Medication Management Considerations for the Older Patient © Mark A. Stratton, Pharm.D., BCPS, CGP, FASHP Professor of Pharmacy and Langsam Endowed Chair in Geriatric Pharmacy College of Pharmacy, University of Oklahoma

Learning Objectives State morbidity and mortality statistics associated with medication related problems in the older patient List factors responsible for “America’s Other Drug Problem” Describe changes that predispose older patients to increased morbidity and mortality from medication therapy Compare and contrast potentially inappropriate medications in the elderly with safer alternatives Discuss management considerations to minimize DRPs

Did You Know… One-third of hospital admissions by patients over 75 are linked to drug related problems (DRPs) Either due to an adverse drug reaction (ADR) or to the effects of poor adherence 51% of all deaths and 39% of hospitalization due to ADRs occur in the elderly 50,000-75,000 older people die each year due to a drug related problem…making this the fifth leading cause of death in the geriatric population Half of these deaths are considered to be preventable

Did You Know… Estimated cost of inappropriate medications and their consequences in older people approaches $200 billion/year $32.8 billion associated with DRPs resulting in LTC admissions Now referred to as “America’s Other Drug Problem”

Contributors to “America’s Other Drug Problem ” Polypharmacy (Rx and OTC) Consequences of drug-drug interactions Adherence issues Pharmacokinetic changes of aging Pharmacodynamic changes of aging Effects of co-morbidity on kinetics and dynamics

Polypharmacy Over 30% of prescription medications are taken by those over the age of 65 (13% of population) An estimated 40 to 50% of OTC medications are consumed by older people Over 80% of older people take at least one medication per day An estimated 25% of all prescribed medications for older people are potentially inappropriately selected or dosed (Beer’s List) An estimated 30% of all medications for older people are considered unnecessary

Inappropriate Medications Beer’s List – a list of approximately 140 medications and doses considered to be potentially inappropriate for the elderly in that the risk exceeds the benefit and there exist a safer alternative (Fick, DM et al. J Am Geriatr Soc 2012) Use of medications on this list is associated with decreased quality of life, increased risk of hospitalizations and prolonged hospitalizations. Insulin, warfarin and digoxin account for one-third of ER visits due to ADRs in the elderly. This points out that although a medication might be justified we are not appropriately monitoring these for side-effects such as blood glucose, INRs and serum levels or ECGs.

Drug-Drug Interactions Increased likelihood of clinically significant drug-drug interactions with increased number of medications used Increased morbidity and mortality associated with drug- drug interactions in the elderly due to decreased physiologic reserve

Adherence Issues Prior to the start of Medicare Part D on January 1, 2006 one-third of older people failed to take medications as prescribed due to cost issues Today, while Medicare Part D has resulted in increased utilization of medications by the elderly, 10 to 15% still have accessibility issues due to cost. “Doughnut Hole” effect Low income subsidy qualification issues

Pharmacokinetic Changes of Aging Absorption Though numerous structural and physiological age-related changes in the GI tract exist, they are of minimal clinical significance in the absence of gastrointestinal pathology Decreased first-pass after oral administration – morphine, isosorbide dinitrate (Isordil*) Heart failure can affect the absorption of some medications including furosemide (Lasix*) Effects of aging on percutaneous, subcutaneous and intramuscular absorption is largely unknown but in states of poor perfusion expect delayed or incomplete absorption Distribution (volume of distribution) Body Composition Changes Lean-to-fat ratio altered – digoxin (Lanoxin*) Decreased total body water - lithium Protein concentration changes – warfarin (Coumadin*)

Pharmacokinetic Changes of Aging Metabolism (clearance) Liver size, blood flow decline with age altering the metabolism of drugs with high-flow dependent metabolism such as propranolol (Inderal*) and verapamil (Calan*) Some but not all Phase I metabolic pathways performed by the CYP system (oxidation, reduction, hydrolysis) diminish with age Diazepam (Valium*), chlordiazepoxide (Librium*), alprazolam (Xanax*), flurazepam (Dalmane*) Phase II (conjugation) metabolic pathways do not appear to diminish with age Lorazepam (Ativan*), oxazepam (Serax*), triazolam (Halcion*), temazepam (Restoril*)

