2019 Oregon Dental Conference® Course Handout

Ann Spolarich, RDH, PhD Course 3158: “Pharmacologic Management of the Geriatric Patient: Practice Considerations for Oral Health Care Professionals” Friday, April 5 9 am - 12 pm 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: April 5, 2019 ______COURSE DESCRIPTION: The purpose of this course is to review characteristics and disease trends among the aging population, and oral disease risks associated with and common systemic diseases. Most patients take multiple medications, many of which have oral complications and interactions of significance to dentistry. 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 changes in pharmacokinetics associated with normal aging.

3. Describe the Beers Criteria for potentially inappropriate medication use in older adults.

4. Identify that are associated with an increased risk for falling.

5. Identify drugs that are associated with risk for alteration of the QT interval.

6. Discuss considerations with , benzodiazepines, and opiate use in older adults.

7. Discuss indications and adverse events associated with drugs used for and Parkinson’s disease.

8. Discuss potential uses and risks associated with medications in older adults.

9. Describe different classes of altering medications with indications for use.

*These course materials may not be duplicated without the written consent of the course instructor.

1 I. Pharmacokinetics of Normal Aging • Decreased absorption due to increased stomach acidity (*why elderly use ) • Decreased liver function; more drug unchanged (more “active” drug) • Decreased lean body mass • Increased body fat (drug storage) • Decreased total body water (drug more concentrated in blood) • Decreased plasma proteins (more unbound “active” drug) • Less binding capacity (decreased plasma proteins), less (decreased liver function) and decreased renal function allow for normal doses of drug to act at overdose levels in the geriatric patient • Give lower dose

• Liver diseases = in most cases, drug metabolism is reduced due to diminished function of the cytochrome P-450 system; dosing must be reduced • Renal diseases = results in renal impairment of drug excretion; dosing must be modified on the basis of renal clearance values of the drug

II. Benzodiazepines • Commonly abused • Prescribers rarely understand addictive quality of these meds with related complications in elderly patients • Patients receive prescriptions from multiple providers • Patients develop “benzo-abstinence syndrome” due to unavailability of drug or during hospitalization for other medical problem

Indications for BDZs • Chronic anxiety o Should assess for depression o Prescribe with slow discontinuation of BDZs • Depression • Sleep disturbance o Chronic insomnia significant problem in elderly o Rarely improves with long-term use of BDZs o Nightly use of BDZs lose effectiveness after 3-6 mos (tolerance) o Requires steadily increasing doses to initiate sleep • Long-term use produces significant physical dependence or addiction

Complications of BDZs • Exacerbates chronic medical problems o COPD, GERD • Increases length of stay and morbidity in hospitalized patients • Higher rates of MVA and falls • Significant additive effect with other drugs (opiates, alcohol) • Prolonged half-life predisposes to easy intoxication • Withdrawal syndrome occurs after stopping (similar to alcohol withdrawal) • Withdrawal often happens following admission to hospital for other medical reason (e.g. surgery) • Treatment for BDZ abuse: o Detoxification and withdrawal o Appropriate therapy for psychiatric problems

2 o Long-term addiction treatment (e.g. AA, NA) • If less than 2 years of life remaining, remain on BDZs but monitor dosages • Most have very long half-lives • Most are metabolized to active compounds • Repeated dosing results in accumulation of drug in the body • triazolam (Halcion) – shortest half-life of oral meds o fast onset of action o *no kinetic data reported with multiple titration doses (used for oral conscious sedation) ƒ “unlabeled” use o elderly experience greater sedation and increased psychomotor impairment ƒ much higher risk for oversedation

III. *Beers Criteria • 3 lists of medications that pose potential risks outweighing potential benefits for people 65 and older • Medications that are potentially inappropriate because: o pose high risks of adverse effects o limited effectiveness in older patients o alternatives are available • Medications that are potentially inappropriate for those with certain diseases or disorders: o drugs may exacerbate health problems • Medications to be used with caution: o more risks than benefits o may be the best choice for a particular individual if administered with caution o medications need to be tailored to the unique needs of each patient • Benzodiazepines are to be avoided for treatment of: o Insomnia o Agitation o Delirium • Flumazenil = BDZ antagonist = “blocker” drug • Will not block CNS effects from alcohol, barbiturates, general or opiates • May not reliably reverse respiratory depression/hypoventilation o Establish airway o Provide ventilation • BDZ reversal may cause seizures = be prepared to manage

IV. Opiates in Older Adults

• Not all pain responds to same medications • When should treatment be intensified? • Unresolved pain or continued complaints of pain despite escalating doses of prescription opioids: o Disease progression o Self-medication of co-morbid psychiatric and/or physical complaints o Diversion o Pseudo-addiction = providing analgesia stops behaviors • Altered CYP450 enzymes • Reluctance to report adequate pain relief o Fear that care will be reduced o Fear that clinician will stop searching for underlying cause of pain

