Anna Dabu M.D.

University of Western Ontario June 2009

Outline
Definition
Epidemiology Drug response and pharmokinetics in the elderly

Rational drug use in the elderly

Definition
No standard definition for polypharmacy
Unnecessary use vs. absolute number of medications

Epidemiology
For those > 65 years of age
44% of men and 57% of women use 5 medications/ wk 12% both genders 10 meds/wk
1059 rural community-dwelling patients (mean age 74.5 years) 50% took 2-4 over the counter medications 2590 noninstitutionalized patients 47% and 59% took a vitamin or mineral 11% and 14% took herbal supplements

Inappropriate drug use in up to 40% of nursing home patients!

Adverse Drug Events

10% of ER visits
10-17% of hospital admissions Commonly: electrolyte, renal, gastrointestinal tract,

hemorrhagic and endocrine abnormalities Others: prolongation of QT interval: fluoxetine and amitriptyline
RF for polypharmacy: age, multiple health care providers,

increased co-morbidities, institutionalization, low socioeconomic status, dementia

Drug response in the elderly

Increased sensitivity to drugs

Barbiturates, opiods, cyclic antidepressants, benzodiazepines, central alpha-agonists

Increased sensitivity to changes in thermoregulation

caused by drugs
Phenothiazines, anticholinergics

Decreased sensitivity of baroreceptors resulting in

increased risk of postural hypotension

Phenothiazines, nitroglycerin, nifedipine, prazosin, diuretics

Drug response in the elderly

Increased risk of falls if concurrent use of CNS active drugs

Increased susceptibility to SIADH if taking SSRIs

Drug absorption and distribution in the elderly

risk of harm: GI motility

opiods and antihistamines

in fat: lean body mass Increased [ ] morphine, lithium, levodopa, digoxin, acebutolol
Lower plasma albumin

Decreased protein binding Sulfonylureas, warfarin

Drug metabolism in the elderly

phase I metabolism (oxidation and reduction)
Altered first-pass metabolism Propranolol, verapamil, nifedipine Induction or inhibition of cytochrome p450 Inhibitors of 3A4: nefazodone, ciprofloxacin, norfloxacin, ketoconazole, erythromycin Metabolized by 3A4: amitriptyline, doxepin, benzodiazepines, hydrocodone, amiodarone in renal function (drug elimination) Altered renal clearance

Aspirin, digoxin, lithium

Direct alteration in renal function Lithium intoxication with thiazide diuretic, ACEI, NSAID

Rational Drug use in the Elderly

1. Beers criteria 1991, 1997, 2002 Expert panel of 13 geriatricians agreed on 18 medications/medications classes that should be avoided because either ineffective or high-risk for elderly

Amitritypline, chlorpropamide, disopyramide, doxepine, gastrointestinal antispasmodics, long half-life benzodiazepines (flurazepam, chlordiazepoxide, diazepam), methyl dopa, sedative or hypnotic agents, petnazocine, meperidine, ticlodipine

Beers Criteria
4 drug-drug interactions to avoid Specific dosing recommendations: Digoxin maximum of 0.125mg/day (except rx for atrial arrythymias) Short-half life benzodiazepines max/day:

Alprazolam 2 mg Lorazepam 3 mg Oxazepam 60 mg Temazepam 15 mg Triazolam 0.25 mg Zolpidem 5 mg Ferrous sulfate 325 mg

Warfarin with aspirin/NSAID/dipyridamole/ticlodipine

Rational Drug Use in the Elderly

2. McLeod et al. Defining inappropriate practices in

prescribing for elderly people: a national consensus panel CMAJ 1997; 156;385-91
Beers criteria unacceptable for our purposes 32 member multi-disciplinary panel developed a list of

71 practices in prescribing for elderly people and rates the clinical significance and risk to patient of each, alternative therapies and percent of panel agreeing with alternative

McLeod et al. 1997

Inappropriate practice of prescribing psychotropic

drugs for elderly people

Discourage prescribing long-half life benzodiazepines to

treat insomnia

Clinical signif. 3.72 May cause falls, fractures, confusion, dependence, withdrawal Non-pharmacologic rx or short-half life benzodiazepine instead

McLeod et al, 1997

Inappropriate practice of prescribing NSAIDS and

other analgesics for elderly people

Long-term prescription of NSAIDS to treat

osteoarthritis for patients with chronic renal failure

Clin signif. 3.56 may worsen renal failure and cause salt and water retention Non-drug therapy, acetaminophen

Summary
Polypharmacy in the elderly is not uncommon Polypharmacy predisposes to increased adverse drug

reactions and hospitalizations Older persons are at increased risk because physiological changes in aging result in altered drug response and kinetics Risk factors for polypharmacy are: age, number of healthcare providers and co-morbidities, institutionalization Beers Criteria and McLeod (CMAJ 1997) - resources for physicians

References
Bryan D.H., W. Klein-Schwartz, F. Barrueto. Polypharmacy and the Geriatric Patient. Clinics in Geriatric Medicine (2007) 23: 371-390
Fick, D.M., J.W. Cooper, W.E. Wade, J.L. Waller, J.R. Maclean, M.H. Beers. Updating the Beers Criteria for Inappropriate Medication Use in Adults. Archives of Internal Medicine (2003) 163:2716-2724. Hanlon, J.T., L.A.Shrimp, T.P. Semla. Recent Advances in Geriatrics: Drug Related problems in the Elderly. The Annals of Pharmacotherapy (2000) 34: 360-365 McLeod, P.J., A. Huang, R.M. Tamblyn, D.C. Gayton. Defining Inappropriate Practices in prescribing for elderly people a national consensus panel. CMAJ (1997) 156: 385-391