Aging, Drugs, and Alcohol
AGING, DRUGS, AND ALCOHOL
One of the most important developments of the twentieth century has been the enormous rise in worldwide population in general, and especially the survival of an estimated six hundred million people aged sixty or older (Ikels, 1991). The increase in the percentage of elderly in the total population results from medical, economic, and social factors plus a decline in the birthrate. According to 1989 U.S. Bureau of the Census figures, persons over sixty-five represented 12 percent of the U.S. population, and it is projected that this proportion will almost double by the year 2030—since the baby-boom generation, born after 1945, will start reaching 65 in 2010.
This fastest-growing segment—the elderly—uses pharmacological and health services more often than any other part of the population (Brock, Guralnik, & Brody, 1990). Aging people are more susceptible to infectious disease. Many suffer from multiple chronic diseases and often from conditions that have grown slowly worse throughout their lifetimes. Some conditions are the result of accidents and some are from degenerative diseases. The latter include many kinds of cancer; diseases of the immune system such as lupus; diseases of the heart and blood vessels such as stroke and hardening of the arteries; diseases of the glands such as diabetes; bone and joint diseases such as arthritis and osteoporosis; and diseases of the lungs such as emphysema. Like the rest of the population, the elderly also suffer from psychiatric disorders, some of which may respond to medication. Hence physicians (sometimes multiple physicians) often prescribe multiple medicines for treatment. If each physician does not know all the medications prescribed by all the other physicians treating the patient, two or more of these medications may interact, sometimes even causing death (Monane, M; Monane, S; & Semla, 1997; Stein, 1994). Although they comprised only 12 percent of the U.S. population in 1988, the aging accounted for 35 percent of prescription-drug expenditures (Health Care Financing Administration, 1990). Furthermore, the elderly—like the rest of the population—may also take over-the-counter drugs such as aspirin or allergy tablets, smoke tobacco, drink caffeine-laden and alcoholic beverages, and even use illicit drugs. Because of certain changes in their bodies, their responses to all medicines and to the interactions of one drug to another drug, and of medicines to alcohol, may differ from those in younger people (Montamat, Cusack, & Vestal, 1989).
The use and abuse of alcohol is a public-health problem. Among people sixty-five years of age and older, 33 percent report using some alcohol (National Household Survey on Drug Abuse, 1999). About 6 percent of the elderly are considered heavy drinkers (more than two drinks per day), but about 5 to 12 percent of men and 1 to 2 percent of women in their sixties are problem drinkers (Atkinson, 1984). Alcoholism and prescription-drug abuse may result in physical, psychological, and social illnesses and premature death among the elderly from either severe withdrawal symptoms, medical complications, or suicide. Medicines intended to affect the mind (including ones intended to combat psychosis, depression, anxiety, and sleep problems) are commonly prescribed for the elderly (Rummans, Evans, Krahn, & Fleming, 1995). Studies suggest that the benzodiazepines or other sedative-hypnotics are the most commonly prescribed classes of these medicines. The effects of these medicines add to and interact with those of alcohol (Scott, 1989). All these factors taken together—alcohol, old age, multiple diseases, and multiple medications—can lead to poisonous, even fatal, interactions of two or more medicines. The complexities of alcohol, age, and drug interactions are discussed in the sections that follow.
NORMAL AGING AND BODILY CHANGES
Today, there is great interest in gerontology, the study of aging, because there are now more older persons in society than ever before, and their number is expected to rise dramatically. The present goal of gerontology is not necessarily to increase the life span but rather to increase the health span— that is, the number of years that a person will enjoy good health. Aging comprises multiple ongoing processes; disease and disability are disruptions.
