Drug Use in the Elderly

Prof. Dr. Mirko Petrovic

Department of Geriatrics, Ghent University HospitalHeymans Institute of Pharmacology, Ghent University

5th EACPT Summer School Ghent, 24-27 August 2007

I will prescribe regimens for the I will prescribe regimens for the good of my patients according to my ability and my judgment and never ability and my judgment and never do harm to anyone.

(Hippocrates, ~ 400 BC)

Co-Morbidity Polypharmacy

The percentage of population with prescriptions, and the

y yp y

The percentage of population with prescriptions, and the number of medications per individual, increase with age.

Features of Polypharmacy

Medication not indicatedDuplicate medicationsConcurrent interacting medicationsContraindicated medicationsInappropriate dosageDrug treatment of adverse drug reactionImprovement following discontinuance

Pharmacological Principles

• pharmacological agents work via high affinity bi di h i ll l ( )binding to their cellular targets (receptors)

• agonist binding to receptors initiates physiological functions

• antagonist binding to receptors blocks agonists g g p gfrom gaining access

Ph ki tiPharmacokinetics

• Defined as : The handling of a drug within the bodythe body

– Including:

• Absorption

• Distribution• Distribution

• Metabolism

• Elimination

Pharmacokinetic Principles

absorption

biotransformationplasma proteinbinding

free drug gin circulation

i tissue storage(fat, muscle, bone)

elimination

target site availability

Pharmacokinetic Factors

drug solubility• determines absorption and distribution parameters• determines absorption and distribution parameters• the partition coefficient of a drug is determined by a

ratio of its fat solubility and its water solubilityy ytherapeutic window

• the concentration range at which a drug is effective without causing undesirable physiological effects

adverse drug reactionsd i bl id ff f d h• undesirable side effects of drug therapy

• may be dose-related or idiosyncratic

P di i f t t d dPredisposing factors to adverse drugeffects in the elderly

• Physiologic changes due to aging• Drug - disease interactions• Drug- Drug interactions (polypharmacy)Drug Drug interactions (polypharmacy)• Compliance

iti– cognition– functional status– personal beliefs– financial issues

Other Risk factors

• Female gender

• Low educational status

• Low socio economic status• Low socio-economic status

Lechevallier-Michel N. Eur J Clin Pharmacol 2005; 60: 813-9

Age-related changes which affect pharmacokinetics

• decreased lean body mass• affects drug distribution

• decreased levels of serum albumin• affects drug distribution

• decreased liver functionff t d t b li /bi t f ti• affects drug metabolism/biotransformation

• decreased renal functionaffects drug eliminationaffects drug elimination

Drug absorption changes in the elderly

gastrointestinal system (rarely significant clinically)gastrointestinal system (rarely significant clinically)• acid production generally unchanged

• multiple prescriptions increase the probability of drug• multiple prescriptions increase the probability of drug-drug interaction which may alter absorption

• splanchnic blood flow decreases (with little effect on splanchnic blood flow decreases (with little effect on drug absorption)

Pharmacokinetics: distribution

• affects the concentration of drug available at the target

absorption

plasma protein• solubility: hydrophilic

vs. lipophilic drugs

• protein bindingf d

biotransformationbinding

p g

• C = D / VdC, concentrationD dose

free drug in circulation

D, doseVd,, volume of

distributiontissue storage(fat, muscle, bone)

elimination

target site availability

Drug distribution changes in the elderly

fluid and tissue compartments• decrease in total body water

• increase in fat compartmentp

• decrease in muscle mass

plasma drug-binding proteins (rarely significant clinically)p g g p ( y g y)• decrease in serum albumin levels

• no change in α-acid glycoprotein levelsg g y p

Pharmacokinetics: biotransformation

enzymatic reactions preparing drugs for elimination enzymatic reactions preparing drugs for elimination Phase I reactions:

• oxidation: catalyzed by cytochrome P450 enzymesPh II tiPhase II reactions:

• conjugation: addition of small chemical groups which increase solubility to facilitate elimination

Drug metabolism changes in the elderly

liverliver

• decrease in hepatic blood flow often associated with decreased First Pass Effectdecreased First Pass Effect

• Phase I metabolism decreased

• Phase II metabolism generally preserved• Phase II metabolism generally preserved

Pharmacokinetics: elimination

• removal of drug from the body by excretion

l li i ti• renal elimination:glomerular filtrationtubular secretion

• other minor pathways of elimination:

fecesbreathsweatsaliva

Drug elimination changes in the elderly

decrease in renal functions

• decreased blood flow to the kidneys

• decreased glomerular filtration• decreased glomerular filtration

• decreased tubular secretion

• decline in creatinine clearance

• serum creatinine is NOT an accurate reflection of creatinine clearance in the elderlyclearance in the elderly

