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GI Agents: Part I


 

Gastrointestinal complaints are common in pregnancy and during the postpartum period. They include conditions such as nausea and vomiting, constipation, diarrhea, heartburn, and erosive gastroesophageal reflux disease.

Antiemetics. Nausea and vomiting is the most frequent GI complaint in pregnancy. Many oral and parenteral antiemetics are available to treat nausea and vomiting of pregnancy (NVP). All are considered low risk for developmental toxicity (growth retardation, structural defects, functional and behavioral deficits, or death).

The most commonly prescribed over-the-counter agent for this condition is doxylamine (Unisom), usually combined with vitamin B6 (pyridoxine). These two drugs were the components of Bendectin, which was removed from the market by its manufacturer in 1983, but classified by the Food and Drug Administration as safe and effective. Other commonly used oral medications for NVP include prochlorperazine (Compazine), metoclopramide (Reglan), trimethobenzamide (Tigan), promethazine (Phenergan), and ondansetron (Zofran).

The most severe form of nausea, hyperemesis gravidarum, occurs in less than 1% of pregnancies and requires hospitalization and intravenous antiemetics, such as droperidol (Inapsine), prochlorperazine, and ondansetron.

Laxatives. Seven types of products act as laxatives: saline (phosphates and magnesium hydroxide and its salts); stimulants/irritants (cascara, bisacodyl, casanthranol, senna, and castor oil); bulking agents (methylcellulose, polycarbophil, and psyllium); emollient (mineral oil); fecal softeners (docusate); hyperosmotics (glycerin, lactulose); and tegaserod (Zelnorm).

With the exception of lactulose and tegaserod, all of these products are available over the counter, and most do not cause direct embryo/fetal toxicity. However, castor oil, which is converted to ricinoleic acid in the gut, is an irritant that may induce premature labor. Improper use of saline laxatives can cause electrolyte imbalances, and mineral oil will prevent absorption of fat-soluble vitamins.

Of the laxatives, bulking agents and fecal softeners are the best choices in pregnancy. Cascara sagrada and senna are excreted into breast milk and are compatible with breast-feeding, although they may cause diarrhea in a nursing infant.

Tesgaserod, a serotonin type-4 receptor agonist, is approved for women with irritable bowel syndrome whose primary bowel symptom is constipation (and for idiopathic constipation in those under age 65). Limited animal and human data suggest a low risk for embryo/fetal toxicity, but the drug is best avoided during lactation because of the absence of any human data.

Antidiarrheal agents. The antidiarrheal agents diphenoxylate and its active metabolite, difenoxin, are meperidine-related narcotics. Available as Lomotil and Motofen when combined with atropine to prevent abuse, they present low risk in pregnancy. Although there is potential for toxicity in a nursing infant, infrequent use is probably compatible with nursing. Loperamide (Imodium) is low risk in pregnancy and lactation. Alosetron (Lotronex), a serotonin antagonist, has both antiemetic and antidiarrheal properties. It is indicated only in women with IBS whose primary symptom is severe, chronic diarrhea. Based only on animal data, it is considered low risk in pregnancy. Because severe GI toxicity (constipation, ischemic colitis) has been reported in adults, it should be avoided during lactation. Bismuth subsalicylate, such as Pepto-Bismol and Kaopectate, should not be used in pregnancy or lactation.

Antacids. Antacids available to treat heartburn include calcium carbonate, magnesium hydroxide and oxide, and aluminum hydroxide and carbonate. Systemic absorption of antacids is negligible, so recommended doses are safe in pregnancy and lactation. Sodium bicarbonate should be avoided because it is absorbed systemically and could cause alkalosis.

Antisecretory agents. These agents, used for heartburn and GERD, include the histamine H2 antagonists cimetidine (Tagamet), famotidine (Pepcid), nizatidine (Axid), and ranitidine (Zantac) and the proton pump inhibitors esomeprazole (Nexium), lansoprazole (Prevacid), omeprazole (Prilosec), pantoprazole (Protonix), and rabeprazole (Aciphex).

Low strengths of the histamine antagonists are available over the counter, but omeprazole is the only PPI available without a prescription. All of these antisecretory agents are low risk in pregnancy. The histamine antagonists are compatible with breast-feeding. In contrast, the PPIs have carcinogenic and mutagenic properties, so prolonged use while breast-feeding should be avoided.

Misoprostol (Cytotec), another antisecretory agent and a prostaglandin E1 (PGE1) analogue, is a proven human teratogen. It should only be used in pregnancy for its off-label indications: uterine stimulation and cervical ripening. Although its use during lactation has not been reported, naturally occurring PGE1 is excreted into milk and may protect the GI tract in nursing infants.

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