Several factors once thought part of normal human aging have now been shown to be diseases. With aging, the immune system no longer performs as it once did. For example, the thymus gland, one of the central pacemakers of the immune system, gradually decreases in size, and eventually most of it is replaced by fat and connective tissue. The risk of cancer and autoimmune diseases increases among the elderly. An older person exhibiting a weaker response to bacteria and may produce auto-antibodies (antibodies which work against his or her own tissues), instead of defending against foreign parasites and aggressors (Weksler, 1990). This problem, if it occurs, shows that the immune system is no longer functioning normally. These immune changes may be responsible for the increased risk among the elderly of sickness and death from infectious diseases. A decline in the hormonal system may affect many different organs of the body. For example, diabetes is a common development in older persons. The pancreas makes insulin, but cells in the body cannot utilize it as effectively as they used to do. Both thyroid-stimulating hormone produced in the pituitary gland and thyroid hormone secreted by the thyroid gland itself show a decline with advancing age. This process is functionally reflected in a decrease in the basal metabolism of as much as 20 percent from age thirty to age seventy. Thus, aging may result in part from the loss of hormonal activities and a decline in the functions they control.
With advancing age, persons tend to have slower reactions to stimuli, wider variations in function, and slower return to resting states. This decline in stability within the body (or homeostasis) is found in a number of body systems. For example, the sensitivity of the baroreceptors, which help maintain a normal blood pressure by changing the heart rate and the tension in blood vessels, declines with age. Likewise, the elderly are prone to being too hot (hyperthermia) or cold (hypothermia) because of a weakened ability to regulate body temperature. A large proportion of age-related problems in the stomach and intestines, such as constipation, are caused and made worse by long-term abuse of laxatives, poor eating habits, not drinking enough fluids, and lack of exercise. Some elderly persons are not aware of the importance to their general health of diet and exercise. For example, diseases involving hardening of the arteries are less prevalent in populations that eat no meat and little fat.
For large populations, increased age is associated with increased variability in most dimensions of health. Thus it is difficult to discriminate between normal and abnormal states. Moreover, even those aging changes considered usual or normal within a defined population do not necessarily happen in a particular aging person.
AGING AND ALTERED DRUG RESPONSE
Some drugs act differently in old persons than they do in the young or middle-aged. The difference stems from age-related changes in pharmacokinetics, the bodily processes that absorb, distribute within the body, make use of, and excrete medicines (Vestal & Cusack, 1990). All these factors can affect the levels of medicines in blood and tissues. For example, with aging, the percent of water and lean tissue (mainly muscle) in the body decreases, while the percent of fat tissue increases. These changes can affect the distribution of a drug to different parts of the body, the length of time that it stays in the body, as well as the amount that is absorbed by body tissues. One reason that drinking the same amount of alcohol has a greater effect on the elderly is that there is a smaller volume of total body fluids, resulting in higher blood-alcohol levels than in the young (Vestal et al., 1977). Most medicines are eliminated from the body by metabolism in the liver followed by excretion by the kidney. (To a limited extent, metabolism occurs in other organs as well, including the stomach and intestines, the kidneys, and the lungs.) Although enzymes continue in general to metabolize at the same rate in the old as in the young, both the total weight of the liver as a percentage of total body weight and the total blood-flow through the liver decrease with aging (Loi & Vestal, 1988). As a result, the overall capacity of the liver to convert some medicines to their inactive break-down products declines with age. For example, some studies show that medicines such as diazepam (Valium), alprazolam (Xanex), chlordiazepoxide (Librium), propranolol, valproic acid, lidocaine, and theophylline are metabolized at a slower rate in old persons than in young ones. This decline is highly variable, however, and not all drugs metabolized by the liver show an age-related slowing in the rate of metabolism. In fact, the metabolism of alcohol by the liver does not decline with age (Vestal et al., 1977).
The most consistent physiological change with aging is a decline in kidney function. Both the rate at which tiny blood vessels in the kidney filter the blood and the total flow of blood through the kidneys decline with age. As a result, medicines that are in general excreted by the kidneys regularly are excreted more slowly in the urine of the elderly and hence build up more quickly in their bloodstream. This fact is particularly important for medicines with a narrow therapeutic window (a small difference between the amount of the medicine which is enough to do any good and the amount of the medicine which is poisonous) such as digoxin, aminoglycoside antibiotics, lithium, and chlorpropamide (Greenblatt, Sellars, & Shader, 1982).
