surgeons
Information Statement
Antibiotic Prophylaxis for Bacteremia in Patients with Joint Replacements
11
February 2009
http://www.aaos.org/about/papers/advistmt/1033.asp
Given the potential adverse outcomes and cost of treating an infected joint replacement, the
AAOS recommends that clinicians consider antibiotic prophylaxis for all total joint
replacement patients prior to any invasive procedure that may cause bacteremia.* This is
particularly important for those patients with one or more of the following risk factors.
Table 1. Patients at Potential Increased Risk of Hematogenous Total Joint Infection8,10-16,18

All patients with prosthetic joint replacement.

Immunocompromised/immunosuppressed patients

Inflammatory arthropathies (e.g.: rheumatoid arthritis, systemic lupus erythematosus)

Drug-induced immunosuppression

Radiation-induced immunosuppression

Patients with co-morbidities (e.g.: diabetes, obesity, HIV, smoking) *

Previous prosthetic joint infections

Malnourishment

Hemophilia

HIV infection

Insulin-dependent (Type 1) diabetes

Malignancy

Megaprostheses *
*criteria different from 2003 AAOS/ADA recommendations
OraVerse

Novalar Pharmaceuticals, Inc. has received FDA approval for a new first- in-class local
anesthetic reversal agent
12








Reverses soft tissue anesthesia and associated functional deficits from dental local
anesthetics
Phentolamine mesylate
Produces alpha-adrenergic block of relatively short duration, resulting in vasodilitation
when applied to vascular smooth muscle
OraVerse™ increases local blood flow in submucosal tissue
Approval for use is based on data from several clinical studies, including two Phase 3
studies in adults and adolescents age 12 and older and a Phase 2 pediatric study
484 dental patients enrolled across the two Phase 3 studies
No serious adverse events reported
Most common adverse reaction reported in test group that was greater than control:
transient injection site pain
Adult and Adolescent Trial Highlights (Hersh et al, 2008)




Two studies were conducted with a total of 484 adult and adolescent dental patients, aged
12 through 92
Median time to recovery of normal lip sensation in the mandible was 70 minutes for
OraVerse patients (55% faster than the control), and in the maxilla was 50 minutes (62%
reduction in time)
Median time to observed recovery of normal function (speaking, smiling, drinking) was
60 minutes for patients receiving OraVerse
o 43% and 50% faster than the control in the maxilla and mandible respectively
The majority of adverse events were mild and resolved within 48 hours
Pediatric Trial Highlights (Tavares et al, 2008)