3 o Misconceptions or misunderstanding regarding opioid treatment

*Avoid concurrent use of opiates and benzodiazepines whenever possible

Alternative Interventions to Pain Management • Musculoskeletal pain = acetaminophen or NSAIDS • Neuropathic pain = tricyclic antdepressants or anti-epileptics; topical anesthetics for localized neuropathic pain o Sympathectomy = weak evidence • Neuralgia = local anesthetics + steroids; botulinum toxin • pain = steroids, hyaluronic acid • Cognitive behavioral therapy • Physical activity • Assistive devices • Transcutaneous electrical nerve stimulation (Tens units) • Massage

Should we use opiates in older adults? • Frequent occurrence of both cancer and non-cancer persistent pain o opioid are appropriate for moderate to severe persistent pain • Challenges: factors involved in making appropriate choices, monitoring the beneficial effects of pain relief and managing side-effects • Goals of using opioids = improved function and quality of life

Opiates and End of Life Care • Pain management in the elderly is undertreated • Challenges with pain management: o co-morbidities o polypharmacy o cognitive dysfunction • In the geriatric population, the assessment of pain requires measurement of: o pain intensity o delineation of opioid responsiveness o clarification of the impact of pain on patient’s ƒ psychological ƒ social ƒ spiritual ƒ existential domains

V. Drugs and Falls • Many drugs increase risk for falling o Antihypertensives (orthostatic hypotension) o Antidepressants o Sedative o o Benzodiazepines o Opiates o NSAIDS o *Alcohol • Risk assessment and prevention

4 VI. Drugs that Alter the QT Interval

• Drugs that prolong the QT interval: o Fluoroquinolone antibiotics ƒ moxifloxacin (Avelox) ƒ ciprofloxacin (Cipro) ƒ levofloxacin (Levaquin) o Macrolide antibiotics ƒ azithromycin (Zithromax) ƒ clarithromycin (Biaxin) o Azole ƒ fluconazole (Diflucan) ƒ ketoconazole ƒ itraconazole (Sporanox) o Epinephrine

Lexicomp® Database 2013; Mosholder AD, Mathew J, Alexander JJ, Smith H, Nambiar S. Cardiovascular risks with azithromycin and other antibacterial drugs. N Engl J Med. 2013 May 2;368(18):1665-8.

VII. Considerations with Antibiotics

Clarithromycin/Azithromycin • Caution in = hepatotoxic o Can lead to hepatitic failure, death • Discontinue immediately if symptoms of hepatitis: o Malaise, nausea, vomiting, abdominal colic, fever • Alters QT interval of the = caution with vasoconstrictor o Elderly at greater risk o Avoid if uncorrected hyperkalemia or hypomagnesemia o Avoid if bradycardia o Avoid if taking Class I or Class III antiarrhythmics o Contraindicated in patients with ventricular arrhythmias (including torsade de pontes)

Pseudomembranous Colitis • Greatest number of -associated cases of C diff diarrhea are from cephalosporins • Also clindamycin o *may occur with many antibiotics

VIII. MAJOR TRANQUILIZERS/ANTIPSYCHOTICS

A. 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

5 -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 - effects = blockade in chemoreceptor trigger zone of the medulla

-All antipsychotics have high therapeutic index -Not addictive

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 - = decrease plasma levels of antipsychotics -Antipsychotics may alter efficacy of antihypertensive medications *monitor vital signs

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TYPICAL ANTIPSYCHOTICS ATYPICAL ANTIPSYCHOTICS chlorpromazine (Thorazine) = Schizophrenia, aripiprazole (Abilify) = Commonly used agent in nausea/vomiting, intractable hiccups, schizophrenia, treatment and stabilization of combativeness 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 clozapine (Clozaril) = Schizophrenia; severe OCD, psychotic disorders and schizophrenia; improves childhood psychosis, attempted suicide, substance outcomes in patients with psychoses who are abuse recovery nonadherent with oral antipsychotics Side effect: agranulocytosis – susceptibility to , hypersalivation (others cause xerostomia), weight gain, reduced risk of EPS haloperidol (Haldol) olanzapine (Zyprexa) = Schizophrenia, bipolar RX for schizophrenia and Tourette’s; severe disorder, acute agitation behavioral problems in children -EPS of TMJ pimozide (Orap) = suppression of severe motor and olanzapine and fluoxetine (Symbyax) = treatment phonic tics with Tourette’s of depressive episodes associated with bipolar -prolongs QT interval: consult physician prior to disorder administering vasoconstrictor prochlorperazine (Compro, Compazine) = paliperidone (Invega) = Schizophrenia antiemetic; psychosis, anxiety -EPS side effect: torticollis (neck muscle spasm) promethazine (Phenadoz, Phenergan, quetiapine (Seroquel) = Schizophrenia, acute Promethegan) = antiemetic, antihistamine, manic episodes and/or depressive episodes with sedative, motion sickness, post-operative pain, bipolar disorder (monotherapy or with lithium) -EPS side effect: tardive dyskinesia, Parkinson’s syndrome, akathisia is most common in elderly patients thiothixene (Navane) = psychotic disorders in risperdone (Risperdal) = Commonly used agent in children, rapid tranquilization of agitated child; schizophrenia, acute mania and/or patients with dementia irritability/aggression with bipolar disorder, -prolongs QT interval: consult physician prior to behavioral problems with dementia, Tourette’s administering vasoconstrictor 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 EPS = extrapyramidal effects

