Disease Modifying Anti Rheumatic Agents (DMARDS)

by Pravin Shukle, MD

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    Let's move on to the disease modifying anti rheumatic agents or DMARDs. Now remember these all drugs are cytotoxic agents. So you shouldn't just jump on the bandwagon to get people on DMARDs without any kind of experience with these drugs. The first of them and the prototypical DMARD is methotrexate. Now we often give methotrexate once a week. And because they also affect folic acid activity, we give it with folic acid supplementation. This is an antifolate drug. It inhibits dihydrofolate reductase. What is that relevant? Because this reduces thymidine synthesis. Now remember thymidine is one of the agents used in DNA, so if you have less thymidine, you're going to have less expression of DNA fragments. The primary mechanism is used in cancer chemotherapy and it limits a cancer cell from dividing because there's less DNA. In rheumatoid arthritis, there are multiple mechanisms of action. Number 1, there is accumulation of adenosine. Number 2, it inhibits the T cells. Number 3, it suppresses intercellular adhesion molecules of the T cells so the T cells can't attach to their target. And remember T cells are very important in inflammation. And finally, it inhibits interleukin 1 beta binding to the cell surface receptors which is the primary mechanism of how inflammation is occuring in rheumatoid arthritis. So, there's multiple ways that methotrexate is working in RA that make it a very effective anti-RA drug. Methotrexate is also used in other diseases as well. Let's move on to the T-lymphocyte agents. The most well known and I would call it the prototypical drug is sulfasalazine. Now, sulfasalazine is metabolized to 5-ASA. And yes that is related to aspirin. It works through an unknown mechanism and it is used extensively in Crohn's disease. Now, we're gonna talk a lot more about sulfasalazine...

    About the Lecture

    The lecture Disease Modifying Anti Rheumatic Agents (DMARDS) by Pravin Shukle, MD is from the course Inflammation Pharmacology.

    Included Quiz Questions

    1. DMARDS are cytotoxic drugs.
    2. DMARDS are similar to aspirin.
    3. DMARDS are similar to NSAIDs.
    4. DMARDS are similar to COX-2 inhibitors.
    5. DMARDS are similar to chemotherapy and should rarely be used.
    1. Methotrexate
    2. A combination of NSAIDs
    3. Indomethacin
    4. Ketorolac
    5. Unfortunately there are no other alternatives.
    1. Patients have to get their plasma levels checked regularly.
    2. Patients must take folate with this drug to ensure some normal cell development.
    3. Patients must take vitamin B6 to prevent peripheral nerve damage.
    4. Patients must have their hearing checked periodically.
    5. Patients must be monitored for lung fibrosis.
    1. Very few side effects.
    2. Long half life, requiring fewer dosages.
    3. Short half life, ensuring patients do not overdose.
    4. No GI upset, but some central nervous system disfunction.
    5. Increases weight gain.

    Author of lecture Disease Modifying Anti Rheumatic Agents (DMARDS)

     Pravin Shukle, MD

    Pravin Shukle, MD

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