treatment of Crohn's disease and IBD- medchem

what is the active agent of sulfasalazine, olsalazine, and balsalazide

5-aminosaliclicylic acid

what are the adverse effects of sulfasalazine thought to be due to

the sulfapyridine moiety

in aminosalicylates what bond is cleaved by the action of bacteria in the large bowel

• diazo bond

• N=N

is sulfapyridine absorbed into the bloodstream

yes, its well absorbed into the blood stream

is 5-aminosalicylic acid absorbed from the distal bowel

• poorly absorbed

• can therefore reach high concs. in the lumen of the colon or rectum

how is mesalazine formulated

formulated in a pH-dependent modified release tablet that delivers 5-ASA to the distal small and colon

how is balsalazide cleaved

by flora in the distal bowel

what is the structure of olsalazide

• 2 molecules of 5-ASA

• poorly absorbed but azo bond is split by flora in the distal small bowel and colon to release 2 molecules of 5-ASA

how do you number cholesterol

what are the characteristic features of glucocorticoids

• C21 pregnane skeleton

• 17 beta-CO.CH2OH side chain

• 11beta-hydroxyl group

• carbon4-3-keto usually

• 17 alpha-hydroxyl group (usually)

what does a change in ring A geometry in glucocorticoids give

gives increased glucocorticoid receptor affinity

what are the 2 possible conformations of the 3 keto bond

• half chair

• flattened boat

what are the 3 structural changes that have proved particularly valuable in use of adrenocorticoids

1. introduction of carbon1-2- double bond

2. introduction of a 9 alpha flour substituent

3. introduction of an alpha-hydroxy substituent in the 16 position

what does an introduction of a substituent in the 16 position do to glucocorticoid activity and mineralocorticoid activity

• alpha hydroxy substitution reduces mineralocorticoid activity without affecting glucocorticoid activity

• alpha and beta- methyl substitution increases glucocorticoid activity and reduces mineralocorticoid activity

what is azothiopurine a prodrug of

6-mercaptopurine

how is azothiopurine a good prodrug

slowly converted to 6-MCP by reaction with glutathione allowing for more sustained activity