Falls & Medications: A Case-Based Approach

Saurabh Patel, PharmacistOrillia Soldiers’ Memorial Hospital

Emergency Medicine & Complex Continuing Care Services

September 23, 2014

Disclosure

None

Objectives

l Understand how medications may contribute to falls & falls-related injuries

l Appreciate serious consequences of falls caused by medications

l Identify medications associated with falls & falls-related injuries

l Take-home points to prevent medication-related falls

Case 1 – Falls as a clue to …..

l 69 y/o female presented to ER with 2 days history of multiple falls, ataxic gait, confusion, weakness, slurred speech, diarrhea, and unexplained ↑ LFTs

l Diagnostic Imaging• CT Head – atrophy, scarring from previous infarction

involving the left occipital lobe, and small left thalamic lacunar infarct

• Doppler – Negative for DVT

l Relevant lab parameters on admission:• Na = 145; K = 2.8; SCr = 142 (CrCl = 24 ml/min)• ALP = 404; ALT = 65; GGT = 687• Phenytoin = 80 (40-80)• Hgb = 90; RBC = 3.09; Plt = 175• Occult Blood = Negative• Positive for Morphine & Benzo on Urine Screen

l Albumin next day:• Alb = 26

Case 1 – Falls as a clue to …..

l PMHx:• Stroke• Anemia• Seizure disorder• Cognitive Impairment (MOCA 15/30)• Alcohol and Opioid abuse• Depression

Case 1 – Falls as a clue to …..

Case 1 – Medications on Admission (15)

• Tylenol 500mg QID• Lipitor 40mg daily• Reactine 20mg daily• Vitamin B12 1000 mcg daily• Plavix 75mg daily• Domepridone 5mg TID• Folic Acid 1mg daily

• Furosemide 40mg daily• Eltroxin 0.1mg daily• Metoprolol 100mg BID• Pantoprazole 40mg BID• Cipralex 10mg daily• Mirtazapine 15mg qHS• Phenytoin 350mg qHS• Quetiapine 100mg qHS

Diagnosis on Admission: • Acute Stroke• Diarrhea and Increase in LFTs NYD

In-Hospital, Next Day:• Code Blue at 10:00• Death at 10:15 due to cardiac arrest • K+ = 7.7 in AM

Case 1 – Falls as a clue to …..

What Happened?

l Phenytoin Corrected for Albumin = 129 µmol/L

l Falls as a clue to Phenytoin Toxicity• Phenytoin Toxicity +/- Stroke

• Ataxia & confusion & weakness (à Falls)• N/V/Diarrhea• Elevated LFTs

Neurology 2012; 79: 145-151

Medications & Falls

Phenytoin Toxicity Falls & Immobility Opioids and Benzo for pain & sleep

DiarrheaHypokalemia Potassium Supplement

Decline in Renal Fxn

Hyperkalemia Cardiac Arrest

Furosemide

Mirtazapine + Quetiapine + Cipralex

CVA; Alcohol + Opioid abuse;

depression; anemia

Neurology 2012; 79: 145-151

Polypharmacyl ≥ 5 medications?

•Taking medication(s) without clinical indication

l Consequences•Adverse drug reactions•Diminished functional status•Geriatric syndromes (Falls)q ≥ 4 Medications increases risk of falls

•Nonadherence• Increase healthcare utilization

1. New Engl J Med 1994; 331: 821-827 2. Am J Geriatr Pharmacother 2007; 5:345-351 3. Clin Geriatr Med 2012; 173-186

Pharmacokinetic ChangesProcess Effect on Drug Deposition

Absorption -Reduced first pass metabolism leads to increased bioavailability of some drugs

Distribution -↑ concentration of albumin-bound drugs-↑ half-life of lipophilic drug due to altered Vd-↑ permeability of blood brain barrier

Metabolism - Reduction in liver mass and decreased hepatic blood flow

Elimination - Increased half-life of renally eliminated drugs due to declining renal function

