Lecture 33 - Drugs to Treat IBD and Gallstones

Question 1

5-aminosalicylates (5-ASA) is used for ______ (mild, moderate, or severe?) Crohn’s and UC. They tend to be absorbed in the ______ intestine (though not in the _____ intestine). They work ______, not systemically.

Answer 1

Mild

Small

Large

Topically

Question 2

_________ and _________ are 5-ASAs linked to AZO. How does this affect their availability?

Answer 2

Sulfasalazine and Balsalazide

AZO compound is broken down by bacteria abundant in the large intestine, so this is where they become available.

Question 3

______ is a glucocorticoid that is an analog of prednisolone with a delayed, pH-controlled release formulation.

Answer 3

Budenoside

Question 4

Treatment for MODERATE Crohn’s and UC involves ____ analogs. They are given _____ (route?) as pro-drugs, and their conversion/accumulation can take up to _____ months before they become therapeutic (their active form is ____-_______). With this is mind, they should be combined with ________ until they become therapeutic.

Answer 4

Purine analogs (i.e. azothioprine and 6-mercaptopurine)

IV

4 months

6-thioguanine

Glucocorticoids

Question 5

Purine analogs have a high incidence of _____ and _____ (from liver and bone marrow toxicity). They also interact with _______, leading to toxicity.

Answer 5

Anemia and Leukopenia

Allopurinol

Question 6

______ can be given orally, subQ, or IM. It acts via _____-mediated DNA synthesis inhibition and inhibition of activated _____-cells (which decreases immune activity). Even at low doses, 30% of patients will experience adverse effects of liver and bone marrow tox.

Answer 6

Methotrexate

Folate-mediated

T-cells

Question 7

Anti-_____ Ab therapy is reserved for SEVERE UC and Crohn’s.

______ is administered IV, while the others are administered SubQ –> think about what this means for half-life.

______ is the one unique to Crohn’s therapy and ______ is unique to UC. The other two are used in both.

Answer 7

Anti-TNF Ab

Infliximab (IV means it will have shorter half-life).

Certolizumab –> Crohn’s

Golimumab –> UC

Question 8

Patients can form antibodies to antibodies (ATA) when given monoclonal antibody therapy. Which route of administration makes this more likely?

Answer 8

IV

Question 9

When anti-TNF Abs are ineffective, IBD patients can be treated with ______, which is a monoclonal Ab against cell _____ proteins –> prevents autoimmune cells from reaching GI mucosa. Side effects are related to decreased immune activity (so common cold, bronchitis, etc..) but also headaches and joint pains.

Answer 9

Vedolizumab

Adhesion

Question 10

______ (an antibiotic) can also be used to suppress T-cell activity. Its side effects include HTN, ____ damage, and infection.

Answer 10

Cyclosporin

Kidney

Question 11

_______ (so named bc it is common in bears) is given to increase bile flow, enterohepatic _____, and decrease hepatic production of ______ –> so obv it will decrease incidence of gallstones. It is the first line therapy for _____ _____ ______.

Answer 11

Ursodiol

Circulation

Cholesterol

Primary Biliary Cholangitis

Question 12

______ is a 5-ASA available throughout the small and large intestines. _______ER is a version dependent on _____ and moisture for release (Apriso is released at greater than or equal to _____ and Delzicol, Asacol-HD, and Lialda are released at greater than or equal to _____) –> how does this affect their availability?

Answer 12

Mesalamine

Mesalamine ER

pH

Apriso –> pH greater than or equal to 6

Delzicol, Asacol-HD, Lialda –> pH greater than or equal to 7. –> higher pH –> more distally available.