5HT3 Receptor antagonist

- for women with IBS with diarrhea

- decreases gastic motility

- withdrawn 11/2000 - need special certification to rx

- ADR: severe constipation, life threatening acute colitis

Stimulates 5HT4 Receptors

- for women with IBS with constipation

- stims peristaltic reflex

- alters secretion in intestine

- reduces visceral sensitivity

CONTRIND: renal and hepatic impairment

Activates Cl- channels

- for chronic idiopathic constipation

- ADR: nausea, diarrhea

- CONTRAIND: pregnancy

colonic bacteria break Azo bond and release 5-ASA

- 5-ASA = active component

- local - only works in colon

- Different drugs have different site of action

ADRs: rash, fever, colitis, proctitis, diarrhea, toxic at high doses, sulfa allergies

5-Aminosalicylate

- 3-4gm/day, BID or QID based on tolerance

- ADR: sperm abnormalities, hypersens., N/V, hemolysis, folate def.

5-ASA

ENEMA form: if disease limited to rectum/sigmoid

PENTASA: capsule form = ethylcellulose coated time released so more active in SI - ileum

ASACOL: distal ileum/colon

- highly effective for REMISSION

- do NOT use as maintenance therapy

- IV or roral

- budesonide 5-asa<budenoise<prednisone

Prevent TNF binding to receptors

- use for acute/chronic chrons

- remission/maintenance therapy in pts with inadequate response to mesalamine/steroids

ADR: infection, antibody development, infusion rxn

- INFLIXIMAB, ADALIMUMAB, CERTOLIZUMAB

- maintenance therapy

- 6-MERCAPTOPURINE: steroid refractory pts

- METHOTREXATE: folate antag. hepatic toxic

- CYCLOSPORINE: used to prevent need for colectomy. quick response: IV for 1-2weeks

6-thioguanine nuctleotide (GTP) - incorp. into small GTPase (rac1) --> rac1 is essential for activation of gut Tcells --> therefore preventing activation and preventing inflammation

- high specificity and fast acting

Azo<6-mercap<6-thioguanine

anti-TNF

- IgG1 monoclonal AB, neutralizes soluble TNF-alpha

- USE: RA, Chrons, fistula healing

- Limited by antibody production (up 60%)

-25% murine

- CDP571: only 5% murine and 95% human = greater effect in pts w >10mg/L of CRP 

        - not drastically better than original

recombinant monoclonal AB specific for TNF-alpha

- binds to TNF-alpha and prevent binding to receptor

- lysises surface TNF expressing cells with complement

- safe and effective by 4 weeks

- mesalamine enemas (topical)

- steroid enemas (topical)

- oral slfasalazine or mesalamine

- oral steroids: budesonide

**topical = best**

- Mild/mod: oral mesalamine or sulfasalazine w or w/o topical

- Mod/Severe: steroids, Mercaptopurine/azathioprine for steroid-dep remissions

Cyclosporine if unresponsive to steroids

Antibiotic if acute infection

Mild/Mod: mesalamine or budesonide (PO)

Acute severe disease: IV steroids

-Anti-TNF

-Antibiotics

-Immunomodulators