Ph d iPharmacodynamics

• study of the interaction between a pharmacological agent and its target tissuepharmacological agent and its target tissue

• Involves:the mechanism – the mechanism,

– intensity, k d – peak and

– duration of a drug’s physiological actions

Physiological changes in elderly patients affecting pharmcodynamics

target organ changesd d d i bl ff t f h th• decreased desirable effects of pharmacotherapy

• increased adverse effects

homeostasis changes• decreased capacity to respond to physiological decreased capacity to respond to physiological

challenges and the adverse side effects of drug therapy (eg. orthostatic hypotension)

Adverse Drug Reactions

The elderly are 2-3 times more at risk for adverse drug reactions due to:

d d t t• reduced stature• reduced renal and hepatic functions• cumulative insults to the body (eg disease cumulative insults to the body (eg., disease,

diet, drug abuse)• higher number and potency of medications• altered pharmacokinetics• noncompliance

Common problems of drug administration in the elderly

• reduced homeostasis– decreased renal and hepatic functionsp– increased target organ sensitivity

• polypharmacy– increased chance of adverse drug reactions

• lack of available data– fewer clinical trials on elderly populations

• non-compliancep

Geriatric Assessment

• Physical Assessment

• Cognitive Assessment

• Psychologic Assessment• Psychologic Assessment

• Social Assessment

• PHARMACOTHERAPY – key component!component!

Utility and clinical significance

• positive correlation between potentially i i d ibi d fi d b h inappropriate drug prescribing, as defined by the Beers criteria, and adverse drug reactions

• Geriatric evaluation and management reduces serious adverse drug reactions by 35%

• Reduces suboptimal prescribing, in frail elderly patients.p

Schmader K.E. Am J Med 2004; 116: 394-401Chang C.M. Pharmacotherapy 2005; 25: 831-8

Clinical Significance

• Inappropriate medication use increased the likelihood of experiencing at least one adverse health outcome (hospitalizations, ( p ,emergency department visits, or deaths) more than twofoldmore than twofold.

Perri M. Ann Pharmacother 2005; 39: 405-11

Good news

• significant decline in the use of potentially

• inappropriate drugs by elderly patients,

• particularly those drugs linked to the most• particularly those drugs linked to the most

• severe outcomes. (25% - 21%)

Stuart B. Am J Geriatr Pharmacother 2003; 1: 61-74

Bad news

• Approximately 7 million elderly patients still received potentially inappropriate drugs in 1999

• Underscoring the continued need for effective interventions to improve effective interventions to improve prescribing for this vulnerable population.

Stuart B. Am J Geriatr Pharmacother 2003; 1: 61-74

Rules of prescribing in older adults

• Start low , go slow• Try to limit number of medications and avoid prescribing “a Try to limit number of medications and avoid prescribing a

pill for every ill”• Try not to start two drugs at the same time• Make sure it is the right dose• Avoid “inappropriate medications”- Beers criteria• Watch out for potential drug drug drug disease interactions• Watch out for potential drug-drug, drug-disease interactions• Make sure patient and caregiver understand what the

medication is for, how and when to take it, possible side ffeffects

• Avoid expensive new medications that have not been shown to be superior to less expensive generic alternativesp p g

Rules of prescribing

A k i b ll di i (i l di OTC h b l • Ask patient about all medications (including OTC, herbal prep)

• Ask patient how each medication is being takenp g• Look for medications with duplicate therapeutic or

pharmacologic profilesEli i t di ti• Eliminate unnecessary medications

• Simplify the medication regimen – fewest possible number of medications and doses per dayp y

• Always review any changes in writing with the patient and caregiver

• If possible use technology to monitor parameters of • If possible, use technology to monitor parameters of efficacy and eliminate duplicative therapy, and also to detect potential drug–drug interactions and drug disease interactionsinteractions

Considerations for pharmacotherapy in the elderly• Is drug therapy required?• Choice of appropriate

d d tidrug and preparation• Dosage regimen to

accommodate changes in gphysiology

• Detailed monitoring and periodic re-evaluation of periodic re evaluation of drug therapy

• Clear and simple instructionsinstructions

SSummary

• changes in the physiology of the elderly alter responses changes in the physiology of the elderly alter responses to drug therapy

• pharmacokinetic changes affect the effective i f d i h b dconcentration of drug in the body

• pharmacodynamic changes alter the body’s response to the drug therapythe drug therapy

• adverse drug reactions are more common in the elderly and can be avoided with better primary carep y

Quality of medication prescribing in Belgian Quality of medication prescribing in Belgian nursing homes

Results and conclusions are based on analyses of the databank of the field study yPrescribing in Homes for Elderly in Belgium (PHEBE) performed in order of the Belgian Health Care Knowledge C tCentre

