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C123MANAGING THE GERIATRIC PATIENTANN ESHENAUR SPOLARICH, RDH, PHDTHURSDAY, FEBRUARY 21

Chicago Dental Society MWM & REGIONAL MEETING COURSE EVALUATION

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RETURN EVALUATION CARD TO: DO NOT FOLD CARD. FOR CDS PERMANENT FILES.Chicago Dental SocietyAloysius F. Kleszynski, DDS401 N. Michigan Ave., Suite 200, Chicago, IL 60611-5585

COURSE TITLE: Pharmacologic Management of the Geriatric Patient: Oral Health Care Considerations

COURSE INSTRUCTOR: Ann Eshenaur Spolarich, RDH, PhD COURSE CREDITS: 3 CEUs COURSE DATE: February 22, 2013 _____________________________________________________________________________ COURSE DESCRIPTION: The purpose of this course is to review characteristics and disease trends among the aging population, and oral disease risks associated with medications and common systemic diseases. Most patients take multiple medications, many of which have oral complications and drug interactions of significance to dentistry. Medication therapies, oral drug and disease complications, drug interactions and dental practice management considerations will be discussed. Recommendations for treatment modifications and oral hygiene self-care programs will be provided. LEARNING OBJECTIVES: Upon completion of this continuing education program, course participants will be able to: 1. Describe common oral disorders observed in the elderly population, including

xerostomia, taste and smell disorders, orofacial muscular disorders, and lichenoid drug reactions.

2. Discuss the pathophysiology of common diseases associated with aging, including

cardiovascular disease, gastrointestinal problems, and depression. 2. Identify the major classes of medications associated with and/or used to treat these

conditions. 4. Discuss the oral side effects and other adverse events associated with each of these

disease states and related medication therapies. 5. Identify modifications necessary to safely treat patients who present with these medical

conditions. 6. Recommend appropriate oral hygiene strategies for each of these patient populations. *These course materials may not be duplicated without the written consent of the course instructor.

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I. Selected Agents for the Treatment of Depression

-dopamine-reuptake inhibitor - bupropion (Wellbutrin, Zyban) -depression, smoking cessation -increased risk for seizures; alcohol lowers seizure threshold -risk for emergent hypertension *take BP on patients using this drug -monoamine oxidase inhibitors (MAOIs)

-isocarboxazid (Marplan) -phenelzine (Nardil) -selegiline (Atapryl, Eldepryl, Selpak) -tranylcypromine (Parnate)

-atypical, non-endogenous or neurotic depression -depression associated with Parkinson’s disease -investigational for ADHD, Alzheimer’s, Schizophrenia -post-traumatic stress disorder *take BP on patients using these drugs -selective serotonin reuptake inhibitors (SSRIs)

-citalopram (Celexa) -escitalopram oxalate (Lexapro) -fluoxetine (Prozac, Sarafem) -paroxetine (Paxil) -sertraline (Zoloft)

-over 15 approved indications -depression, geriatric depression, generalized anxiety disorder, social phobias, social anxiety disorders, diabetic neuropathies, anorexia, bulimia, premenstrual syndrome, obsessive compulsive disorder (OCD), panic attacks/disorders *biggest US market sellers: Paxil and Zoloft -sertraline (Zoloft) is only drug approved for use in children for OCD -recent concerns over whether use of SSRIs in adolescents increases risk for suicide: increased number of cases of suicide attempts prompted FDA to require relabeling of these drugs -agitation, anxiety, hostility, aggression = known side effects -watch for signs of change in depression and related behaviors or any of the above side effects during first 6 weeks of therapy: highest risk time period for suicide attempt -venlafaxine (Effexor) -selective serotonin/norepinephrine reuptake inhibitor

-depression, anxiety, panic disorder; investigational for OCD, hot flashes, neuropathic pain, ADHD -raises BP (diastolic) and heart rate *take BP on patients using this drug

-tetracyclic - maprotiline (Ludiomil) -depression, anxiety with depression -investigational:bulimia, enuresis, pain, panic attacks, tension headaches, cocaine withdrawal

-tricyclics (secondary amines)

-amoxapine (Ascendin) -desipramine (Norpramin) -nortriptyline (Aventyl, Pamelor) -protriptyline (Vivactil)

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-treatment of depression in conjunction with psychotherapy -adjunctive therapy for chronic pain, peripheral neuropathies -investigational for substance-related disorders, ADHD

-tricyclics (tertiary amines)

-amitriptyline (Elavil, Vanatrip) -clomipramine (Anafranil) -doxepin (Sinequan) -imipramine (Tofranil) -trimipramine (Surmontil) -treatment of depression with psychotherapy -chronic pain, neuropathic pain, migraines, depression with anxiety

*take BP on patients using these drugs

General Adverse Effects - orthostatic hypotension - sedation - dizziness, light-headedness

II. MAJOR TRANQUILIZERS/ANTIPSYCHOTICS A. Pharmacology and Use

-Older term: neuroleptic drugs -A chemically diverse but pharmacologically similar class of drugs used to treat a variety of conditions -Used in the treatment of:

-Psychotic disorders – Schizophrenia, paranoia -Acute delirium and dementia -Manic episodes during induction of lithium -Movement disorders – Huntington’ disease, Tourette’s syndrome, ballismus -Intractable hiccups -Severe nausea and vomiting

-Individual drugs bind to a variety of receptors and act as antagonists:

-dopaminergic, alpha1 and alpha2 adrenergic, serotonergic (5-HT), muscarinic, H1 histamine, sigma opioid

-Blockade of dopaminergic transmission in various areas of brain is thought to be responsible for their major effects

-Antipsychotic action = blockage in prefrontal cortex and limbic areas -Extrapyramidal side effects = blockade in basal ganglia -Antiemetic effects = blockade in chemoreceptor trigger zone of the medulla

-All antipsychotics have high therapeutic index

-Not addictive

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B. Side Effects

-Extrapyramidal side effects: Parkinsonism – akinesia (difficulties in initiating movement), tremor, rigidity Caused by blockade of D2 receptors in basal ganglia

-Akathisia = restless legs syndrome; Caused by D2 receptor blockage in basal ganglia -Dystonia – sustained muscular contraction -Tardive Dyskinesia – abnormal movements, particularly of face and tongue, but may also be of trunk and limbs

-Noticeable after at least 6 months of chronic treatment - begins with spastic, thrusting tongue movement, body restlessness, changes in HR & respiration

*Most extrapyramidal side effects are treatable with anticholinergic drugs

Sedation and autonomic side effects are caused by blockade of histamine, cholinergic and adrenergic receptors

