In the treatment of inflammatory bowel disease (IBD) are different classes of substances useful. Details of their selection are discussed in the individual disease (see treatment of Crohn’s disease and ulcerative colitis treatment). 5-aminosalicylic acid (5-ASA, mesalamine) 5-ASA inhibits the production of prostaglandins and leukotrienes and has other beneficial effects on the inflammatory cascade. Because 5-ASA is only active intraluminal and on the other hand quickly absorbed in the proximal small intestine, it must be prepared in a form that ensures a delayed absorption on oral administration. Sulfasalazine, the original substance in this class, delays absorption by 5-ASA is complexed with a sulfur compound to sulfapyridine. The complex is cleaved by the bacterial flora in the lower ileum and in the colon and 5-ASA is released. However, the sulfur compound causes a number of side effects produced (eg. as nausea, dyspepsia, headache), interferes with the absorption of folate (folic acid) and can sometimes serious side effects cause (z. B. hemolytic anemia or agranulocytosis and rarely hepatitis , pneumonia or myocarditis). A reversible decrease in sperm count and motility occurs in up to 80% of the men. Sulfasalazine initial should be taken with the meal, in a low dose (z. B. g po 0.5 2 times a day) increased and the dose and frequency should slowly over several days to 1-1.5 g 4 times a day become. Patients should folic acid supplement (1 mg po) and her blood and her liver function tests should be checked daily every 6-12 months. As a side effect of mesalamine acute interstitial nephritis can occur rarely; regular monitoring of renal function is recommended as the interstitial nephritis is reversible with early detection in most cases. Drugs which complex 5-ASA with other carriers seem to be equally effective and have fewer side effects. Olsalazine (5-ASA-dimer) and balsalazide (5-ASA conjugated with an inactive compound) are cleaved by bacterial azoreductases (such as sulfasalazine). These drugs are mainly active in the colon and are therefore less effective in a proximal infection of the small intestine. The Olsalazindosis is 1000 mg p.o. 2 times a day and balsalazide 2.25 g p.o. 3 times a day. Olsalazine sometimes causes diarrhea, v. a. in patients with a Pancolitis. This problem can be reduced by a slow increase of the dose and administration at mealtimes. Other formulations of 5-ASA have a jacket that leads to delayed and / or slowed release. Asacol HD® (typical dose 3 times daily 1600 mg po) and Delzicol® (800mg 3 times daily) are forms of 5-ASA with sustained release are coated with an acrylic polymer, the pH-dependent resolution, a delay of the release the drug until its reaches the distal ileum or colon is delaying. Pentasa® (1 g 4 times a day p.o.) is 5-ASA encapsulated in ethyl cellulose and with delayed release microgranules which release 35% of the drug in the small intestine. Lialda® (2400 to 800 mg p.o. once / day) and Apriso® (1500 mg p.o. once / day) are combined formulations with sustained release and extended release, which can be given once / day; less frequent dosing may improve compliance. All these formulations of 5-ASA are therapeutically equivalent to about. 5-ASA is also as suppositories (500 or 1000 mg at bedtime or 2 to 3 times daily) or as an enema (4 g bedtime or 2 times daily) in proctitis and left-sided Kolonbefall available. This rectal preparations are effective for both acute treatment and for long-term treatment of proctitis and linsseitigem Kolonbefall and have an enhanced efficacy in combination with oral 5-ASA. Patients who can not tolerate enemas because of a rectal irritation, 5-ASA foam should be given. Corticosteroids Corticosteroids are used to treat acute inflammation flare-ups in most forms of IBD when the effect of 5-ASA compounds is inadequate. However, corticosteroids are not suitable for maintenance therapy. Serious illness hydrocortisone 300 mg / day i.v. or methylprednisolone 60-80 mg / day continuously or in divided doses (eg. B. 30-40 mg 2 times daily p.o.) administered. is used in light disease activity compared oral prednisone or prednisolone 40 to 60 mg once daily. Treatment is continued until the symptoms go back (usually 7-28 days) and then tapered off once a day with a weekly reduction of 5 to 10 mg to 20 mg, and further reduced to 2.5-5 mg weekly depending on the clinical reaction with simultaneous start of maintenance treatment with 5-ASA or immunomodulators. Side effects of short-term treatment with corticosteroids at high doses are hyperglycemia, hypertension, insomnia, hyperactivity and acute psychotic episodes. Hydrocortisone enema or foam used in proctitis and left-sided colonic involvement. As an enema 100 mg in 60 ml of isotonic solution be administered 1 or 2 times daily. The inlet should be retained in the bowel as long as possible; instillation before bedtime, the patient is positioned in the left lateral position and with high mounted hips, prolongs the retention and provides a broader distribution. Is this treatment