A trial was conducted in 152 pediatric patients aged 4 through 11 years.
A subset of 115 patients, aged 6-11, were included in the efficacy evaluation
Median time to recovery of normal lip sensation was 60 minutes for OraVerse patients,
47% faster than control in the maxilla and 67% faster in the mandible
OraVerse had no effect on adverse events, pain or post-treatment analgesic use compared
to control
MANAGEMENT OF ORAL SIDE EFFECTS CAUSED BY MEDICATIONS
FLUORIDE THERAPY
13
For caries control:
Prescription fluorides for supplemental home use:
1.1% neutral sodium
5000 ppm
Clinpro 5000 Anti-Cavity Toothpaste (3M ESPE),
gel or dentifrice
Prescription Control Rx (Discus Dental), Fluoridex Daily Defense
Dentifrice and Gel (Discus Dental), NUPRO
NuSolutions Toothpaste (Dentsply), Oral B Neutracare
(P&G), PreviDent 5000 Booster toothpaste, PreviDent
Gel, PreviDent 5000 Plus (Colgate), ProDenRx
Dentifrice and Gel (Zila), Topex Take Home Care
(Sultan Healthcare)
0.2% neutral sodium
920 ppm
CaviRinse (3M ESPE), NaFrinse (Medical Products
rinse
Prescription Laboratory), Oral B Fluorinse (P&G), PreviDent
Dental Rinse (Colgate), ProDenRx Rinse (Zila)
1.1% sodium and
5000 ppm
Phos-Flur (Colgate)
acidulated
Prescription
phosphate gel
0.4% stannous
1000 ppm
Fluoridex Daily Defense Sensitivity Relief (Discus
fluoride gel
Dental); Gel-Kam Oral Rinse (Colgate), Kid Kare Plus
0.4% Stannous Fluoride Brush-on Dentifrice, Kids
Kare 0.4% Stannous Fluoride Brush-on Gel (Zila),
ProDenRx 0.4% Stannous Fluoride Brush-on Gel
(Zila), Topex Take Home Care (Sultan Healthcare)
0.63% stannous
30 ml dose PerioMed (3M ESPE), Fluoridex Daily Renewal
fluoride rinse
dilution = 7 (Discus Dental)
mg fl- ion
and 22 mg
stannous
ion
Over-the-counter supplemental fluorides for home use:
0.05% neutral sodium rinse 230 ppm
Reach Act, Fluorigard, NaF rinse
acidulated, NaF rinse neutral
0.044% sodium and
200 ppm
Phos-Flur (Colgate); OrthoWash (3M
acidulated phosphate rinse
ESPE)
0.4% stannous fluoride gel 1000 ppm
Gel-Kam Treatment Gel (Colgate),
Just For Kids (3M ESPE), Omni Gel
(3M ESPE), Oral B Stop (P&G)
0.0221% sodium fluoride
Listerine Total Care, Listerine Smart
Rinse (J&J)
Fluoride Varnishes: 22,600 PPM sodium fluoride
5% sodium fluoride varnish
(in-office use only)
varnish in a tube or single-unit
dose dispensers
AllSolutions (Dentsply)
Duraphat (Colgate)
Duraflor (A.R. Medicom)
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Enamel Pro Varnish with ACP
(Premier)
FluoroDose (Centrix)
Fluoridex Lasting Defense
(Discus Dental)
Profluorid Varnish (VOCO)
Vanish (Omni/3M EPSE)
VarnishAmerica with xylitol
(Medical Products Laboratories)
Vella with xylitol (Preventech)
Waterpik UltraThin (Teledyne)
SALIVARY REPLACEMENT THERAPY
1. OTC Artificial Saliva Preparations:
PRODUCT
Entertainer’s Secret®
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Moi-Stir®
Mouthkote®
Salivart®
Salix®
-carboxymethylcellulose = gives feeling of viscosity
-relief while product is in contact with the tissues
-convenience
-some contain preservatives: parabens (PABA) = allergy potential
2. Biotene product line (Laclede Pharmaceuticals): toothpaste, oral gel, mouthrinse,
chewing gum
-contain 3 key salivary enzymes found in natural saliva
-sodium fluoride
-xylitol
3. Orajel product line (Del Pharmaceuticals, Inc.): dry mouth moisturizing gel and spray
- moisturizing gel and spray
-18% glycerin
-sorbitol (gel); xylitol (spray)
-moisturizing toothpaste
-thione antioxidant complex
-sodium monofluorophosphate (0.18% w/v fluoride ion)
-sugar-free; sorbitol, xylitol
-no sodium lauryl sulfate
4. Oasis (GlaxoSmithKline)
-mouthwash or mouth spray
-“TriHydra” technology
-hydrophilic polymers, xanthum gum, glycerine and carboxymethylcellulose
-relieves symptoms for up to 2 hours
5. Two prescription drugs now available to stimulate salivary flow:
Salagen (5 mg pilocarpine hydrochloride)
-cholinergic agonist that stimulates muscarinic acetylcholine receptors in the
salivary glands to increase serous salivary flow.
-need to take the drug for a minimum of 90 days to see optimum effects
-contraindicated if known hypersensitivity to the drug, uncontrolled asthma or
narrow-angle glaucoma
-drug interactions associated with pilocarpine include anticholinergic medications (eg.
antiparkinsonion drugs, carbamazepine, digoxin, sedative antihistamines, tricyclic