-orthostatic hypotension -blurred vision -dry mouth -nasal congestion -constipation -urinary retention

C. Drug Interactions of Significance to Dentistry -Antipsychotics potentiate the actions of

-sedatives -analgesics -antihistamines

-Antipsychotics potentiate the respiratory depression caused by opioids -Antacids = decrease absorption of antipsychotics -Anticonvulsants = decrease plasma levels of antipsychotics -Antipsychotics may alter efficacy of antihypertensive medications

*monitor vital signs TYPICAL ANTIPSYCHOTICS ATYPICAL ANTIPSYCHOTICS chlorpromazine (Thorazine) = Schizophrenia, nausea/vomiting, intractable hiccups, combativeness

aripiprazole (Abilify) = Commonly used agent in schizophrenia, treatment and stabilization of bipolar disorder -Low risk of EPS -Does not cause as much weight gain as other antipsychotics, but may be less effective than others

fluphenazine (Prolixin) = management of psychotic disorders and schizophrenia; improves outcomes in patients with psychoses who are nonadherent with oral antipsychotics

clozapine (Clozaril) = Schizophrenia; severe OCD, childhood psychosis, attempted suicide, substance abuse recovery Side effect: agranulocytosis – susceptibility to infection, hypersalivation (others cause xerostomia), weight gain, reduced risk of EPS

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haloperidol (Haldol) RX for schizophrenia and Tourette’s; severe behavioral problems in children -EPS of TMJ

olanzapine (Zyprexa) = Schizophrenia, bipolar disorder, acute agitation

pimozide (Orap) = suppression of severe motor and phonic tics with Tourette’s -prolongs QT interval: consult physician prior to administering vasoconstrictor

olanzapine and fluoxetine (Symbyax) = treatment of depressive episodes associated with bipolar disorder

prochlorperazine (Compro, Compazine) = antiemetic; psychosis, anxiety -EPS side effect: torticollis (neck muscle spasm)

paliperidone (Invega) = Schizophrenia

promethazine (Phenadoz, Phenergan, Promethegan) = antiemetic, antihistamine, sedative, motion sickness, post-operative pain, anesthetic -EPS side effect: tardive dyskinesia, Parkinson’s syndrome, akathisia is most common in elderly patients

quetiapine (Seroquel) = Schizophrenia, acute manic episodes and/or depressive episodes with bipolar disorder (monotherapy or with lithium)

thiothixene (Navane) = psychotic disorders in children, rapid tranquilization of agitated child; patients with dementia -prolongs QT interval: consult physician prior to administering vasoconstrictor

risperdone (Risperdal) = Commonly used agent in schizophrenia, acute mania and/or irritability/aggression with bipolar disorder, behavioral problems with dementia, Tourette’s

ziprasidone (Geodon) = schizophrenia, acute manic or mixed episodes with bipolar disorder with or without psychosis, acute agitation with schizophrenia -prolongs QT interval: consult physician prior to administering vasoconstrictor

Why are Cholinesterase Inhibitors typically used?

• Indirect-Acting Cholinergic Drugs • Also known as “cholinesterase inhibitors” • These drugs stop the breakdown of acetylcholine (via cholinesterase), which allows for the

concentration of acetylcholine to build up = acetylcholine remains active and stimulates the PANS

• These drugs produce PANS stimulation • Dementia with Alzheimer’s disease • Investigational for mild to moderate dementia with Parkinson’s disease • Examples:

o donepezil (Aricept) o rivastigmine (Exelon) o galantamine (Razadyne)

Side Effects of Direct-Acting and Indirect-Acting Cholinergic Drugs

• nausea, vomiting, diarrhea (by increasing GI activity) • salivation, sweating (increased gland secretions) • bronchoconstriction

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• constricted pupils • Paralysis at high doses (effect at neuromuscular junction) • CNS = confusion

Anticholinergic Drugs for Parkinson’s Disease

• benztropine (Cogentin) • trihexyhenidyl (not in U.S.; Canadian drug)

Anticholinergic Drugs (Parasympatholytics)

• Prevent the action of acetylcholine at the postganglionic PANS nerve endings • “blocker” drugs or antagonists • Block the receptor site for acetylcholine • Do not prevent release of ACH • Acetylcholine cannot act on receptors in smooth muscle, glands or the heart • Also called antimuscarinic drugs (block muscarinic receptors but not nicotinic receptors)

Pharmacologic Effects of Anticholinergic Drugs

• Reduce PANS activity o Skin = decrease sweating o GI = decrease salivation, decreased gut motility o Urinary tract = urine retention o Respiratory = bronchodilation o CNS = decreased concentration/memory; sedation; possible hallucinations and coma

Adverse Reactions to Anticholinergic Drugs

• Frequently are extensions of their pharmacologic effects • Xerostomia • Blurred vision, photophobia • Tachycardia • Fever • Urinary and GI stasis • Hyperpyrexia (elevated temperature) • Hot, dry flushed skin (lack of sweating) • Toxicity = CNS excitation = delirium, hallucinations, convulsions, respiratory depression

III. ORAL HEALTH CONSIDERATIONS FOR NEUROPSYCHIATRIC CONDITIONS

- most neuropsychiatric medications cause xerostomia -watch for opportunistic infections -loss of protective effects: viral, fungal, bacterial infections -traumatic aphthous ulcers - lack of interest in performing daily self-care - increased demineralization, caries and gingival disease - lack of interest/motivation to seek treatment

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- caution with epinephrine = Monitor vital signs! -use vasoconstrictors cautiously with all classes of antidepressants except SSRIs -tricyclics and monoamine oxidase inhibitors -venlafaxine (Effexor) – depression, anxiety, OCD, ADHD --all drugs for ADHD -some antipsychotics = consult drug reference guide

-SSRIs = bruxism: increased extrapyramidal effects -burning mouth syndrome = observed in depression and anxiety; tricyclics

IV. PEPTIC ULCER DISEASE 1. Incidence and Prevalence -among most common human ailments -peak prevalence occurs in young adulthood (age 30 to 50 years) -first degree relatives have threefold higher risk -higher prevalence seen among: -smokers -heavy drinkers -hyperparathyroidism -renal dialysis patients -use of NSAIDS for longer than 1 month -death (from complications) of disease occur in elderly

2. Etiology -primary aggressive factor: Helicobacter pylori infection -present in more than 90% of cases

-contributing factors: -acid hypersecretion -cigarette smoking -psychological and physical stress – increases acid secretion -use of NSAIDS for longer than 1 month