1. Pharmacol Rev 2004; 56:163-184 2. Clin Geriatr Med 2012; 28:273-286

Pharmacodynamic Changes

l Age-related changes:•⇑ sensitivity to sedation and

psychomotor impairment with benzodiazepines

•⇑ sensitivity to anti-cholinergic agents

l Decreased clearance and increased sensitivity to medications in older adults

l Use low doses and slower titration to decrease the risk of drug intolerance and toxicity

l Careful monitoring of medications for efficacy and safety at regular interval to ensure successful outcomes

14

Clinical Implications

Medications & Falls

Sensory

CNS

MusculoskeletalFalls & Falls-

related Injuries

Balance, sedation, fatigue, dizziness, gait disturbances, confusion,cognitive impairment

Muscle weakness, peripheral neuropathyVisual impairment,

vestibular dysfunction, hearing impairment Hypotension, hypoglycemia

1. Studenski S.A. (2010). Falls. In Fellit H.M, Rockwood K, Woodhouse K (Ed.), Brocklehurst’s textbook of geriatric medicine andgerentology (pp. 894-902). Philadephia, PA: Saunders Elsevier. 2. Can Fam Physician 2011; 57: 771-776

Medications & Falls

Sensory

CNS

MusculoskeletalFalls & Falls-related Injuries

Antipsychotics, Antiepileptics, Antidepressants, Anti-Parkinsonian,Metoclopramide, Anticholinergics, Opioids, Alcohol, Sedatives, Hypnotics

Steroids, Statins, FluoroquinolonesAnticholinergics, OpioidsCV medications

Hypoglycemic agents

1. J Am Geriatr Soc 1999; 47 (1): 30-39 2. J Am Geriatr Soc 1999; 47 (1): 40-50 3. Drugs Aging 2012; 29 (5): 359-3764. Arch Intern Med. 2009;169(21):1952-1960 5. Drugs Aging 2012; 29 (1): 15-30 6.

Evidence

l Medications as a risk factor for falls• Derived from cohort, case-control, and cross-

sectional studies (& meta-analyses)• Confounding factors• Small sample sizes• Statistical analysis• Dose or duration not addressed• Lack of fall definition (patient reporting vs.

documented fall)

Evidence

Medication Class OR (95% CI)Antihypertensives 1.26 (1.08 - 1.46)

Sedatives/Hypnotics 1.31 (1.14 - 1.50)Neuroleptics/Antipsychotics 1.71 (1.44 - 2.04)

Antidepressants 1.72 (1.40 - 2.11)Benzodiazepines 1.60 (1.46 - 1.75)

Diuretics* 1.03 (0.84 – 1.26)ß-Blockers 1.14 (0.97 – 1.33)Narcotics* 0.89 (0.50 - 1.58)NSAIDs 1.65 (0.98 - 2.77)

Arch Intern Med. 2009;169(21):1952-1960J Am Geriatr Soc 2011; 59:430-438

Case 2

l A 95 y/o female admitted to hospital for multiple falls and right hip fracture from LTC. • Confused and dehydrated• Multiple bruises on body including head, face,

shoulder, and hip

Case 2

l Diagnostic Imaging:• X-Ray – Right proximal femur fracture in the

intertrochanteric area extending down into the subtrochanteric area

• CT Head – 7 mm bleed in right temporal region (small and superficial)

Case 2l Past Medical History:

• Anemia• Heart failure• Dementia• COPD• Hypertension• TIA• Hypothyroidism• Left hip replacement• Depression• Osteoarthritis• Osteoporosis

In Hospital…

l ORIF performedl Post-op

• Pain from ribs • LLL pneumonia

l Palliative

Case 2 – Medications (19)

• Citalopram 10mg daily• Lorazepam 0.5mg TID and 1mg

qHS• Tramacet 37.5mg – ½ tab BID• Tylenol 325mg q4hr PRN• ECASA 81mg daily• Calcium 500mg daily• Vitamin D 1000 IU daily• Vitamin B12 1000mcg IM q

monthly• Eltroxin 0.1mg daily• Folic acid 5mg a day

• Furosemide 40mg BID• Nitro-Dur patch 0.4mg daily• Micro-K 8mEq once daily• Symbicort 200/6 – 2 inhalations

QID• MV once daily• Natrual Tears 2 drops for dry eyes

PRN• Voltaren Emugel to shoulders 3

times a day PRN• Lactulose 15mL daily at HS• Senokot 8.6mg qHS PRN

What happened?

