Pharmacotherapy
Andrew B. Repasy, M.D.
Changes in body composition,
physiologic changes with aging, and effects of co-morbidity result
in changes in pharmacodynamics in the elderly.
Adverse drug reactions are more common in the elderly, e.g., what
might be a minor irritation to a younger person could lead to
debilitation, oversedation, urinary incontinence, fecal impaction
or delirium in an older adult. Clearly, the potential for iatrogenesis
is high. Unfortunately, most studies of drugs in the literature
and the studies required for FDA approval have traditionally excluded
the elderly, so published data on actions and risks may be inaccurate
for this population.
It must be remembered that drug use is especially prevalent in
the elderly, who are also the largest consumers of OTC drugs,
especially cold remedies, anti-inflammatory agents, sedative/hypnotics,
vitamins and laxatives. All of these medications, either individually
or in combination, could pose a risk to the older patient.
Pharmacokinetics - absorption, distribution, metabolism,
elimination.
Clearance (Cl) measures the ability of the body or organ
system to remove a drug.
Volume of Distribution (Vd) is the space in which a drug
is stored in the body. Changes in body composition with aging
include increased total body fat, decreased total body water,
and lean body mass. The Vd of fat- or water- soluble drugs will
be affected by these changes. For example, neuroleptics are fat-soluble
and have a larger Vd. Lanoxin is water-soluble and has a smaller
Vd.
Decreased plasma protein/albumin leads to an increased
free concentration of extensively protein-bound drugs and results
in changes in both therapeutic and adverse effects. Examples are
anti-inflammatory agents and coumadin.
Elimination Half-Life (T½) is the time it takes
for the concentration of a drug to decrease by half of its original
value.
Changes in the clearance of a drug and the distribution of the drug alter the drug's half-life. With few exceptions, this means that the dosages required for desired effects are reduced in the elderly. In other words, start low, go slow.
Drug Absorption
Changes in the gastrointestinal tract generally affect absorption
minimally. These may include: decreased salivation, esophageal
motility disorders, decreased gastric acidity, decreased gastric
emptying, increased intestinal transit time, decreased absorption,
possibly decreased active absorption, and decreased splanchnic
blood flow.
Hepatic Metabolism
Hepatic clearance or elimination of drugs is reduced in the elderly
to a variable extent. This is primarily:
Standard liver function tests do not predict hepatic metabolism because they reflect synthetic, not degradation function. Important examples of medications to remember are: Nonsteroidal anti-inflammatory drugs (highly protein-bound), benzodiazepines (and metabolites), lidocaine.
Renal Function
Changes in renal function affect the clearance of drugs that are
primarily excreted by the kidney, e.g., Lanoxin. Renal blood flow
also declines linearly with age as does the kidney's ability to
acidify, concentrate and dilute urine. This may alter the effects
of medications whose site of action is the genitourinary system.
Glomerular filtration rate (GFR) falls approximately 1ml/min each
year after the age of 40.
Decreased muscle mass with aging means decreased creatinine synthesis,
so it is important to remember that "normal" BUN and
creatinine values do not mean normal renal function in the elderly.
GFR should always be estimated in the elderly. This can be easily
done using the Cockcroft-Gault equation for GFR in the steady
state.
Obesity leads to underestimation
of GFR, and malnourishment and decreased muscle mass lead to overestimation
of GFR.
Nephrotoxic drugs such as aminoglycosides, beta-lactam antibiotics,
salicylates, lithium and cimetidine accumulate in patients with
renal insufficiency. This can lead to a vicious cycle of worsening
renal insufficiency and worsening toxic effects in other organ
systems due to changes in renal clearance of medications.
Pharmacodynamics - the effect of a medication
at its site of action.
This often leads to unanticipated and unwanted side effects such
as: increased response, decreased response, or increased side
effects. For example, despite increased propanolol levels in elderly
patients secondary to decreased liver clearance, the response
to a given dose is often less pronounced in the elderly.
Examples of altered pharmacodynamics in the elderly
I. Cardiovascular drug effects
II. Central and Autonomic
Nervous System effects
III. Endocrine effects
IV. Immune system effects
V. Respiratory system
effects
VI. Anticoagulants
Summary
Pharmacokinetics, pharmacodynamics, weight, age, homeostasis and
disease states especially affecting liver, kidney, and cardiac
function all play an important role in how drugs will affect your
elderly patient. Always estimate GFR, know the elimination pathways
of the drugs you give, start low, go slow and avoid polypharmacy.
Does this patient need this drug? What about a lower dose? What
about non-drug Rx,e.g., counseling instead of sedative-hypnotics,
physical therapy instead of pain medications? Whenever a new clinical
problem arises, investigate whether medications could be the culprit.
Expect toxicity of drugs, especially CNS toxicity.
Monitor all prescriptions regularly; always ask
about OTC drugs.