Statins and Myasthenia Gravis
3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor) have that effect of reducing blood lipid and anti-inflammation, It can reduce the incidence of cerebrovascular diseases and coronary heart disease. In the past 10 years, the application of statins has increased significantly. Although most patients are generally well tolerated to statins, the drugs still have certain side effects, such as myalgia and rhabdomyolysis in severe cases.
In theory, Statins may induce or aggravate myasthenia gravis symptoms, However, it is not caused by affecting the transmission of neuromuscular junctions. Pharmacological mechanism studies have found that, Statins can inhibit T cell activation, Inducing the transformation of helper T (Th) cells to Th2 cells, acting on B cells and cytokines, enhancing B cell-mediated immune abnormalities, thus aggravating the autoimmune response of myasthenia gravis patients and inducing the occurrence of diseases or aggravating the disease. Up to now, there have been reports of aggravating symptoms in patients with autoimmune diseases after taking statins.
In 2002, Parmar et al. Reported a patient with myasthenia gravis symptoms after using statins. After taking statins for 3 months, he developed eyelid ptosis and general weakness. The symptoms relieved after 6 weeks of withdrawal, but due to poor blood lipid control, myasthenia symptoms occurred again 2-3 months after taking the drugs again, and recovered after several weeks of withdrawal. The patient was diagnosed as myasthenia gravis, but his serological AchR antibody was negative and no repeated electrical stimulation examination was performed. Therefore, some people questioned the diagnosis of MG.
In 2008, Oh et al. Reported that 54 of 170 patients with myasthenia gravis with definite diagnosis took statins, of which 6 cases had aggravated symptoms after taking the drugs, all of which occurred within the first 8 weeks after taking the drugs. 2 of these 6 cases were accompanied by an increase in serum AchR level, and 3 cases had rapid relief after stopping taking statins.
Jesse et al. Also reported 2 cases of myasthenia gravis symptoms after taking statins. All of them developed extraocular muscle paralysis about 4 weeks after taking drugs, and improved after stopping taking statins and adjuvant low-dose hormone therapy.
Although statins may theoretically aggravate the disease, There are also cases reported in reality, But the drug is not absolutely taboo, We can’t stop eating because of choking. For patients with myasthenia gravis complicated with hypercholesterolemia, Statins should still be used according to the indications. Doctors should inform patients of this possibility in advance, and closely observe the changes of myasthenia and whether there are other side effects during taking the drug. Once there is any occurrence, they should adjust or stop using statins immediately, so as to solve the contradiction between medication theory and practice.
What should be paid attention to when taking glucocorticoid for myasthenia gravis patients?
So far, glucocorticoid is still the main drug for the treatment of this disease, with high cost performance. Once the specialist recommends adding hormone according to the patient’s situation, the patient should pay attention to the following issues:
1. More than 50% of systemic patients may have transient symptoms aggravation in the early stage (within 7-10 days) of high-dose hormone application, generally lasting for about 1 week, and crisis may occur in serious cases. Patients need to understand and prepare for this;
2. Long-term hormone administration requires calcium supplement, potassium supplement is required for those with large doses, and gastric protective agent is required for those with stomach discomfort.
3. Hormones should be taken once a day in the morning to reduce the impact on endocrine.
4. Do not reduce the dose without authorization, but under the guidance of a specialist.
Is there any difference between what and several oral glucocorticoids commonly used by myasthenia gravis patients?
Oral glucocorticoids commonly used in neurology to treat myasthenia gravis include prednisone (5 mg), dexamethasone (0.75 mg) and methylprednisolone (4 mg). In terms of dose conversion, prednisone 5 mg is equivalent to 0.75 ng dexamethasone or 4 mg methylprednisolone, and its tablets can be exchanged one by one, for example, 10 prednisone (50 mg) can be exchanged for 10 dexamethasone (7.5 mg) or 10 methylprednisolone (40 mg).
In terms of anti-inflammatory activity, dexamethasone > methylprednisolone > prednisone, but there is no sufficient evidence to show that there are obvious differences between several drugs in terms of immunosuppressive effect. There are reports that the immunosuppressive effect of methylprednisolone is better than that of the other two hormones.
Dexamethasone had the longest half-life, Long-term use is easy to cause endocrine axis disorder, Therefore, dexamethasone is not recommended for long-term oral treatment of myasthenia gravis patients. Prednisone is currently the most commonly used. It is cheap, The curative effect is obvious, However, it needs to be metabolized by the liver as an active product before it can play its role, which is easy to cause liver function abnormalities in some patients. Methylprednisolone can play its role directly without liver decomposition, thus having little impact on the liver. For patients with obvious liver function abnormalities, methylprednisolone can be considered instead of prednisone for treatment.