Pharmacokinetic Changes of Aging Elimination (clearance) Majority of people over the age of 50 lose 10% of renal function per decade Digoxin, aminoglycosides, vancomycin, pencillins, cephalosporins, salicylate metabolites, quinolones, etc. Reliability of the Cockroft-Gault equation for estimating CrCl Underestimates true CrCl in older people of normal weight Overestimates true CrCl in older people who are under weight This is of particular importance in adjusting doses of antibiotics in the elderly patient with an acute infectious disease

Pharmacodynamic Changes of Aging Alterations in receptor affinity Alterations in receptor number Enhanced or diminished post-receptor response

Pharmacodynamic Changes of Aging Central nervous system sensitivity Enhanced receptor response Reduced CNS dopamine Increased EPS symptoms Reduced serotonin receptor function Enhanced sensitivity to antidepressants Altered GABA-benzodiazepine receptor function Increased sensitivity to benzodiazepine, alcohol, barbiturate Reduced CNS acetylcholine Enhanced anti-cholinergic side effects Sedation, confusion, psychosis, delirium Urinary retention, constipation Use of drugs with anticholinergic effects are associated with a decline in various measures of cognitive function, especially in the very old or those with pre-existent dementia

Common Drugs With Anticholinergic Effects AntihistaminesAntipsychoticsAntidepressantsAntispasmodics Chlorpheniramine Hydroxyzine Diphenhydramine Chlorpromazine Haloperidol Thioridazine Clozapine Amitriptyline Nortriptyline Imipramine Doxepin Protriptyline Belladonna alkaloids Dicyclomine Hyoscyamine Oxybutynin Propantheline Tolterodine AntiemeticsAntiulcerantsAntiparkinsoniansAntidiarrhealsMiscellaneous Dimenhydrinate Meclizine Promethazine Trimetho- benzamide Cimetidine Ranitidine Amantadine Benztropine Diphenoxylate/ atropine Clonidine Codeine

Pharmacodynamic Changes of Aging Alterations in Na, K-ATPase and Ca ++ channels leads to enhanced toxicity of digoxin and antiarrhythmics Changes in homeostatic control mechanisms (baroreceptors) making orthostatic changes in blood pressure more likely from antihypertensive. Impaired glucose counter-regulation predisposes elders to hypoglycemia from antidiabetic agents

Medication Classes Requiring Special Consideration in the Elderly

Antihypertensives/Diuretics Principles: Increased likelihood of electrolyte disturbances Start low (HCTZ 12.5 mg) Cornerstone for hypertension management Define goals especially in the very old

Other Antihypertensives Principle: Select agents which act peripherally and are not highly lipophilic Avoid agents which act centrally or are highly lipophilic Preferred: ACE inhibitors, ARBs, CC blockers, atenolol New JNC-VIII recommendations may change the order of preferred agents in the elderly (2012) Avoid: Methyldopa, clonidine, propranolol Short-acting nifedepine

Antiarrhythmics/Digitalis Glycosides Principles: Increased cardiosensitivity and altered kinetics Pay attention to ECG effect to assess toxicity Avoid antiarrhythmic drugs as first-line treatment for atrial fibrillation (i.e. amiodarone, dronedarone)

Antianxiety/Sedative Agents Principles: Select agents which are short-acting, without active metabolites Evaluate need for therapy frequently Use lowest possible dose for the shortest possible time Avoid agents which are long-acting with active metabolites Preferred Oxazepam (Serax ® ), lorazepam (Ativan ® ), triazolam (Halcion*), temazepam (Restoril*) Zolpidem (Ambien ® ), Zaleplon (Sonata ® ), Eszopiclone (Lunesta ® ) – use one-half the adult dose in geriatric patients Even the short acting agents above are now on the new Beer’s list Ramelteon (Rozerem ® ) – melatonin agonist Avoid Diazepam (Valium ® ), chlordiazepoxide (Librium ® ), flurazepam (Dalmane ® ), alprazolam (Xanax ® )

