Chapter 11 - Drug Therapy In Geriatrics

CHAPTER 11

DRUG THERAPY

IN

GERIATRIC PATIENTS

Older patients are more sensitive to drugs than younger adults. - show wider individual variations - experience more adverse drug reactions and drug-drug interactions Principle Underlying Factors: - altered pharmacokinetics (secondary to organ system degeneration) - multiple and severe illnesses - multiple drug therapy - poor compliance - individualization of treatment is essential: each patient must be monitored for desired responses and adverse responses and the regimen must be adjusted accordingly - usual objective is to reduce symptoms and improve quality of life since cure is generally impossible

I.

PHARMOCOKINETICS CHANGES

IN THE

ELDERLY

- there is a gradual, progressive decline in organ function which can alter the absorption, distribution, metabolism, and excretion of drugs - changes increase drug sensitivity and varies greatly among patients A.

ABSORPTION - altered GI absorption is not a major factor in drug sensitivity - the percentage of an oral dose that becomes absorbed does not change with age - the rate of absorption may be slowed (because of delayed gastric emptying and reduced splanchnic blood flow) - responses may be somewhat delayed - gastric acidity is reduced in the elderly and may alter the absorption of certain drugs B.

DISTRIBUTION Major Factors: • increased percent body fat which provides a storage depot for lipid soluble drugs - plasma levels of these drugs are reduced, causing a reduction in responses • decreased percent lean body mass causes water soluble drugs (e.g., ethanol) to be distributed in a smaller volume - concentrations of these drugs is increased, causing their effects to be more intense • decreased total body water

•

- albumin levels are only slightly reduced in healthy adults but can be significantly reduced in malnourished adults reduced concentration of serum albumin - because of reduced albumin levels, protein binding of drugs decreases, causing levels of free drug to rise and effects may be more intense

C.

METABOLISM - rates of hepatic drug metabolism tend to decline with age - underlying factors include reduced hepatic blood flow, reduced liver mass, and decreased activity of some hepatic enzymes - because liver function is diminished, the half-lives of certain drugs may be increased, thereby prolonging responses D. EXCRETION - undergoes progressive decline - drug accumulation secondary to reduced renal excretion is the most important cause of adverse drug reactions in the elderly - decline in renal function is the result of reduction sin renal blood flow, glomerular filtration rate, active tubular secretion, and number of nephrons - co-existence of renal pathology can further compromise kidney function - proper index of renal function is creatinine clearance – not serum creatinine levels - creatinine levels do not reflect kidney function in the elderly because the source of serum creatinine – lean muscle mass – declines in parallel with the decline in kidney function - as a result, creatinine levels may be normal even though renal function is greatly reduced polypharmacy – take many drugs

II.

PHARMACODYNAMIC CHANGES

IN THE

ELDERLY

- in support of the possibility of altered pharmacodynamics is the observation that beta-adrenergic blocking agents (drugs used for cardiac disorders) are less effective in the elderly than in younger adults - possible explanation for this observation include: o reduction in the number of available beta receptors o reduction in the affinity of beta receptors for beta-receptor blocking agents

III.

ADVERSE DRUG REACTIONS (ADRS)& DRUG INTERACTIONS - ADRs are seven times more common in the elderly than in younger

adults - vast majority of these reactions are dose related – not idiosyneratic - symptoms are often nonspecific (e.g., dizziness, cognitive impairment), making identification of ADRs difficult Most • • • • • • • •

Important Factors: drug accumulation secondary to reduced renal function polypharmacy (treatment with multiple drugs) greater severity of illness presence of multiple pathologies greater use of drugs that have a low therapeutic index increased individual variation secondary to altered pharmacokinetics inadequate supervision of long-term therapy poor patient compliance

Measures to Reduce ADR Incidence: • take a thorough drug history, including OTC meds • accounting for the pharmacokinetic and pharmacodynamic changes that occur with aging • initiating therapy with low doses • monitoring clinical responses and plasma drug levels to provide a rational basis for dosage adjustment • employing the simplest regimen possible • monitoring for drug-drug interactions and iatrogenic illness • periodically reviewing the need for continued drug therapy, and discontinuing medications as appropriate • encouraging the patient to dispose of old meds • taking steps to promote compliance

IV.

PROMOTING COMPLIANCE

- some patient never fill their prescriptions - some fail to refill their prescriptions - some don’t follow the prescribed dosing schedule - noncomp0liance can result in therapeutic failure (from underdosing or erratic dosing, which is the most common) or toxicity (from overdosing) Contributing Factors to Unintentional Noncompliance: • forgetfulness • failure to comprehend instructions (because of intellectual, visual or auditory impairment) • inability to pay for medications

•

use of complex regimens (several drugs taken several times a day)

Contributing Factors to Intentional Noncompliance: • patient’s conviction that the drug was simply not needed in the dosage prescribed • unpleasant side effects • expense Steps to Promote Compliance: • simplifying the regimen • explaining the treatment plan using clear, concise verbal and written instructions • choosing an appropriate dosage form (e.g., liquid if patient has difficulty swallowing) • labeling drug containers clearly and avoiding containers that are difficult to open • suggesting the use of a calendar, diary or pill counter for record of drug administration • asking the patient if he / she has access to a pharmacy and can afford the medication • enlisting the aid of a friend, relative, or visiting healthcare professional • monitoring for therapeutic responses, adverse reactions and plasma drug levels