Parkinson’s disease is a disease in which the “movement-regulating part” of the brain is impaired, making it impossible for the body to move smoothly.
When we move our body, the brain releases a substance called “dopamine” to adjust the body so that it can move smoothly. However, when the dopaminergic nerve cells in the brain are degenerated and this “dopamine” is deficient, the brain brakes the movement more than necessary and cannot move smoothly.
As a result, you may move slowly, your arms may be difficult to bend and stretch, you may fall more easily, and your limbs and chin may quiver when you are still.
In order to improve these symptoms, drug treatment to supplement the deficient “dopamine” is effective.
Side effects of taking Parkinson’s disease medication
The focus of treatment is replacement therapy for the deficient “dopamine” with the dopamine precursor L-dopa and dopamine receptor agonists.
The brain has a function called the “blood-brain barrier (BBB)” that limits the transfer of substances from the blood to the brain.
Even if you take dopamine directly, it will be repelled by this BBB, so take L-dopa, a precursor of dopamine that can pass through the BBB.
These are effective for Parkinson’s symptoms, especially L-dopa, which is the most effective treatment, but it also has side effects.
Side effects caused by excess dopamine
First of all, I will explain the side effects that occur due to excess dopamine.
Gastrointestinal symptoms; nausea, vomiting, loss of appetite, constipation
Dopamine receptors are present not only in the brain but also in the gastrointestinal tract. It occurs when L-dopa, which has not been transferred to the brain, is metabolized to dopamine in the periphery and stimulates the digestive tract.
【measures】
- Taking L-dopa immediately after eating can reduce irritation to the digestive tract.
- By using a mixture of carbidopa that inhibits the metabolism of L-dopa in the periphery, irritation to the digestive tract can be suppressed.
Taking antiemetics before meals can help reduce nausea.
Involuntary movement (dyskinesia)
Dyskinesia is a symptom of unconscious movement of the limbs and mouth. Dopamine This is caused by an excess of dopamine in the “striatum” of nerve cells.
【measures】
- Reduce the dose.
- A drug that promotes the release of dopamine from the “striatum” is also used.
Psychiatric symptoms (hallucination, delirium, insomnia, sudden sleep)
Dopamine is a neurotransmitter that excites and tensions your feelings. Therefore, it is said that excessive dopamine in the brain causes hallucinations, delirium, and insomnia.
【measures】
- Reduce the dose.
Cardiovascular symptoms (orthostatic hypotension / lower leg edema)
Dopamine receptors are present not only in the brain but also in the heart. It occurs when L-dopa, which has not migrated to the brain, is metabolized to dopamine in the periphery and stimulates receptors in the heart.
【measures】
- By using a mixture of carbidopa that inhibits the metabolism of L-dopa in the periphery, irritation to the heart can be suppressed.
- Lightheadedness can be suppressed by using a hypotension drug together.
- Edema can be improved by massaging the lower legs and taking diuretics.
Side effects of long-term use
Next, I will explain the side effects that occur without long-term use.
wearing-off phenomenon
It occurs because the degeneration of dopamine nerve cells in the brain progresses and the storage capacity of dopamine decreases.
Symptoms appear several years after taking L-dopa.
Even if L-dopa is supplemented, it cannot be stored in dopamine neurons, so dopamine is released at once and the duration is shortened. In addition, the symptoms of dyskinesia may worsen due to the large fluctuation in concentration between when it is released at once and when it is depleted.
on-off phenomenon
Although it is extremely rare, it is a phenomenon in which Parkinson’s symptoms suddenly worsen or improve regardless of the time of administration or blood concentration. It is thought to be caused by changes in L-dopa concentration and changes in dopamine receptor sensitivity.
【measures】
- By increasing the number of doses of L-dopa, the duration of the medicinal effect is extended.
- Although less effective than L-dopa, it is used in combination with a dopamine receptor agonist that has a longer duration of action and a more stable blood concentration.
- A COMT inhibitor that suppresses the degradation of L-dopa in the blood and a MAO-B inhibitor that suppresses the degradation of dopamine in the brain are used in combination.
- A COMT inhibitor that suppresses the degradation of L-dopa in the blood and a MAO-B inhibitor that suppresses the degradation of dopamine in the brain are used in combination.
- A dopamine activator and an adenosine receptor antagonist that enhance the action of L-dopa and prolong the duration are used in combination.
Side effects caused by sudden interruption
Next, I will explain the side effects that occur due to sudden interruption.
Neuroleptic malignant syndrome
The detailed cause is unknown, but it is thought to be related to the rapid decline in dopaminergic nerve function.
In addition to high fever and impaired consciousness, muscle rigidity and myoglobinuria (reddish brown urine) due to rhabdomyolysis are observed.
【measures】
- Delayed treatment can lead to death, so detect it early and prevent it from becoming more severe.
- Resume L-dopa administration and then gradually reduce it.
- Administer sufficient infusion and cool the body.
In addition to drugs that supplement dopamine or maintain dopamine levels,
There are anticholinergic drugs that reduce the relative excess of acetylcholine due to dopamine deficiency. In addition to mild Parkinson’s disease, it is often used to treat “drug-induced Parkinson’s syndrome” caused by drugs for the treatment of schizophrenia.
Side effects caused by deficiency of acetylcholine
Next, I will explain the side effects caused by deficiency of acetylcholine.
- Peripheral anticholinergic effect (constipation, dry mouth, difficulty urinating)
- Central anticholinergic effect (dementia)
【measures】
- The use of laxatives and enemas can improve constipation.
- Salivary gland massage and licking candy promote saliva production.
- Avoid taking it for the elderly and those with impaired cognitive function.
References
Illness can be seen vol.7 Brain / nerve (published by Medic Media Co., Ltd.)
year note 2015 (published by Medic Media Co., Ltd.)
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