Selected topics in gastroenterology: sources for IBD A/ Literature in english: 1/ M.A. Simmons - Pharmacology an illustrated review 2012: 273-277 2/ P. Rang, M. Dale - Pharmacology 2007: 395-396 B/ Literature in czech: 1/ H. Lullmann, Kl. Mohr – Bar. atlas
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Selected topics in gastroenterology: sources for IBD A/ Literature in english: 1/ M.A. Simmons - Pharmacology an illustrated review 2012: 273-277 2/ P.
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Selected topics in gastroenterology: sources for IBD
A/ Literature in english:
1/ M.A. Simmons - Pharmacology an illustrated review 2012: 273-2772/ P. Rang, M. Dale - Pharmacology 2007: 395-396
B/ Literature in czech:1/ H. Lullmann, Kl. Mohr – Bar. atlas farmakologie(2/ Příprava na zk. z vnitřního lékařství – skripta studentů)
1/ Crohn's disease (ileitis terminalis)chronic segment. inflamm. that affects all layers of the intestinal wall, localization is very often in terminal ileum + colon, but manifestation can be anywhere in the GIT
aetiology + pathogenesis: asocc. with HLA-DR1, smoking, shorter breastfeeding
2/ Ulcerative colitis = idiopathic proctocolitisrecurrent inflamm. disease of colon and rectum
pathogenesis: thought to be autoimm.: assoc. with HLA-DR2, Ig-A nephritis, autoimm. hepatitis among others
goal of therapy: reduce inflamm. response by drugs such as steroids and sulfasalazine + biolog. therapy (anti TNF-alpha, more modern)
Colitis ulcerosa and morbus Crohn – therapeutic options
• Antiinflammatory drugs
1/ mesalazin (Pentasa), active ingredient from sulfasalazine
2/ inhibition of leucocyte migration natalizumab (Tysabri): anti-integrine eff.
• Supplementation- Vit. B12 inj. (contraind. in cancer)
Non-specific inflammatory bowel disease
A) Regimen approach• Specific diet
effective, also avoiding oranges, grain legumes etc. can help
B) Influencing of pathophysiological processes• Bowel antiinflammatory drugs: aminosalicylates • Biological therapy, immunosuppressive drugs• Corticosteroids:• Hydrocortisone: rect. supposit.: local effects• Prednison: perorally 30-60mg daily if more severe
C) Complications• Antimicrobial drugs if infection (perianal festering compl.)
metabolized to Mesalazine • the main anti-inflammatory drugs used to treat ulcerative
colitis
• sometimes remission or at least maintaining disease with these drugs alone, can be used in combination
anti-inflammatory action in all these drugs - produced by5-aminosalicylic acid (5-ASA) = Mesalazine: inhibition of prostaglandine and
leukotriene synthesis
• 5-ASA is produced from the pro-drugs in the intestine
SULFASALAZINE and MESALAZINEacute attacks of Crohn´s dis. and ulc. colitis treated with sulfasalzine and
mesalazine, crohn disease may also involve use of steroids
antiinflamm. effects: COX inhibition, inhibition of lipooxygenase, free radicals inactivation
p.o. 1-4g daily (2-3x daily 250-500mg); clysma, supp. (PENTASA)– after therapy for acute problems maintenance therapy (1/2 dose) for
months/ years (success achieved within weeks)
Adv. Eff.: less with mesalazine than after sulfasalazine – nephrotoxicity, interactions (↑toxicity p.o. antidiabetics, methotrexate); if used together with corticosteroids, risk of GIT bleeding is increased
Aminosalicylates, continued
• Sulfasalazine– 75% non-absorbable, in the large bowel bacterial degradation 5-ASA (+
sulfapyridine)– 500mg 2-4x daily till 1g 3-4x daily; maintenance dose is 500mg 4 x daily– sulfasalazine has more ADVERSE effects than mesalazine: headache, dyspeptic
disorders, allergy, reduced sperm count and damage of red / white blood cells haemolytic anemia, hepatotoxicity etc. (patients on high dose of sulfasalazine require folic supplementation to maintain normal blood cell count)
• Olsalazine and balsalazide (not registered in CZ)
Anatomical localization of effect of aminosalicylates
Corticosteroids / Glucocorticoids• local use: supp., enema/clysma, foam – when problem localised near rectum
• systemic use: prednison or prednisolon, budesonide, hydrocortison
effective in both ulcerative colitis and Crohn dis. in inducing a remission in acute persistent disease, systematically used until control of inflamm. is achieved then tapered down and discontinued
•Azathioprin, 6-merkaptopurine - false substrate for purine biosynthesis and reduction of NK-cells in immune system – in patients with severe disease (longer-lasting highly active inflammation)
•Methotrexate (folic acid antagonist) – inhibits dihydrofolate reductase which reduces purine and pyrimidine synthesis in lymphocytes (i.m. - than p.o. 10-15 mg weekly) and inhibits cell growth in rapidly proliferating tissues like bone marrow = control of blood counts
•Cyclosporine A in severe colitis – corticosterid-resistant – short-term treatment with Cyclosporine A that reduces IL-2 synthesis in T-helper lymphocytes (effect after 6-8 weeks)
Biotransformation of azathioprine
Indications for operation
Morbus Crohn• Perforation, peritonitis
• Ileus
• Massive bleeding
• Pronounced stenosis
• Fistula, abscess
• Failure of conservative therapy
Colitis ulcerosa• Perforation, peritonitis• Proven precancerosis• Toxic megacolon• Pronounced stenosis• Long severe disease course
(surgery as prevention of
carcinoma development)
Treatment of festering complications with ATB• Festering (putrefactive) complications:1) active colitis ulcerosa2) Crohn´s disease
• Ciprofloxacin: broad-spectrum chinoline ATB that blocks DNA gyrasis /CIFLOXINAL,CIPHIN, CIPLOX/
• Metronidazole: well passing to CNS, bones etc., anaerobic pathogens + against - aerobic /EFLORAN, ENTIZOL, METROZOL/
Use: used for smooth muscels contraction, especially in tubular organs of the GIT - to prevent spasms of the stomach, gall or urinary bladder, GIT dyskinesis
- psoriatic artritis and psoriasis, ancylosing spondylitis
B/ inhib. of leucocyte migration: natalizumab - multiple sclerosis
Intestine infection, diarrhea: possible ther. options• Cloroxine (ENDIARON)
• bacteriostatic, g+, g-, against Candidas (in dysmicrobia following ATB use)• No resistance• No absorption – local effect, low toxicity, usually well tolerated • + oxyphenone – spasmolytic; + further combinations with peripheral „opioids“ (loperamide,
difenoxylate)• Possible risk of neurotoxicity in longterm therapy, appl. for max. 7-10 days
• Rifaximine (NORMIX)
nonabsorbable ATB – inhib. of RNA-synthesis; children from 2 years, bactericidal eff., g+, g-, risk of resistance
• Nifuroxazide (ERCEFURYL)
nonabsorbable, bacteriostatic chemotherapeutic for ac. infection diarrhea
• Co-trimoxazol = sulfamethoxazol+trimethoprim: from 6 yrs (BISEPTOL)
Antibiotics for ACUTE CHOLECYSTITIS and CHOLANGITIS