antidepressants), cholinergic medications (eg. antiglaucoma drugs) and beta-adrenergic
blocking drugs
-indicated for radiation therapy patients and Sjogren’s syndrome
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- dosage: for radiation therapy patients:
- 5 mg tid (15-30 mg per day); 12 weeks of therapy may be
needed before beneficial response can be assessed
- dosage: for Sjogren’s patients:
- 5 mg qid; efficacy has been established after 6 weeks of use
Evoxac (cevimeline)
-cholinergic agonist used to treat xerostomia in patients with Sjogren’s syndrome
- dosage: 30 mg tid
-contraindications: hypersensitivity to drug or any of its components, uncontrolled
asthma, narrow-angle glaucoma, acute iritis, conditions where miosis is undesirable
-use with caution in patients with CV disease, asthma, COPD, decreased visual acuity,
the elderly, or in those with kidney problems
ANTIMICROBIALS
-an important adjunct in managing the oral complications of xerostomia
-reduce plaque formation, and to prevent or reduce the severity of gingivitis
-promotes a healthy oral ecosystem
-OTC and prescription antimicrobials available on the market from which to choose.
-Biotene® oral care products - contain key enzymes found in natural saliva
-lactoferrin is bacteriostatic, and kills both aerobic and facultative organisms by
binding iron necessary for bacterial growth
-lysozyme causes bacterial cell lysis by binding to the cell wall
-lactoperoxidase converts the hydrogen peroxide produced by bacteria to
hypocyanite, a highly reactive oxidizing agent that effects bacterial acid
production and growth
-lactoferrin, lysozyme and lactoperoxidase are all extremely effective against
Streptococcus mutans
-Chlorhexidine gluconate (Peridex®, PerioGard®) = 0.12% chlorhexidine
-a broad spectrum antibacterial dental rinse that demonstrates both bacteriostatic
and bactericidal properties
-binds to the bacterial cell wall, and at low concentrations, alters cellular osmotic
equilibrium which results in leakage (bacteriostasis), and at high concentrations,
results in cell death
-chlorhexidine binds to tooth structure, oral mucosa and salivary proteins
-exhibits a high degree of substantivity, enabling a slow release of the agent over
time
-chlorhexidine rinses are the only prescription mouthwashes that have FDA
approval for efficacy in the reduction of supragingival plaque microorganisms
and gingivitis
-SunStar Butler has introduced alcohol-free chlorhexidine in 2006
-percentage concentration is the same (still 0.12%)
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-FDA considers it an “equivalent” due to percentage concentration
-vehicle is different from other chlorhexidine products on the market
-Listerine® antiseptic mouthrinse - essential oils
-the first and only ADA approved OTC product that reduces and prevents plaque
and gingivitis when used in conjunction with daily brushing and flossing
-essential oil mouthrinse kills bacteria and opportunistic microorganisms within
30 seconds (Thymol, Eucalyptol, Menthol, Methyl Salicylate)
-additional mechanisms of action for Listerine® have recently been elucidated:
-shown to alter cell surface structure, leading to loss of cell wall integrity, cell
lysis and death. These alterations also include changes in cell surface
functions, most notably, decreased cellular attachment and aggregation.
-inhibits the ability of bacteria to coaggregate, thus reducing plaque
accumulation
-full strength Listerine® prevents cell growth in early colonizing plaque
bacteria
-mouthrinse is free from side effects, does not promote microbial resistance and
does not disrupt the balance of the oral ecosystem
-
Other agents available as mouthrinses exhibit antibacterial properties, but do not
possess good substantivity:
-stannous fluoride = thought be antibacterial in addition to its carioprotective and
desensitizing effects
-cetylpyridinium chloride = rupture bacterial cell walls and alter cytoplasmic
contents; bind strongly to plaque and tooth surfaces (Cepacol, Scope, Advanced
Formula Viadent; alcohol free: Crest Pro Health Rinse, BreathRx )
-oxygenating agents = damage bacteria by altering cell membrane permeability
-sanguinarine = an extract derived from the plant root Sanguinaria canadensis,
decreases bacterial cell enzyme activity, and is effective against a broad
