Monograph: |
5-AMINO SALICYLIC ACID
Mesalazine or Mesalamine are the official names given to 5-amino salacylic acid. Realising that 5-ASA is the active moiety in ulcerative colitis,but is not effective atall because of inability to reach large bowel(it is absorbed in small bowel)it has been formulated as delayed release preparations by coating with acrylic polymer.such preparations are reliable to deliver 5-ASA to distal small bowel and colon.
The different preparations having 5-ASA are as following
1. sulfasalazine
2. mesalazine
3. olsalazine
4. balsalazine
SULFASALAZINE : - it is a compound of 5-ASA with sulfapyridine linked through an azo band.
Having low solubility it is poorly absorbed from the ileum. The azo bond is split by colonic bacteria to release 5-ASAand sulfapyridine. The former exerts a local antiinflammatory effect, probably by inhibiting PG synthesis (and may be other mediators like leukotrienes,PAP as well as migration of inflammatory cells into bowel wall), decreases mucosal secretion - affolds considerable relief in ulcerafive colitis and related inflammatory bowel diseases. Given during an exacerbation it reduces number of stools, abdominal cramps and fever but is less effective than corticosteroids; may be employed for mild to moderate
exacerbation. A dose of 3-4 g/day induces remission over a few weeks in many cases, but relapses are common after stoppage. Maintenance therapy with 1.5- 2 g/day has been found to postpone relapse as long as taken. The primary value of sulfasalazine is in maintaining remission, while corticosteroids are reserved to treat acute exacerbations.
The beneficial effect of sulfasalazine is clearly not due to any antibacterial action(bowel flora remains largely unaffected): sulfapyridinc moiety only serves to carry 5-ASA to the colon without being absorbed proximally. However, part of the released sulfapyridine is absorbed in the colon and is responsible for adverse effects like rashes,fever, joint pain, haemolysis and blood dyscrasias. Nausea, vomiting, headache and anaemia are other frequent side effects. Male infertility is reported.
Sufasalazine has also been used as a disease modifying drug in rheumatoid arthritis:
the absorbed sulfapyridine appears to be responsible for the therapeutic effect.
Masalazine (Mesalamine) These are the official names given to 5-ASA. Realizing that
5-ASA is the active moiety in ulcerative colitis, but is not effective orally because of inability
to reach the large bowel ( it is absorbed in the small intestine), it has been formulated as
delayed release preparations by coating with acrylic polymer. Such preparations appear to be
reliable for delivering 5-ASA to distal small bowel and colon: a 400 mg tablet is estimated to
provide quantities of 5-ASA that would be released from lg of sulfasalazine. A daily dose of
IA g has been found to improve over 50% patients of ulcentive cotitis. Less than half of the
5-ASA released from these preparations is absorbed, acetylatod in the liver and excreted in
urine. Like sulfasalazine, the primary use ofmesalazine is in preventing relapses, though it
may also be employed to treat mild to moderate exacerbations.
Adverse effects Coated mesalazine is better tolerated than sulfasalazine. Side effects noted
are nausea, dianhoea, abdominal pain and headache. Rashes and hypersensitivity reactions
are rare. Bone marrow depression and decreased sperm count has not occurred. Mesalazine
has some nephrotoxic potential - is contraindicated in renal and hepatic impairment.
Drug interactions Coated mesalazine may enhance the gastric toxicity of glucocorti-
coids and hypoglycaemic action of sulfonylureas. Interaction with coumarins, furose-
mide, spironolactone, methotrexate and rifampicin are possible.
5-ASA enemas.- Another mode of deliveryof5-ASAto colon is to administer it by a retention enema: 1-2 g
enema once or twice daily is effective in distal ulcerative colitis, including some refractory cases.
Olsalazine - It consists of two molecules of 5-ASA coupled together by azo bond. It is poorty absorbed in the ileum, the azo bond is split in the colon to provide 5-ASA locally. No separate carrier moiety is needed. Olsalazine is probably the most reliable preparation for delively of 5β’ASA to the colon. However, it often aggravates diarrhoea initially by decreasing transit time through bowels.
|