Non-biological DMARDs Flashcards
(33 cards)
What is the standard initial tx of RA?
A non-bio DMARD (MTX), an NSAID, and a Corticosteroid.. Milder cases get Hydroxychloroquine over MTX
If initial tx fails, what do you do next?
Give a 1st line biologic (targeted) tx like a TNF-alpha blocker with or without MTX
What if the targeted tx fails?
Some docs try a different TNF-alpha blocker, others switch to a completely different targeted therapy
What is important for longer remission, less joint destruction, and a better QOL?
Early aggressive treatment
What did the AMPLE trial show?
Found that triple therapy with MTX, Sulfasalazine, and Hydroxychloroquinone is just as effective (and much CHEAPER) than using MTX with a biological agent
What did the TEAR trial show?
Showed that initiating tx with MTX as a monotherapy was just as effective as initiating tx with a double or triple therapy. You can always add drugs to the MTX if you need to and the pt will turn out just the same. Moral of the story: Start with MTX and go from there
MTX MOA?
Inhibits AICAR transformylase (involved in synthesis of inosine monophosphate) –> increased circulating adenosine!!
What does increased circulating adenosine do?
Decreases: lymphocyte proliferation, IL-1, INF-gamma, TNF, histamine release from basophils and chemotaxis of neutrophils
Increases: IL-4
What happens to MTX when it gets into the cell?
When it gets into the cell is undergoes polyglutamation –> intracellular retention
Where is MTX metabolized?
Liver- enterohepatic circulation increases half life
Where is MTX eliminated?
Kidney
ADEs of MTX?
Immunosuppression, skin rxn, GI toxicity in pts with ulcerative cholitis (esp w/ concurrent NSAID use), pulm fibrosis, blood dyscrasias, infection, bleeding
Contraindications of MTX?
Alcoholics, liver dz, pregnancy (cat X), HIV infection, vaccinations
How do you monitor MTX?
CBC, LFTs, Cr/BUN, serum uric acid, pregnancy test
Which MTX adverse effects were given their own heading in Sweatman’s document?
- Immunosuppression
- Pulmonary toxicity
- Child bearing age
- Vaccinations
When is sulfasalazine used?
When pt has inadequate response to NSAIDs
What are the 2 metabolites of sulfasalazine and how is the drug metabolized into said metabolites?
Sulfasalazine is metabolized into sulfapyridine and mesalamine by colonic bacteria
What is the active metabolite of Sulfasalazine and what does it do?
Mesalamine: it is anti-inflammatory by inhibiting PG and LT
What is the fate of the other metabolite, sulfapyridine?
It is acetylated in the liver. Pts who are slow acetylators can have build up of sulfapyridine
ADEs of Sulfasalazine?
Fatal blood dyscrasias. Also do not give to pts who are hypersensitive to salicylates or sulfonamides
What is Leflunomide metabolized to? The active metabolite??
A77 1726
What does A77 1726 do?
Inhibits dihydroorotate dehydrogenase (DHODH). DHODH is key in pyrimidine synthesis
What does the inhibition of DHODH lead to?
Cell cycle arrest of B and T cells
Is Leflunomide cytostatic or cytotoxic at clinical levels?
Cytostatic
