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