Why are Cholinesterase Inhibitors typically used?

• Indirect-Acting Cholinergic Drugs • Also known as “cholinesterase inhibitors”

7 • 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)

Other Drugs for Alzheimer’s Disease memantine (Namenda) – only drug shown to be effective in later stages tacrine (Cognex) – rarely prescribed due to serious side effects, including possible liver damage

Side Effects of Direct-Acting and Indirect-Acting Cholinergic Drugs • nausea, vomiting, diarrhea (by increasing GI activity) • salivation, sweating (increased gland secretions) • bronchoconstriction • 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

8 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

IX. ORAL HEALTH CONSIDERATIONS FOR NEUROPSYCHIATRIC CONDITIONS

- most neuropsychiatric medications cause xerostomia -watch for opportunistic -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 - 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

X. DRUGS THAT ALTER BLEEDING

ANTIPLATELET MEDICATIONS

- = antiplatelet drug -blocks cyclo-oxygenase, an enzyme associated with clot formation -inhibits aggregation -prevents formation on atherosclerotic plaques -lowers risk of MI in those with increased risk for atherosclerosis/thrombogenesis -lowers risk of MI and in those with previous history of MI and stroke, , post-coronary 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 (n=1358) with hospitalized patients with an 2 3 groups: never taken an oral antiplatelet agent (n=930), Hx of prior use (n=355), recently discontinued use (n=73)

9 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 . 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. 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 . Eur Heart J. 2006 Nov;27(22):2667-74. Epub 2006 Oct 19.

other anti-platelet medications:

aspirin and (Aggrenox) cilostazole (Pletal)

– used for those who are intolerant to aspirin, when aspirin therapy has failed, and implantation Lowers risk of stent Low risk of bleeding complications compared to other strategies

(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

(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

10 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

(Brilinta) – newest agent on the market Indications: acute coronary syndrome (MI, stroke); prevent late stent thrombosis Used Off-label for non-ST-elevation acute coronary syndrome, aspirin intolerant patients

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 , Society 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 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

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

11 MEDICATIONS • derivatives/ K Antagonist o • (anticoagulant) • (anticoagulant) o (Orgaran) *Canadian drug – prevention of DVT following orthopedic surgery or in patients with non-hemorrhagic stroke • Low Molecular Weight Heparin () o dalteparin (Fragmin) – prevention and treatment of DVT/VTE; unstable angina o enoxaparin (Lovenox) – acute coronary syndromes; DVT prophylaxis o nadroparin (Fraxiparine) *Canadian drug - acute coronary syndromes; DVT prophylaxis o tinzaparin (Innohep) *Canadian drug – treatment of DVT/PE; prevent DVT/PE following orthopedic surgery; prevent clotting in indwelling IV lines and circuit during hemodialysis • Direct Inhibitors (anticoagulants) o – px/tx of thrombosis with heparin-induced thrombocytopenia (HIT); adjunct to PCI if at risk for HIT o (Angiomax) – with ASA for unstable angina receiving PCI; undergoing PCI with risk for HIT o etexilate (Pradaxa) – prevention of stroke and systemic embolism with nonvalvular ; postop thromboprophylaxis for hip/knee replacement o desirudin (Iprivask) *US drug – prophylaxis of DVT for hip replacement • Factor Xa Inhibitors (anticoagulants) o (Eliquis) - thromboprophylaxis for hip/knee replacement; nonvalvular atrial fibrillation o (Arixtra) – thromboprophylaxis for hip/knee replacement; unstable angina; non-ST segment elevation MI o (Xarelto) – thromboprophylaxis for hip/knee replacement; treatment of DVT; nonvalvular atrial fibrillation; treatment of PE