spectrum of bacteria (Viadent)
-Triclosan (Colgate Total toothpaste)
-antimicrobial agent in dentifrice form
-both antimicrobial and anti-inflammatory properties
-unique technology of delivery mode: PVM/MA copolymer = GANTREZ
-copolymer allows binding to surfaces with slow release
-copolymer also promotes adhesion/uptake of triclosan on enamel, plaque and
soft tissue
-triclosan: broad spectrum, substantive to 12 hours
-antimicrobial effect: decreases plaque viability
-anti-inflammatory effect: dampens stimulation of the production of IL1-beta and
TNF alpha = inflammatory mediators (cytokines) that destroy tissue and bone
-over 60 well-controlled studies documenting efficacy
-Prevent caries
-Prevent and reduce plaque formation
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-Reduce gingivitis and bleeding up to 88%
-Retard the progression of periodontitis
-Reduce calculus formation up to 55%
-Removes stain/whitening up to 50%
-Reduce oral malodor
-Reduces anaerobic bacteria on tongue up to 93% and in saliva up to 88%
-two studies that demonstrate reduction in interleukin B and TNF alpha
-no adverse effects on oral soft/hard tissues
-no emergence of resistant organisms
-no contraindications for waiting between rinsing/brushing
-triclosan does not react with chlorhexidine or essential oils (copolymer sticks
well enough so that it is not washed away by rinsing)
-triclosan = local host modulation (versus Periostat: systemic host modulation)
-Crest Pro Health dentifrice
-stannous fluoride multi-care dentifrice
-older formulations: adverse taste and staining effects; instable in aqueous
solutions
-0.454% stabilized stannous fluoride with sodium hexametaphosphate
-sodium hexametaphosphate = pyrophosphonate (anti-calculus/anti-staining)
-polymer of repeated pyrophosphate subunits
-stronger affinity to calcium hydroxyapatite in enamel and dentin
-greater prevention of crystallization at enamel surface (calculus
prevention) and adsorption of stains from chromogens (staining)
-sodium hexametaphosphate has been unstable: dual phase packaging to keep
separate from other ingredients (Crest Dual Action Whitening dentifrice)
-now reformulated into a silica-based low-water dentifrice to reduce hydrolysis of
sodium hexametaphosphate and to maintain effective pyrophosphate levels
-12 hour substantivitiy
-two 6 month gingivitis studies: 25.8% reduction in gingivitis; 27.4% reduction in
bleeding
-8 week brushing trial demonstrated statistically significant reductions in
sensitivity
-40 clinical studies support claims of anticaries effects of stannous fluoride: in
vitro studies suggest protection of lesion initiation and progression with this
dentifrice compared to conventional dentifrice
-6 month study showed anticalculus efficacy that was 56% lower than that of
Colgate Total
-in vitro, clinical and consumer studies show no difference in staining between
Crest Pro Health and Colgate Total
-Natural Dentist Health Gums Moisturizing Antigingivitis Mouthrinse
-contains all natural formulation
-germ kill of 40 oral pathogens, including Strep mutans and some red complex
-comparable to Listerine in terms of pathogen reduction
-4 published clinical trials and MIC laboratory data to support efficacy
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ANTIFUNGALS
- fungal infections occur as a result of alterations in oral flora, immunosuppression and
underlying systemic disease (diabetes, xerostomia, anemia, chemo, inhaled steroids)
- opportunistic infections
- clinical presentation:
- pseudomembranous appearance (bright red with overlying white
pseudomembrane)
- atrophic appearance (tongue)
- hyperkeratotic appearance (denture stomatitis)
- symptomatic geographic tongue
- angular cheilitis
-drug therapy includes topical and systemic medications depending upon the extent and
severity of the infection.
-azole antifungals are used to treat chronic, extensive mucocutaneous candidiasis
-polyenes are used to treat local candidiasis (topicals)
-antifungals are being used in combination with corticosteroids, such as nystatin and
triamcinolone (Mycolog II®), to treat both the fungal infection and the inflammation of
angular cheilitis
- medications must be used for a minimum of 48 hours after the disappearance of
clinical signs and symptoms; re-evaluate condition 14 days after therapy has been
completed
