Drugs used to treat diarrhea are called antidiarrheal drugs. Based on the specific mechanism of action, they are divided into different groups: adsorbents, antimotility drugs (anticholinergics and opiates), and probiotics (also known as intestinal flora modifiers and bacterial replacement drugs). The specific classes and the drugs in each are listed in Table 51-1. Antidiarrheal and laxative drugs do not have the classic pharmacokinetics of other drugs, and thus pharmacokinetics tables such as those presented throughout the book are not included in this chapter.

Antidiarrheal drugs have varying mechanisms of action. Adsorbents act by coating the walls of the GI tract. They bind the causative bacteria or toxin to their adsorbent surface for elimination from the body through the stool. Adsorption is similar to absorption but differs in that it involves the chemical binding of substances (e.g., ions, bacterial toxins) onto the surface of an adsorbent. In contrast, absorption refers to the penetration of a substance into the interior structure of the absorbant or the uptake of a substance across a surface (e.g., the absorption of dietary nutrients into the intestinal villi). The adsorbent bismuth subsalicylate is a form of aspirin, or acetylsalicylic acid, and therefore it also has many of the same drug effects as aspirin (see Chapter 44). Activated charcoal not only is helpful in coating the walls of the GI tract and adsorbing bacteria but also is useful in cases of overdose because of its drug-binding properties. The antilipemic drugs colestipol and cholestyramine (see Chapter 27) are anion exchange resins that are sometimes prescribed as antidiarrheal adsorbents and lipid-lowering drugs. Besides binding to diarrhea-causing toxins, they have the additional benefit of decreasing cholesterol levels.

Anticholinergic drugs work to slow peristalsis by reducing the rhythmic contractions and smooth muscle tone of the GI tract; they also have a drying effect and reduce gastric secretions. They are used in combination with adsorbents and opiates (see later in the chapter). Anticholinergics are discussed in detail in Chapter 21.

Probiotics are products obtained from bacterial cultures, most commonly Lactobacillus organisms, which make up the majority of the body’s normal bacterial flora. These organisms are commonly destroyed by antibiotics. Probiotics work by replenishing these bacteria, which helps to restore the balance of normal flora and suppress the growth of diarrhea-causing bacteria.

The primary action of opiates (see Chapter 10) in diarrhea treatment is to reduce bowel motility. A secondary effect that makes opiates beneficial in the treatment of diarrhea is reduction of the pain associated with diarrhea by relief of rectal spasms. Because they decrease the transit time of food through the GI tract, they permit longer contact of the intestinal contents with the absorptive surface of the bowel, which increases the absorption of water, electrolytes, and other nutrients from the bowel and reduces stool frequency and net volume.

The adverse effects of the antidiarrheals are specific to each drug family. Most of these potential effects are minor and are not life threatening. The major adverse effects of specific drugs in each drug class are listed in Table 51-2. Probiotics do not have any listed adverse effects.

The adsorbents can decrease the effectiveness of many drugs, primarily by decreasing the absorption of certain drugs. Examples include digoxin, quinidine, and hypoglycemic drugs. The oral anticoagulant warfarin (see Chapter 26) is more likely to cause increased bleeding times or bruising when coadministered with adsorbents. This is thought to be because the adsorbents bind to vitamin K, which is needed to make certain clotting factors. Vitamin K is synthesized by the normal bacterial flora in the bowel. The toxic effects of methotrexate are more likely to occur when it is given with adsorbents.

The therapeutic effects of the anticholinergic antidiarrheals can be decreased by coadministration with antacids. Amantadine, tricyclic antidepressants, monoamine oxidase inhibitors, opiates, and antihistamines, when given with anticholinergics, can result in increased anticholinergic effects. The opiate antidiarrheals have additive central nervous system (CNS) depressant effects if they are given with CNS depressants, alcohol, opioids, sedative-hypnotics, antipsychotics, or skeletal muscle relaxants.

Bismuth subsalicylate can lead to increased bleeding times and bruising when administered with warfarin as well as aspirin and other nonsteroidal antiinflammatory drugs. It can also cause confusion in the elderly. Cholestyramine, when administered with glipizide, can result in decreased hypoglycemic effects. Cholestyramine also decreases the absorption of any drug that is given within 2 hours of it. It is important not to give any drug within 2 hours before or 2 hours after cholestyramine.

For dosage information on the antidiarrheal drugs, see the table on p. 832.

The anticholinergics atropine and hyoscyamine are used either alone or in combination with other antidiarrheals because they slow GI tract motility. These drugs are referred to as belladonna alkaloids and are discussed in Chapter 21. Their safety margin is not as wide as that of many of the other antidiarrheals, because they can cause serious adverse effects if used inappropriately. For this reason, they are available only by prescription.