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Flashcards in Lower GI Drugs Deck (34)
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1

IBS 1st line strategy does not involve medication. 

Patients may keep a food diary and try sequential:

  1. Exclusion of gas-producing foods
  2. Low fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs)
  3. Lactose and/or gluten omission

2

IBS + constipation, treat with ____, a chloride channel activator laxative

IBS + constipation, treat with lubiprostone, a chloride channel activator laxative

3

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

4

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

5

Proposed MOA theories of aminosalicylates:

composite endpoint of these pathways is _____ 

gross reduction of inflammatory mediators with resultant control of IBD processes

  1. COX and LOX pathway modulation
  2. NF-κB inhibition (important transcription factor for proinflammatory cytokines)
  3. Cellular immunity inhibitition
  4. Scavenges reactive oxygen metabolites

6

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

7

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

8

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

9

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

10

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

11

____ 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 

12

describe the anatomic distribtution of IBD drugs

13

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)

14

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

15

____ 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

16

AE's of IBD patients treated with prednisone, prednisolone, hydrocortisone

  • adrenal suppression
  • hyperglycemia
  • immunosuppression
  • osteoporosis

17

____ 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

18

list immunosuppressant drugs used for IBD treatment 

Mercaptopurine, Azathioprine, Methotrexate 

19

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

20

___ 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

21

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

22

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

23

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

24

___ 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

25

anti-TNFa AEs

  • Th1 suppression
    • severe infections including invasive fungal disease
    • reactivation of latent TB
  • Antibodies can develop against them eliminating therapuetic response
  • Increased risks of lymphoma, acute hepatic failure, CHF

26

___ is a monoclonal antibody targeting several integrins on circulating inflammatory cells

Disrupts leukocyte vascular wall ___ and ___

Natalizumab is a monoclonal antibody targeting several integrins on circulating inflammatory cells (anti-integrin)

Disrupts leukocyte vascular wall adhesion and migration

 

27

drug indicated in moderate to severe, unresponsive Crohn’s disease

Natalizumab

28

Natalizumab AE's

  • oppportunistic infections
  • PML - progressive multifocal leukoencephalopathy 
    • JC polyomavirus reactivation

29

categorize IBD drugs into mild, moderate, and severe treatments 

Mild:

  • Sulfasalazine, Mesalamine, Balsalazide 5-ASA
  • Antibiotics
  • Budesonide Topical corticosteroid

Moderate:

  • 6-MP, Azathioprine, Methotrexate immunosuppressants 
  • Prednisone, Prednisolone Oral corticosteroid
  • Infliximab, Adalimumab TNF Antagonists

Severe:

  • Infliximab, Adalimumab TNF Antagonists
  • IV corticosteroids
  • Natalizumab anti-integrin
  • Cyclosporine immunosuppressant 
  • Surgery

30

Pancreatic insufficiency is defined as secretion of pancreatic enzymes falling below ___ of normal, impairing __ and __ digestion

Pancreatic insufficiency is defined as secretion of pancreatic enzymes falling below 10% of normal, impairing fat and protein digestion