Another mechanism of age-related changes in the response to some medicines is an apparent change in how sensitive the nerve cells are to the presence of the drug and how well they take the drug inside the nerve cell through tiny pipe-like structures called receptors which are found in the cell wall. In general, drugs acting on the central nervous system produce a stronger effect in older patients. Any drug that affects alertness, coordination, and balance will likely cause more falls and other accidents in elderly persons than in younger ones. Thus, hangover effects of sedative-hypnotic drugs and other mind-altering medicines such as antipsychotics, antidepressants, and anxiolytics) are common and often more serious in the elderly. The dangerous consequences of the hangover effects, such as falls which cause broken hips, suggest, in part, that the receptors in the nerve cells in the elderly are more sensitive, even super-sensitive, to the presence of these medicines. In contrast to mind-altering medications, the response of the heart to stimulation by adrenalin and other such substances is diminished in the elderly. For example, a larger dose of isoproterenol is needed to achieve the same increase in heart rate in the elderly as in the young (Vestal, Wood, & Shand, 1979).
AGING AND ADVERSE DRUG REACTIONS
In general, because of multiple and chronic diseases, older patients often take multiple prescription and over-the-counter drugs. Persons over sixty-five may take seven or more prescription drugs in addition to some over-the-counter drugs (Stewart & Cooper, 1994). However, such multiple-drug therapy predisposes the elderly to an increased risk of unintended, adverse drug reactions (ADRs). The overall incidence of ADRs in this age group is two to three times that found in young adults. Although the results of studies vary, about 20 percent of all adverse drug reactions occur in the elderly (Korrapati, Loi, & Vestal, 1992); they may result from drug overuse, from drug misuse, from slowed drug metabolism, or from slow elimination of the drug in the urine. These bad side-effects may be caused or increased by age-related chronic diseases, by intake of alcohol, and/or by incompatibilities between the foods and the medicines which the elderly person takes. Furthermore, ADRs are more severe than among young adults. At increased risk are women, persons living alone, persons suffering from multiple diseases, persons taking multiple drugs (especially prescribed by multiple physicians who do not each know what the other physicians have prescribed), persons with poor nutritional habits, and persons with less sharp sense perceptions or mental clarity. Some of the age-related physiological causes for increased levels of medicines remaining in the bloodstream and examples of increased sensitivity of nerve cells to drugs have already been discussed. The elderly who drink regularly, even if they are not alcoholic, place themselves at increased risk for bad interactions between alcohol and their medicines. This risk would be greater still if an elderly person combined alcohol, prescription medicines, and illegal drugs. Thus, since both the kidneys and the liver are often slower at eliminating substances from the body in old age, medicines should generally be taken at lower initial doses by older patients.
AGING AND ALCOHOLISM
Alcohol is an addictive drug for many individuals. Although its victims often do not recognize their alcoholism as a disease, it does meet the medical criteria for a disease: it has definite symptoms; it is chronic; and it often progresses until it causes death—but it is treatable. It destroys its victims not only physically but also mentally, emotionally, and spiritually. Many people with this disease die from physical complications, from accidents, even from suicide. In Western society, smoking cigarettes and excessive drinking of alcohol are two of the most insidious forms of drug abuse. Yet they are often considered socially acceptable. In the United States, two-thirds of all adults use alcohol occasionally. It is estimated that between 2 and 10 percent of persons over the age of sixty suffer from heavy drinking that interferes with their health and well-being. These persons by definition suffer from alcoholism (Jinks & Raschko, 1990). If cigarette smoking is excluded, alcoholism is by far the most serious drug problem in the United States and in most other countries. Alcohol and drug abuse causes thousands of premature deaths, and the cost of complications contributes billions of dollars to any large nation's health expenditure.
Men in their sixties continue to drink at a rate that is almost equal to that of their twenties, but fortunately problem drinking decreases in the mid-seventies. The prevalence of alcoholism and problem drinking is lower in women than in men. A large majority of male alcoholics have strong family histories of alcoholism, begin problem drinking early in life, and become alcoholics not slowly and gradually but suddenly and severely. These are the early-onset or problem drinkers, called type II alcoholics (Rigler, 2000; Atkinson, 1984). It is suspected that alcoholism in this group is largely genetic. The other main group consists of later-onset alcoholics. They may drink from grief, loneliness, or a need to numb pain and to try to escape from other consequences of poor health. The many losses and stresses of later life make the elderly especially vulnerable to alcoholism and suicide (Schonfeld& Dupree, 1991). Depression puts the elderly at particular risk for suicide, especially when it is heightened by alcohol and drug abuse.