-NSAID-induced ulcers occur more often in stomach than duodenum -concomitant use of aspirin, alcohol, corticosteroids and anticoagulants increases

risk -obsessive compulsive disorder – increases acid secretion -caffeine – increases acid secretion -alcohol – alters cell permeability, leads to cell death = injures mucosa 3. Treatment

-if ulcer is confined and uncomplicated: antisecretory drugs -if H pylori is present: antisecretory drugs with antimicrobials -combination therapy is used: -tetracycline and metronidazole or amoxicillin and clarithromycin with proton-pump inhibitor or bismuth subsalicylate (Pepto-Bismol) -treatment lasts for 2 weeks -modification of factors that contribute to ulceration

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Medications - OTC antacids - weak bases that interact with stomach acid to form water and salt; raise gastric pH - composition: aluminum hydroxide, magnesium hydroxide, calcium carbonate - Histamine H2 receptor antagonists - OTC meds used to manage symptoms of heartburn, acid indigestion, benign gastric and duodenal ulcers, GERD, hypersecretory conditions and erosive esophagitis - cimetidine (Tagamet), famotidine (Pepcid), nizatidine (Axid) and ranitidine

hydrochloride (Zantac) - Proton pump inhibitors

- bind to H+/K+-ATPase enzyme system (proton pump) in parietal cells which reduces acid secretion - reduce gastric secretions, neutralize gastric acid after release, protect gastric mucosa from damage -chronic use is linked to stomach cancer -associated with osteoporosis and risk for hip fracture - esomeprazole (Nexium), lansoprazole (Prevacid), omeprazole (Prilosec), pantoprazole (Protonix), esomeprazole (Nexium), rabeprazole (Aciphex)

4. Dental Considerations -thorough medical history review for risk factors and symptoms -avoid prescribing: aspirin, aspirin-containing products, NSAIDS -use acetaminophen (Tylenol) -Cox-2 inhibitors (Celebrex) -H2 receptor blockers like cimetidine (Tagament) decrease the metabolism of many drugs: -diazepam, lidocaine (adjust dosage) -H pylori is found in dental plaque = reservoir for infection/reinfection -good oral hygiene; frequent scaling and root planing -use of antibiotics = Candidiasis will require antifungal therapy -oral manifestations of peptic ulcer disease: -vascular malformations of lip (macules, venous pool) -enamel erosion -GI medications: -taste alteration -blood dyscrasias = increased risk for infections, bleeding -xerostomia

- OTC antacids bind to other meds in the stomach = antacids and tetracycline - OTC antacids alter absorption, bioavailability and elimination of many drugs - wait 2 hours before/after taking antacids before taking other meds

- histamine H2 receptor antagonists and proton pump inhibitors decrease the availability of azole antifungals

- Tagamet and Zantac alter effects of warfarin - Tagamet increases serum concentrations of some benzodiazepines, lidocaine and the quinolone antibiotics

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DRUG ORAL SIDE EFFECTS omeprazole (Prilosec®) xerostomia, taste alteration, esophageal

candidiasis, pharyngeal pain pantoprazole (Protonix®) xerostomia, taste alteration, pharyngitis, increased

cough, aphthous stomatitis, gingivitis, glossitis, halitosis, oral moniliasis, tongue discoloration, herpes simplex, erythema multiforme

nizatidine (Axid®) xerostomia, laryngeal edema ranitidine bismuth citrate (Tritec®) taste alteration, darkening of tongue ranitidine hydrochloride (Zantac®) erythema multiforme rabeprazole (Aciphex™) xerostomia, mouth ulcerations esomeprazole (Nexium™) xerostomia, ulcerative stomatitis, taste loss

Oral side effects associated with gastrointestinal medications V. CARDIOVASCULAR DISEASE DRUGS THAT ALTER BLEEDING ANTIPLATELET MEDICATIONS -aspirin = antiplatelet drug -blocks cyclo-oxygenase, an enzyme associated with clot formation -inhibits platelet aggregation -prevents thrombus formation on atherosclerotic plaques

-lowers risk of MI in those with increased risk for atherosclerosis/thrombogenesis -lowers risk of MI and stroke in those with previous history of MI and stroke, unstable angina, post-coronary artery bypass grafting

-one enteric coated 325 mg tablet of aspirin daily or 81 mg low dose aspirin Sudden Discontinuation of Aspirin

Discontinuing the use of aspirin increases mortality risk 1 Large clinical trial (n=1358) with hospitalized patients with an acute coronary syndrome 2

3 groups: never taken an oral antiplatelet agent (n=930), Hx of prior use (n=355), recently discontinued use (n=73) Among recently discontinued aspirin group, mostly due to physician recommendation prior to surgery, there was a higher 30 day rate of death or MI and adverse bleedings than among prior users No difference in the incidence of death or MI at 30 days between nonusers and prior users. Recent withdrawal displayed worse clinical outcomes than nonusers.

1. Ho PM, Spertus JA, Masoudi FA, et al. Impact of medication therapy discontinuation on mortality after myocardial

infarction. Arch Intern Med. 2006 Sep 25;166(17):1842-7. 2. Collet JP, Montalscot G, Blanchet B, et al. Impact of prior use or recent withdrawal of oral antiplatelet agents on acute

coronary syndromes. Circulation. 2004 Oct 19;110(16):2361-7. Epub 2004 Oct 11.

A meta-analysis reviewing data from over 50,000 patients showed that aspirin non-adherence/withdrawal was associated with a three-fold higher risk for major adverse cardiac events. 3 Risk was even greater among patients with coronary stents.

Risk was amplified by a factor of 89 in patient who had undergone stenting.

