GI Pharmacology IBD

Question 1

Specific goals of IBD pharmacotherapy:

Answer 1

– Controlling acute exacerbations of the disease
– Maintaining remission
– Treating specific complications such as fistulas

Question 2

Mesalamine (5-ASA) -based therapy

Answer 2

MOA: inhibits prostaglandin / NFĸB activity (abs. in SI only)

USE:
-Ulcerative colitis (first-line)
-Crohn’s (off label)

Question 3

Sulfasalazine

Answer 3

5ASA, 30 in SI / 70 in colon

AE:
-Systemic effects: Sulfapyridine
-Pruritus, rash
-GI: pain, lose appetite, N/V
-Impairs folate abs. (supplement)

Question 4

Olsalazine and Balsalazide

Answer 4

5ASA

AE:
-Well tolerated, secretory diarrhea

Question 5

Prednisone, budesonide, hydrocortisone

Answer 5

Glucocorticoids

MOA: inhibit PLA2, decrease prostaglandins/leukotriens and cytokines/chemokines

USE: ACTIVE ulcerative colitis and Crohn’s

AE:
-Moon face, fat deposits
-Hyperglycemia
-Increase risk of infection
-NA/Fluid retention
-Thin extremities/skin, bruise, striae
-GI distress/increase acid
-Osteoporosis

Question 6

Glucocorticoid Formulations

Answer 6

-Oral
-Controlled
-Enemas
-Suppositories

Question 7

Mercaptopurine (6-MP), Azathioprine

Answer 7

Immunosuppressive agents
-Prodrugs

MOA: false nucleotides, strand break, inhibit inf. cell proliferation

USE: remissioin in ulcerative colitis and Crohn’s

AE:
-Bone marrow suppression
-Alopecia, rash
-N/V
-Hepatoxicity
-Increased risk of infections, sensitivity rxn, malignancies

Question 8

Immunosuppressive agents: 6MP and Azathioprine Monitoring

Answer 8

-CBCs and liver function tests required in all patients

-TPMT levels low = BM depression (measure TMPT levels before therapy)

DDI:
-Allopurinol (needs dose reduction)

Question 9

Methotrexate (MOA, USE, AE)

Answer 9

Immunosuppressive agent, folic acid antagonist

MOA: inhibitor of dihydrofolate reductase, impaired DNA synth

USE: remission of ulcerative colitis/Crohn’s

AE
-Derm: alopecia, photosensitive, rash
-GI: dia/N/V, hepatotoxicity
-Hema: bone marrow suppression
-Renal impairment

Question 10

Methotrexate (Monitoring/DDI/Contra)

Answer 10

DDI
-Salicylates, NSAIDs, penicillin

Contra
-Pregnancy, hepatic disease

Monitoring
-CBCs and liver function tests (1-3mo)

Question 11

Anti-TNF therapy

Answer 11

Four monoclonal antibodies
-Infliximab, adalimumab,
certolizumab, golimumab

MOA: bind to TNF, prevent binding

USE: IAG (UC) and IAC (CD)

AE:
-Increase risk of infections (need TB test)
-Antibodies to the anitbody (infliximab)
-Infusion rxn: fever, HA, dizzy, hypo
-Hepatic rxn (failure)
-Malignancy (lymphomas)

Question 12

Natalizumab

Answer 12

Anti-Integrin therapy

MOA: antibody against VLA4, reduced extravasation of lymphocytes

USE: remission of CD

AE:
-P. Multifocal leukoencephalopathy
-Hepatotoxicity

Question 13

Vedolizumab

Answer 13

Anti-Integrin therapy

MOA: antibody against integrin (a4b7), reduced extravasation of lymphocytes into GI tract

USE: remission of CD and UC

AE:
-Hepatotoxicity, less risk of PML