l A week ago, lorazepam 1mg at HS was added to help patient “sleep”

Benzodiazepines

ABIM & AGS - Choosing Wisely • Don’t recommend percutatenous feeding tubes in patients with advanced

dementia; instead offer oral assisted feeding• Don’t use antipsychotics as first choice to treat BPSD• Avoid using medications to achieve hemoglobin A1C < 7.5% in most 65 and older;

moderate control is generally better

•Don’t use benzodiazepines or other sedative-hypnotics in older adults as first choice for insomnia, agitation or delirium

• Don’t use antimicrobials to treat bacteriuria in older adults unless specific urinary tract symptoms are present

J Am Geriatr Soc 2013; 61: 622-631

Benzodiazepines

Drugs Aging 2012; 29 (8): 639-658

BenzodiazepinesDrug Class Amnestic deficits: short-

term or long-term memoryNon-amnestic deficits:

concentration/information processing/planning/psycho

motor speedBenzodiazepines üüü üüü

Non-benzodiazepines ü ü

1st generation antihistamines

ü üüü

Tricyclic antidepressants ü üüü

Other anticholinergics ü ü

Opioid drugs ü ü

Drugs Aging 2012; 29 (8): 639-658Slide from presentation by Dr. Tannenbaum: First do no harm: reducing morbidity and mortality from polypharmacy in modern medicine

Benzodiazepines & Falls or Falls-related injuries

OR/RR/HR

<1 1 to 2 ≥ 2

High dose or dose increases

üü ü

Duration (>30 days) ü

Short-half life üüü

Time to event < 2 weeks

üü

With interacting drugs

üü

Advanced Age (> 80)

ü

1. Age & Aging 2013; 42: 764-770 2.J Clin Epidemiology 2000; 53: 1222-1229 3. Pharmacoepidemiology and Drug Safety 2010; 19: 1248-1255 4. Age & Aging 1996; 25: 273-278 5. Arch Intern Med 1995; 155:1801-1807 6. Br J Clin Pharmacol 2008; 276-282 7. J Am Geriatr Soc 2011; 59: 1883-1890

Benzodiazepine De-Prescribing

l A letter outlining clinician’s concerns, adverse effects of the benzodiazepines, and advice on tapering schedule showed 2-fold increase in reduction and cessation of benzodiazepines

l One time assessment by geriatrician and 1-hour lecture on falls-risk increasing drugs (benzodiazepines) reduced use of benzodiazepines by 35%

l EMPOWER RCT – A de-prescribing package discussed with patient by pharmacist or physician showed ARR of 22% (27% vs. 5%) in use of benzodiazepines at 6 months

1. Br J Pract 2011; 61:e573-e578 2. Age and Aging 2010; 39: 313-319 3. JAMA Intern Med 2014; 174(6): 890-898

Case 3

l 82 y/o gentleman bed-ridden for 3 days due to fear of falling

l Medical Hx:• HTN

l Medications • Amlodipine 5mg daily• Lisinopril 5mg daily

Case 3

l Newly diagnosed Mitral Valve Regurgitation• Started on Ramipril 10mg daily

l Average BP readings over 3 days:• 110/90• 100/85• 100/70 (Supine), 80/60 (Standing)

Case 3

What happened?l High dose of Ramiprill Lisinopril not discontinued by the

cardiologist, family MD, or the pharmacist

Reporting of Falls & Falls-related Injuries in Landmark Antihypertensive Trials

Trial Mean or Median Age

Dosage Regimen Titration/Run in Phase

Falls or Falls-related injuries reported

ALLHAT 67 Chlorthalidone 12.5-25 mg daily Amlodipine 2.5-10mg daily Lisinopril 10-

40mg daily

Yes No

HOPE 66 Ramipril 2.5-10mg daily Yes No

EUROPA 60 Perindopril 2-8mg daily Yes No

HYVET 84 Perindopril 2-4mg dailyIndapamide 1.5mg daily

Unclear No

ACCOMPLISH 68 Benazepril 20-40mg daily AND amlodipine 5-10mg daily or HCTz 12.5-25mg daily