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3. Biondi-Zoccai GG, Lotrionte M, Agostoni P, et al. A systematic review and meta-analysis on the hazards of discontinuing or not adhering to aspirin among 50,279 patients at risk for coronary artery disease. Eur Heart J. 2006 Nov;27(22):2667-74. Epub 2006 Oct 19. other anti-platelet medications: aspirin and dipyridamole (Aggrenox) cilostazole (Pletal)

ticlopidine (Ticlid) – used for those who are intolerant to aspirin, when aspirin therapy has failed, and coronary stent implantation

Lowers risk of stent thrombosis Low risk of bleeding complications compared to other strategies

clopidogrel (Plavix)

Replaced use of ticlopidine Lower rates of major adverse cardiac events and mortality compared with ticlopidine Better safety-tolerability profile

Lower risk of neutropenia Indications: reduce rate of TE (MI, stroke, vascular death) in patients with recent MI or stroke; reduce rate of TE in patients with unstable angina managed medically or with PCI (with or without stents); reduces rate of death and TE in patients with ST-Sement elevation MI managed medically Dosing: 300 mg loading dose; 75 mg daily (with aspirin 81-325 mg daily) Problems:

Drug interactions Slow onset of action Wide variability in patient response

Includes “no” response

prasugrel (Effient) *new drug approved in July 2009 Approved for patients with acute coronary syndromes undergoing PCI Indications: Reduces rate of thrombotic cardiovascular events (eg, stent thrombosis) in patients with unstable angina, non-ST-segment elevation MI, or ST-elevation MI (STEMI) managed with percutaneous coronary intervention Loading dose of 60 mg followed by maintenance dose of 10 mg Manufacturer labeling states to also take 75-325 mg aspirin once daily upon recommendation of provider

clopidogrel (Plavix) and prasugrel (Effient)

Prodrugs Noncompetitive antagonists of P2Y12 receptor Inhibit ability of adenosine diphosphate (ADP) to induce platelet aggregation and decreases subsequent platelet aggregation Block receptor for the life of the platelet = irreversible effect action is independent of and additive to aspirin

Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents: a science advisory from the American Heart Association, American College of Cardiology, Society

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for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with representation from the American College of Physicians.

Grines CL, Bonow RO, Casey DE Jr, Gardner TJ, Lockhart PB, Moliterno DJ, O'Gara P, Whitlow P; American Heart Association; American College of Cardiology; Society for Cardiovascular Angiography and Interventions; American College of Surgeons; American Dental Association; American College of Physicians. William Beaumont Hospital, Royal Oak, Michigan, USA. J Am Dent Assoc. 2007 May;138(5):652-5.

Abstract BACKGROUND: and Overview. Dual antiplatelet therapy with aspirin and a thienopyridine has been shown to reduce cardiac events after coronary stenting. However, many patients and health care providers prematurely discontinue dual antiplatelet therapy, which greatly increases the risk of stent thrombosis, myocardial infarction and death. CONCLUSIONS AND CLINICAL IMPLICATIONS: This advisory stresses the importance of 12 months of dual antiplatelet therapy after placement of a drug-eluting stent and educating patients and health care providers about hazards of premature discontinuation. It also recommends postponing elective surgery for one year, and if surgery cannot be deferred, considering the continuation of aspirin during the perioperative period in high-risk patients with drug-eluting stents. PMID: 17473044

*Link to download free full text copy: http://jada.ada.org/cgi/content/full/138/5/652 3 Recommendations from Advisory Statement (listed above):

Those concerned about peri/postprocedural bleeding must be aware of catastrophic risks of premature discontinuation

-Consult cardiologist to discuss optimal patient management strategies Elective procedures with significant risk of peri/postoperative bleeding should be deferred until patient has completed an appropriate course of thienopyridine therapy:

-12 months after DES implantation if they are not at high risk of bleeding -Minimum of one month for bare-metal stent implantation

Patients with DES who are to undergo subsequent procedures that mandate discontinuation of drug therapy, aspirin should be continued if at all possible

-Restart thienopyridine as soon as possible after the procedure because of concerns of late stent thrombosis

platelet glycoprotein IIb/IIIa receptor antagonists (fibrinogen receptor inhibitors): -used in combination with aspirin and heparin to treat unstable angina -decrease the incidence of death and MI -inhibit final common pathway involved in adhesion, activation, aggregation abciximab (ReoPro) eptifibatide (Integrilin) tirofiban (Aggrastat)

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NSAIDS

Ibuprofen has a very short half-life (2-4 hours)

Withhold for 4-6 half-lives prior to invasive dental surgical procedures (about 1 day prior to treatment)

Cause bleeding as a side effect, especially GI bleeding FDA Black Box Warning: NSAIDs are associated with an increased risk of adverse cardiovascular thrombotic events, including fatal MI and stroke.

In 2006, the FDA issued an informational statement to healthcare professionals stating that “ibuprofen can interfere with the anti-platelet effect of low dose aspirin (81 mg per day), potentially rendering aspirin less effective when used for cardioprotection and stroke prevention. Healthcare professionals should advise consumers and patients regarding the appropriate concomitant use of ibuprofen and aspirin.” 1 The concern is that concurrent use of these medications can increase risk for adverse cardiac events, and thus, the FDA issued the following considerations:

• “Counseling patients about the appropriate timing of ibuprofen dosing if they are also taking aspirin for cardioprotective effects.

• With occasional use of ibuprofen, there is likely to be minimal risk from any attenuation of the antiplatelet effect of low dose aspirin, because of the long-lasting effect of aspirin on platelets.

• Patients who use immediate release aspirin (not enteric coated) and take a single dose of ibuprofen 400 mg should dose the ibuprofen at least 30 minutes or longer after aspirin ingestion, or more than 8 hours before aspirin ingestion to avoid attenuation of aspirin’s effect.

• Recommendations about the timing of concomitant use of ibuprofen and enteric-coated low dose aspirin cannot be made based upon available data.

• Other nonselective OTC NSAIDs should be viewed as having the potential to interfere with the antiplatelet effect of low-dose aspirin unless proven otherwise.

• Prescribing analgesics that do not interfere with the antiplatelet effect of low dose aspirin for high risk populations.” 1

1. U.S. Food and Drug Administration. U. S. Department of Health and Human Services. Information for Healthcare Professionals: Concomitant Use of Ibuprofen and Aspirin. New Information [9/2006] - Concomitant Use of Ibuprofen and Aspirin. Available at: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm125222.htm

ANTICOAGULANT MEDICATIONS

• Antithrombins o antithrombin o heparin

• Coumarin derivatives o warfarin (Coumadin, Jantoven)

• Thrombin inhibitors o argatroban – px/tx of thrombosis with heparin-induced thrombocytopenia (HIT); adjunct

to PCI if at risk for HIT

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o bivalirudin (Angiomax) – with ASA for unstable angina receiving PCI; undergoing PCI with risk for HIT

o dabigatran etexilate (Pradaxa) – thromboprophylaxis for hip/knee replacement o desirudin (Iprivask) – prophylaxis of DVT for hip replacement o fondaparinux (Arixtra) – thromboprophylaxis for hip/knee replacement o lepirudin (Refludan) – anticoagulation with HIT o rivaroxaban (Xarelto) – thromboprophylaxis for hip/knee replacement

ANTITHROMBINS

• Antithrombin III (Atryn, Thrombate III)

o given to those with an antithrombin III deficiency • Heparin - enhances the inhibition rate of clotting proteases by antithrombin III impairing normal

hemostasis and inhibition of factor Xa. • Low molecular weight heparins - strongly inhibit factor Xa; higher ratio of antifactor Xa to

antifactor IIa activity than unfractionated heparin.