- efficacy of topical drugs is dependent upon contact with the lesions
- some topical preparations contain sugar - may choose to prescribe vaginal preparation
- in addition to antifungals, consider chlorhexidine or essential oil mouthrinses for
long term prevention
- prescription antifungals for systemic use if patient is refractory to topicals:
*cautions: liver function and multiple drug interactions
- Nizoral 200 mg (ketoconazole)
- Diflucan 100 mg (fluconazole)
Topical Antifungal Medications:
Mycostatin® pastilles
nystatin (polyene)
Mycostatin® oral suspension nystatin (polyene)
4-5 troches/day for 14 days
1 tsp 4-5 times/day; rinse and
hold in mouth for 2 minutes
before spit/swallow; do not
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Mycostatin®ointment/cream
(also available as a powder)
nystatin (polyene)
Mycelex® troche
clotrimazole (azole)
*contains sucrose: use
caution in diabetics
Fungizone® oral suspension
amphotericin B (polyene)
*manufacturer is
discontinuing; can continue to
obtain until supply is
exhausted
Mycolog® II
nystatin and triamcinolone
(polyene)
eat/drink for 30 minutes
afterwards
apply 4-5 times/day; apply to
dentures prior to each
insertion; do not eat/drink for
30 minutes afterwards
dissolve 1 troche in mouth 5
times/day for 14 days
1 ml swish & swallow 4
times/day between meals
apply at bedtime and after
each meal
Topical nystatin:
- is well-tolerated, non-sensitizing
- soak dentures in nystatin suspension overnight
- nystatin ointment can be placed in denture and worn during day (like an adhesive)
Systemic Azole Antifungal Medications:
Diflucan®
fluconazole
200 mg immediately, then
100 mg
100 mg daily for 10-14 days
Nizoral®
ketoconazole 200 mg/day (1 tablet/day) for
200 mg
10-14 days
ANTIVIRALS
- viral infections: acute onset of symptoms
- vesicular eruption of soft tissues
- rupture of vesicles leaves ulcerations
- ulcerations are generally small in size
- if left untreated, ulcerations coalesce to form large lesions
- primary infection can present as: gingivostomatitis, recurrent lip lesions (herpes
labialis), intraoral ulcers (recurrent intraoral herpes) that involve oral/perioral tissues
- primary infection is systemic that leads to acute gingivostomatitis involving multiple
tissues: buccal mucosa, lips, tongue, floor of mouth, gingiva
- management of viral infections is generally palliative (although acyclovir is now
used for prevention of primary infections)
- treatment of primary infections includes combination therapy:
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- acyclovir
- topical anesthetic rinses (eg. Benadryl, Xylocaine viscous, OTC
benzocaine products )
- fluids, vitamins and mineral supplements and rest
Antiviral Medications for Herpes Simplex:
Zovirax® tablets
Zovirax® ointment 5%
acyclovir
acyclovir
Denavir® cream 10mg/g
(1%)
Valtrex®
penciclovir
Abreva (OTC)
docosanol 10%
Viroxyn® (OTC)
alcohol/benzalkonium
chloride
valacyclovir
200 mg q 4 hours for 2 weeks
apply q 3 hours (6 times/day)
for 7 days
apply every 2 hours (lips and
face only) for 4 days
2 grams bid for 1 day at
prodrome
apply locally as directed 5
times per day; start at
prodrome and continue until
lesions have healed; do not
apply directly to inside of
mouth or around eyes
single dose applicator/vial; at
prodrome, rub medication
into lesion until medication is
gone (10 seconds)
ORAL ULCERATIONS (NON-VIRAL) AND PAIN CONTROL
-Recurrent Aphthous Stomatitis:
- patients with recurrent aphthous should be evaluated for iron, folic acid and/or
vitamin B12 deficiency
- severe recurrent aphthous may be treated with an oral suspension of tetracycline
- regular use of Listerine has been shown to reduce the frequency, duration and
severity of lesions; chlorhexidine has been shown to reduce duration of lesions
-localized ulcerations:
- OTC topical anesthetic agents containing benzocaine in protective preparations
- Benzocaine and tetracaine (Viractin) are esther anesthetics; therefore, caution
must be used when recommending these OTC products to clients with reported
allergies to anesthetics or to PABA
- Debacterol (sulfonated phenolics in aqueous solution) - therapeutic cauterization
- dry ulcer, apply directly to lesion, keep in contact for 5-10 seconds;
(larger lesions may need up to 2 minutes); rinse immediately, and
expectorate with water