Antipsychotic Agents Principles Use least sedating agents with minimal anticholinergic side effects and minimal orthostatic changes in blood pressure. Be aware of black box warning – increased risk of sudden death and CVA in patient with dementia Consider GDR (Gradual Dose Reduction) in long term care residents as required by CMS guidelines Preferred Atypical antipsychotics Risperidone (Risperdal ® ) – first choice amongst atypicals based on cost, effectiveness and side-effect profiles Olanzapine (Zyprexa ® ) Ziprasidone (Geodon ® ) Quetiapine (Seroquel ® ) Aripiprazole (Abilify ® ) Avoid Older antipsychotics – haloperidol, thioridazine

Antidepressants Principles Use least sedating agents with minimal cardiotoxicity, minimal anticholinergic side effects and minimal orthostatic changes in blood pressure Treat to remission, “start low – go slow – but go” Preferred SSRIs: sertraline (Zoloft ® ), paroxetine (Paxil ® ), fluvoxamine (Luvox*), citalopram (Celexa ® ), escitalopram (Lexapro ® ) Mixed: bupropion (Wellbutrin ® ), venlafaxine (Effexor ® ), Duloxetine (Cymbalta ® ), vilazodone (Viibryd*) Tricyclic Antidepressant: Secondary amines – nortriptyline (Aventyl ® ), desipramine (Norpramin ® ) Tetracyclics – mirtazapine (Remeron ® ) Avoid Select tertiary amine tricyclic antidepressants – amitriptyline (Elavil ® ), imipramine (Tofranil ® )

Anticoagulants Principles Be aware of increased sensitivity to warfarin, especially in patients with decreased protein. Be aware of increased risk of bleeding. Re-evaluate need for therapy frequently. Start low - go slow. Increased risk of bleeding with low molecular weight heparins and parenteral factor Xa inhibitor (fondaparinux) in patients over 75. Likely more bleeding risk with the direct thrombin inhibitor, dabigatran, in patients over 75 as well – possibly use ½ dose. Potentially greater bleeding risk of the oral Xa inhibitors as well.

Analgesics Principle Be aware of increased GI risk associated with NSAIDS. Supplement with PPI to prevent GI bleeding if long term use is indicated COX-2 Inhibitors: celecoxib (Celebrex ® ) Be aware of salt and water retaining properties in patients with hypertension or CHF and other potential CV effects. Due to these risk the 2009 AGS guidelines recommend use of NSAIDs with extreme caution. Use acetaminophen and mild opioids may be more appropriate. Maximum daily acetaminophen dose is 3 grams per day Be aware of increased sensitivity to narcotic analgesics. Be aware of additive CNS depressant effect of narcotics with other agents. Avoid Ketoralac,meperidine or pentazocine

Antiulcer Therapy Preferred Proton Pump Inhibitors May have concern regarding Calcium homeostasis increasing risk of osteoporosis (and fractures), and Vitamin B 12 deficiency anemia Use H-2 antagonist carefully, use one-half the usual adult dose Avoid Cimetidine (Tagamet*)

Hypoglycemic Agents Principles Be aware of altered glucose counter-regulatory response to hypoglycemia. Be aware of altered presentations of hypoglycemic symptoms Initiate therapy at one-half the usual adult dose Avoid First generation sulfonylureas (chlorpropamide) and second generation - glyburide Possible increased mortality in the elderly on rosiglitazone compared to pioglitazone. More fracture risk with pioglitazone.

OTCs/Herbals Principles Be aware of increased sensitivity Monitor for drug-drug interactions carefully

Management Considerations Minimize number of medications, attempt gradual dose reduction Maximize non-pharmacologic alternatives Titrate therapy to the individual patient Improve monitoring of narrow therapeutic index drugs (warfarin, insulin, digoxin, etc.) Educate the patient and caregiver Review all medications annually Improve communications skills (practitioner and consumer) Use a single pharmacy for all medication needs, learn how to utilize your pharmacist to help manage medications and cost Improve interdisciplinary communication and cooperation Use extra caution during transitions between care facilities and providers (reconciliation)

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