Heparin • Naturally-produced anticoagulant (anti-thrombin) • Synthetic version given by IV • Indications: prevention and treatment of thromboembolic disorders • Anticoagulant for dialysis procedures • Heparin Lock flush used to clear IV lines • Produces immediate anticoagulation effect • Patient admitted to hospital is started on heparin and warfarin: heparin produces initial effect

Low Molecular Weight Heparins • Use: prevention of DVT with or without PE; reduce risk for PE; acute unstable angina; non-Q-

wave MI • Mechanism: Inhibit factor Xa and IIa (thrombin)

o dalteparin (Fragmin) o enoxaparin (Lovenox) o tinzaparin (Innohep)

Indications for enoxaparin (Lovenox) • Acute coronary syndromes: Unstable angina, non-ST-elevation, and ST-elevation MI • DVT prophylaxis: Following hip or knee replacement surgery, abdominal surgery, or in medical

patients with severely-restricted mobility during acute illness who are at risk for TE complications

• DVT treatment (acute): Inpatient treatment (patients with and without PE and outpatient treatment (patients without PE)

o Note: High-risk patients include those with one or more of the following risk factors: >40 years of age, obesity, general anesthesia lasting >30 minutes, malignancy, history of deep vein thrombosis or pulmonary embolism

• Used following hip and knee replacement – at least 10 days and o until risk for DVT has subsided or o patient is adequately anticoagulated on warfarin

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COUMARIN DERIVATIVES • warfarin (Coumadin, Jantoven) • interferes with liver synthesis of vitamin-K dependent clotting factors • effects occurs in 4 to 5 days • when patient is admitted to hospital with stroke, there is a 1 to 2 day overlap period with heparin

following warfarin administration to prevent hypercoagulable state o Heparin produces immediate effect o Takes 4-5 days for effects of warfarin to occur

• Indications for warfarin: o Prophylaxis and treatment of TE disorders (venous and pulmonary) and embolic

complications that arise from atrial fibrillation or cardiac valve replacement o Adjunct to reduce risk of systemic embolism (recurrent MI, stroke) after MI

• Investigational: prevention of recurrent TIA • Many things can upset a patient’s level of anticoagulation from warfarin:

o Fever o Flu o Diarrhea or vomiting o Use of many drugs, including antibiotics o Change in diet (consumption of green leafy vegetables increases vitamin K intake =

promotes clotting) Need vitamin K to synthesize clotting factors in liver Warfarin shuts off production of these clotting factors

**Key messages: warfarin causes the greatest number of drug interactions

o Always check compatibility prior to issuing a prescription o Always ask about the INR and monitor INR status across time to examine trends in

anticoagulation control

THROMBIN INHIBITORS

dabigatran (Pradaxa) • FDA approved October 2010 • Thrombin inhibitor • Prodrug = lacks anticoagulant activity

o converted in vivo to active dabigatran • specific, reversible, direct thrombin inhibitor that inhibits both free and fibrin-bound thrombin • prevents thrombin-mediated effects, and by inhibiting thrombin-induced platelet aggregation • Dabigatran inhibits coagulation by preventing thrombin-mediated effects, including cleavage of

fibrinogen to fibrin monomers, activation of factors V, VIII, XI, and XIII • Indications: • Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation • Postoperative thromboprophylaxis after total hip or knee replacement

o Knee replacement – up to 10 days o Hip replacement – up to 35 days

• compared to warfarin (Coumadin) • advantages: no monthly monitoring; fewer drug-drug and drug-diet interactions • disadvantages: very expensive; twice daily dosing

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• in studies, patients who took Pradaxa had fewer strokes than those taking warfarin o RE-LY trial = Randomized Evaluation of Long-Term Anticoagulation Therapy

• adverse effects: bleeding, GI effects

Indications for Direct Antithrombins (Thrombin Inhibitors) • Prevent/reduce ischemia with unstable angina • Prevent DVT following hip replacement • Prevent/treat thromboembolism • Treatment of heparin-induced thrombocytopenia (HIT) rivaroxaban (Xarelto) (riv a ROX a ban) • New drug – FDA approval announced July 1, 2011 • First and only oral anticoagulant approved in US for orthopedic surgery • Factor Xa inhibitor • Mechanism: inhibits platelet activation and fibrin clot formation via direct, selective, and

reversible inhibition of factor Xa in both the intrinsic and extrinsic coagulation pathways • Indications:

o Postoperative thromboprophylaxis in patients who have undergone hip or knee replacement surgery

• Adults: Postoperative thromboprophylaxis: o Knee replacement: 10 mg once daily; recommended total duration of therapy: 12-14 days o Hip replacement: 10 mg once daily; total duration of therapy: 35 days

fondaparinux (Arixtra) (fon da PARE i nuks) • Factor Xa inhibitor

o causes an antithrombin III-mediated selective inhibition of factor Xa • Interrupts the blood coagulation cascade and inhibits thrombin formation and thrombus

development • Indications: • Prophylaxis of deep vein thrombosis (DVT) in patients undergoing surgery for hip replacement

and knee replacement • hip fracture (including extended prophylaxis following hip fracture surgery) • abdominal surgery (in patients at risk for thromboembolic complications) • treatment of acute pulmonary embolism (PE) • treatment of acute DVT without PE • Usual duration: 5-9 days

o up to 10 days following abdominal surgery o up to 11 days following hip replacement or knee replacement

• Extended prophylaxis is recommended following hip fracture surgery o has been tolerated for up to 32 days total

• Acute DVT/PE treatment: o Note: Start warfarin on the first treatment day and continue fondaparinux until INR is

between 2 and 3 (usually 5-7 days) (Hirsh, 2008)

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COMMON ORAL PROBLEMS IN ELDERLY PATIENTS Disease or Drug Induced Xerostomia

Caries and Demineralization Tooth Sensitivity Periodontal Disease Fungal Infections Viral Infections Pain and Ulcerations Food Packing/Decreased Oral Clearance Oral signs and symptoms associated with drug-induced xerostomia Caries Enamel demineralization Enamel erosion Cemental abrasion on exposed root surfaces Dentinal hypersensitivity Increased gingivitis and periodontal infection Opportunistic infections Increased viral infections Oral ulcerations/stomatitis Taste alteration Dry, cracked, bleeding lips Fissured, sore tongue Angular cheilitis Friable oral mucosa Difficulty speaking, chewing, Difficulty wearing dentures or appliances swallowing Drug classes that produce neural effects on the salivary glands The following are examples of anticholinergic drugs that reduce the volume of serous saliva:

Antidepressants Antiemetics Antihistamines Antihypertensives

Anti-parkinsonian drugs Antipsychotics Antispasmodics

The following are examples of sympathomimetic drugs that produce a viscous, mucinous saliva:

Amphetamines Appetite suppressants

Bronchodilators Decongestants

Sources: Sreeby LM, Schwartz SS: A reference guide to drugs and dry mouth, 2nd ed, Gerodontol 14:33-47, 1997;Porter SR, Scully C, Hegarty AM: An update of the etiology and management of xerostomia, Oral Surg Oral Med Oral Pathol Pral Radiol Endod 97:28-46, 2004; Nähri TO, Meurman JH, Ainamo A: Xerostomia and hyposalivation: causes, consequences and treatment in the elderly, Drugs & Aging 15:103-116, 1999.

Drug classes associated with causing xerostomia

Antiacne agents Antianxiety agents Anticholinergics/Antispasmodics Anticonvulsants Antidepressants Antidiarrheals

Antiemetics Antihistamines Antihypertensives

Anti-inflammatory analgesics Antinauseants Anti-parkinsonian agents

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Antipsychotics Anorexiants Bronchodilators

Decongestants Diuretics Muscle Relaxants

Narcotic Analgesics Sedatives

Source: USP DI® Drug Information for the Healthcare Professional, vol 1, ed. 24, Englewood, CO, Micromedix, Inc., 2004.

Taste and Smell Disorders Drugs that alter taste

Alcohol detoxification agents Alzheimer’s medications

Analgesics (NSAIDS) Anesthetics (general and local)

Anorexiants Antacids

Antianxiety agents Antiarthritics

Anticholinergics Anticonvulsants

Antidepressants Antidiabetics (oral hypoglycemics)

Antidiarrheals Antiemetics

Antifungals Antigout medications

Antihistamine (H1) antagonists Antihistamine (H2) antagonists

Antihyperlipidemics Antiinfectives

Anti-inflammatory/antiarthritics Antimigraine agents

Antiparkinson agents Antipsychotics

Antithyroid medications Antivirals

Anxiolytics/sedatives Asthma preventives

Bronchodilators Calcium-affecting drugs

Cancer chemotherapeutics Cardiovascular medications

CNS stimulants Decongestants

Diuretics Glucocorticoids

Gallstone solubilization agents Hemorheologics

Immunomodulators Immunosuppressants

Irritable bowel syndrome medications Methylxanthines

Nicotine replacement drugs Ophthalmics

Proton pump inhibitors Retinoids, systemic

Salivary stimulants Skeletal muscle relaxants

Vitamins

Source: Gage TW, Pickett FA: Mosby’s dental drug reference, ed. 7, St. Louis, 2005, Elsevier Mosby.

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Systemic drugs associated with lichenoid drug reactions

Category Agents

Analgesic agents NSAIDs, propoxyphene/acetaminophen, acetaminophen/codeine

Antianxiety drugs benzodiazepines

Antiarrhythmics quinidine

Anticonvulsant drugs Depakote

Antineoplastic drugs levamisole

Cardiovascular agents Beta-adrenergic blockers, angiotensin II antagonist, calcium channel blockers, cardiac glycoside, methyldopa, thiazide diuretics, potassium supplements

Gastric acid secretion inhibitors H2-antagonists

Hormone replacement Thyroid hormone, insulin, sulfonylureas, metformin, oral contraceptives, estrogen, progesterone

Photographic Dyes

Uricosuric agent Allopurinol

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: February 21, 2013 ________________________________________________________________________ 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. 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. List several new dental drugs and discuss their indications for use in practice. 4. Discuss the management of oral side effects caused by medications. *This material may not be reproduced without the written permission of the author.

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TOP 20 MOST COMMONLY PRESCRIBED MEDS 2011

(Total Prescriptions Dispensed) 1. hydrocodone and acetaminophen 2. hydrocodone and acetaminophen 3. levothyroxine sodium 4. lisinopril 5. Lipitor 6. simvastatin 7. Plavix 8. Singulair 9. azithromycin 10. Crestor 11. Nexium 12. levothyroxine sodium 13. metoprolol tartrate 14. hydrocodone and acetaminophen 15. Synthroid 16. Lexapro 17. Proair HFA 18. ibuprofen 19. trazodone HCl 20. amoxicillin INDICATIONS DRUGS pain relievers hydrocodone and acetaminophen,

ibuprofen hypercholesterolemia Lipitor, simvastatin, Crestor hypertension lisinopril, metoprolol adverse thromboembolic events Plavix endocrine disorders levothyroxine, Synthroid antibiotics amoxicillin, azithromycin antidepressants Lexapro, trazodone GERD, reflux or hypersecretory disease Nexium respiratory disease Singulair, ProAir HFA PAIN RELIEVERS 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).

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BRAND NAME: Caldolor, Ibu, Motrin GENERIC NAME: ibuprofen THERAPEUTIC CATEGORY: NSAID USE: management of mild to moderate pain; inflammatory diseases and rheumatoid disorders, fever, dysmenorrhea ORAL COMPLICATIONS: none DRUG INTERACTIONS: Ibuprofen and other non-selective NSAIDS can interfere with the antiplatelet and cardioprotective effects of aspirin: follow appropriate timing of dosing. Avoid use in aspirin-allergic patients. Ibuprofen may increase the levels of anticoagulants, antiplatelet drugs, bisphosphonates, cyclosporine, digoxin, haloperidol, lithium, methotrexate, NSAIDS, potassium-sparing diuretics, quinolone antibiotics, salicylates, thrombolytic agents, vancomycin and vitamin K antagonists. Levels of ibuprofen may be increased by ACE inhibitors, angiotensin II receptor blockers, antidepressants (tricyclic, teriary amine), systemic corticosteroids, glucosamine, herbs that have anticoagulant or antiplatelet properties, NSAIDS, probenecid, SSRIs, serotonin/norepinephrine reuptake inhibitors. Ibuprofen may decrease the levels of ACE inhibitors, angiotensin II receptor blockers, antiplatelet agents, beta blockers, loop diuretics, potassium-sparing diuretics, salicylates and thiazide diuretics. Levels of ibuprofen may be decreased by bile acid sequestrants, NSAIDS and salicylates. Avoid alcohol. HYPERCHOLESTEROLEMIA 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). 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. BRAND NAME: Crestor GENERIC NAME: rosuvastatin calcium THERAPEUTIC CATEGORY: HMG-CoA reductase inhibitor USE: used with dietary therapy for hyperlipidemias to reduce elevated total cholesterol, LDL-C, apolipoprotein B and triglycerides in patients with hypercholesterolemia and for treatment of familial hypercholesterolemia ORAL COMPLICATIONS: none

