Part 26 (2/2)
No human reproduction studies with mazindol (Mazanor) have been published.
DEXFENFLURAMINE.
Dexfenfluramine is a dextroisomer of fenfluramine, a serotoninergic agent. Information on dexfenfluramine and exposure during pregnancy have not been published.
ANTIFLATULENTS, LAXATIVES, AND ANTIDIARRHEALS.
Gastric motility is decreased during pregnancy (Little, 1999) and constipation is a relatively common complaint in pregnant women. Various iron preparations may also contribute to constipation in the pregnant patient. Laxatives are frequently used during pregnancy. The majority of such agents are absorbed very little, if at all, from the gastrointestinal tract. Overall, they should have no systemic effects or pose any serious threat to the fetus.
Antiflatulents SIMETHICONE.
Simethicone (Phazyme, Myliam, Gas-X, Gas Relief) is the most commonly used antiflatulent. There are no human or animal reproductive studies available. Simethicone is logically not expected to cause systemic effects or have access to the fetalplacental unit, because simethicone is not absorbed from the gastrointestinal tract. It is contained in several antacid preparations.
232.
Nutritional and dietary supplementation during pregnancy CHARCOAL CHARCOAL No information has been published regarding the use of charcoal during pregnancy, although activated charcoal capsules and tablets are used for relief of gas. Notably, it is not absorbed systemically.
From a practical standpoint, it has no clear indications for use during pregnancy, neither does this agent offer any advantage over simethicone. However, it should be used without hesitation when it is needed in the treatment of acute poisoning.
CALCIUM CARBONATE.
This agent in combination with magnesium hydroxide (Mylanta) is utilized as both an antacid and an antiflatulent. This combination can be used safely in pregnancy, avoiding chronic high doses which pose a risk (hypercalcemia, etc).
Laxatives and purgatives Laxatives/purgatives can generally be divided into several cla.s.ses depending on the mode of action: (1) emollients and softeners; (2) bulk-forming agents; (3) stimulants; and (4) saline, hyperusmetic, or lubricant agents (Box 12.2). Fortunately, there are few side effects a.s.sociated with the use of these agents. Allergic reactions are rare. Chronic use of the agents should be avoided because diarrhea and electrolyte imbalances may occur.
Box 12.2 Laxatives and purgatives Emollients and softeners Docusate sodium (Colace plus numerous others) plus combinations Docusate calcium (Surfak, Pro-Cal-Sof) plus combinations Docusate pota.s.sium (Dialose, Diocto-K, Kasof) Bulk-forming agents Psyllium (Metamucil, Konsyl-D, Pro-Lax, Serutan, plus several others) Methylcellulose (Citrucel, Cologel) Malt soup extract (Maltsupex) Polycarbophil (Fibercan, Equalactin, Mitrolan) Stimulants Castor oil Bisacodyl (Dulcolax plus others) plus combinations Casanthrunol (Black-Draught) plus combinations Cascara sagrada plus combinations Phenolphthalen (Ex-Lax plus others) plus combinations Senna (Senokot plus others) plus combinations Saline, hyperosmotic, or lubricant agents Mineral oil (Kondremul plus others) plus combinations Glycerin Lactulose (Chronulac plus others) Magnesium citrate (Citroma; Citro-Nesia) Magnesium hydroxide (Milk of Magnesia) plus combinations Antiflatulents, laxatives, and antidiarrheals Antiflatulents, laxatives, and antidiarrheals 233.
DOCUSATE.
This agent is an emollient-type laxative used either singly as a stool softener or in combination with other laxatives. Congenital anomalies were not increased in frequency among the offspring of over 800 women who utilized this agent in early pregnancy (Aselton et al et al., 1985; Heinonen et al et al., 1977; Jick et al et al., 1981). Docusate is not absorbed systemically.
CASANTHRANOL AND CASCARA SAGRADA.
The anthraquinone cathartics belong to the stimulant cla.s.s of laxatives. They are used as monotherapy or in combination with other laxatives. Congenital anomalies were not increased in frequency among offspring of mothers who utilized either casanthranol (21 patients) or cascara sagrada (53 patients) in early pregnancy (Heinonen et al et al., 1977).
SENNA.
Senna is also an anthraquinone laxative. No human reproduction studies have been published. It is very unlikely that it poses any risk to the fetus because this agent is minimally absorbed from the gastrointestinal tract.
PHENOLPHTHALEIN.
Phenolphthalein (Ex-Lax, Feen-A-Mint, Atophen, Medilax, Modone, Espotabs) is a commonly utilized agent in commercial preparations. In one mouse study, decreased litter size and fertility were observed, but no somatic effects (Anonymous, 1997).
LACTULOSE.
This agent is utilized as a laxative and for lowering serum ammonia in cases of hepatic encephalopathy. Although there are no human reproduction studies, this agent is not absorbed from the gastrointestinal tract for the most part, and thus is unlikely to be a.s.sociated with adverse fetal effects.
MINERAL OIL.
Mineral oil is a lubricant laxative. There are no published human epidemiological or animal teratology studies with this agent. However, chronic use of mineral oil as a laxative might interfere with the absorption of fat-soluble vitamins such as vitamin K and D, and thus theoretically could have adverse fetal effects.
CASTOR OIL.
There are no published human epidemiological or animal teratology studies with this agent. There are also no reports of an a.s.sociation of adverse fetal effects with the use of castor oil during pregnancy. It has been a commonly held belief that this agent would stimulate labor and it is often utilized for this purpose in women close to term. However, little scientific data support the use of this agent as a potent stimulant of labor.
