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Questions posted in the
Neurology and Neurosurgery Forum have been answered by doctors from The Cleveland Clinic Foundation.
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Subject: Re: Myasthenia Gravis : In trying to achieve a therapeutic dosage of medications to control symptoms of myasthenia gravis, should a certain level of mestinon be tried before adding prednisone? Which drug has the most undesirable side effects in long term use? Does the Cleveland Clinic in Fort Lauderdale have any neurologists who are knowledgable about myasthenia gravis. I will appreciate any response to my posting.
Hello. Myasthenia gravis (MG) is a autoimmune disorder. In MG the body makes antibodies against acetylcholine receptors, Acetycholine is a very important chemical messenger. It is released by nerve terminals, goes to muscles where it is taken up by acetylcholine receptors. Acetylcholine functions by signalling the muscles to contract. The acetylcholine receptor antibodies that are present in MG block acetylcholine from being taken up by the muscle and so prevent the muscle from contracting as well as it should. This clinically results in weakness. There are 2 approaches to treating MG. The first is treatment of the SYMPTOMS of weakness. This is done by drugs such as Mestinon (physostigmine) which are acetylcholinesterase inhibitors. They function by blocking the enzyme (acetylcholinesterase) that normally breaks up acetylcholine and allows the acetylcholine to be present for a longer period of time. The increased amount of acetylcholine present counteracts the effects of the lower uptake by the receptors in MG and results in improvement in muscle contraction. The second approach is to treat the CAUSE of the problem by trying to decrease the production of the acetylcholine antibodies. One way this is done is by using drugs which suppress the immune system. Prednisone is a drug that is commonly used for this. It must be started carefully; if suddenly started in high doses it may cause a temporary worsening of symptoms before symptoms improve. Imuran (azothioprine) is another immunosuppressive drug that is used in MG. It takes approximately 6 months to take effect, and it is used for longterm control of MG rather than acute treatment. All immunosuppressive drugs have side effects. Because these drugs suppress the bodys immune system they are at increased risk for developing infections. Patients taking Prednisone chronically may have weight gain, especially around their face. People on prednisone may also develop osteoporosis (thinning of the bones) predisposing them to fractures. Prednisone may cause high blood sugars and it may induce diabetes in people. (This resolves when prednisone is stopped). People already with diabetes may have a hard time controlling their blood sugar levels. Patients on Imuran may develop low white blood cell counts or platelet counts (another component of blood) and these levels need to be checked regularly. A few people develop nausea and vomiting during the first few months of treatment with Imuran. Although liver abnormalities do occur, they are rare. Still, liver enzymes should be checked periodically while taking Imuran. Another way to alter the production of acetylcholine antibodies is by removing the thymus gland, which generates many of the antibodies. This takes years to have an effect so this also is for longterm control of MG. Occasionally, a procedure called plasmaphoresis is done. With this, blood plasma, which contains the acetylcholine antibodies, is removed and exchanged. This procedure is often done when patients are in myasthenic crisis and are very weak because it results in improvement in symptoms within a few days rather than weeks or months. There is no threshold Mestinon dose one should be on before starting an immunosuppressive drug. In fact, unless a myasthenics symptoms are mild and not very disabling, they are often treated simultaneously with both Mestinon andimmunosuppressants to attack the disease from 2 different angles. Because immunosuprressants have different onsets of action and different side effect profiles, decision on which drugs to use and when needs to be decided individually for each patient. |
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