Ulcerative colitis is a disease of the large intestine (the colon and rectum), where the lining of the intestine becomes red and swollen (inflamed) and ulcers develop. This can cause symptoms of frequent and bloody stools together with stomach cramps.
Ulcerative colitis causes inflammation of the intestine which leads to problems such as ulceration and bleeding. This causes symptoms such as abdominal pain and diarrhoea. Crohn's disease is a condition which causes inflammation of any part of the gastrointestinal system. When the inflammation is in the area where the small intestine joins the large intestine, then it is called Crohn's ileo-colitis.
Ulcerative colitis is the result of an abnormal response by your body's immune system. Normally, the cells and proteins that make up the immune system protect you from infection. In people with IBD, however, the immune system mistakes food, bacteria, and other materials in the intestine for foreign or invading substances. When this happens, the body sends white blood cells into the lining of the intestines, where they produce chronic inflammation and ulcerations.
Crohn's disease can affect any part of the Gastrointestinal (GI) Tract, but ulcerative colitis affects only the colon. Additionally, while Crohn's disease can affect all layers of the bowel wall, ulcerative colitis only affects the lining of the colon.
While both ulcerative colitis and Crohn's disease is types of Inflammatory Bowel Diseases (IBD), a disorder that affects the muscle contractions of the colon.
Inflammatory Bowel Syndrome (IBS) is not characterized by intestinal inflammation. Ulcerative colitis (UC) is an idiopathic chronic inflammatory disease of the colon that follows a course of relapse and remission. In a small number of cases, ulcerative colitis is associated with extra-intestinal features.
- Distal disease (left-sided colitis): colitis confined to the rectum (proctitis) or rectum and sigmoid colon (proctosigmoiditis)
- More extensive disease includes: left-sided colitis (up to the splenic flexure, 40% of patients), extensive colitis (up to the hepatic flexure) and pancolitis (affecting the whole colon, 20% of patients)
- Some patients with pancolitis may have involvement of the terminal ileum due to an incompetent ileocaecal valve
Sign and Symptoms:
- bowel movements become looser and more urgent
- persistent diarrhea accompanied by abdominal pain and blood in the stool
- stool is generally bloody
- cramp abdominal pain
Therapeutic Indication:
For the treatment of mild to moderate Ulcerative Colitis and Crohn's disease.It can also be used continuously to help prevent attacks.
Pharmacology:
Mechanism of action and pharmacodynamic effects:
It has been established that mesalazine is the active component of sulphasalazine which is used for the treatment of Ulcerative Colitis and Crohn's disease. Based on clinical results, the therapeutic value of mesalazine after oral as well as rectal administration appears to be due to local effect on the inflamed intestinal tissue, rather than to systemic effect.
Increased leucocyte migration, abnormal cytokine production, increased production of arachidonic acid metabolites, particularly leukotriene B4 and increased free radical formation in the inflamed intestinal tissue are all present in patients with inflammatory bowel disease. The mechanism of action of mesalazine is not fully understood although mechanisms such as activation of the γ-form of peroxisome proliferator-activated receptors (PPAR-γ) and inhibition of nuclear factor-kappa B (NF-κB) in the intestinal mucosa has been implicated. Mesalazine has in-vitro and in-vivo pharmacological effects that inhibit leucocyte chemotaxis, decrease cytokine and leukotriene production and scavenge for free radicals.
The risk of Colo-Rectal Cancer (CRC) is slightly increased in Ulcerative Colitis. Observed effects of mesalazine in experimental models and patient biopsies support the role of mesalazine in prevention of colitis-associated CRC, with down regulation of both inflammation dependent and non-inflammation dependent signaling pathways involved in the development of colitis-associated CRC. However data from meta-analyses, including both referral and non-referral populations, provide inconsistent clinical information regarding the benefit of mesalazine in the carcinogenesis risk associated with Ulcerative Colitis.
Pharmacokinetic properties:
Absorption:Bioavailability of mesalazine after oral administration can be estimated to approx. 30%, based on urine recovery data in healthy volunteers. Maximum plasma concentrations are seen 1-6 hours post-dose.
The transit and release of mesalazine after oral administration are independent of food co-administration, whereas the systemic exposure may be increased.
Distribution:Mesalazine does not cross the blood-brain barrier. Protein binding of mesalazine is approximately 50%.
Metabolism: Mesalazine is metabolised both pre-systemically by the intestinal mucosa and systemically in the liver to N-acetyl-mesalazine (acetyl-mesalazine) principally by NAT-1.
Some acetylation also occurs through the action of colonic bacteria. The acetylation seems to be independent of the acetylator phenotype of the patient.
Elimination: Due to continuous release of mesalazine throughout the gastrointestinal tract, the elimination half-life cannot be determined after oral administration. However, once the formulation is not present in the GI tract elimination will follow the plasma half-life of orally or IV administered uncoated mesalazine, which is approximately 40 minutes.
Contraindications:
- Hypersensitivity to mesalazine, any of its excipients, or salicylates
- The drug should not be used in children under two, people with kidney disease, or people who are allergic to aspirin
Drug Interactions:
Combination therapy with azathioprine, or 6-mercaptopurine or thioguanine have in several studies shown a higher frequency of myelosuppressive effects, and an interaction seems to exist, however, the mechanism behind the interaction is not fully established. Regular monitoring of white blood cells is recommended and dosage regime of thiopurines should be adjusted accordingly.
There is weak evidence that mesalazine might decrease the anticoagulant effect of warfarin.
Pregnancy & Lactation:
There is no data on use in pregnant women, but the drug does cross the placenta and is excreted in breast milk.
Warning & Precaution:
This has been prescribed for the patient's specific condition only.
Side effects:
- Diarrhoea
- Nausea and vomiting
- Abdominal pain or bloating
- Excess gas in the stomach and intestines (flatulence)
- Headache
- Dizziness
- Inflammation around the heart. Tell your doctor if you experience chest pains or palpitations
- Decrease in the normal numbers of blood cells in the blood
- Allergic skin rashes
- Worsening of colitis symptoms
Storage:
Store below 25º C.
Store in the original package, as the product is sensitive to light. Do not freeze.