Laxative Use and Abuse in the Older Adult: Part I
At the conclusion of this activity, participants should be able to:
1. Discuss the clinical definition of constipation and to be able to identify its potential causes, particularly in the elderly.
2. Explain the clinical approach to constipation in the elderly.
3. Recognize opioid-induced constipation as a common source of morbidity in the elderly.
4. Describe the role of dietary fiber in the prevention and management of constipation in this population.
The word “laxative” is derived from the Latin word laxus, which means “loose."1 Laxatives are substances that stimulate defecation and aid in the smooth transit of fecal material through the gastrointestinal tract. The use of laxatives became commonplace in the early 19th century when the practice of medicine was based upon the “humoral theory” of the body, a theory formulated in Greece in the 4th century BC by Hippocrates. The humoral theory maintained that disease occurred when the equilibrium between the four humors (blood, phlegm, yellow bile, black bile) was disrupted. Laxatives were used to purge the body in order to expel ailments and restore the body’s natural equilibrium.2 The most commonly used laxative at the time was calomel (mercurous chloride), a drug that often led to the loss of hair and teeth from acute mercury intoxication. Other commonly employed laxatives included jalap, gamboge, senna, castor oil, cream of tartar, and aloe.3
Today, the most common indication for the use of laxatives is for the treatment of constipation. Constipation is considered the most common gastrointestinal disorder in the United States, resulting in an estimated 2 million annual visits to physicians. The estimated prevalence of constipation ranges from 2% to 28%, and the incidence increases with age.4 The incidence of constipation in the elderly is as high as 20%, with 20-30% of patients over age 65 using some form of laxative therapy. Most people resort to over-the-counter laxatives for relief of constipation, as evidenced by annual laxative sales of over $700 million. There are an estimated 700 or more varieties of over-thecounter and prescription laxatives available today.5 With such widespread use of laxatives, it is prudent that physicians develop a clear understanding of their proper use and potential adverse effects. Laxatives work in many different ways, and therefore an understanding of the potential causes of constipation may help guide choice of therapy.
In this two-part article, we review the current state of knowledge concerning available laxatives, their mechanism of action, indications for their use, adverse effects, and their potential for abuse. Part I addresses the approach to constipation, opioidinduced constipation, and natural laxatives. Part II, to be published in the May issue of Clinical Geriatrics, will discuss the pharmacologic agents used to maintain bowel regularity (ie, bulk-forming laxatives, emollients, lubricant laxatives, osmotic laxatives, stimulant laxatives, prokinetic agents, and a new locally acting agent). It will also discuss the potential for abuse and future implications.
THE APPROACH TO CONSTIPATION
No discussion on laxatives would be complete without mention of constipation. The management and treatment of this condition is challenging, as there is no standard definition for constipation, and the term has different meanings for both patients and healthcare providers. A common misconception is that daily bowel movements are essential for health maintenance. However, multiple studies have demonstrated that healthy individuals may have as few as 3 bowel movements per week without any detrimental effects to their health.6 The frequency of bowel movements may vary in different individuals; however, it is the change in a person’s normal bowel habits that should warrant a visit to their physician. No consistent evidence exists for what constitutes effective management of constipation, and laxatives may not be appropriate in all patients with constipation.
The initial assessment of any individual with constipation should involve the investigation of associated risk factors, although it is not always possible to identify an underlying cause. Constipation may have somatopathic or functional causes. Somatopathic constipation may be the result of underlying diseases such as cancer, neurologic conditions, diverticulosis, hypothyroidism, and others. Functional constipation may be the result of inadequate fluid and fiber intake, immobility or lack of exercise, or due to medications such as opioids.6
Therefore, a thorough patient history, including dietary habits and a complete list of medications, should always be obtained in order to help make this distinction. The first step in the management of constipation should be to rule out lifethreatening organic causes such as bowel obstruction. Once this has been done, studies have demonstrated that most patients will respond to lifestyle modifications involving an increase in dietary fiber intake (20-35 g/day), adequate fluid intake (1.5-2 L/day, if not contraindicated because of cardiac or renal disease), an increase in physical activity, and avoidance of certain constipating foods such as chocolate, refined flour products, and wheat.7 Educating patients on dietary habits and on the possible causes of constipation is also an essential part of management (Table I).
When diet and lifestyle modifications fail to relieve constipation, pharmacological therapy may be necessary. However, as there is currently limited evidence to support which laxatives are clinically superior, choice of agent still remains largely at the discretion of the treating physician. Thus, there is pressing need for further research on the effectiveness of the different classes of laxatives in order to establish clear-cut guidelines for their use. While managing constipation, physicians must also remember that the use of laxatives is not always necessary and that long-term use of these agents should be avoided wherever possible.
Constipation associated with the use of opiates deserves particular attention, as it is reported to occur in at least 41% of patients receiving longterm opioid therapy.8 Opioid-induced constipation falls under the category of “iatrogenically induced constipation,” which refers to constipation precipitated by the administration of various pharmacological agents. Although many drugs are known to contribute to constipation, narcotics are the primary offenders.
