Pharmacology Ch.

11 Outline

Drug therapy in Geriatric patients

Drug use among the elderly is disproportionately high b/c of increased severity of
illness, presence of multiple pathologies, excessive prescribing

Principle factors underlying complications are:

– Altered pharmacokinetics (secondary to organ system degeneration)

– Multiple and severe illnesses
– Multiple drug therapy
– Poor adherence

Since the elderly generally suffer from chronic illnesses, the usual objective is to
improve quality of life and reduce symptoms, since cure is generally impossible

Pharmacokinetic changes in elderly

- The aging process can affect all phases of pharmacokinetics
- decline begins in early adulthood on
- Pharmacokinetic changes may be minimal in patients who have remained
physically fit

Absorption
percentage of oral dose that becomes absorbed does not change w/age
- rate of absorption changes (because of delayed gastric emptying and reduced
splanchnic blood flow)
- drug response may be somewhat delayed.
- Gastric acidity is reduced in the elderly and may alter absorption of certain drugs
(some drugs require high acidity to dissolve, so absorption may be decreased)

Distribution
4 major factors alter drug distribution in the elderly:

1. increased percent body fat (provides storage depot for lipid soluable drugs, so
plasma levels of these drugs are reduced, causing reduced response.)

2. decreased percent lean body mass – water soluble drugs become distributed in a
smaller volume, so concentration of these drugs is increased, causing more intense
effects

3. decreased total body water – same as #2

4. reduced concentrations of serum albumin – in malnourished adults, protein

binding of drugs decreases, causing levels of free drug to rise, so drug effects may
be more intense.
Metabolism
Rates of hepatic drug metabolism tend to decline w/age
- reduced hepatic blood flow
- reduced liver mass
-decreased activity of some hepatic enzymes.

B/c liver fnc is diminished, the half lives of certain drugs may be increased,
prolonging responses.

Responses to oral drugs that ordinarily undergo extensive first pass metabolism
may be enhanced.

Decline of drug metabolism varies greatly among individuals

Excretion
Renal drug fnc and drug excretion undergo progressive decline in beginning
adulthood
** drug accumulation secondary to reduced renal excretion is most important cause
of adverse drug rxns in elderly

Decline in renal fnc is result of reductions in renal blood glow, GFR, active tubular
secretion and # of nephrons.

Coexistence of renal pathology can further compromise kidney fnc.

Creatinine clearance, not serum creatinine levels indicate proper renal fnc.

In elderly, source of serum creatinine - lean muscle mass – declines in parallel w/

decline in kidney fnc, so kidney fnc may be normal when levels are low

Pharmacodynamic changes in elderly

Alterations in receptor properties may underlie altered sensitivity to some drugs,

but info is ltd.

Adverse drug rxns

7 times more common in elderly than young adults

- the vast majority is not idiosyncratic, but are dose related

Factors that predispose older pts to ADRs

– Drug accumulation secondary to reduced renal fnc

– Polypharmacy
– Greater severity of illness
– Mult pathologies
– Greater use of drugs that have low therapeutic index
– Increased individual variation
– Inadequate supervision of long term therapy
– Poor patien adherence

Reducing ADRs

– Taking thorough drug history (inc. OTCs)

– Accounting for pharmacokinetic and pharmacodynamic changes
– Initiating therapy w/low doses
– Monitoring clinical responses and plasma drug levels for rational basis for
dosage adjustment
– Employing the simplest regimen
– Monitoring for drug-drug interactions and iatrogenic illness
– Periodically reviewing the need for cnt’d drug therapy and discontinuing
when poss.
– Encouraging patient to dispose of old meds
– Taking steps to promote adherence

Promoting adherence

As many as 40% of elderly fail to take meds as prescribed