Lower GI Drugs Flashcards
IBS 1st line strategy does not involve medication.
Patients may keep a food diary and try sequential:
- Exclusion of gas-producing foods
- Low fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs)
- Lactose and/or gluten omission
IBS + constipation, treat with ____, a chloride channel activator laxative
IBS + constipation, treat with lubiprostone, a chloride channel activator laxative
list drugs to treat diarrhea-predominant IBS
- loperamide (opioid agonist)
-
alosetron (5-HT3 antagonist)
- inhibits afferent 5- HT3 receptors to reduce noxious visceral sensations such as bloating, nausea and pain
-
hyoscyamine, dicyclomine, glycopyrrolate, methscopolamine (anticholinergics)
- antispasmodic effect on the G.I. tract
- limited to short-term relief of acute diarrhea predominant episodes d/t numerous unpleasant side effects
Aminosalicylates (3) are used for ____ of IBD remission
Active group is ____
MOA remains unknown
Sulfasalazine, Balsalazide, Mesalamine are used for long term maintenance of IBD remission
Active group is 5-aminosalicylic acid (5-ASA).
MOA remains unknown
Proposed MOA theories of aminosalicylates:
composite endpoint of these pathways is _____
gross reduction of inflammatory mediators with resultant control of IBD processes
- COX and LOX pathway modulation
- NF-κB inhibition (important transcription factor for proinflammatory cytokines)
- Cellular immunity inhibitition
- Scavenges reactive oxygen metabolites
clinical efficacy of 5-ASA depends on achieving ____
clinical efficacy of 5-ASA depends on achieving high concentrations at the target site
ex. oral 5-ASA is absorbed in jejunum, having no therapeutic effect in the ileum, colon, rectum
Sulfasalazine consists of 5-ASA linked to ____ by an azo bond
sulfapyridine group ____ absorption in the ____ after oral ingestion → higher drug availability in ____ and ____
Sulfasalazine consists of 5-ASA linked to sulfapyridine by an azo bond
sulfapyridine group reduces absorption in the jejunum after oral ingestion → higher drug availability in small intestine and colon
the majority of sulfasalazine passes into the ___ where it gets reduced by coliform bacterial enzyme, ____, to sulfapyridine and 5-ASA
5-ASA acts therapeutically in the colon and may even “backwash” into the ___ to act there
the majority of sulfasalazine passes into the colon where it gets reduced by coliform bacterial enzyme, azoreductase, to sulfapyridine and 5-ASA
5-ASA acts therapeutically in the colon and may even “backwash” into the terminal ileum to act there
Sulfasalazine AE’s are attributed to systemic absorption of the ____
up to 40% of pts are unable to tolerate Sulfasalazine
List the AE’s
Sulfasalazine AE’s are attributed to systemic absorption of the sulfapyridine group
Up to 40% of pts are unable to tolerate Sulfasalazine
- nausea, GI upset, headaches
- arthralgias, myalgias
- bone marrow suppression
- hypersensitivity reactions
Balsalazide consists of one 5-ASA linked to an ___ and ____ carrier molecule causing no adverse effects
it delivers maximal amounts of 5-ASA to the ____
Balsalazide consists of one 5-ASA linked to an inert and unabsorbed carrier molecule causing no adverse effects
it delivers maximal amounts of 5-ASA to the colon
____ is physically packaged 5-ASA in ___-release or __-sensitive microgranules that release the active drug into ____ of the gut actively affected by IBD
AE?
Mesalamine is physically packaged 5-ASA in timed-release or pH-sensitive microgranules that release the active drug into the desired specific portion of the gut actively affected by IBD
Well-tolerated
describe the anatomic distribtution of IBD drugs
Glucocorticoids (3) are used to induce remission of _____ of IBD
Prednisone, Prednisolone, Budesonide, are used to induce remission of acute exacerbations of IBD
(not indicated for maintaining remission)
describe how glucocorticoids cause immunosuppressive and anti-inflammatory effects
- interactions with intracellular glucocorticoid response elements
- inhibition of phospholipase A2 and COX-2
- inhibition of NF-κB
____ and ____ are glucocorticoids of choice for oral therapy in IBD (daily dosing d/t duration of action)
___ is administered via enema for sigmoid and rectal IBD flares
Prednisone and prednisolone are glucocorticoids of choice for oral therapy in IBD (daily dosing d/t duration of action)
Hydrocortisone is administered via enema for sigmoid and rectal IBD flares
AE’s of IBD patients treated with prednisone, prednisolone, hydrocortisone
- adrenal suppression
- hyperglycemia
- immunosuppression
- osteoporosis
____ is used for topical effects on the luminal surface of inflamed bowel
rapid 1st pass metabolism → ___ systemic bioavailability
benefit = decreased systemic ____ compared to prednisolone
Budesonide is used for topical effects on the luminal surface of inflamed bowel
undergoes rapid 1st pass metabolism → low systemic bioavailability
benefit = decreased systemic adverse effects compared to prednisolone
list immunosuppressant drugs used for IBD treatment
Mercaptopurine, Azathioprine, Methotrexate
Mercaptopurine and Azathioprine are immunosuppressive ___ metabolites with ___-sparring effect
What are they used for and dose-related toxities?
Mercaptopurine and Azathioprine are immunosuppressive purine metabolites with steroid-sparring effect
- Use: induction and maintenance of IBD remission
- Toxicities: nausea, vomiting, hepatotoxicity, bonemarrow suppression
___ markedly reduces xanthine oxidase activity, which breaks down 6-MP
co-administration of this drug with 6-MP can precipitate life threatening ____
___ should be used cautiously in patients taking ___ or ____
Allopurinol markedly reduces xanthine oxidase activity, which breaks down 6-MP
co-administration of this drug with 6-MP can precipitate life threatening leucopenia
Allopurinol should be used cautiously in patients taking 6-MP or Azathioprine
Methotrexate inhibits ____ (enzyme needed for thymidine and purine production)
it reduces inflammatory actions of ___
for IBD, it is given at relatively __ doses, preventing antiproliferative effect
Methotrexate inhibits dihydrofolate reductase (enzyme needed for thymidine and purine production)
it reduces inflammatory actions of IL-1
for IBD, it is given at relatively low doses, preventing antiproliferative effect
MTX AE’s
these can be reduced by ___ supplementation without reducing anti-inflammatory actions
- bone marrow depression
- megaloblastic anemia
- mucositis
AE’s are reduced by folate supplementation without reducing anti-inflammatory actions
TNF is a key hemoral mediator of releasing proinflammatory cytokines
Anti-TNFa drugs, ___ and ___, are indicated in __ and __ treatment of IBD
TNF is a key hemoral mediator of releasing proinflammatory cytokines
Anti-TNFa drugs, Infliximab and Adalimumab, are indicated in acute and chronic treatment of IBD
___ is given for moderate - severe colitis which is not responsive to mesalamine or corticosteroids
Infliximab is given for moderate - severe colitis which is not responsive to mesalamine or corticosteroids