Opiates are known to affect bowel function in several ways, and their effects are mediated by specific opioid receptors in both the central nervous system, as well as in the gastrointestinal tract. Opiates can delay gastric emptying by inducing gastroparesis secondary to spasms in the antropyloric region. Furthermore, these agents delay stool transit time throughout the gastrointestinal tract and decrease overall peristalsis.9 These changes in the contractility of the bowel wall can be seen within 5-25 minutes of administration of the opiate, and tend to be dose-related. Although some tolerance develops to the effects of opiates in the gastrointestinal tract, constipation tends to persist unless further therapeutic measures are taken.10
The treatment of opioid-induced constipation should focus on the use of preventive strategies to avoid primary constipation. Using lower doses of opiates will not prevent this form of constipation because the doses that induce constipation are approximately fourfold less than the analgesic dose.11 Strategies to prevent primary constipation include increasing dietary fiber intake, maintaining adequate fluid intake, and ensuring proper physical activity. However, patients on long-term opioid therapy will usually require further therapy, and should thus be started on a bowel regimen to typically include either a stimulant or an osmotic laxative. Bulk-forming laxatives are not appropriate in opioid-induced constipation, as they will allow the colon to stretch and accommodate the bulk but will not help with propulsion. As a result, the use of these agents may result in bowel obstruction.12 In addition, oral opioid receptor antagonists such as naloxone, naltrexone, and nalmefene have been shown to help ameliorate the opioid effects in the gastrointestinal tract. However, these agents are not recommended for routine use as they cross the blood-brain barrier and may reverse the analgesic effects of the narcotics, and possibly even induce withdrawal symptoms.13
In conclusion, opioid-induced constipation is a very common condition that is often overlooked and undermanaged. Careful attention to this problem is necessary, as this condition often becomes a major detriment to quality of life and is a major source of morbidity, particularly in the elderly population.
Despite the wide availability of pharmacological agents for maintaining bowel regularity, many people continue to resort to natural laxatives as their first form of therapy. The most popular and well-researched of the natural laxatives is dietary fiber. The term dietary fiber was first coined in 1953 by prominent nutritionist E.H. Hipsley.14 A variety of definitions of dietary fiber exist globally, some based primarily upon analytical methods used to isolate and quantify fiber, whereas others are physiologically based. Although the definition continues to evolve, one accepted form states that “dietary fiber consists of the remnants of edible plant cells, polysaccharides, lignin, and associated substances resistant to digestion by the alimentary enzymes of humans."15
Inadequate fiber intake as a function of the modern diet is generally accepted to be the leading cause of idiopathic constipation in Western society. The current recommendations for adult dietary fiber intake put out by the Institute of Medicine of the National Academies is between 21 and 38 grams per day. Most healthy Americans consume an average of 14-15 grams per day, much less than the recommended intake in the United States. Specific recommendations for the elderly have not yet been published, although studies suggest that intake of 10-13 grams of dietary fiber per 1000 kcal should be encouraged.16 Due to reduced caloric intake in the elderly, a high-fiber diet may not be sufficient to maintain bowel regularity. A fiber supplement is often required to improve bowel function in these cases. This is particularly true for elderly individuals who are physically inactive.
As one of the oldest known laxatives, the role of dietary fiber in the prevention and management of constipation is well known. However, its benefits in health maintenance and disease prevention have been largely underplayed. Dietary fiber exists in various proportions of soluble and insoluble forms, each with their own unique health benefits. Generous amounts of soluble fiber can be found in such foods as oat bran, oatmeal, fruits, and peas/beans (Table II). Studies suggest that soluble fibers play a role in lowering blood cholesterol levels. Although the exact mechanism for this effect remains unknown, it is believed that an increase in viscosity of the luminal contents interferes with bile acid reabsorption from the ileum, thereby slowing cholesterol synthesis.17
Furthermore, considerable experimental evidence suggests that soluble fibers have a role in the management of diabetes mellitus. Soluble fibers are believed to increase the expression of certain peptides, which reduce gastric emptying rates, promote glucose uptake and disposal into peripheral tissues, and reduce hepatic glucose output. Studies suggest that patients with adult-onset diabetes may actually be successfully treated with high dietary fiber alone, and that those taking insulin can often reduce their requirements by adhering to a fiber-rich diet.18 Insoluble fibers increase overall stool volume and stimulate normal bowel contractions, thus reducing transit time through the colon. Apart from their laxative effect, insoluble fibers have been shown to prevent the symptoms associated with conditions such as irritable bowel syndrome and diverticulitis.16 Insoluble fibers can be found in such foods as apples, broccoli, cabbage, corn, carrots, and potatoes.
Adequate intake of dietary fiber prevents the formation of diverticula by providing adequate bulk in the colon, so less-forceful contractions are needed to propel fecal matter distally. Moreover, there has been some evidence to suggest that a high-fiber diet is protective against colorectal cancer; however, more research is needed to confirm this association.16
Other frequently employed natural laxatives include psyllium, cascara sagrada, aloe, Rhamnus frangula, and prune juice. Prune juice contains the substance dihydrophenylisatin, which is responsible for its laxative properties. Although presently there are no recommended or set guidelines for the use of laxatives, natural laxatives due to their low cost, limited side-effect profiles, and numerous additional health benefits should be considered as first-line therapy to maintain bowel regularity prior to moving on to other pharmacologic methods.
Constipation is a challenging condition faced by clinicians in the every day care of elderly patients. Although it is not always possible to identify a single underlying cause, the initial approach to constipation in the elderly should involve a detailed investigation of associated risk factors, medications, dietary regimens, and bowel habits. The management of constipation in this population should focus on increasing dietary fiber (both soluble and insoluble), encouraging adequate fluid intake, and promoting physical activity. Only when these lifestyle modifications have failed should pharmacologic therapy be implemented. Lastly, it is important for clinicians to recognize the frequent association between constipation and opioid use in the older adult. Patients on longterm opioid therapy should be maintained on scheduled laxative regimens in order to improve their quality of life.