ALCOHOL AND ITS COMPLICATIONS IN THE ELDERLY
Health-care costs for a family with an alcoholic member are typically twice those for other families, and up to half of all emergency-room admissions are alcohol-related. Alcohol abuse contributes to the high health-care costs of elderly beneficiaries of government-supported health programs. In general, the medical complications of alcohol abuse observed in older individuals are the same as those found in younger alcoholics. They include alcoholic liver disease, acute and chronic inflammation of the pancreas, gastrointestinal (affecting the stomach and intestines) bleeding and other GI-tract diseases, an increased risk of infections, and disturbances in metabolism. The elderly tolerate GI bleeding and infection less well than do younger persons. They are particularly prone to vitamin deficiencies, malnutrition (that is to getting too few calories overall and consuming too little protein on a daily basis), anemia, loss of bone mass (lighter, weaker bones are more apt to break), diseases of the central and peripheral nervous systems, heart conditions, and cancer. Finally, alcohol-induced degeneration of the brain and the rest of the nervous system will add to the effects of the normal loss of nerve cells that occurs with age.
A number of studies have shown that alcohol in moderate amounts is actually a good medicine for the elderly (even the Prohibition Amendment permitted the sale of alcohol for medicinal purposes) and that it improves social interaction, mental alertness, and several signs of physical health. Alcohol is primarily a drug which depresses or deadens the central nervous system (CNS). Paradoxically, in moderate amounts it may seem to act as a stimulant with mood-elevating effects that account for its popularity. What it is actually doing in these cases is to depress or deaden inhibitions. The lack of inhibitions contributes to feelings of relaxation, confidence, and euphoria. However, alcohol abuse can result in serious damage to the brain and to the rest of the nervous system. It can cause brain tissue to shrink or waste away, unsteadiness and lack of coordination in movement, and damage to nerves throughout the body. Large doses of alcohol cause inflammation of the stomach, pancreas, and intestine that can hurt the digestion of food and the absorption of nutrients into the bloodstream. The adult population appears less knowledgeable about the many adverse effects of alcohol on health than about the effects of smoking. For example, although many people recognize that heavy alcohol drinking often leads to cirrhosis of the liver, only about one-third are aware of the association between alcohol use and cancers of the mouth and throat. Alcohol use can lessen the effectiveness of routine drug therapy or can create new medical problems requiring additional therapy. Excessive alcohol use together with medications in the elderly can severely compromise and complicate a well-planned therapeutic program. Thus, even casual use of alcohol may be a problem for the elderly, particularly if they are taking medications that interact badly with alcohol. Difficulties can also arise from the interaction of alcohol and over-the-counter (OTC) medications. The combination of alcohol and prescribed or OTC sleeping pills, for example, could decrease intellectual function by producing an organic brain syndrome; frequent results include confusion, falls, wild swings in emotions, and other adverse drug reactions (Adams, 1995).
PRECAUTIONS WHILE USING ALCOHOL
Patients with liver disease and GI ulcers should not use alcohol. Alcohol should be avoided by patients with damage, caused by previous drinking, to the heart muscle or other muscles. Clearly, it should be taken only in strict moderation or not at all. For older individuals who have no medical reasons to the contrary and who take no drugs (prescription or over-the-counter or illegal) that interact with alcohol, one drink a day is a prudent level of alcohol consumption. In general, the use of alcohol in the presence of any particular disease or medication is a matter that the physician and patient must decide.