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DRUG INTERACTIONS: The anticoagulant effects of warfarin may be increased by rosuvastatin: monitor carefully. Rosuvastatin increases the serum concentrations of the hormonal contraceptives ethinyl estradiol and norgestrel. Concurrent administration of other cholesterol lowering medications (gemfibrozil, clofibrate, fenofibrate or niacin) may increase the risk for myopathy and rhabdomyolysis. Metal containing antacids may decrease the plasma concentratins of rosuvastatin: administer antacids at least 2 hours after dosing. Bile acid sequestrants may reduce the absorption of rosuvastatin. HYPERTENSION 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. 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. ADVERSE THROMBOEMBOLIC EVENTS BRAND NAME: Plavix GENERIC NAME: clopidogrel THERAPEUTIC CATEGORY: antiplatelet agent USE: reduce risk of atherosclerotic events in patients with history of recent MI, stroke, or established peripheral arterial disease; acute coronary syndrome (unstable angina) ORAL COMPLICATIONS: none DRUG INTERACTIONS: Clopidogrel interfere with the metabolism of many medications, including oral hypoglycemics, phenytoin and some NSAIDS, increasing risk for toxicity. Concurrent use of clopidogrel with naproxen increases risk for GI bleeding. Anticoagulant medications taken with antiplatelet medications increases risk for bleeding. Atorvastatin (Lipitor) and macrolide antibiotics

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(clarithromycin, erythromycin) decrease the effects of clopidogrel. Many herbs interact with Plavix and increase risk for bleeding: discontinue 14 days prior to surgery. ENDOCRINE DISORDERS 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. ANTIBIOTICS 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. 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.

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ANTIDEPRESSANTS 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. BRAND NAME: Oleptro GENERIC NAME: trazodone THERAPEUTIC CATEGORY: serotonin reuptake inhibitor/antagonist USE: major depressive disorder ORAL COMPLICATIONS: xerostomia, taste alteration DRUG INTERACTIONS: Sedative effects may be increased with alcohol and other CNS depressants; levels of trazodone may be increased by buspirone, SSRIs and venlafaxine. Trazodone may decrease levels/effects of dabigatran. Avoid use of methylene blue (used to treat methemoglobinemia and UTI). GERD OR HYPERSECRETORY DISEASE 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. RESPIRATORY DISEASE BRAND NAME: Singulair GENERIC NAME: montelukast THERAPEUTIC CATEGORY: leukotriene-receptor antagonist USE: prophylaxis and chronic treatment of asthma; seasonal allergies; perennial allergic rhinitis ORAL COMPLICATIONS: none DRUG INTERACTIONS: Phenylketonuric patients should be informed that the chewable tablets contain phenylalanine. Carbamazepine, phenobarbital, phenytoin, rifampin, and nafcillin may decrease the levels of montelukast. St. John’s wort may also decrease the levels of montelukast.

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BRAND NAME: ProAir HFA GENERIC NAME: albuterol THERAPEUTIC CATEGORY: beta 2-adrenergic agonist USE: asthma, chronic obstructive pulmonary disorder (COPD) ORAL COMPLICATIONS: xerostomia, altered taste, vomiting, tooth discoloration DRUG INTERACTIONS: Increased toxicity (cardiovascular effects) is noted when albuterol is used with any of the following drugs: MAO inhibitors (Marplan, Nardil, Parnate), tricyclic antidepressants (Elavil), sympathomimetic agents (amphetamines, dopamine) and inhaled anesthetics(malignant arrhythmias). The effect of albuterol is decreased when used with nonselective beta blockers. When used with inhaled ipratropium (Atrovent), an increase in the duration of bronchodilation may occur. REFERENCES FOR TOP 20 MEDICATIONS Top 200 Medications for 2011. Source: IMS Health. Available at: http://www.pharmacytimes.com/publications/issue/2012/July2012/Top-200-Drugs-of-2011 Physicians’ Desk Reference, ed. 65. Montvale, Medical Economics Co, Inc., 2011. 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. 18th ed. Hudson, Lexi-Comp Inc., 2012. 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. FDA WATCHES AND WARNINGS varenicline (Chantix)

FDA Safety Alert and Public Health Advisory Statement Patients should be provided with a medication guide highlighting neuropsychiatric symptoms receiving this medication Angioedema, serious skin reactions, visual impairment, accidental injury July 2011 – relabeling changes due to cardiovascular concerns; FDA is requiring manufacturer to conduct meta-analysis of clinical trials to examine risks:

http://www.fda.gov/Drugs/DrugSafety/ucm259161.htm#safety azithromycin, clarithromycin

May be associated with liver failure

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tramadol (Ultram, Ultracet) FDA safety labeling revision Potential risk for potentially life-threatening serotonin syndrome Serotonin syndrome may occur with use of tramadol alone or with concurrent use of SSRIs, tricyclic antidepressants, MAOIs Adverse events may occur at recommended tramadol dose tramadol is indicated for moderate to moderately severe pain in adults for short-term use (≤5 days) for acute pain

MANAGEMENT OF ORAL SIDE EFFECTS CAUSED BY MEDICATIONS

FLUORIDE THERAPY For caries control: Prescription fluorides for supplemental home use: 1.1% neutral sodium gel or dentifrice

5000 ppm Prescription

Clinpro 5000 Anti-Cavity Toothpaste (3M ESPE), 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 rinse

920 ppm Prescription

CaviRinse (3M ESPE), NaFrinse (Medical Products Laboratory), Oral B Fluorinse (P&G), PreviDent Dental Rinse (Colgate), ProDenRx Rinse (Zila)

1.1% sodium and acidulated phosphate gel

5000 ppm Prescription

Phos-Flur (Colgate)

0.4% stannous fluoride gel

1000 ppm Fluoridex Daily Defense Sensitivity Relief (Discus 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 fluoride rinse

30 ml dose dilution = 7 mg fl- ion and 22 mg stannous ion

PerioMed (3M ESPE), Fluoridex Daily Renewal (Discus Dental)

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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 acidulated phosphate rinse

