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.

T½ = ln(2) × Vd/Cl

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.




Copyright ©1999. Northwestern University. All Rights Reserved.
Edited by the Buehler Center on Aging, McGaw Medical Center.
For information regarding content contact:
James R. Webster, j-webster@northwestern.edu

Published electronically by the Galter Health Sciences Library.
For information regarding publication contact:
James Shedlock, j-shedlock@northwestern.edu

Last Updated: June 9, 1999