ALCOHOL AND DRUG ABUSE IN THE ELDERLY
Alcohol, itself a drug, mixes unfavorably with many other drugs, including those purchased over the counter. In addition, use of certain prescription drugs may intensify the older person's reaction to alcohol, leading to more rapid intoxication. Alcohol, when combined substantially and quickly with certain groups of drugs, can dangerously slow down performance skills such as driving, running machinery, and even walking. It lessens judgment, and reduces alertness when taken with drugs such as those prescribed against psychosis, those meant to lessen anxiety, sedative-hypnotics, pain-killers derived from opium, antihistamines, and certain blood-pressure medicines (Table 1). Large amounts drunk quickly reduce the clearance of some drugs by the liver. In contrast, alcohol consumed on a regular basis brings on the manufacture of enzymes in the body, leading in turn to accelerated metabolism and increased clearance of some drugs, including blood-thinners, oral diabetic medicine, and medicine prescribed against convulsions. Thus, these therapeutic drugs can become less effective, so the patient needs closer monitoring. Alcohol-drug interactions do not generally result directly in death. However, there is evidence for a contributory role of alcohol in drug-related fatalities, for example, in car accidents. Anyone who drinks even moderately should ask a physician or pharmacist about possible alcohol-drug interactions.
It is very difficult to determine the actual incidence of combined drug and alcohol use by the elderly, but it is likely to be reasonably high for the following reasons: the average adult over sixty-five takes two to seven prescription medicines daily in addition to over-the-counter medications; most elderly persons do not view alcohol as a drug and therefore falsely assume that modest amounts of alcoholic beverages can do little harm to an already aged body; and few elderly persons hold to the traditional notion that mixing alcohol and medications will have bad consequences. Certainly not every medication reacts dangerously with alcohol; however, a variety of drugs interact consistently. The most dangerous of these reactions occurs when alcohol is combined with another CNS depressant. Since alcohol itself is a potent CNS depressant, its use with antihistamines, barbiturates, sedative-hypnotics, or other mind-altering drugs adds to and reinforces synergistic CNS-depressant effects, effects that in turn may inhibit one's mental alertness and even consciousness as well as one's control of movement (Gerbino, 1982). In one study, diazepam, codeine, meprobamate (Equanil), and fluorazepam (Dalmane) were the top four agents responsible for drug-alcohol interactions (Jinks & Raschko, 1990). Antihistamines, including diphenhydramine (Benadryl), dimenhydrinate (Dramamine), and most cold medications and anticholinergics such as scopolamine, which are found in over-the-counter medications, can also cause confusion in the elderly. An important consideration in the elderly is the confused and altered behavior that so regularly follows excessive consumption of alcohol. Many times, elderly alcoholics show symptoms of falls, confusion, and self-neglect. Such changes may lessen the elderly patient's ability to adhere to a prescribed treatment, and increase the risk of mistakes or mishaps in dosage (Gerbino, 1982). Some of the well-described interactions are discussed in the following sections.
ALCOHOL AND ANALGESICS
Aspirin is the active ingredient in many over-the-counter arthritis pain formulas and in numerous nonprescription combination headache-and-minor-pain products. The ability of aspirin to cause inflammation of the stomach, erosion of the GI tract, and GI bleeding is well recognized. Alcohol not only produces inflammation of the stomach but also increases the risk of GI bleeding caused by aspirin and other nonsteroidal anti-inflammatory drugs (Bush, Sholtzhauer, and Imai, 1991). Elderly people at high risk for bleeding should avoid regular use either of alcohol or of aspirin. Chronic alcohol abuse can cause poisoning of the liver in a patient taking acetaminophen (Tylenol), probably because it leads to the production of enzymes which in turn lead to the formation of poisonous intermediary breakdown products of the Tylenol.
ALCOHOL AND CENTRAL NERVOUS SYSTEM (CNS) DEPRESSANT MEDICINES
Alcohol and medicines that by themselves depress the CNS, when combined with each other, may depress the system more than either does by itself. Much controversy exists as to whether the combined effect is merely additive (what one would expect by adding the two effects together) or whether it is synergistic (greater than the sum of its two parts), whether each somehow reinforces the action of the other as well as adding its own action. When combined with CNS depressants, alcohol—even in small quantities—produces undesirable and sometimes dangerous effects. The interaction of alcohol with benzodiazepine drugs, however, may be much greater in the elderly than in the other age groups. This is especially true for diazepam (Valium) and chlordiazepoxide (Librium). Commonly observed side-effects include high blood pressure, sleepiness, confusion, and depression of the CNS that may lead to slowing down of breathing, or even to stopping it. Two drinks can bring about a drug-alcohol interaction with a medicine that depresses the CNS (Hartford & Samorajski, 1982). Therefore, as a general rule, elderly patients should be instructed to stay away from alcohol while taking such medicines, including benzodiazepines, barbiturates, muscle relaxants, and antihistamines (both by prescription and as over-the-counter cold remedies or sleeping aids). Alcohol increases the clinical effects of these drugs, which already are hazardous in a segment of the population with decreased agility and greater danger of serious complications from falls and other accidents.