ANTITHROMBINS

• III o given to those with an antithrombin III deficiency • Heparin - enhances the inhibition rate of clotting proteases by antithrombin III impairing normal and inhibition of factor Xa. • Low molecular weight - 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

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Low Molecular Weight Heparins • Use: prevention of DVT with or without PE (following hip and knee replacement); reduce risk for PE; acute coronary syndromes: acute unstable angina; non-ST-elevation MI; non-Q-wave MI • Mechanism: Inhibit factor Xa and IIa (thrombin)

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) ƒ Need vitamin K to synthesize clotting factors in liver ƒ 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) • 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 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)

13 • advantages: no monthly monitoring; fewer drug-drug and drug-diet interactions • disadvantages: very expensive; twice daily dosing • in studies, patients who took Pradaxa had fewer than those taking warfarin o RE-LY trial = Randomized Evaluation of Long-Term Anticoagulation Therapy • adverse effects: bleeding, GI effects

*new for dabigatran = idarucizumab (humanized antibody fragment (FAB))

Indications for Direct (Thrombin Inhibitors) • Prevent/reduce ischemia with unstable angina • Prevent DVT following hip replacement • Prevent/treat thromboembolism • Treatment of heparin-induced thrombocytopenia (HIT)

Novel Oral Anticoagulants apixaban (Eliquis) – treatment of DVT, PE; nonvalvular atrial fibrillation, thromboprophylaxis after hip/knee replacement (Bevyxxa) – prophylaxix of VTE in hospitalized adults; not studied in patients with prosthetic heart valves (Savaysa) – treatment of DVT, PE following 5 to 10 days of initial therapy with parenteral anticoagulant fondaparinux (Arixtra) - thromboprophylaxis for hip/knee replacement or hip fracture; treatment of DVT/PE in conjunction with warfarin rivaroxaban (Xarelto) - thromboprophylaxis for hip/knee replacement; nonvalvular atrial fibrillation; treatment of DVT/PE; extended anticoagulant to reduce risk for recurrence of DVT/PE

Current evidence: apixaban (Eliquis) - best documented alternative to warfarin and aspirin for stroke prevention in the broad population with AF rivaroxaban (Xarelto) – good alternative to warfarin in AF; most data in DVT and ACS

*New reversal agent: Andexxa (FDA approved May 2018) – for apixaban and rivaroxaban only

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

14 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 Antihistamines Antihypertensives Anti-parkinsonian drugs Antipsychotics Antispasmodics

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

Amphetamines Appetite suppressants

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 Antipsychotics Anorexiants Bronchodilators Decongestants Muscle Relaxants Narcotic Analgesics Sedatives

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

15 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 /sedatives Asthma preventives Bronchodilators Calcium-affecting drugs Cancer chemotherapeutics Cardiovascular medications CNS Decongestants Diuretics Gallstone solubilization agents Hemorheologics Immunomodulators Immunosuppressants Irritable bowel syndrome medications Methylxanthines Nicotine replacement drugs Ophthalmics Proton pump inhibitors Retinoids, systemic Salivary stimulants relaxants

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

16 Systemic drugs associated with lichenoid drug reactions

Category Agents agents NSAIDs, propoxyphene/acetaminophen, acetaminophen/codeine Antianxiety drugs benzodiazepines Antiarrhythmics quinidine drugs Depakote Antineoplastic drugs levamisole Cardiovascular agents beta-adrenergic blockers, angiotensin II antagonist, calcium channel blockers, , 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

17 POST TEST

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: April 5, 2019

1. All of the following are normal physiological changes of aging that can affect drug handling in the body EXCEPT? a. Decreased liver function b. Decreased kidney function c. Increased body fat d. Increased total body water The correct answer is D

2. All of the following are medications that are included in the Beers criteria used to inform appropriate medication use in older adults EXCEPT? a. Medications that are potentially inappropriate because of high risk for adverse effects b. Medications that should only be used with caution because their benefits outweigh known risks c. Medications that may be inappropriate because use may exacerbate existing health problems d. Medications that have limited documented effectiveness in older adults and better alternatives are available The correct answer is B 3. All of the following drugs increase risk for falling EXCEPT? a. Alcohol b. Benzodiazepines c. Antihypertensives d. Epinephrine

The correct answer is D 4. All of the following drugs classes are known to alter the QT interval of the heart, thus increasing risk for an arrhythmia EXCEPT? a. Penicillins b. Fluoroquinolones c. Macrolides d. Azole antifungals The correct answer is A

5. All of the following drugs are used to prevent late-stent thrombosis EXCEPT? a. ticlopidine b. clopidogrel c. ticagrelor d. warfarin The correct answer is D 6. Antiplatelet and anticoagulant medications should always be discontinued prior to invasive dental procedures. a. True b. False The correct answer is B