Precautions for taking azathioprine in myasthenia gravis patients
Azathioprine acts through metabolite 6-mercaptopurine and can competitively inhibit hypoxanthine involved in cell DNA and RNA synthesis. It mainly acts on T and B cells in the proliferative stage, AZA inhibited the expression of T and B cell surface receptors (CD2) and blocked mitogen-induced and antibody-induced responses. AZA inhibited antigen and mitogen-induced T cell proliferation in vitro to a weaker extent than cyclophosphamide (CTX). It has mild anti-inflammatory effect, which may be related to the inhibition of monocyte precursor cell division.
Azathioprine is commonly used in myasthenia gravis patients who have ineffective hormone application, have hormone reversal indications or need to reduce hormone dosage. Some doctors also use hormone and azathioprine at the initial stage of treatment for systemic myasthenia gravis. Retrospective studies show that when azathioprine is used for first-line or second-line treatment, 70-90% of the patients improved, but the onset of the effect was rather slow, lasting for 3-12 months. Compared with patients with prednisone alone, patients with prednisone combined with azathioprine had fewer recurrences, higher remission rates, and finally took a small dose of prednisone.
The initial dose of azathioprine is 50 mg, twice a day. Blood routine examination should be conducted once a week from the beginning of taking the medicine. If the white blood cells are less than 4000, the amount should be halved. If the white blood cells are less than 3500, azathioprine should be stopped. The dose of some patients can be increased to 2-3 mg/kg per day.
Azathioprine was well tolerated in most patients, However, a few patients will have side effects. About 10% of the patients will have fever, nausea, vomiting, abdominal pain, etc. Within the first few weeks of treatment. About 10% of the people have azathioprine-methyltransferase gene mutation. Enzyme activity decreases, azathioprine metabolism decreases, and toxicity increases. Leukopenia and liver function damage are important side effects and should be monitored regularly. Azathioprine has teratogenic effects and is forbidden for pregnant women.
Recent evidence-based medical evidence suggests that, Azathioprine can be used as a first-line drug for long-term immunosuppressive maintenance therapy of myasthenia gravis. There are 1-2 levels of evidence, Grade A recommends that azathioprine is also one of the few immunosuppressants that list myasthenia gravis as their indications in the instructions. Other immune drugs such as cyclophosphamide, cyclosporine, tacrolimus and even hormones are widely used in the treatment of myasthenia gravis, but their instructions do not mention the indications of myasthenia gravis!
Do myasthenia gravis patients need to take pyridostigmine for life?
First of all, it is clear that the therapeutic effect of pyridostigmine is symptomatic but not cause-specific. We know that myasthenia gravis is an autoimmune disease with neuromuscular junction acetylcholine transmission disorder. The effect of pyridostigmine is only to increase the amount of acetylcholine in synaptic space relatively, This is only a palliative, The pathogenesis of myasthenia gravis has not been touched: Autoimmune abnormalities. Therefore, We call pyridostigmine symptomatic replacement therapy. “when that patient has apply hormones or other immunosuppressive agent or the immune system has been corrected due to changes in the body itself, Clinically, the symptoms of myasthenia are improved, the condition is no longer obviously fluctuating, and it is meaningless to use pyridostigmine again when taking pyridostigmine no longer affects the symptoms. At this time, pyridostigmine can be stopped under the guidance of a doctor, and the patient may still be taking hormones or other immunosuppressants at this time, which is not in conflict.
Therefore, when myasthenia symptoms are well controlled, old patients can try to reduce pyridostigmine or even stop taking it. Of course, this must be done under the guidance of experienced doctors.
Myasthenia gravis patients take pyridostigmine gastrointestinal symptoms how to do?
Cholinesterase inhibitor bromopyridine is an important symptomatic treatment drug for myasthenia gravis. Some patients can improve their symptoms in about three quarters of an hour after taking it. However, Some patients will have obvious digestive tract symptoms after taking the drug. Including abdominal pain, diarrhea, nausea, vomiting and other gastrointestinal spasms. Although the symptoms of patients can disappear once they stop using the drug, a few patients will still be afraid to take the drug because of fear of side effects. How to solve this problem is a clinical neurologist who needs to pay attention to explain and educate patients.
If the patient has mild symptoms of the digestive tract, It can be done without any treatment or drug reduction. If the patient’s symptoms obviously affect his living conditions, strategic treatment is needed. You can reduce pyridostigmine to half a dose first. For example, pyridostigmine was originally one tablet three times a day, but it was changed to three times a day, half a tablet each time. If the patient can tolerate it, continue to take it and add it after 1-2 weeks.
If the patient’s symptoms are still obvious after being reduced to half a dose, anticholinergic drugs anisodamine (654-2), atropine or probensin can be considered, and pyridostigmine can be taken at the same time, and anticholinergic drugs can be gradually stopped after the patient tolerates them.
If the patient has severe gastrointestinal reactions and is extremely afraid of rejection, only immunosuppressive agents are used, but the patient should be informed that immunosuppressive agents will take a long time to take effect and need to wait patiently.
Author: Huashan myopathy group
The article was reprinted by Clove Garden authorized by the author.