ALCOHOL AND MIND-ALTERING DRUGS
When alcohol is combined with mind-altering (psychotropic) drugs such as those prescribed to fight psychosis and depression, the combined effects of alcohol and the medicine are less predictable than with other drugs. Antipsychotic drugs inhibit the metabolism of alcohol and may thus markedly increase its effects on the CNS in the elderly. Antidepressants increase the response to alcohol and harm one's control over one's motions— a significant hazard in the elderly for whom falls often lead to broken bones. Depression of the CNS may range from drowsiness to coma and therefore death, because acute alcohol consumption may increase the CNS effects of antidepressants. Alcohol may also increase the risk of dangerously lowering body temperature in the elderly taking tricyclic antidepressants. Hence the avoidance of alcohol in elderly patients taking any of these drugs is a prudent recommendation (Scott & Mitchell, 1988).
ALCOHOL AND OTHER DRUGS
Many elderly patients with adult-onset (Type II) diabetes take antidiabetic pills instead of insulin. When alcohol is taken along with pills such as sulfonylureas, it may cause dangerously low levels of blood sugar, especially in patients whose diet calls for decreasing the eating of carbohydrates. Another problem associated with this combination is an Antabuse-like reaction (fortunately quite rare and usually mild), causing nausea, vomiting, headache, blurred vision, and flushing. However, symptoms of severe Antabuse-like reactions include speeding up of the heart to more than one hundred beats a minute, abdominal distress, sweating, episodes of low blood pressure, death of heart muscle, and tearing of the esophagus brought about by vomiting; psychosis may also occur, and fatal reactions have been reported. Use of alcohol at the same time with a variety of other drugs (Table 2) can also lead to an Antabuse-like reaction. Cough medicines may contain a narcotic pain-killer such as codeine in combination with antihistamines. When taken together with alcohol, these drugs are hazardous and can cause altered alertness, even loss of consciousness, and may slow down one's breathing or even stop it. Despite the fact that heart disorders are very common in older individuals, few of those who suffer from these problems modify their drinking patterns. This tendency may be dangerous, since as little as one cocktail can severely reduce the efficiency of the heart in the presence of heart disease. For example, alcohol consumption in a person suffering from angina (pain felt in the heart during physical activity) can mask the pain that might otherwise serve as a warning signal of a heart attack (Horowitz, 1975).
ALCOHOL AND ILLICIT DRUGS
Abuse of hallucinogens, illicit psychomotor stimulants and sedatives, and marijuana is uncommon in old age; use of these drugs by the elderly is almost exclusively by longstanding users of opium-like substances and by aging criminals. The low incidence of this type of substance abuse in old age may result from the fact that users of illegal drugs die young, and even from the fact that the use of such drugs by the elderly is often underreported. However, problem drinkers may abuse drugs such as sedatives, opioids, marijuana, and amphetamines. Sometimes these drugs are used in combination with alcohol; at other times, such drugs are taken in preference to alcohol, and alcohol is used only when the drug of choice is not available.
Elderly people are the fastest-growing segment of world population and consume about 25 percent of all the medicines prescribed. Their capacity to handle medication differs from that of the young because of age-related changes in various systems of the body. Alcohol abuse among older people (as in any other) can lead to falls, fractures, and other similar medical complications. The addition of medications (prescription and over-the-counter) to alcohol drinking can lead to disastrous complications and even premature death. However, in the absence of any indications to the contrary such as the taking of the medications discussed above, drinking a small quantity of alcohol may be beneficial in some elderly persons. In case of doubt, the elderly and their families or caregivers are encouraged to seek the advice of the pharmacist or family physician and to follow the guidelines given in Table 3.
(See also: Social Costs of Alcohol and Drug Abuse )
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Madhu R. Korrapati
Robert E. Vestal
Revised by James T. McDonough, Jr.
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