Home » Health » Medicine

I Take Methotrexate For Rheumatoid Arthritis And I'm Concerned About The Side Effects...

Nov 13, 2007
Since the early 1980's methotrexate has assumed the position of "gold standard" as a disease modifying anti-rheumatic drug (DMARD) for rheumatoid arthritis (RA). It is effective, relatively safe, and also relatively inexpensive.

In the past methotrexate was used either as a single agent or in combination with other DMARDS such as hydroxychloroquine (Plaquenil) or sulfasalazine (Azulfidine). With the advent of the newer biologic drugs, methotrexate is most often used in combination with these biologics for patients with active RA.

Methotrexate works by blocking an enzyme called dihydrofolate reductase. The end result of this action is a reduction in purines and pyrimidines, inhibition of T-cell activation, and reduction of inflammation through the release of a substance called adenosine. Therefore, methotrexate has both anti-inflammatory properties as well as disease-modifying properties.

Generally, methotrexate is well tolerated and safe; however, it is discontinued as a result of side effects not infrequently. Most of the side effects related to the low doses used in rheumatoid arthritis are preventable and reversible.

Because of the mechanism of action through the antagonism of folate metabolism, there are toxicities that are sometimes seen.

The most common are mouth ulcers, soreness in the mouth, drop in white blood cell counts, drop in platelet counts, and anemia. These side effects can usually be prevented by giving a patient supplemental folic acid. In our clinic we give patients anywhere from one to three mgs per day.

One tactic that seems to help with some of the side effects is to split dose the methotrexate- ie., have the patient divide up their dose so that they are taking their tablets over a 24 hour period of time once a week instead of all at gulp.

Patients who develop gastrointestinal upset with tablets occasionally do better with subcutaneous methotrexate.

There are also side effects that are not dependent on folate metabolism. These include fatigue, rheumatoid nodule formation, liver damage, and lung damage. Lung damage can be due to fibrosis which can occur over time or there can be an acute syndrome consisting of pneumonitis (lung inflammation), accompanied by fevers, chills, shortness of breath, and respiratory failure. Rare instances of kidney damage have occurred. A much more common scenario though occurs when patients with poorly functioning kidneys are given methotrexate and develop methotrexate toxicity as a result of accumulation of the drug.

There is some data that implicates adenosine as being responsible for some of these side effects. Since methotrexate increases adenosine levels, this is an intriguing possibility. This is being evaluated particularly in a liver disease model. Methotrexate and ethyl alcohol both appear to increase adenosine output from liver cells. In animal models, this paves the way for liver fibrosis. When compounds that block adenosine are given, the liver fibrosis doesn't occur.

The trend now is to use somewhat lower doses of methotrexate and institute biologic drugs earlier. This may also help offset methotrexate toxicity since toxicity to a certain extent is dose dependent.

Monitoring for methotrexate toxicity through the use of monthly laboratory testing of blood count and liver function tests, as well as clinical evaluation goes a long way towards preventing many of the potential problems associated with this drug.
About the Author
Nathan Wei, MD FACP FACR is a rheumatologist and Director of the Arthritis and Osteoporosis Center of Maryland. He is a Clinical Assistant Professor of Medicine at the University of Maryland School of Medicine. For more info: Arthritis Treatment
Rating:
Please Rate:
(Average: Not rated)
Views: 152
Print Email Report Share
Article Categories
    • Artists
    • Gambling
    • Humanities
    • Humor
    • Movies
    • Music
    • Photography
    • Tattoos
    • Television
    • Classic Cars
    • Motorcycles
    • Recreational Vehicles
    • SUVs
    • Trucks
    • Vans
    • Branding
    • Business Opportunities
    • Careers and Jobs
    • Corporate
    • Customer Service
    • Direct Mail
    • Entrepreneurship
    • Ethics
    • Financing
    • Franchising
    • Home-Based Business
    • Human Resources
    • Import and Export
    • Leadership
    • Management
    • Market Research
    • Marketing and Advertising
    • Negotiation
    • Network Marketing
    • Networking
    • Organizational
    • Presentation
    • Project Management
    • Public Relations
    • Small Business
    • Strategic Planning
    • Team Building
    • Telemarketing
    • Training
    • Data Recovery
    • Databases
    • Games
    • Hardware
    • Networks
    • Operating Systems
    • Programming
    • Security
    • Software
    • Spyware and Viruses
    • Ask an Expert
    • College and University
    • Home Schooling
    • K-12
    • Languages
    • Online Education
    • Psychology
    • Accounting
    • Credit
    • Currency Trading
    • Debt Consolidation
    • Insurance
    • Investing
    • Leasing
    • Loans
    • Mortgage
    • Mutual Funds
    • Personal Finance
    • Stock Market
    • Structured Settlements
    • Taxes
    • Wealth Building
    • Coffee
    • Cooking
    • Gourmet
    • Recipes
    • Wine and Spirits
    • Arts and Crafts
    • Babies
    • Collecting
    • Elderly Care
    • Genealogy
    • Hobbies
    • Parenting
    • Pets
    • Pregnancy
    • Woodworking
    • Feng Shui
    • Gardening
    • Home Appliances
    • Home Security
    • Interior Design
    • Landscaping
    • Affiliate Programs
    • Article Marketing
    • Auctions
    • Audio
    • Banner Advertising
    • Blogging
    • Broadband
    • Domain Names
    • E-Books
    • E-Commerce
    • Email Marketing
    • Ezines and Newsletters
    • Forums
    • Internet Marketing
    • Link Popularity
    • Pay-Per-Click
    • Podcasting
    • RSS
    • Search Engine Marketing
    • Search Engine Optimization
    • Security
    • Social Media
    • Spam
    • Video
    • Viral Marketing
    • Web Design
    • Web Development
    • Web Hosting
    • Copyright
    • Cyber Law
    • Intellectual Property
    • National, State, Local
    • Patents
    • Regulatory Compliance
    • Trademarks
    • Buying
    • Selling
    • Baseball
    • Basketball
    • Boating
    • Cycling
    • Extreme Sports
    • Fishing
    • Football
    • Golf
    • Hockey
    • Hunting
    • Martial Arts
    • Running
    • Scuba Diving
    • Soccer
    • Swimming
    • Tennis
    • Dating
    • Divorce
    • Marriage
    • Weddings
    • Astrology
    • Buddhism
    • Christianity
    • Faith
    • Hinduism
    • Islam
    • Judaism
    • Meditation
    • Metaphysical
    • New Age
    • Cable and Satellite TV
    • Cell Phones
    • Communication
    • Gadgets and Gizmos
    • GPS
    • Satellite Radio
    • Video Conferencing
    • VoIP
    • Addictions
    • Coaching
    • Goal Setting
    • Motivational
    • Stress Management
    • Time Management
    • Clothing
    • Electronics
    • Fashion
    • Gifts
    • Jewelry
    • Causes and Organizations
    • Environment
    • History
    • Holidays
    • Men's Issues
    • Nature
    • Philosophy
    • Politics
    • Women's Issues
    • World Affairs
    • Air Travel
    • Camping
    • Cruises
    • Destinations
    • Outdoors
    • Article Writing
    • Book Reviews
    • Copywriting
    • Fiction
    • Non-Fiction
    • Poetry
    • Quotes
    • Screenplay
    • Tools and Resources