Physical Address
304 North Cardinal St.
Dorchester Center, MA 02124
Gastro-intestinal medications, hypolipidemic agents and spasmolytics
Gastrointestinal symptoms are common in pregnancy. Approximately 50% of women manifest episodes of heartburn. This is a consequence of the gastro-esophageal reflux due to the physiological reduction in the tone of both the stomach wall and the gastro-esophageal junction. In most cases, symptoms are controlled by a modification in the patient’s diet and lifestyle. However, if a pharmacologic therapy is needed, antacids are the first choice. If antacids are ineffective, then H2 receptor antagonists and Proton Pump Inhibitors (PPIs) may also be used ( ranitidine and omeprazole , respectively, are the best investigated medications of these two groups). In the case of a Helicobacter pylori infection, the triple therapy including omeprazole, amoxicillin and clarithromycin can be prescribed during pregnancy when indicated.
Constipation is another common condition in pregnancy, especially in the third trimester; it is usually a consequence of pressure being exerted by the uterus on the intestine, and high levels of progesterone, which reduce the contractility of the intestinal smooth muscle. If adequate hydration and a diet rich in fiber are not sufficiently effective, bulking agents may be used. After the bulking agents, lactulose and macrogol are the drugs of choice during pregnancy.
In cases of acute diarrhea during pregnancy, priority is to be given to symptomatic therapy with fluid replacement and balancing of electrolytes. With the exception of infections that require a specific antibiotic treatment, it is rare that acute diarrhea requires a treatment that would exceed dietetic measures. In such cases, charcoal and apple pectin can be safely used; loperamide may be used, for short periods, but only in selected cases.
The management of inflammatory bowel diseases (IBD) is more complex. Generally, in order to reduce complications, pregnancy should ideally be initiated when the disease is not active, and it is very important to promptly recognize and adequately treat any exacerbations of disease during gestation. Aminosalicylic acid preparations, in particular mesalazine , are the drugs of first choice in the treatment of IBD. When necessary, local or systemic corticosteroids, azathioprine or 6-mercaptopurine may also be used. Other drugs should be considered only if the aforementioned agents have failed.
In the case of gestational cholestasis, a disorder characterized by generalized pruritus that usually occurs in the second and third trimester, the drug of first choice is ursodeoxycholic acid (UDCA).
Another very complex scenario is the management of hyperlipidemia in pregnancy. When prescribing a possible lipid-lowering therapy, the physiological increase of cholesterol and triglyceride levels in pregnancy should be taken into consideration, which is essential for fetal development, and risks and benefits should be balanced. Initial treatment should consist of a proper diet and a reduction and/or control of body weight. Only in severe and selected cases, should drug therapy be considered after the first trimester of pregnancy. Moreover, obese women require expert pregnancy management and appetite suppressants are contraindicated during pregnancy.
2.5.1
Antacids
Antacids are basic compounds, which neutralize hydrochloric acid in the gastric secretions.
The following are currently available as single drugs: sodium bicarbonate , aluminum phosphate , calcium carbonate and carbaldrate that have an effect similar to aluminum hydroxide . The latter is mainly offered as combination drugs.
Hydrotalcite , magaldrate , and almasilate contain fixed combinations of aluminum- and magnesium-containing antacids.
In addition, there are combination drugs of various compositions; e.g. of calcium carbonate and magnesium salts , of a substance that contains aluminum such as algeldrate combined with magnesium salts, and of combinations containing alginic acid or licorice root extracts (see Chapter 2.19 ).
Aluminum hydroxide and aluminum phosphate neutralize the stomach acid forming aluminum chloride. Up to 20% of an oral dose can be absorbed. Elimination takes place primarily via the kidneys. Animal tests indicate that absorbed aluminum salts also reach the fetus. While occasionally it has been argued that aluminum absorbed from antacids could possibly lead to functional derangements of the central nervous system or the kidneys of the fetus, no clinical evidence of this has been found.
In the presence of gastric hydrochloric acid, alginic acid or alginate form a viscous gel that “floats” on the gastric contents, acts as a mechanical barrier, and thus reduces the gastro-esophageal reflux. A study with 150 pregnant women indicates effectiveness and safety during the second and third trimester ( ). Another multicenter, prospective study did not suggest an increased risk of negative outcomes for exposure during the second and third trimester ( ).
Calcium carbonate neutralizes hydrochloric acid by forming calcium chloride, carbon dioxide, and water. About 15–30% of the orally ingested dose is absorbed. Patients with normal kidney function are not in danger of hypercalcemia when taking medications with calcium carbonate in therapeutic doses. Excessive calcium intake from antacids, combined with mineral preparations and considerable daily milk consumption, can result in the rare milk-alkali syndrome during pregnancy (e.g. ). Therefore, the maximum daily intake of elementary calcium should not exceed 1.5 g (corresponding to 3.75 g calcium carbonate).
Hydrotalcite releases magnesium and aluminum ions depending on the gastric pH.
The use of sodium bicarbonate can lead to a metabolic alkalosis.
There is no evidence that any of the discussed antacids is linked to teratogenicity.
Recommendation
Antacids may be used throughout pregnancy. Fixed combinations of aluminum- and magnesium salts as well as combination drugs should be preferred. The recommended therapeutic doses are not to be exceeded.
2.5.2
Sucralfate and pirenzepine
Sucralfate is composed of a water-insoluble aluminum-saccharose compound. It adheres to the surface of ulcers, protects the mucosa, and is virtually not absorbed.
