Medication in the Elderly Erica Wang BScPharm, PharmD, ACPR, BCPS

The Elderly… Have different goals of therapy Have a variable response to medications Are more sensitive to adverse reactions Have reduced renal function Increased risk for bleeding Are at increased risk for falls

Therapeutic index. Therapeutic index. For any drug, there is a relationship between dose and efficacy (black lines) and a second relationship between dose and toxicity (gray lines). These curves are derived from populations and efficacy may be incomplete, as indicated in these examples. The arrows on each plot identify the dose at which 50% of the response is seen, and the therapeutic index is indicated by the open arrow at the bottom of each plot. Some drugs considered here, such as warfarin and clopidogrel, have narrow therapeutic indices, whereas others (β-blockers, statins) have wider ones. DNA variants may modulate the relationship between efficacy and toxicity in populations and in individuals. Dan M. Roden et al. Circ Res. 2011;109:807-820 Copyright © American Heart Association, Inc. All rights reserved.

Goals of Therapy Reduce mortality Reduce morbidity Maximize quality of life Maintain functional capacity Reduce functional decline Maintain independence Prevent cognitive decline and depression Prevent falls Maximize balance, flexibility, strength Prevent adverse drug effects Ensure compliance

Aging Frailty Multimorbidity Cognitive decline Sensory impairment (hearing and visual) Balance impairment Sarcopenia Osteoporosis Risk for falls

Poll Everywhere The elderly are at increased risk for falls due to: A) Muscle weakness B) Impaired balance or gait C) History of falls D) Medications E) All of the above

Anticholinergics Drug Class Examples Antidepressants TCA (amitriptyline) SSRIs (Paroxetine) Antiemetics Antipsychotics Loxapine, methotrimeprazine, quetiapine Antihistamines Diphenhydramine, hydroxyzine Opioids Morphine, hydromorphone, fentanyl Parkinson’s medications

Statins Elderly have reduced muscle mass Increasing age increases risk for sarcopenia Muscle mass reduces to ~15% of total body weight (TBW) in those ~75 years of age 30% of TBW in younger adults Reduced muscle mass results in reduction in strength Increases risk for incidence of disability and mortality Combined with other co-morbid age-related changes, elderly with myalgias are at increased risk of falls

Statins Elderly are at risk of many adverse effects of statins Muscle toxicity Cognitive changes Diabetes

ASPREE Trial ASPirin in Reducing Events in the Elderly Multi-centered, randomized, double-blind, placebo-controlled trial in Australia and USA Planned enrollment N=19000 Clinical question: in an elderly individual without CVD, does ASA 100mg daily compared to placebo increase the years of life free from physical and cognitive disability? Recruitment ended 2014 Expected trial results in 2018

Bleeding Advanced age is associated with platelet dysfunction, decreased clotting factor synthesis and increased fragility of blood vessels

Antiplatelets Benefits Proven (secondary prevention) Potential Reduce mortality Prevent cardiovascular events Prevent cerebrovascular events Reduce peripheral arterial disease progression Potential Reduce risk of vascular dementia Reduce risk of functional decline Decrease risk of cancer Reduce depression

Antiplatelets ASA P2Y12 Inhibitors Dual antiplatelet therapy (DAPT) Clopidogrel Ticagrelor Prasugrel Ticlopidine Dual antiplatelet therapy (DAPT) ASA + P2Y12 inhibitor Advanced age results in platelet dysfunction ASA has 2 mechanisms for bleeding Acid in contact with GI mucosa Reduction in platelet aggregation P2Y12 inhibitors have varying risks for bleeding Ticlopidine > clopidogrel > ticagrelor > prasugrel Avoid prasugrel for > 75 years of age and hx CVA (increased risk of ICH) DAPT duration should be limited to minimum

Anticoagulants Warfarin Non-vitamin K oral anticoagulants (NOACs) Dabigatran, Rivaroxaban, Apixaban, Edoxaban IV unfractionated heparin (UFH) Low molecular weight heparins (LMWH) Enoxaparin, dalteparin, tinzaparin, nadroparin Bivalirudin Fondaparinux Argatroban Advanced age results in redcued synthesis of clotting factors Increased risk of bleeding in elderly on anticoagulants Generally, elderly are on lower doses Low body weight Reduced renal function Poor nutritional status Some have age-specific and renal function-specific dosage adjustments

J Clin Epidemiol 2002;55(2):157-163 Risk of GIB

Take Home Points Goals of therapy differ between elderly patients Prevention of falls is very important Elderly have variable response to medication effects, so start low and go slow Be extra vigilant and monitor for adverse effects of medications Involve your pharmacist to help 