| lor: #ffffff;" /> | | | | One tactic that seems to help with some of the side |
| Since the early 1980’s methotrexate has | | | | effects is to split dose the methotrexate- ie., have the |
| assumed the position of “gold standard” | | | | patient divide up their dose so that they are taking their |
| as a disease modifying anti-rheumatic drug (DMARD) | | | | tablets over a 24 hour period of time once a week |
| for rheumatoid arthritis (RA). It is effective, relatively | | | | instead of all at gulp. |
| safe, and also relatively inexpensive. | | | | Patients who develop gastrointestinal upset with |
| In the past methotrexate was used either as a single | | | | tablets occasionally do better with subcutaneous |
| agent or in combination with other DMARDS such as | | | | methotrexate. |
| hydroxychloroquine (Plaquenil) or sulfasalazine | | | | There are also side effects that are not dependent on |
| (Azulfidine). With the advent of the newer biologic | | | | folate metabolism. These include fatigue, rheumatoid |
| drugs, methotrexate is most often used in combination | | | | nodule formation, liver damage, and lung damage. Lung |
| with these biologics for patients with active RA. | | | | damage can be due to fibrosis which can occur over |
| Methotrexate works by blocking an enzyme called | | | | time or there can be an acute syndrome consisting of |
| dihydrofolate reductase. The end result of this action is | | | | pneumonitis (lung inflammation), accompanied by |
| a reduction in purines and pyrimidines, inhibition of T-cell | | | | fevers, chills, shortness of breath, and respiratory |
| activation, and reduction of inflammation through the | | | | failure. Rare instances of kidney damage have |
| release of a substance called adenosine. Therefore, | | | | occurred. A much more common scenario though |
| methotrexate has both anti-inflammatory properties as | | | | occurs when patients with poorly functioning kidneys |
| well as disease-modifying properties. | | | | are given methotrexate and develop methotrexate |
| Generally, methotrexate is well tolerated and safe; | | | | toxicity as a result of accumulation of the drug. |
| however, it is discontinued as a result of side effects | | | | There is some data that implicates adenosine as being |
| not infrequently. Most of the side effects related to the | | | | responsible for some of these side effects. Since |
| low doses used in rheumatoid arthritis are preventable | | | | methotrexate increases adenosine levels, this is an |
| and reversible. | | | | intriguing possibility. This is being evaluated particularly in |
| Because of the mechanism of action through the | | | | a liver disease model. Methotrexate and ethyl alcohol |
| antagonism of folate metabolism, there are toxicities | | | | both appear to increase adenosine output from liver |
| that are sometimes seen. | | | | cells. In animal models, this paves the way for liver |
| The most common are mouth ulcers, soreness in the | | | | fibrosis. When compounds that block adenosine are |
| mouth, drop in white blood cell counts, drop in platelet | | | | given, the liver fibrosis doesn’t occur. |
| counts, and anemia. These side effects can usually be | | | | The trend now is to use somewhat lower doses of |
| prevented by giving a patient supplemental folic acid. In | | | | methotrexate and institute biologic drugs earlier. This |
| our clinic we give patients anywhere from one to three | | | | may also help offset methotrexate toxicity since |
| mgs per day. | | | | toxicity to a certain extent is dose dependent. |