On behalf of the research consortium: On behalf of the research consortium:

Vander Stichele R, Van de Voorde C, Elseviers M, Verrue C, Soenen K, Petrovic M, Chevalier P, Smet M, Defloor T, Soenen K, Petrovic M, Chevalier P, Smet M, Defloor T, Mehuys E, Somers A, Gobert M, Devriese S, De Falleur M, Bauwens M, Christiaens T, Spinewine A, Ramaekers D

PHEBE

• A cross-sectional descriptive study

• Nursing homes (> 30 beds, including long term care beds) in the provinces of term care beds) in the provinces of Antwerp, East Flanders and Hainaut (public and private homes)(public and private homes)

• 2510 residents in 112 nursing homes were randomly selected

Chronic medication

• 1 1% of the residents had no medication1.1% of the residents had no medication

• 22.7% of the residents had 1-4 chronic medications

• 53.1% of the residents had 5-9 chronic medications

• 20.8% of the residents had 10-14 chronic medications

• 2.1% of the residents had more than 14 chronic medicationsmedications

Prevalence of medication usage per g ptherapeutic group in Belgian Nursing homes

diabetica

park inson

s tatines

nsaid

betablockers

vitam ines

vasodilators

cab

diuretics

aspirine

anti-ulcer

ace-inhibitors

laxativa

antidepressants

analgis ics

diuretics

0 10 20 30 40 50 60 70 80

psycholeptica

One m edication m ore than one

Q lit f di ti ibiQuality of medication prescribing

Th i i f ibi li i di d d h Three existing sets of prescribing quality indicators, adapted to the setting of the elderly, were applied

• ACOVE Criteria (Assessing Care of Vulnerable Elders) for underprescribing

• Beers Criteria for inappropriate prescribingpp p p g

• Bednurse Criteria (Bergen District Nursing Home Study) for nursing home residentsStudy) for nursing home residents

ResultsResults

Underutilisation according to 7 ACOVE criteria was observed with regard Underutilisation according to 7 ACOVE criteria was observed with regard to cardiovascular risk in heart failure (HF), diabetes and osteoporosis respectively

23 % of residents with HF did not receive beta blockers

20 % of residents with HF did not receive ACE-I

18 % of residents with myocardial infarction in their medical history did not receive beta blockers

15 % of residents with osteoporosis did not receive bisfosfonates/VitD/Calcium

11 % of residents with myocardial infarction in their medical history did not 11 % of residents with myocardial infarction in their medical history did not receive aspirin

9 % of residents with diabetes did not receive aspirin

8 % of residents with osteoporosis who received bisphosphonate or Vit D did not receive calcium supplements

Beers Criteria : % of residents scoring on individual items (N=1,730)

f luoxetine

clorazepate potassium

diazepam

amitriptyline

dipyridamole

amiodarone

nifedipine

ergoloid mesylates

digoxin

oxybutynin

amiodarone

0 1 2 3 4 5 6 7 8

Bednurse Criteria: Prevalence of patients scoring on indivual items (N=1730)

L t i b f l it

Heart failure and verapamil

Combinat ion ant ihypertensives and NSAIDS

Combinat ion Iron and NSAID

Combinat ion diuret ics and NSAIDS

Long act ing benzo: clorazepate

Inappropriate: pentazocine

Long act ing benzo: nitrazepam

Long act ing benzo: f lunitrazepam

Combinat ion ACE and Potassium or potassium saving diuret ic

Combinat ion Iron and ant ithrombotics

Chronic NSAID

Combinat ion Psychotropics: N05+N05

Long act ing benzo: clobazam

0,0 5,0 10,0 15,0 20,0 25,0 30,0

Combinat ion Psychotropics: N05+N06

Chronic use of ant ipsychot ics (all pat ients)

Combinat ion ACE and Potassium or potassium saving diuret ic

• 12 % of the residents used antipsychotics• 25 % of the residents used a combination of antidepressants and antipsychotics • 25 % of the residents used a combination of antidepressants and antipsychotics or benzodiazepines

• 4 % of the residents used multiple antidepressants• 2 % of the residents used long-acting benzodiazepine2 % of the residents used long acting benzodiazepine• 4 % of the residents used chronic NSAID• 11 % of the residents used combination of medicines with a risk of hyperkalemia

Conclusions

• Beta blockers and ACE-I are not often enough prescribed in residents with heart failure as well as prescribed in residents with heart failure as well as post-myocardial infarction

• A limited group of inappropriate use of digoxine • A limited group of inappropriate use of digoxine, oxybutinine and amiodarone was identified by Beers CriteriaBeers Criteria

• A high prevalence of chronic use and combination of psychotropic medicationof psychotropic medication