Treatments for Parkinson's disease

Parkinson's disease is a common disease among the elderly. There are slightly more male patients with Parkinson's disease than female patients. The full name of Parkinson's disease is idiopathic Parkinson's disease. We also call Parkinson's disease tremor paralysis. Parkinson's disease can easily lead to many complications, so we must actively treat Parkinson's disease. Although it is difficult to treat Parkinson's disease, we still have ways to treat it.

There are many ways to treat Parkinson's disease. We can choose traditional Chinese medicine such as acupuncture, Chinese medicine and diet therapy, or we can use Western medicine and rehabilitation therapies.

1. Early treatment of PD

In the early stage of PD, the DA neurons retained in the substantia nigra-striatum system can compensate by increasing DA synthesis. It is recommended to use physical therapy (massage, hydrotherapy) and sports therapy (joint movement, walking, balance and language training, facial expression muscle training), etc., strive for the cooperation of the patient's family, encourage the patient to exercise more actively, and try to postpone the time of drug treatment. If the disease affects the patient's daily life and work, drug treatment is required.

2. Medication

PD is currently still treated mainly with drugs to restore the balance of the striatal DA and Ach neurotransmitter systems, using anticholesterol and DA neurotransmitter function-improving drugs to improve symptoms but cannot prevent the progression of the disease.

Medication principles:

① Start with a small dose and increase slowly, trying to achieve satisfactory therapeutic effects with a smaller dose.

② Treatment plans should be individualized, and drugs should be selected based on the patient's age, symptom type and severity, employment status, drug prices and financial affordability.

③ Do not add medication blindly or stop medication suddenly; it needs to be taken for life.

④The drug treatment of PD is complicated. Auxiliary drugs introduced in recent years, such as DR agonists, MAO-B inhibitors, catechol-O-methyltransferase (COMT), etc., can be used in combination with compound dopa to enhance the efficacy, reduce symptom fluctuations, and reduce the dosage of compound dopa. The efficacy of using it alone is not ideal. The pros and cons should be weighed and the combination of drugs should be appropriately selected.

(1) Anticholinesterase drugs: They are effective for tremor and rigidity, but less effective for bradykinesia. They are suitable for younger patients with obvious tremor. Commonly used medications include artane 1-2 mg orally, 3 times a day, and kemadrin 2.5 mg orally, 3 times a day, which can be gradually increased to 20-30 mg/d. Others such as cogentin, cycrimine, akineton, etc. have similar effects to Antan. Side effects include dry mouth, blurred vision, constipation and difficulty urinating, and in severe cases, hallucinations and delusions. It is contraindicated for patients with glaucoma and prostatic hypertrophy as it may affect memory function and should be used with caution in elderly patients.

(2) Amantadine: It promotes the release of DA at nerve endings, prevents its reuptake, and has anticholeretic effects. It is a glutamate antagonist that may have a neuroprotective effect and can slightly improve hypokinesia, rigidity, and tremor. It can be used alone or in combination with Amantadine in the early stages. The initial dose is 50 mg, 2 to 3 times/day. After 1 week, increase to 100 mg, 2 to 3 times/day. Generally, it should not exceed 300 mg/day, and should not exceed 200 mg/day for the elderly. The efficacy of the drug can last from several months to 1 year. There are fewer side effects, such as restlessness, confusion, livedo reticularis of the lower limbs, ankle edema and arrhythmia. It should be used with caution in patients with renal insufficiency, epilepsy, severe gastric ulcers and liver disease, and is prohibited for breastfeeding women. Its derivative memantine hydrochloride can also be used

hydrochloride).

(3) Levodopa (L-dopa) and compound levodopa: L-dopa is an effective drug or gold standard for the treatment of PD. As a DA precursor, it can pass through the blood-brain barrier and be taken up by brain DA neurons before being decarboxylated into DA, thus improving symptoms and having a special therapeutic effect on reduced movement. Since more than 95% of L-dopa is decarboxylated into DA in the periphery and only about 1% enters the brain through the BBB, in order to reduce peripheral side effects and enhance therapeutic effects, a compound preparation (compound L-dopa) made of L-dopa and peripheral dopa decarboxylase inhibitor (DCI) in a ratio of 4:1 is often used, and the dosage is reduced by 3/4 compared with L-dopa.