200 ppm Phos-Flur (Colgate); OrthoWash (3M 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) Enamel Pro Varnish with ACP (Premier)

FluoroDose (Centrix)

Fluoridex Lasting Defense (Discus Dental)

Prevident (Colgate)

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® 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 (GlaxoSmithKline): 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

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4. Oasis (Oasis Consumer Healthcare) -mouthwash or mouth spray -“TriHydra” technology: hydrophilic polymers, xanthum gum, glycerine and

carboxymethylcellulose; relieves symptoms for up to 2 hours 5. GC Dry Mouth Gel (GC America)

-alcohol free, sugar free, neutral pH, applied as needed

6. Salese (Nuvora) -lozenge with water absorbing polymer plus xylitol; raises pH; Dentiva: antimicrobial 7. Colgate Dry Mouth Relief Mouthrinse (Colgate Oral Pharmaceuticals)

-fluoride mouthrinse (0.02% sodium fluoride = 90 ppm); tri-polymer system to help coat soft tissues; moisture retention; alcohol free; soothing, mild flavor

8. 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 - dosage: for radiation therapy patients: - 5 mg tid (15-30 mg per day); 12 weeks of therapy - 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

-3 FDA and ADA approved antimicrobials: chlorhexidine, Listerine® and triclosan (Colgate® Total) - Other agents available as mouthrinses exhibit antibacterial properties, but do not

possess good substantivity: -stannous fluoride = antibacterial. carioprotective and desensitizing effects

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-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) -Crest Pro Health Rinse with CPC has data to support 12 hour substantivity = vehicle improves bioavailability

-oxygenating agents = damage bacteria by altering cell membrane permeability

-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 -Triclosan (Colgate® Total toothpaste) -antimicrobial agent in dentifrice form = decreases plaque viability -both antimicrobial and anti-inflammatory properties -unique technology of delivery mode: PVM/MA copolymer = GANTREZ

-copolymer allows binding to surfaces with slow release; promotes adhesion/uptake of triclosan on enamel, plaque and soft tissue

-triclosan: broad spectrum, substantive to 12 hours -over 75 clinical trials to support safety and efficacy of Colgate® Total -anti-inflammatory effect: dampens stimulation of the production of IL1- beta and TNF alpha = inflammatory mediators (cytokines) that destroy tissue and bone = local 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)

- silica-based low-water dentifrice to reduce hydrolysis of sodium hexametaphosphate and to maintain effective pyrophosphate levels

-12 hour substantivitiy Important take home messages with antimicrobials: - chlorhexidine and CPC are cations: drug reactions with SLS and fluoride = wait 30 minutes after brushing or vigorously remove all toothpaste residue before rinsing - chlorhexidine and Listerine have been shown to kill 7 species of Candida - chlorhexidine and Listerine kill multiple species of Strep: Strep mutans

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- chlorhexidine and Listerine have been shown to reduce incidence and severity of aphthous ulcers 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, 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 Topical Antifungal Medications: nystatin ointment apply thin coat to affected area (or inner surface of denture) 4-5

times per day Mycelex ® 10 mg troches (clotrimazole)

disp: 70 troches; dissolve 1 troche in mouth 5 times per day until gone; leave any prosthesis out during treatment and soak prosthesis in nystatin liquid suspension overnight

Nizoral® 2% cream (ketoconazole)

apply thin coat to affect areas (or to inner surface of denture) after meals

iodoquinol and hydrocortisone cream

apply locally to affected area 3-4 times per day for 10 days to 2 weeks, then re-evaluate

nystatin and triamcinolone acetonide ointment

apply locally to affected area 4 times per day for 10 days to 3 weeks and then re-evaluate

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)

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Systemic Azole Antifungal Medications: Diflucan® 100 mg tablets

fluconazole

Take 2 tablets on day 1, then 1 tablet daily for 14 days until gone *a shorter course may be adequate; extensive infection may require second course of treatment

Nizoral® 200 mg

ketoconazole

Take 1 tablet daily with a meal for 14 days *may cause irreversible liver damage with long-term use (greater than 3 weeks)

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: - acyclovir

- topical anesthetic rinses (eg. Benadryl, Xylocaine viscous, OTC benzocaine products )

- fluids, vitamins and mineral supplements and rest Antiviral Medications for Herpes Simplex: Zovirax® 200 mg tablets acyclovir take 1 capsule 5 times per day for 10 days or 2

capsules 3 times per day for 10 days Zovirax® ointment 5% acyclovir apply q 3 hours (6 times/day) for 7 days Denavir® cream 10mg/g (1%)

penciclovir apply every 2 hours (lips and face only) for 4 days

Valtrex® 500 mg valacyclovir 2 grams twice daily for 1 day at prodrome (separate doses by 12 hours)

Abreva (OTC) docosanol 10% apply locally as directed 5 times per day; start at prodrome and continue for 4 days; do not apply directly to inside of mouth or around eyes

Viroxyn® (OTC) alcohol/benzalkonium chloride

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

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- 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 -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; Oral Balance®

Topical prescription agents for aphthous lesions: amlexanox oral paste 5% Apthasol® apply 4 times per day (after

meals and at bedtime) until area heals

triamcinolone acetonide Dental Paste

Oralone®0.1%; Kenalog in Orabase® 0.1%

apply after each meal and at bedtime

chlorhexidine oral rinse Peridex®, PerioGard® rinse with 20 ml for 30 sec tid fluocinonide 0.05% (used for oral inflammatory lesions that do not respond to Kenalog in Orabase®)

Lidex® ointment mixed 50/50 with Orabase (30 grams total)

apply thin layer to oral lesions 4 times per day

clobetasol propionate 0.05% Temovate® apply small quantity with a cotton tip applicator to affected area 3-4 times daily

betamethasone 0.1% ointment apply small quantity with a cotton tip applicator to affected area 3-4 times daily

dexamethasone elixir 0.5 mg/5 mL

Decadron® rinse with 1 teaspoon for 2 minutes 4 times per day and expectorate

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Topical OTC agents for aphthous/pain control: Benzyl alcohol Zilactin® Gel apply q 3-4 hours Benzocaine 10% Zilactin® B apply q 3-4 hours Lidocaine 2.5% Zilactin L apply q 3-4 hours Diphenhydramine Benadryl® Elixir swish with 1 tsp for 2 min before

each meal (can be used as a swish and swallow)

Benzocaine, gelatin, pectin and sodium carboxymethylcellulose

Orabase® with Benzocaine apply 3-4 times/day

Tetracaine Hydrochloride 1% Viractin® apply 3-4 times/day up to 7 days