Yes No

ACCORD-BP 62 ACEI, ARBs, BB, Diuretics, CCBs, vasodilators, alpha-blockers, or

combination

No No

ONTARGET 66 Ramipril 2.5mg-10mg dailyTelmisartan 40-80mg daily

Yes No

1. JAMA 2002; 288: 2981-2997 2. N Engl J Med 2000;342:145-53 3. Lancet 2003; 362: 782–88. 4. N Engl J Med 2008;358:1887-98 5. N Engl J Med 2008;359:2417-28 6. N Engl J Med 2010;362:1575-85 7. N Engl J Med 2008;358:1547-59

Antihypertensives & Falls or Falls-related Injuries

l Moderate-intensity antihypertensives were associated with increase in risk of serious fall-related injuries (HR 1.40, 95% CI, 1.03-1.90). There was 2-fold increase in risk of fall-related injuries with antihypertensive medications with a previous fall injury.

l Risk of falls increased by 25% (OR 1.25, 95% CI, 1.15–1.36). There was no significant association with any other class of antihypertensive.

l Hypertensive elderly who began receiving an antihypertensive drug had a 43% increased risk of having a hip fracture during the first 45 days following treatment initiation (incidence rate ratio, 1.43; 95% CI, 1.19-1.72)

1. JAMA Intern Med 2014;174(4):588-595 2. Age and Ageing 2010; 39: 592–597 3. Arch Intern Med. 2012; 172(22):1739-1744.

Antihypertensives & Falls or Falls-related Injuries

l Moderate-intensity antihypertensives were associated with increase in risk of serious fall-related injuries (HR 1.40, 95% CI, 1.03-1.90).There was 2-fold increase in risk of fall-related injuries with antihypertensive medications with a previous fall injury.

l Risk of falls increased by 25% with thiazides (OR 1.25, 95% CI, 1.15–1.36). There was no significant association with any other class of antihypertensive.

l Hypertensive elderly who began receiving an antihypertensive drug had a 43% increased risk of having a hip fracture during the first 45 days following treatment initiation (incidence rate ratio, 1.43; 95% CI, 1.19-1.72)

1. JAMA Intern Med 2014;174(4):588-595 2. Age and Ageing 2010; 39: 592–597 3. Arch Intern Med. 2012; 172(22):1739-1744.

Antihypertensives & Falls or Falls-related Injuries

l Moderate-intensity antihypertensives were associated with increase in risk of serious fall-related injuries (HR 1.40, 95% CI, 1.03-1.90). There was 2-fold increase in risk of fall-related injuries with antihypertensive medications with a previous fall injury.

l Risk of falls increased by 25% with thiazides (OR 1.25, 95% CI, 1.15–1.36). There was no significant association with any other class of antihypertensive.

l Hypertensive elderly who began receiving an antihypertensive drug had a 43% increased risk of having a hip fracture during the first 45 days following treatment initiation (incidence rate ratio, 1.43; 95% CI, 1.19-1.72).

1. JAMA Intern Med 2014;174(4):588-595 2. Age and Ageing 2010; 39: 592–597 3. Arch Intern Med. 2012; 172(22):1739-1744.

Fear of Falling

l Decrease in physical and mental performance

l Loss of independence and social isolation

l Loss of confidence is associated with anxiety and depression

l Decreased QOL

Age and Ageing 2008; 37:19-24http://www.phac-aspc.gc.ca/seniors-aines/publications/public/injury-blessure/seniors_falls-chutes_aines/index-eng.php

Practical Considerations

v Medications’ review is an integral part of fall assessmentv Question both new and old medicationsv Start medications at the lowest dose and titrate

slowlyvMonitor judiciously for side effects for first month

v Taper and discontinue medications that may cause falls

v Vitamin D 1000 IU once daily with or without calcium

Cochrane Database Syst Rev. 2012 Dec 12;12:CD005465. doi: 10.1002/14651858.CD005465.pub3 Cochrane Database Syst Rev. 2012 Sep 12;9:CD007146. doi: 10.1002/14651858.CD007146.pub3

N Engl J Med 2012;367:40-9

Questions