effective, they should be continued daily for 2-4 weeks, then be tapered every 2nd day for 1-2 weeks and then slowly over 1-2 weeks. Budesonidi is a corticosteroid with high (> 90%) first-pass effect in the liver, therefore the oral administration at low adrenal suppression at the GIT can be very effective. Orally administered budesonide has fewer side effects than prednisolone, but it has a slower effect and is typically used for less severe forms of the disease. Budesonide is effective in maintaining remission for 3-6 months, but has not yet proven to be effective for long-term maintenance therapy. The drug is approved for Crohn’s disease of the small intestine, and an enteric, sustained-release form is ulcerative colitis are available. The dose is 9 mg once daily. Outside the US, it is also available as an enema. All patients who have (including budesonide) started with corticosteroids, oral vitamin D should be given 400 to 800 units / day and 1200 mg calcium / day. Immunomodulatory drugs The antimetabolites azathioprine, 6-mercaptopurine and methotrexate also be used in combination therapy with biologics. Azathioprine and 6-mercaptopurine azathioprine and its metabolite 6-mercaptopurine inhibit T-cell functions and can cause T-cell apoptosis. They have a long-term effect could decrease Kortikosteroidbedarf and maintained remission for years. The onset of action of these drugs often occurs only after 1-3 months, so corticosteroids may not be completely discontinued before at least the second month. The dose of azathioprine is generally from 2.5-3.0 mg / kg p.o. once a day, 6-mercaptopurine 1-1.5 mg / kg p.o. once a day, but varies depending on the individual metabolism of the substance. The most common side effects are nausea, vomiting and malaise. The possible occurrence of bone marrow suppression must be regular examinations of white blood cell counts are (times 2 in the first month, then every 1-2 months a week) monitored. In 3-5% of patients pancreatitis or high fever occurs; both represents an absolute contraindication to the drug. More rarely seen hepatotoxicity, their potential occurrence should be ruled out by blood tests every 6-12 months. These drugs are associated with an increased risk of lymphoma and skin cancer from non-melanoma type) before starting these medications, tests should patients be carried out to determine the activity of Thiopurinemethyltransferase (TPMT) to measure an enzyme that azathioprine and 6- mercaptopurine to its active metabolite 6-thioguanine (6-TG) and 6-methylmercaptopurine (6-MMP) transforms. Patients should also have genotype tests for known low activity of this enzyme variants. After taking these drugs, it is useful to measure the level of 6-TG and 6-MMP in order to guarantee a safe and effective drug dosages. The therapeutic efficacy correlated with 6-TG levels 230-400 picomole per 8 x 108 erythrocytes. Myelotoxicity can occur if 6-TG levels are> 400th Hepatotoxicity may occur if 6-MMP levels> 5000 picomoles per 8 x 108 erythrocytes. The concentrations of metabolites are also useful in patients who do not respond to resistance from failure to adhere to unterscheiden.Methotrexat Many patients with severe, kortikosteroidresistentem or -abhängigem Crohn’s disease can of methotrexate 15-25 mg po or s.c. benefit weekly, even those who have not responded to azathioprine or 6-mercaptopurine. Side effects include nausea, vomiting and asymptomatic pathological liver function tests. Some of the side effects can Folic acid 1 mg po be reduced once a day. Women taking methotrexate should use at least one form of birth control. In addition, couples should stop wanting children methotrexate for at least 3 months in advance. Monthly blood and liver function tests with albumin should be performed for the first 3 months of therapy every 8-12 weeks during therapy. Risk factors for hepatotoxicity, alcohol, obesity, diabetes mellitus and possibly psoriasis. Preferably, patients with these conditions should not be treated with methotrexate. Liver biopsies before treatment are not recommended; but they are carried out if the results of 6 out of 12 tests increased in a year show AST levels. Myelosuppression, pulmonary toxicity and nephrotoxicity may also auftreten.Cyclosporin and tacrolimus cyclosporine, which blocks lymphocyte activation can colitis in patients with severe colitis, which does not respond to corticosteroid therapy, and where a colectomy should be performed otherwise with methotrexate therapy, develop beneficial effect. The only well-documented use of cyclosporine is the treatment of drug-resistant fistulas or pyoderma. The initial dose of 24 mg / kg i.v., given as a continuous infusion over 24 h. In response to therapy is passed to an oral dosage of 6-8 mg / kg once a day with an early dose of azathioprine or 6-mercaptopurine. Long-term treatment (> 6 months) is contraindicated due to multiple side effects (kidney damage, convulsions, opportunistic infection, hypertension, neuropathy). In general, patients are given no cyclosporine, unless there are reasons not to