POLYPHARMACY

Pio L. Oliverio, MD

Fellow, Geriatrics

SVCMC, Jamaica, NY

February 27, 2006

Definition

POLYPHARMACY Use of several drugs or medicines together

in the treatment of disease, suggesting indiscriminate, unscientific, or excessive prescription

(Stedman’s Medical Dictionary)

Definition

POLYPHARMACY The administration of many drugs at the

same time

DRUG is any substance that affects the physical

and mental functioning of a living organism

2/3 of residents in long term care facilities receive 3 or more medications daily

7 different medications per patient per day Overall average per resident

Older adults spend $3 billion annually on prescriptions

Epidemiology and Prevalence

Epidemiology and Prevalence

Direct correlation between age of the patient and the number of prescriptions they take daily

90% of older adults take at least one prescription daily most take two or more prescriptions daily

Medication Underuse/Overuse

UNDERUSE – when available drugs are not used maximally for correct indication

OVERUSE – when a particular medication is used excessively even if not properly indicated

Polypharmacy Admission

3 and 10% - in two studiesResult in several billions of dollars in

yearly health care expenditures

Commonly Prescribed Medications

Cardiovascular drugs Antihypertensives Analgesics Sedatives Anti-inflammatory GI preparations (laxatives)

Definition

PHARMACOKINETICS management of the drug by the body

PHARMACODYNAMICS target organ’s sensitivity to the drug

Decreased drug absorption Small bowel resection Malabsorption Multiple drugs Antacids

Active transport - e.g. in nutrients and vitamins

Passive transport – most common

Antacids decrease absorption of Cimetidine Digitalis Tetracycline Phenytoin Quinolones Ketoconazole Iron

YOUNG ELDERLY

Drug absorption FasterSlower/ decreased

Metabolism Faster Slower

Excretion Faster Slower

Fat: lean body mass

Volume distribution

Duration that a particular drug exerts its effort depends on:Volume distribution (Vd)Metabolism of the drugThe clearance of the drug

All three factors change with age

Volume distributionterm used to relate the amount of

drug in the body to the concentration of drug in the plasma

Vd =Cpo

Dose

Vd is determined by Degree of plasma protein bindingThe patient’s body composition

Changes substantially with ageAdipose tissue increases

18-36% in males 36-48% in females

Elderly↓ body water and lean body mass

lower Vd ↑ drug concentration↑ body fat large Vd prolongation

of half life unless the clearance increases (unlikely in the elderly)

The increase in adipose tissue larger Vd for lipid soluble drugs causing half life (T1/2) to be prolonged clinically important with the CNS drugs i.e. benzodiazepines and barbiturates

Total body water composition decrease by 15%, consequently the Vd of water soluble drugs is decreased increased drug serum concentration

Plasma protein concentration also ↓ with age↑ increased amt of free (active) drug in the body Drugs have ↑ concentration due to ↓ plasma

protein Digoxin Theophylline Phenytoin warfarin

DRUG METABOLISM

Phase 1Cytochrome P – 450 enzyme system

Oxidation, reduction, hydrolysisDeclines with increasing ageDrugs involved

Ketoconazole, erythromycin, SSRI

DRUG METABOLISM

Phase 2Conjugation/ biotransformation

Acetylation, glucoronidation, sulfationUsually not effected by age

Not safe to assume efficient drug metabolism in geriatrics pt with normal liver function

Effects Of AgeOn Renal Function

Wide inter-individual variation in the rate of decline in renal function with increasing age

i.e. renal function declines by 40-50% between ages 20 and 90, - this is an average decline

Can cause over or under dosing

Effects Of AgeOn Renal Function

↓ muscle mass ↓ creatinine production

Serum creatinine may be normal at a time when renal function is reduced.

Serum creatinine does not reflect renal function accurately in the elderly

Use creatinine clearance to determine renal function.

Formula to estimate renal function (Cockcroft & Gault)

Creatinine clearance = (140 – age) X body weight in kg / 72 X serum creatinine (x 0.85 in females)

Drugs given in reduced doses to elderly Aminoglycosides Benzodiazepines Digoxin Haloperidol Metoclopramide Thyroxine Vitamin D

Drugs with ↓ renal elimination

Aminoglycosides ACE-I Digoxin Diuretics Lithium H2 blockers

Pharmacodynamics The study of the effects of drugs at the receptor

level Changes in the end-organ response to a drug

due to Change in the receptor binding Decrease in receptor number Altered translation response to a receptor

Pharmacodynamics

Increase in receptor response is noted Benzodiazepines Warfarin Opiates

Adverse Drug Reactions

Primum non nocere “first do no harm” Applicable when drugs are prescribed for geriatric

population Older adults are more at risk Can be reduced by decreasing number of

medications

Adverse Drug Reactions

Frequent symptoms Confusion (75%) Nausea Loss of balance Change in bowel pattern Sedation

Adverse Reactions – Risk Factors

Advanced age Female Hepatic/ renal insufficiency Polypharmacy Lower body weight History of prior drug reaction

Reasons for inappropriate medication ordering

Multiple problems and complaints may consult several health care professionals

Use of multiple pharmacies OTC medication history Time limitations during office visits

Consequences

Non-adherence Adverse drug reactions Drug-drug interactions Increased risk of hospitalizations Medication errors Increased costs from treatment of adverse

events

Strategies for Elderly Compliance Make drug regimens and instruction as

simple as possible Instruct relatives and care givers on the drug

regimen Make sure patient can get to a pharmacist,

can afford the prescription, and can open the container

Strategies for Elderly Compliance

Enlist others (HHA, pharmacist) to help ensure compliance

Use aids (special pill boxes and drug calendars)

Keep updated medication record Review knowledge of and compliance with

regimens regularly

Factors not affecting compliance

AgeSexEducationDisease severity

Factors reducing compliance

Multiple medications Frequent dosing schedules Complicated dosing instruction Expensive medications

Promote compliance

Reducing the number of prescribed drugs Simplifying dosage regime Evaluating patient’s functional ability to take

medication

Inability to self-medicate

Cognitive impairment Decreased dexterity Sensory/motor deficits Number of medications

Measures of Compliance

Direct method drug concentration in the blood, urine, or saliva

Indirect method Therapeutic response Self report Pill counts Pharmacy records

Principles of Drug Prescribing

Make a diagnosis before drug therapy is initiated

Carefully weigh the risks versus benefits Begin with low doses and slowly increase

until effect is reached, monitor for reactions Inquire about the use of OTC and alternative

medications

Principles of Drug Prescribing

Periodically review the list of medications Simplify medication schedule Suspect a medication as the cause of any

major medical or cognitive change Discuss the benefits of the medication and

the consequences of non compliance Inform the patient about potential reactions

Prescribing Practices

Basic elements… Reduction of polypharmacy Coordinated medication plan

Clinicians, pharmacists, older person/ families

Basic tenet… Non pharmacologic therapy is always

initiated first whenever appropriate

Summary

Polypharmacy – epidemiology, prevalence, implications in terms of compliance

Pharmacokinetics + pharmacodynamics Pharmacology of drugs Principles of appropriate prescribing Strategies to improve compliance in the

elderly