The Unique Sensitivity of the Elderly

Elderly individuals have the potential to exhibit sensitivity to a broad range of substances. This is due to internal biological changes associated with the aging body, present state of health, and genetic predisposition. There have been a number of interesting studies elucidating connections between drug sensitivity and the aging body.

As we age our body's internal absorption, distribution, metabolism, and excretion mechanisms change. These differences arise from (1):

Changes in the distribution or transport of drugs/substances as a result of reduction in lean body mass, serum albumin in the plasma, and total body water.

Increase in percentage of body fat.

Changes in body composition and the function of organs which assist in the metabolism and elimination of substances.

Since most drugs are tested and formulated for young adults, consideration must be given to elderly patients when determining proper dosages. A decrease in blood flow, which comes with age, can cause adverse drug effects in the elderly because it limits metabolic rates and thus decreases the rate of drug elimination from the body. The blood is a transport system, shuttling substances to the liver which, plays the major role in metabolizing foreign substances. This decrease in metabolism can prolong the effects of drugs or even lead to overdose and toxicity if dosages are not reduced. There is a lot of variation between elderly individuals capacity to metabolize substances.

Renal (kidney) function in the elderly is reduced by an average of 50%. This too will limit elimination of substances from the body.

Not only do the rates of clearance (elimination fromm the body) change as we age, but our response to drugs changes. A few examples are:

Increased sensitivity to drugs which depress the central nervous system.

Increased sensitivity to side effects such as high blood pressure from psychotropic medication.

Hemorrhage from anti-coagulants.

These may even occur after adjustment of dosage accounting for changes in clearance and response. Since the elderly are more likely to receive medication than other groups, it is necessary to define the proper therapuetic dosage for drugs and minimize drug use where possible.

Oxidative Damage

A growing body of evidence is linking the damage caused by reactive oxygen species (ROS) to age-related diseases such as arthritis, muscular dystrophy, cataractogenesis, pulmonary dysfunction, various neurological disorders, and probably cancer (2). ROS occurs naturally, over time, as we age. A study by Orr and Sohal (3) argues that the production of (ROS) in the body is a contributing factor in the reduction of the body's ability to function on a physical, biological and physiological level and is thus a contributor to aging. ROS is believed to be the main agent of oxidative damage to body tissues, accumulating as we get older. The systems that create ROS also oxidize proteins, which build up as we age. We use proteins to break down unwanted substances in our body as part of the metabolic process. Oxidized proteins are not functional, and as we age larger proportions of our protein pool become oxidized and therefore nonfunctional. The build up of these proteins may also be due to a decrease in the ability to degrade these proteins. These processes may allow for oxidants and harmful chemicals to act upon our body tissues as opposed to being readily metabolized. Concentrations of glutathione, a constituent of metabolism, and its related enzymes are decreased in the gastric mucosa of the aged. This also increases susceptibility to oxidative damage in related tissues (4).

Alzheimer's Disease

An increased life expectancy for adults in the United States has made Alzheimer's a common occurrence among the elderly. Over 50% of the U.S's chronic illness nursing beds are occupied by those suffering from this age related disease. Recent studies have shown that a genetic predisposition and not environmental chemical exposure may lead to the onset of the clinical signs of dementia, which are a trademark of this disease.

Heart Disease

Heart disease in the elderly is the major cause of disability and death. Yet, there is a high sensitivity to drugs as treatment against high blood pressure.

Cancer

There are two prerequisites necessary for cancer: 1) genetic susceptibility; it runs in the family, and 2) environmental insult which triggers development of cancerous cells. The events triggering cancerous cell growth may occur over a long time, making older people more susceptible because of a lifetime of inciting factors. Common cancers among elderly include colon, breast, lung, skin, and prostrate gland. Click here for a description of cancer development.

The aged are also susceptible to skin cancer from direct exposure to UV light. As we age, the three skin layers become thinner and we lose Langerhan's cells, an immune defense of the skin, from the outer layer. This may be why elders are more susceptible to cancer from exposure to UV light than younger people.

References

1. Goodman & Gilman's The Pharmacological Basis of Therapeutics. Ninth Ed. Edit. by Molinoff and Ruddon. McGraw-Hill, New York.

2. ER Stadtman and CN Oliver.1991. J Biol Chem. 266:2005

3. William C. Orr and SS Sohal. 1994. Extension of Life-Span by Overexpression of superoxide Dismutase and Catalase in Drosophila melanogaster. Science, 25 Feb vol. 26:1128-1130.

4. Loguercio C., Taranto D., Vitale LM., Beneduce F., Del Vecchio Blanco C. 1996. Effect of liver cirrhosis and age on the glutathione concentration in the plasma, erythrocytes, and gastric mucosa of man. Free Radical Biology and Medicine, 20(3):483-8.

This page was prepared by Theresa L. Pedersen, UCD EXTOXNET FAQ Team. August 1997.