Drugs Flashcards
(29 cards)
What is preferred agent to induce remission in 90% of UC and 60-90% of Crohn’s patients?
- predinisone
- first line Tx
- effective and affordable
What is a treatment option for corticosteroid tapering if disease is limited to the distal colon?
Sulfasalizine
What two diseases is sulfasalizine effective in treating?
- UC - not Crohn’s (because it is not activated in the primary disease site - small intestine)
- RA
What does the pro-drug sulfasalizine consist of?
- sulfapyridine (antibiotic carrier molecule that prevents early activation)
- mesalamine (5-aminosalicylate)
Where and how is sulfasalizine activated?
prodrug cleaved in colon by bacterial azoreductases
What causes side effects of sulfasalizine?
sulfapyridine is rapidly absorbed from colon and acetylated in the liver (AE’s dependent upon acetylation phenotype - faster clearance = fewer AE’s – INH is also affected by acetylation rates)
How does mesalamine work?
- inhibits COX and LOX pathways reducing inflammation
- scavenges ROS and reduces neut/macro chemotax/phago
- decreases cytokine production and Ig secretion
- LOCALIZED TO COLON!
What molecule plays an important role in mesalamine action?
PPAR gamma (NFkappaB) - precise action unknown
What is azothioprine?
pro-drug that is converted to 6-MP
How does 6-MP work?
inhibits purine synthesis by multiple mechanisms (blocks salvage pathway)
Problem with 6-MP action?
takes 3-6 months to work
How does MTX work?
inhibits DHFR blocking thymidylate synthesis - inhibits immune cell proliferation
Where is MTX active?
bone marrow, also damages gut epithelium (systemic effects)
Two pharm concerns with MTX dosing?
- can accumulate in ascitic, pleural or peritoneal fluids
- can be displaced by drugs that bind plasma proteins = inc tox
MOA of mycophenolate mofetil?
inhibits IMPDH, blocking GMP synthesis (does not block purine salvage pathway, 6-MP does)
Preferential site of action of mycophenolate mofetil?
preferentially inhibits form of IMPDH that is most abundant in lymphocytes
When are cylosporine and tacrolimus used?
in patients refractory to corticosteroids
What is calcineurin?
protein phosphatase that is important in signaling
Calcineurin’s immune role?
calcineurin-FKBP complex activates NFAT TF which is specific to T cells and induces cytokines
How does tacrolimus work?
binds FKBP (peptidyl-prolyl isomerase) which is needed to activate calcineurin
What is a common complication of tacro treatment? Two toxicities?
- diabetes due to negative effects on pancreatic islet cells
- nephro and neurotox
How does cyclosporine work?
- binds to cyclophilin, a peptidyl-prolyl isomerase that activates calcineurin
How is tacrolimus metabolized?
CYP450 3A4
What anti-infectious drugs inhibit CYP450? Induce?
- azole anti-fungals
- rifampin
