What are the adverse reactions of anti-Parkinson's disease drugs? How to deal with them?

Author: Chen Haibo, chief physician of Beijing Hospital

Reviewer: Hu Wenli, Chief Physician, Beijing Chaoyang Hospital, Capital Medical University

As we all know, whether it is Parkinson's disease or Parkinson's plus syndrome, as long as anti-Parkinson's disease drugs are effective, they generally have to be taken for a long time.

In the process of long-term use of anti-Parkinson's disease drugs, some adverse reactions may occur. If not handled properly, it may have a great impact on the human body, so it is particularly important to understand some basic knowledge of anti-Parkinson's disease drugs.

1. What adverse reactions may occur when taking anti-Parkinson's disease drugs?

There are many drugs for Parkinson's disease, and different drugs have different adverse reactions. There are three main types of first-line treatment drugs: levodopa, dopamine receptor agonists, and type B monoamine oxidase inhibitors. In addition, entacapone can also be used as a first-line drug and put in the levodopa series. Other drugs are basically second-line treatment drugs.

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The characteristic of levodopa is that it can directly supplement dopamine, so its therapeutic effect is the best and strongest, which is its advantage. However, it also has disadvantages, especially for young patients with early onset disease, long-term use, especially in large doses, will lead to a phenomenon of end-of-dose.

Wear-off phenomenon means that the effect of a drug can last for five hours after taking it once, and it can be maintained very stably after taking it three times a day. However, as time goes by and the dosage increases, the effect will become shorter and shorter. The effect of a drug may only last for two or three hours after taking it once, and the symptoms will worsen before the next dose. This situation is called wear-off phenomenon.

The wear-off phenomenon has a significant impact on the patient's quality of life. Some patients said that after taking a dose of medicine, they would go to the street to buy groceries at 8 o'clock and return home at 10 o'clock because they would be unable to move at 10:30. Therefore, after a certain period of use of levodopa, this motor complication will occur. Some patients will experience an increase in uncontrollable movements, called dyskinesia, which will also affect the patient's quality of life.

Some people may wonder if other drugs can be used first to slow down the complications caused by levodopa. Some studies have found that if dopamine receptor agonists are used first in the early stage, it is possible to delay the use of levodopa and delay the motor complications of levodopa. Of course, some studies also say that if the daily dose of levodopa does not exceed two tablets, the incidence of motor complications is also relatively low.

Another first-line drug is the monoamine oxidase type B inhibitor, including selegiline and rasagiline, which may potentially slow the progression of the disease and can therefore be used first, or in combination with levodopa or dopamine receptor agonists.

The second-line drugs are amantadine and trihexyphenidyl. Relatively speaking, these two drugs have more side effects, which is one of the reasons why they are used as second-line drugs.

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Benhexol has more side effects, especially for the elderly, such as dry mouth, blurred vision, constipation, cognitive impairment, etc.; Amantadine can easily cause hallucinations, affect sleep, and cause insomnia. So generally speaking, if you want to use it, use it earlier in the day and try not to use it at night.

2. What should I do if adverse reactions occur after taking anti-Parkinson's disease drugs?

We need to make adjustments based on the characteristics of the disease, generally speaking, the main focus is on adjusting the medication.

For example, there are several dosage forms of levodopa in China, one is called dobase hydrazine, the other is compound carbidopa tablets, these two are standard tablets, and there is also a carbidopa levodopa, which is a sustained-release tablet. If the standard tablet is used, its half-life is relatively short, and the end-of-dose phenomenon may occur earlier. If this happens, you can switch to carbidopa levodopa sustained-release tablets, which have a longer half-life, thereby prolonging the duration of drug effect.

In addition, entacapone can be added to reduce the degradation of levodopa, thereby extending the half-life of levodopa in the blood, thereby prolonging the therapeutic effect and reducing the end-of-dose phenomenon.

Of course, monoamine oxidase type B inhibitors, namely selegiline and rasagiline, have similar effects and can prolong the efficacy of levodopa.

Another method is to increase the dopamine receptor agonist, because the half-life of dopamine receptor agonists is generally longer, such as pramipexole, which has an average half-life of 10 hours, and ropinirole, which has a half-life of about 6-8 hours. Therefore, after taking the medicine, it can basically be taken with three meals a day, the efficacy will be relatively stable, and the end-of-dose phenomenon can also be improved. Recently, rotigotine sustained-release microsphere injection has just been launched on the market. It is used once a week and may be better for the end-of-dose phenomenon, but there is still a lack of sufficient clinical experience.

In addition, dyskinesia is caused by an excessive dose of levodopa. If dyskinesia occurs, the dose of the drug needs to be reduced a little each time, but its efficacy will also be reduced. Therefore, if the total dose of the day remains unchanged, this problem can be solved by increasing the number of times. Dyskinesia disappears and the efficacy can continue to be maintained.

If dyskinesia occurs, in addition to reducing the dose of each drug, you can also add the drug amantadine, which can also help to a certain extent. Because it is now found that amantadine has a certain anti-dyskinesia effect, which can solve the complications caused by this drug to a certain extent.

In severe cases, the effects are accompanied by abnormal movements, and some patients feel very painful. Because when the effects are not effective, they are frozen, and when they are effective, they move around all over again, and there is hardly any time to feel comfortable. In this case, we may need to use deep brain stimulation to treat it.

Because deep brain stimulation is a surgical treatment, it implants an electrode in the brain and provides a stimulator externally. The stimulator continuously provides electricity to a specific part of the brain to stimulate the cells, producing an effect similar to that of dopamine, thereby improving symptoms. The electricity is continuous, so it can significantly improve the wear-off phenomenon, and with good efficacy, it can even eliminate the wear-off phenomenon within a period of time.

In addition, the dyskinesia mentioned earlier is often clearly related to the fluctuations in blood drug concentrations. The electrical level of deep brain stimulation is relatively stable, and can also reduce the occurrence of dyskinesia. This is one of our treatment methods.

Of course, these drugs also have some other adverse reactions, such as hypotension. Among the several drugs used to treat Parkinson's disease, almost all have this side effect of lowering blood pressure.

Some patients with hypertension no longer need to take antihypertensive drugs after taking drugs to treat Parkinson's disease. However, for patients without hypertension, some may suffer from low blood pressure after taking them, so there will be some differences in drug selection. For example, dopamine receptor agonists may cause more chances of hypotension, so the dosage of dopamine receptor agonists may be reduced, and other drug types and dosages may be increased. If it really doesn't work, pressor drugs must be used to solve the problem of low blood pressure.