* only available to healthcare providers directly from manufacturer:
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Northern Research Laboratories (888) 884-4675
-generalized oral pain:
- OTC agent such as Chloraseptic® spray
- prescription mouthrinse Xylocaine ® 2% (viscous lidocaine)
- Benadryl® elixir and Benylin® cough syrup
-severe pain, such as that associated with mucositis:
- anesthetic agents may be mixed with OTC coating agents to provide lubrication
and relief from pain
- Benadryl® elixir added in equal amounts to Maalox®, Mylanta® or
Kaopectate®
- Sucralfate (Carafate®), the prescription medication used to treat duodenal
ulcers, may be prepared as a 1 gm/15 mL suspension for use in this population
as well. (A pharmacist should be consulted to assist with the preparation of oral
suspensions.)
-dry, cracked lips: topical water-based product, such as Oral Balance® or K-Y Jelly®
Topical prescription agents for aphthous lesions:
Amlexanox oral paste 5%
Apthasol
Triamcinolone Acetonide
Dental Paste
Chlorhexidine oral rinse
Fluocinonide 0.05%
(used for oral inflammatory
lesions that do not respond to
Kenalog in Orabase)
Kenalog in Orabase 0.1%
Peridex, PerioGard
Lidex ointment mixed 50/50
with Orabase (30 grams total)
apply qid after meals and at
bedtime
apply after each meal and at
bedtime
rinse with 20 ml for 30 sec tid
apply thin layer to oral lesions
4-6 times per day
Topical OTC agents for aphthous/pain control:
Benzyl alcohol
Benzocaine 10%
Lidocaine 2.5%
Zilactin® Gel
Zilactin B
Zilactin L
apply q 3-4 hours
apply q 3-4 hours
apply q 3-4 hours
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Diphenhydramine
Benadryl® Elixir
Benzocaine, gelatin, pectin
and sodium
carboxymethylcellulose
Benzocaine and 2-octyl
cyanoacrylate
Tetracaine Hydrochloride 1%
Orabase® with Benzocaine
swish with 1 tsp for 2 min
before each meal (can be used
as a swish and swallow)
apply 3-4 times/day
Colgate Sooth-N-Seal
dry lesion and apply q 6 hours
Viractin
apply 3-4 times/day up to 7
days
REFERENCES FOR TOP 20 MEDICATIONS
Top 200 Medications for 2008. Source: SDI/Verispan, VONA, www.drugtopics.com
Physicians’ Desk Reference, ed. 63. Montvale, Medical Economics Co, Inc., 2009.
Mycek MJ, Harvey RA, Champe PC: Lippincott’s Illustrated Reviews: Pharmacology. ed. 3.
Philadelphia, Lippincott-Raven, 2006.
Wynn RL, Meiller TF, Crossley HL. Drug Information Handbook in Dentistry. 15th ed. Hudson, LexiComp Inc., 2009.
Gage TW, Pickett FA. Mosby’s Dental Drug Reference. 7th ed. St. Louis, Mosby, Inc., 2005.
Pickett FA, Terezhalmy GT. Dental Drug Reference with Clinical Implications. 2nd ed. Baltimore,
Lippincott Williams & Wilkens, 2008.
REFERENCES FOR PREMEDICATION FOR JOINT REPLACEMENT
American Dental Association, American Academy of Orthopaedic Surgeons. “Advisory
Statement: Antibiotic Prophylaxis for Dental Patients with Total Joint Replacements.” JADA,
July 2003, 134:895-899.
American Academy of Orthopedic Surgeons. Information Statement. Antibiotic Prophylaxis for
Bacteremia in Patients with Joint Replacements. February 2009. Available at:
http://www.aaos.org/about/papers/advistmt/1033.asp
Assael LA. Oral bacteremia as a cause of prosthesis failure in patients with joint replacements. J
Oral Maxillofac Surg. Sept 2009;67(9):1789-90.
American Dental Association. Antibiotic prophylaxis. Available at:
http://www.ada.org/prof/resources/topics/antibiotic.asp
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REFERENCES FOR ORAVERSE
Adult and Adolescent Trials
Hersh EV, Moore PA, Papas AS, et al. Reversal of soft-tissue local anesthesia with phentolamine
mesylate in adolescents and adults. JADA 2008;139(8):1080-1093.
Pediatric Trial
Tavares M, Goodson JM, Studen-Pavlovich D, et al. Reversal of soft-tissue local anesthesia with
phentolamine mesylate in pediatric patients. JADA 2008;139(8):1095-1104.
Pharmacokinetics Trial, Adults
Moore PA, Hersh EV, Papas AS, et al. pharmacokinetics of lidocaine with epinephrine following
local anesthesia reversal with phentolamine mesylate. Anesthesia Progress 2008;55(2):40-48.
REFERENCES FOR FLUORIDES
American Dental Association. Professionally applied topical fluoride: evidence-based clinical
recommendations. Available at:
http://www.ada.org/prof/resources/pubs/jada/reports/report_fluoride_exec.pdf
Accessed September 23, 2009.
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