PRESCRIBING IN THE ELDERLY

Carolyn Glover Registered PharmacistFebruary 28, 2013

Objectives Understand pharmacodynamics and

pharmacokinetics of the elderly Identify high risk patients and high risk

drugs Discuss relevance of drug interactions

and polypharmacy

Age related Physiologic changes Endocrine CNS Cardiovascular Skeletal Genitourinary Immune system Pulmonary Liver

Oral Sensory Renal GI Body composition

Age related changes Increasing comorbidities Polypharmacy Aging results in physiologic changes of

absorption distribution metabolism elimination of drugs

Absorption Gastric PH increases with age Decreased absorptive surfaces and

decreased visceral blood flow Decreased gastric emptying Leads to

increased contact time with stomach-GI bleeds with NSAIDS

Increased PH reduces absorption of medications needing acidic environment

(ie calcium, ketoconazole, iron)

Distribution Increase in adipose tissue leads to increase

in fat soluble medications (benzodiazepines, propanolol, barbituates)

Decrease in body water, leading to lower volume for water soluble medication (increased levels of lithium, gentamicin, ethanol)

Possible reduction is albumin can increase drugs like phenytoin, digoxin, warfarin, theophylline

Metabolism-Hepatic Changes Decrease in hepatic flow as well as

decrease in liver size leads to decrease clearance and increased half life for oxidative metabolism drugs

Medications affected- propanolol, diazepam, morphine

Elderly take more drugs which are competing for the same P450 enzymes to metabolize leading to drug interactions

Elimination Decreased renal blood flow and decreased

renal mass GFR and tubular secretory function decreases

with age Creatinine production deceases with decreased

muscle mass making CrCl more unpredictable HCTZ, atenolol, digoxin, lithium etc. Titrate to effect rather than empirically dosing Look for trending eGFR to make decisions

instead of based on a single Scr result

Pharmacodynamics (Target Organ Sensitivity to Drug)

Can have change in receptor binding, decrease in # of receptors or altered action of receptors

Decrease in receptor response will decrease effect of adrenergic meds (leading to less bradycardia with beta blockers)

Increase in receptor response increases effect and toxicity of morphine

Increase receptor response to anti-cholinergics increases confusion, constipation and urinary retention effects

Who are High risk Patients? Patients with multiple prescribers and/or

multiple co-morbidities Over 85 years (30% of >85yrs had

claims for >10drug classes) More than 6 daily medications Low BMI ( < 22) Cognitive impairment Decreased renal function

Compliance Issues= High Risk Patients Pill burden is the total # pills/day leads

to non-compliance or poor compliance Non compliance can lead to significant

withdrawal events-ie tachycardia with Beta blockers; rebound hyperacidity with PPI; rebound insomnia with benzos

Non Compliance leads to Hospitalization

20% of prescriptions written for seniors are not filled

80% compliance problems due to perception that drug is unnecessary or that it will lead to ADR

Also could be forgetfulness, difficulty hearing or seeing instructions, inability to understand the purpose of the medication, trouble opening vials

What are dangerous Drugs? Survey found 20% of hospital admissions

were due to drug related events 40% of delirium is drug induced Classes of dangerous medications

implicated include psychotropics, NSAIDS, hypoglycemics, diuretics, digoxin, warfarin and anticholinergics (see anticholinergic list in Rxfiles under “dementia”)

How to use High Risk Drugs Caution with these classes of medications

Does the patient even need the drug?Is this the best drug in its class for the elderly?Can you modify the titration to avoid ADRs?

Medications that contribute to hospitalization=warfarin + Insulin + oral antiplatelets + oral Hypoglycemics = 70% of the drug related ER visits

Misuse of Drugs Best practise guidelines are encouraging medication

regimes that are more complex, leading to polypharmacy

Elderly patients have multiple chronic conditions which lead to multiple prescribers, increasing ADRS

Overuse of a particular medication in an effort to improve symptoms resulting in sometime exponential side effects (ie. benzos for sleep)

Underuse of medications from patient (ie. pain medication prescribed as PRN) or from prescriber (warfarin due to hemorrhagic concerns)

Misuse of Drugs Continued.. Most Canadians >80yrs have 2 or more

conditions that require preventative medications like statins, aspirin, beta blockers, ACE inhibitors, anti-hypertensives, bisphosphonates, vitamin D

Patients take medications (prescribed or OTC) in response to symptoms the patient has, often it is an ADR to the preventative medications

Common Prescribing Cascades Ibuprofen hypertension antihypertensive

edema diuretic potassium Gabapentin edema diuretic potassium Lithium tremor propranolol depression

SSRI Amitriptyline cognition donepezil Narcotic constipation sennosides diarrhea

Drug Interactions Drug interactions can require an adjustment in 1

medication, discontinuation of 1 medication or monitoring but continuing with both meds

European study found most common DI adjustments were:Warfarin + ABX(risk of bleed) Warfarin + phenytoin (risk of bleed and phenytoin

toxicity)ACE/ARBS +/- spironolactone +/- potassium

supplements (hyperkalemia)Digoxin + amiodarone/verapamil causing digoxin

toxicity

Significant Drug Interaction Hospital Admissions

Digoxin + furosemide ACE/ARB + potassium supplements Acetaminophen + warfarin

Increase in Adverse events associated when more than 6 meds

DON’T forget to ask about the OTCs that elderly are often taking

Polypharmacy More than 6 medications Any symptom in an elderly patient

should be first considered a drug side effect until proven otherwise. This avoids prescribing further medications

Conditions That Could Result from Polypharmacy QT prolongation Serotonin syndrome Delirium/dementia Xerostomia Falls and unsteadiness

Lack of Evidence Limited info in literatures/studies on drugs

used for patients >80yrs since meds are not generally tested in this population

3/155 RCTs are exclusively with the elderly

Exclusion criteria leads to studying only healthy, older subjects which is NOT the real world patients we deal with every day

Coroner’s report 83yr old death In 2006, AS fell, fractured wrist, ribs and pelvic fracture needing

escalating doses of oxycodone Was on high dose oxycodone from fall 2006.Admitted to retirement

home in 2007-developed abdominal distention, nausea, diarrhea. Txt= loperamide, dimenhydrinate.

Transferred to hospital and found to have heart failure TXT=furosemide, dimenhydrinate, morphine, scopolamine, fleet enema

Died 15hrs after hospital arrival-toxicologic reported supratherapeutic levels of oxycodone, diphenhydramine, morphine, lorazepam acetaminophen and chlorpheniramine

NOTE: heart failure impairs metabolism increasing ADR NOTE: Constipation may present as diarrhea –loperamide should

not be given when pt on opioids NOTE: number of OTC drugs listed

Strategies Use screening tools

Beers criteriaSTOPP/START criteria

Identify prescribing cascadesEngage in “deprescribing”

Appropriateness- Indicated, Compliance, Effective, Safe (ICES)

Calculate and reduce pill burden Adjust guidelines for frail elderly

Find the Balance