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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 28, 2017 _____________________________________________________________________________ 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 changes in pharmacokinetics associated with normal aging. 3. Describe the Beers Criteria for potentially inappropriate medication use in older adults. 4. Identify drugs 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 antibiotics, benzodiazepines, sedatives and opiate use in older adults. 7. Discuss indications and adverse events associated with drugs used for dementia and Parkinson’s disease. 8. Discuss potential uses and risks associated with antipsychotic medications in older adults. 9. Describe different classes of blood altering medications with indications for use. *These course materials may not be duplicated without the written consent of the course instructor. 1 I. II. Pharmacokinetics of Normal Aging Decreased absorption due to increased stomach acidity (*why elderly use antacids) 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 metabolism (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 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 antidepressants 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 sedative hypnotic 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) “unlabeled” use o elderly experience greater sedation and increased psychomotor impairment 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 anesthetics 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 Joint 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 analgesics 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 psychological social spiritual existential domains V. Drugs and Falls Many drugs increase risk for falling o Antihypertensives (orthostatic hypotension) o Antidepressants o Sedative hypnotics o Antipsychotics 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 moxifloxacin (Avelox) ciprofloxacin (Cipro) levofloxacin (Levaquin) o Macrolide antibiotics azithromycin (Zithromax) clarithromycin (Biaxin) o Azole antifungals fluconazole (Diflucan) ketoconazole 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 liver disease = 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 heart = 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 antibiotic-associated cases of C diff diarrhea are from cephalosporins Also clindamycin o *may occur with many antibiotics VIII. 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 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 -Antiemetic 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 -Anticonvulsants = decrease plasma levels of antipsychotics -Antipsychotics may alter efficacy of antihypertensive medications *monitor vital signs 6 TYPICAL ANTIPSYCHOTICS chlorpromazine (Thorazine) = Schizophrenia, nausea/vomiting, intractable hiccups, combativeness fluphenazine (Prolixin) = management of psychotic disorders and schizophrenia; improves outcomes in patients with psychoses who are nonadherent with oral antipsychotics haloperidol (Haldol) RX for schizophrenia and Tourette’s; severe behavioral problems in children -EPS of TMJ pimozide (Orap) = suppression of severe motor and phonic tics with Tourette’s -prolongs QT interval: consult physician prior to administering vasoconstrictor prochlorperazine (Compro, Compazine) = antiemetic; psychosis, anxiety -EPS side effect: torticollis (neck muscle spasm) 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 thiothixene (Navane) = psychotic disorders in children, rapid tranquilization of agitated child; patients with dementia -prolongs QT interval: consult physician prior to administering vasoconstrictor ATYPICAL ANTIPSYCHOTICS 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 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 olanzapine (Zyprexa) = Schizophrenia, bipolar disorder, acute agitation olanzapine and fluoxetine (Symbyax) = treatment of depressive episodes associated with bipolar disorder paliperidone (Invega) = Schizophrenia quetiapine (Seroquel) = Schizophrenia, acute manic episodes and/or depressive episodes with bipolar disorder (monotherapy or with lithium) 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 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) 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 Adverse Reactions to Anticholinergic Drugs Frequently are extensions of their pharmacologic effects Xerostomia Blurred vision, photophobia Tachycardia Fever 8 IX. Urinary and GI stasis Hyperpyrexia (elevated temperature) Hot, dry flushed skin (lack of sweating) Toxicity = CNS excitation = delirium, hallucinations, convulsions, respiratory depression 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 - 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 -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. 9 1. 2. 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. 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 nonadherence/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 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 (many Canadian brand names) – 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 10 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 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 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 ANTICOAGULANT MEDICATIONS Coumarin derivatives/Vitamin K Antagonist o warfarin Heparin (anticoagulant) Heparinoid (anticoagulant) o danaparoid (Orgaran) *Canadian drug – prevention of DVT following orthopedic surgery or in patients with non-hemorrhagic stroke Low Molecular Weight Heparin (anticoagulants) 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 11 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 Thrombin Inhibitors (anticoagulants) o argatroban – px/tx of thrombosis with heparin-induced thrombocytopenia (HIT); adjunct to PCI if at risk for HIT o bivalirudin (Angiomax) – with ASA for unstable angina receiving PCI; undergoing PCI with risk for HIT o dabigatran etexilate (Pradaxa) – prevention of stroke and systemic embolism with nonvalvular atrial fibrillation; postop thromboprophylaxis for hip/knee replacement o desirudin (Iprivask) *US drug – prophylaxis of DVT for hip replacement Factor Xa Inhibitors (anticoagulants) o apixaban (Eliquis) - thromboprophylaxis for hip/knee replacement; nonvalvular atrial fibrillation o fondaparinux (Arixtra) – thromboprophylaxis for hip/knee replacement; unstable angina; non-ST segment elevation MI o rivaroxaban (Xarelto) – thromboprophylaxis for hip/knee replacement; treatment of DVT; nonvalvular atrial fibrillation; treatment of PE o ANTITHROMBINS Antithrombin 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 (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 12 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) 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 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 *new antidote for dabigatran = idarucizumab (humanized antibody fragment (FAB)) 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) 13 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 erosion Dentinal hypersensitivity Opportunistic infections Oral ulcerations/stomatitis Dry, cracked, bleeding lips Angular cheilitis Difficulty speaking, chewing, swallowing Enamel demineralization Cemental abrasion on exposed root surfaces Increased gingivitis and periodontal infection Increased viral infections Taste alteration Fissured, sore tongue Friable oral mucosa Difficulty wearing dentures or appliances 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 Anti-parkinsonian drugs Antihistamines Antipsychotics Antihypertensives 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, 2 nd 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 14 Decongestants Diuretics Narcotic Analgesics Sedatives Muscle Relaxants 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. 15 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 16