Pharmacological Therapeutical Management of IBDs During Pregnancy

As for therapeutic management of IBD during pregnancy, recent studies have shown that pregnant patients should continue pharmacological therapy for the duration of the pregnancy, with the primary aim being to prevent disease relapse given the high risk of negative effects on the foetus. It is necessary that the physician perform a careful preliminary evaluation of the risk/benefit ratio associated with therapy during pregnancy, comparing any harmful effect on the foetus and the expectant mother caused by drugs on one hand and by disease relapse in the absence of pharmacological treatment on the other hand. The results of many studies [23] suggest that it would be best to continue therapy during the disease quiescent stage, treating intensively any recrudescences given the higher danger of the latter in comparison with most available drugs [24].

For patients with IBD, the 5-aminosalicylate (5-ASA) group (mesalamine, sulfasalazine, balsalazide), which have become the mainstay of pharmacological therapy of intestinal inflammatory diseases, may be used on pregnant patients to induce and maintain remission, as there is significant evidence regarding their safety during pregnancy. Many patients may be treated with aminosalicylates only [25-27].

However, for nonresponsive patients or for those allergic to 5-ASA and/or suffering from a more extended disease, corticosteroids are frequently prescribed [28]. Corticosteroids are particularly indicated during the stages of moderate-serious activity analogous to cases of the disease outside the pregnancy period. Many study attest to sufficient tolera-bility of these drugs and their poor effect on the risk of foetal malformations; despite their ability to cross the placental barrier, they are rapidly transformed by placental 11-hydroxigenasis in less active metabolites with a consequent reduction of their levels in placen-tal blood, especially in the case of some types of steroids, such as prednisone. For this reason, suppression of the hypothalamus-hypophysis-suprarenal axis of the foetus is rare. Among the latest steroidal compounds, Budesonide - a synthetic glu-cocorticoid selectively released in the small bowel and therefore particularly indicated in the case of ileal localisation of CD - falls into classification category C of drugs that may be used during pregnancy, as a teratogenic effect was found in animals but not in humans.

Another likely therapeutic option in non-responsive patients or in patients allergic to first-choice drugs is represented by immunosuppressant drugs [30]. Rationale for their use is based on the recognised immunomediated pathogenesis of IBDs, including azathioprine, 6-mercaptopurine, cyclosporine, methotrexate and infliximab. Azathio-prine and 6-mercaptopurine [29], taken in the usual doses, showed no negative effect on gametogenesis or evidence of a likely teratogen effect. However, given the poor number of studies investigating their use in pregnant patients with IBD, it would be best not to begin therapy with these agents during pregnancy.

Cyclosporine is not associated with an increased risk of teratogenesis [29], but given the high incidence of hepatic and kidney toxicity in the expectant mother, it must be exclusively used in pregnant women suffering from fulminating colitis who are non-responsive to steroids in order to avoid an urgent proctocolectomy, which is associated with a high risk of losing the foetus.

Methotrexate [31] is an antimetabolite drug and antagonist of folic acid. It is a teratogen and mutagen and therefore is contraindicated during pregnancy in those planning a pregnancy. Guinea pigs in utero exposed to methotrexate develop craniofacial and cardiovascular malformations and flaws of the neural tube caused by this drug's antagonism of folic acid. For these reasons, patients with IBD beginning therapy with methotrexate should use effective contraceptive methodologies. If conception takes place and interruption of pregnancy is not considered, high doses of folic acid should be administered during the entire course of pregnancy.

Recently, monoclonal antibodies (infliximab) against tumour necrosis factor (TNF) [32] were introduced as therapy for CD. In guinea pigs, these molecules, belonging to the class of biologic drugs, were not associated with a high risk of toxicity, embryotoxicity or teratogenic effect, and from data presently available, there is no definite evidence on the outcome of a woman's pregnancy. As rare cases of foetal death secondary to cerebral and/or pulmonary haemorrhage were found, as well as cardiac malformations such as Fallot's tetralogy and premature delivery, and given the small amount of studies regarding the effect of these drugs during pregnancy, their use is contraindicated in pregnant patients with CD and those planning to become pregnant.

In patients with IBD, some antibiotics, such as metronidazole and the fluoroquinolones, are sometimes used [33] not only to treat intervening infections but as primary therapy to treat CD. However, little data exists regarding the safety of antibiotics during pregnancy. In particular, metronidazole is the teratogen, foetotoxin and carcinogen in the mouse but these effects were not found in humans. For this reason short cycles of therapy with metronidazole may be used relatively safely to treat vaginal candi-dosis during pregnancy.

Regarding fluoroquinolones such as ciprofloxacin, there is no evidence of possible harmful effect on the foetus although available data are still limited.

In addition to the above-mentioned drugs, many studies show that the quality of life of pregnant patients may be incredibly improved by aspecific symptomatic drugs active on more frequently reported symptoms, such as abdominal pain, nausea and diarrhoea [34]. Among these drugs, metoclopramide (Plasil) may be used as an antiemetic without risk of foetal damage. On the contrary, given the small quantity of available data, loperamide, an antihemor-rhoidal drug frequently used by patients with IBD, must be taken cautiously and exclusively by patients where probable benefits are higher than the risks. An alternative to loperamide, kaolin with pectin or cholestyramine may be used, the latter being suggested especially in ileal localisation of CD or in patients with gravidic cholestasis.

Musculoskeletal and some other forms of abdominal pain may be treated safely with acetaminophen whereas non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin, are contraindicated because of the risk of premature delivery, extended labour and extended postpartum haemorrhage [35].

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Cure Tennis Elbow Without Surgery

Everything you wanted to know about. How To Cure Tennis Elbow. Are you an athlete who suffers from tennis elbow? Contrary to popular opinion, most people who suffer from tennis elbow do not even play tennis. They get this condition, which is a torn tendon in the elbow, from the strain of using the same motions with the arm, repeatedly. If you have tennis elbow, you understand how the pain can disrupt your day.

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  • Niina
    Is plasil teratogenic in pregnant women?
    8 years ago

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