Pirenzepine is an anticholinergic drug, presumably only acting on the stomach, where inhibits the muscarinic M1 acetylcholine receptor. About up to 25% of an oral dose is absorbed. Experiences in pregnancy are too limited to allow a precise risk assessment, but there are also no indications of a specific teratogenic effect.
Recommendation
Sucralfate may be used at any time during pregnancy. Pirenzepine, however, should not be prescribed.
2.5.3
H 2 receptor antagonists
Cimetidine , famotidine , ranitidine , nizatidine and roxatidine enhance the healing of gastric and duodenal ulcers by blocking histamine H 2 receptors in the gastric mucosa that induce the secretion of hydrochloric acid.
In some animal species cimetidine induced weak androgenic effects ( ); however, there have been no reports of disruption in gender development in children who had been exposed in utero . A case report from Turkey describes a pregnant woman who developed a marked increase in her transaminase levels by taking ranitidine during the first trimester; after the medication was discontinued levels decreased ( ).
The current experience during the first trimester to exposure of ranitidine in about 1,700 women, of famotidine in almost 1,000, and of cimetidine in about 800 argues against a teratogenic potential in humans ( ). The number and types of malformations were similar in both study and control populations. Also, premature birth and intrauterine growth retardation were not seen more frequently in the exposed groups.
Extensive experience is available for the management of symptoms during late pregnancy. While nizatidine and roxatidine are not under suspicion at the moment, they have been inadequately examined, with each drug so far having been reported in only 15 published pregnancies ( ).
To reduce the risk of aspiration at the time of a caesarean section ranitidine and cimetidine have been applied; they are generally well tolerated by the mother and her fetus.
Recommendation
H 2 receptor antagonists may be used during pregnancy. Ranitidine is the best investigated medication and should be preferred.
2.5.4
Proton pump inhibitors
PPIs such as omeprazole , esomeprazole , an isomer of omeprazole, lansoprazole , pantoprazole and rabeprazole block the enzyme H + /K + -ATPase, which is critical for the secretion of gastric acid.
About 6,000 pregnant women who used PPIs during their first trimester have so far been documented (reported in, for example, ).
Omeprazole is by far the most extensively tested PPI, followed by pantoprazole , lansoprazole and esomeprazole , each with experiences of about 500–1,000 pregnancies. None of the studies indicated an increased risk of malformations; other problems were also not described. One study ( ) has suggested that premature births might be more common after PPI use, although this does not appear to be biologically plausible. Rabeprazole has not been adequately examined. So far there are no indications of any fetotoxic effects.
An association between intrauterine exposure to acid-blocking medications and childhood asthma was found in a study that linked and analyzed a number of Swedish registers. While the normal prevalence is 3.7%, the study noted a prevalence of childhood asthma of 5.6% after exposure. Medications used were PPIs, H 2 receptor antagonists, drugs for the treatment of Helicobacter pylori , and sucralfate; antacids were not included as they are available over-the-counter ( ). Another study evaluating 197,060 singletons born between 1996 and 2008 in northern Denmark observed that prenatal exposure to PPIs and H 2 receptor antagonists was associated with an increased risk of asthma ( ).
Recommendation
Proton pump inhibitors may be prescribed during pregnancy. Omeprazole is the medication of choice of this group.
2.5.5
Bismuth salts
Bismuth salts used previously as an antidiarrheal agent have regained some popularity since the discovery of a link between the occurrence of gastric and duodenal ulcers and an infection with the bacterium Helicobacter pylori . Bismuth salts have an antibacterial effect on Helicobacter pylori . Experiences in pregnancy are too limited to allow a risk assessment. So far there is no indication of a teratogenic effect in humans.
Recommendation
Bismuth salts are relatively contraindicated in pregnancy.
2.5.6
Helicobacter pylori therapy
In the last decades the treatment of Helicobacter pylori has fundamentally changed the management of gastric and duodenal ulcers and of atrophic gastritis. The so-called triple therapy with PPIs, clarithromycin , and amoxicillin or metronidazole , has become standard since it was recommended by consensus conferences held around the world. Although some studies conducted in Asia have confirmed a high eradication rate (>80%), other studies have shown a reduction in efficacy due to the increase in Helicobacter pylori resistance to clarithromycin ( ). According the European Consensus Guidelines on Helicobacter pylori therapy (Maastricht IV/Florence Consensus Report, ) clarithromycin-containing treatments are recommended for first-line empirical treatment only in areas of low clarithromycin resistance. Moreover, treatment regimens using amoxicillin and clarithromycin are equivalent. In areas of high clarithromycin resistance, bismuth-containing quadruple therapies are recommended for first-line empirical treatment ( omeprazole - bismuth - metronidazole - tetracycline , ). In areas where bismuth is not available, the so-called sequential treatment (5-day period with PPI and amoxicillin, followed by a 5-day period with PPI-clarithromycin-metronidazole) or a non-bismuth quadruple treatment (amoxicillin-clarithromycin-metronidazole-PPI) is recommended ( ).
Recommendation
Triple therapy can be undertaken during pregnancy when indicated; omeprazole is the medication of choice among PPIs. Amoxicillin can be safely used during pregnancy and there is no evidence of increased risks of birth defects after prenatal therapy with macrolides, such as clarithromycin (see Chapter 2.6 ). Although human data do not indicate an increased risk, the application of metronidazole should be carefully considered during the first trimester of pregnancy.
Bismuth-containing quadruple therapies are not recommended during pregnancy since bismuth salts are relatively contraindicated (see section 2.5.5 ) and tetracyclines are contraindicated after the fifteenth week of gestation (see Chapter 2.6 ).
2.5.7
You're Reading a Preview
Become a Clinical Tree membership for Full access and enjoy Unlimited articles
If you are a member. Log in here