carry out the safe curative option colectomy. Substituting the drug, the minimum plasma levels between 200 and 400 should be set ng / ml and a prophylaxis against Pneumocystis jirovecii during the concurrent treatment with corticosteroids, cyclosporine and anti-metabolites are considered. Tacrolimus, an immunosuppressive substance that is also used in transplant recipients appears to be as effective as cyclosporine, and can be pulled considered in patients with severe or refractory UC that must not be admitted. Biologics anti-TNF drugs, infliximab, certolizumab, adalimumab, and golimumab, antibodies to tumor necrosis factor (TNF). Infliximab, certolizumab, and Adalimumab are useful, particularly in the prevention or delay of post-operative recurrence of Crohn’s disease. Infliximab, adalimumab, and golimumab are beneficial in refractory or kortikosteroidabhängigen cases of ulcerative colitis. Infliximab is as a single i.v. Infusion of 5 mg / kg over 2 h. This is followed by repeated infusions at week 2 and 6. It is then given every 8 weeks. To maintain remission must if not most patients increasing the dose or the interval be reduced within a year of many. Adalimumab is s.c. in an initial dose of 160 mg and then 80 mg s.c. given from week second After this dose 40 mg s.c. administered every 2 weeks. Patients who can not tolerate the agent or who no longer respond to initial success on infliximab, may respond to therapy with adalimumab. Certolizumab is 400 mg s.c. given every 2 weeks for three doses, and then every 4 weeks for maintenance. Patients who can not tolerate the agent or who no longer respond to initial success on infliximab, may respond to certolizumab. Monotherapy with anti-TNF agents is clearly more effective for both the initial treatment and to maintain remission. Some studies, however, indicate that better results can be achieved when the anti-TNF agents are used in combination with a thiopurine (z. B. azathioprine) or methotrexate. However, given the possible increase in side effects associated with combination therapy, treatment recommendations should be individualized. It begins with the discontinuation of corticosteroids after 2 weeks. The adverse side effects during the infusion (infusion reaction) include immediate hypersensitivity reactions (eg., Skin rash, itching, sometimes anaphylactic) reactions, fever, chills, headache and nausea. Delayed hypersensitivity reactions have also been reported. Subcutaneously administered anti-TNF drugs (eg. As adalimumab) cause infusion reactions, although they can cause local redness, pain and itching (reaction at the injection site). Some patients have died from sepsis as a result of an application of anti-TNF agents, which is why these agents are contraindicated in the presence of uncontrollable bacterial infections. Also reactivation of tuberculosis and hepatitis B has been attributed to the anti-TNF drugs, so you should before applying a screening test for latent TB (with PPD and / or interferon-? release assay and a chest x-ray examination) and perform against hepatitis B virus , Lymphoma, demyelinating disease and liver and hematologic toxicity are other possible concerns with anti-TNF antibody biologics Behandlung.Andere Several immunosuppressive interleukins and anti-interleukin antibodies may also reduce the inflammatory response and are being studied for Crohn’s disease. Vedolizumab and natalizumab are antibodies to leukocyte -Adhäsionsmolekülen. Vedolizumab was approved for moderate to severe UC and Crohn’s disease. on, one assumes that limited its effect on the intestine, it is safer than being used only as a 2nd-line drug through a limited prescribing program for particularly stubborn cases of Crohn’s disease natalizumab. More Antizytokine, Antiintegrine and growth factors are in exploring how to reduce Leukopheresetherapie activated immunocytes. Antibiotics and probiotics Antibiotics Antibiotics are useful for Crohn’s disease, but of limited use in ulcerative colitis, except in the case of toxic colitis). Metronidazole 500-700 mg p.o. can 3 times daily for 4-8 weeks less severe cases of Crohn’s disease control and heal fistulas. Unfortunately force side effects (v. A. Neurotoxicity) often result in treatment discontinuation. Less toxic ciprofloxacin is 500 to 750 mg po 2 times a day. Many experts recommend a combination of metronidazole and ciprofloxacin. Rifaximin, a nonabsorbable antibiotic p.o. in a dose of 200 mg 3 times daily or 800 mg po 2 times a day can also be helpful for the treatment of active Crohn’s disease sein.Probiotika A number of non-pathogenic microorganisms (eg. As symbiotic Escherichia coli, Lactobacillus spp., Saccharomyces), given daily probiotic can act and prevent the development of pouchitis their other therapeutic significance but must first be shown. A therapeutic Infestation with the parasite Trichuris suis was tried with the intention of stimulating the immunity of the T2-helper cells and to reduce the disease activity in Ulcerative Colitis.


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