Antidiarrheal agents Unlike constipation, diarrhea is an uncommon complaint of pregnancy and is usually secondary to medications (especially antibiotics), infections (bacterial, viral, and para-234 Nutritional and dietary supplementation during pregnancy Box 12.3 Antidiarrheal medications Box 12.3 Antidiarrheal medications Bulk agents Absorbents Kaolin and pectin (Kaopectate) Opioid agents site), and abuse of laxatives or lactose intolerance. Fortunately, most cases of acute diarrhea are self-limited and require no specific therapy. Patients should maintain adequate hydration. Antidiarrheals can generally be divided into three major categories bulk-forming agents, absorbents, and opiates (Box 12.3).
BULK-FORMING AGENTS.
These agents are utilized primarily for chronic diarrhea and are listed in Box 12.3. None of these agents are absorbed systemically. Therefore, embryofetal exposure does not occur and there is no a.s.sociated risk.
ABSORBENTS.
The combination of kaolin and pectin (Kaopectate) is probably the antidiarrheal agent most commonly used, including during pregnancy. Its main mode of action is reported to be via absorbent action. There are no epidemiological studies regarding the use of this agent in pregnant women. However, since very little, if any, of it is absorbed from the gastrointestinal tract, it seems very unlikely that this antidiarrheal poses a significant risk to either mother or fetus.
OPIOID AGENTS.
Kaolin and pectin have also been combined with opium and belladonna (Amogel-PG, Donnagel-PG, Donnapectolin-PG, Quiagel-PG) and with paregoric (kapectolin with paregoric, parepectolin). The addition of belladonna and opioid agents results in decreased gastrointestinal mobility. There is little available information regarding the use of opium-containing agents in pregnant women. There were only 36 women with early pregnancy exposure included in the Collaborative Perinatal Project database, but there was no evidence of a significant increase in the frequency of congenital anomalies (Heinonen et al et al., 1977). Almost 100 women were exposed to paregoric in early pregnancy with no significant increase in frequency of congenital anomalies (Aselton et al et al., 1985). There is, however, the possibility of addiction and withdrawal syndrome in neonates whose mothers use this agent on a chronic basis.
Another commonly used antidiarrheal is the combination of diphenoxylate and atropine (Lomotil and others). Diphenoxylate is a compound similar to meperidine and acts primarily to reduce intestinal motility. Of interest is the fact that atropine is included in this preparation in an effort to prevent abuse. Although there is a case report of an infant born with congenital heart disease whose mother used this agent during pregnancy (Ho et al et al., 1975), there are no large epidemiologic studies regarding its use during pregnancy. Moreover, there were less than 10 patients who utilized this agent in early pregnancy included in the Collaborative Perinatal Project (Heinonen et al et al., 1977).
None of the offspring of these women had malformations.
Special considerations 235.
LOPERAMIDE.
This antidiarrheal agent works by decreasing intestinal motility. No human reproduction studies have been published. According to its manufacturer, loperamide was not teratogenic in rats and rabbits. It is an FDA category B drug.
Teratogen Information System (TERIS) and FDA risk ratings for congenital anomalies congenital anomalies The TERIS and FDA risk ratings for drugs in this chapter provide a reasonable summary of risks that are supported by the medical literature. Most of the supporting literature for Table 12.4 has been discussed above.
SPECIAL CONSIDERATIONS.
Most agents utilized for gastrointestinal disease can be safely used in pregnant women, especially after the first trimester.
Nausea and vomiting All pregnant women probably experience nausea to some degree in early pregnancy.
Nausea and vomiting or 'morning sickness' are common symptoms of pregnancy during the first trimester, but most pregnant women do not require antiemetic therapy. Frequent small meals may prove a beneficial way to manage nausea without medical intervention.
Fortunately, hyperemesis gravidarum, the most severe form of pregnancy-a.s.sociated nausea and vomiting occurs in only a small percentage of gravidas. Women with hyperemesis gravidarum may require hospitalization and intravenous hydration, and antiemetic therapy. One of the most effective antiemetic agents for nausea and vomiting a.s.sociated with pregnancy was doxylamine plus pyridoxine (Bendectin). However, this agent is no longer available because of the fear of litigation. When antiemetics are indicated, promethazine suppositories (or occasionally orally) in doses of 25 mg should be used. Other agents which may prove useful for hyperemesis gravidarum are described in Box 12.4.
Such agents as prochlorperazine, promethazine, chlorpromazine, and thiethylperazine may be a.s.sociated with extrapyramidal side effects manifested by dystonia, torticollis, and oculogyric crisis. If it occurs, this unusual syndrome of adverse effects can be treated with diphenhydramine (Benadryl). Importantly, chlorpromazine may be a.s.sociated with significant hypotension when given intravenously. Therefore, suppositories are the preferred route of administration.
In severe cases of hyperemesis gravidarum in which other agents are largely ineffective, ondansetron (Zofran) 32 mg intravenously as a single dose may be effective. It is also available in oral form (8 mg twice a day), but this is much less likely to be effective in cases of hyperemesis gravidarum where almost everything taken orally is vomited.
Reflux esophagitis Reflux esophagitis resulting in heartburn or pyrosis is very common in pregnancy and is thought to be secondary to decreased gastroesophageal sphincter tone with resultant 236 236 Nutritional and dietary supplementation during pregnancy Table 12.4 Table 12.4 Teratogen Information System (TERIS) risk rating for congenital anomalies and Food and Drug Administration (FDA) pregnancy risk: category rating for nutritional supplements and gastrointestinal drugs Teratogen Information System (TERIS) risk rating for congenital anomalies and Food and Drug Administration (FDA) pregnancy risk: category rating for nutritional supplements and gastrointestinal drugs Drugs TERIS risk FDA pregnancy risk rating Aminopterin Moderate to high X.
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