Compound L-dopa dosage forms: including standard tablets, controlled-release tablets, water-soluble tablets, etc. Standard tablets such as Madopar and Sinemet: ① Madopar is composed of L-dopa and benserazide in a ratio of 4:1, and Madopar 250 is L-dopa

200mg + benserazide 50mg, Madopar 125 is L-dopa 100mg + benserazide 25mg; the ingredients of domestic dopaser hydrazide capsules are the same as those of Madopar; ② Parkin (Sinemet

250 and Sinemet 125) are composed of L-dopa and carbidopa in a ratio of 4:1.

3. There are two types of controlled-release agents:

① Sinemet CR: L-dopa

200mg+carbidopa 50mg. A single-layer molecular matrix structure is added to the preparation, and the drug is continuously dissolved and released to achieve a sustained-release effect. The peak plasma concentration is reached 120 to 150 minutes after oral administration. There is a notch in the middle of the tablet, which can be divided into half a tablet for taking to maintain the sustained-release properties.

② Madopar-HBS: L-dopa

It is composed of 100mg + benserazide 25mg and special excipients. When the capsule dissolves, a hydration layer is formed on the surface of the drug matrix, which is gradually released through diffusion.

Madopar dispersible tablets are available in 125 mg L-dopa

100mg + benserazide 25mg. Its characteristics are that it is easily soluble in water, convenient for oral administration, rapidly absorbed, and quickly reaches the therapeutic threshold concentration, so that PD patients in the "off" state can quickly improve their symptoms in a short period of time (about 10 minutes), and the duration of action is basically the same as that of the standard tablet. This dosage form is suitable for PD patients with dysphagia or nasogastric feeding tube, morning akinesia, delayed "on" period, prolonged afternoon "off" period, and end-dose dystonia.

Timing of medication: There is still controversy about when to start compound L-dopa treatment. Long-term use of the drug will lead to complications such as decreased efficacy, symptom fluctuations and movement disorders. Generally, medication should be determined based on the patient's age, nature of work, type of disease, etc. Young patients can postpone its use appropriately, and try to use other anti-PD drugs in the early stage. When patients have to use L-dopa due to occupational requirements, they should use it in combination with other drugs to reduce the dose of compound L-dopa. Elderly patients can choose L-dopa early because they are relatively less likely to develop motor complications and have poor tolerance to combined medications.

Dosage: Start with a small dose, gradually increase the dose according to the condition, and maintain with the lowest effective dose.

① Standard tablets: The initial dose of compound L-dopa is 62.5 mg (1/4 tablet), 2 to 3 times/day, and gradually increased to 125 mg, 3 to 4 times/day as needed; the maximum dose should not exceed 250 mg, 3 to 4 times/day; the efficacy is better when taken on an empty stomach (1 hour before or 2 hours after a meal).

②Controlled-release tablets: The advantages are that they reduce the number of medication times, the effective blood drug concentration is stable, the action time is long, and symptom fluctuations can be controlled; the disadvantages are low bioavailability and slow onset of action. When standard tablets are converted into controlled-release tablets, the daily dose should be increased accordingly and taken in advance. It is suitable for patients with symptom fluctuations or early mild symptoms.

③ Water-soluble tablets: easily dissolve in water, rapidly absorbed, take effect in 10 minutes, and the duration of action is the same as that of standard tablets. They are suitable for patients with dysphagia, morning akinesia, "on-off" phenomenon and end-dose dystonia.

Side effects: Common peripheral side effects include nausea, vomiting, hypotension and arrhythmia (occasionally), etc., which can be gradually adapted to after taking the medicine. Taking the medicine after meals and adding metoclopramide can alleviate gastrointestinal symptoms. Central side effects include symptom fluctuations, movement disorders and mental symptoms. Symptom fluctuations and movement disorders are common long-term complications, which often appear 4 to 5 years after taking the drug. It is contraindicated for patients with angle-closure glaucoma and mental illness.

(4) DA receptor agonists: DA includes five types of receptors, and the D1R and D2R subtypes are closely related to the treatment of PD. The common action characteristics of DR agonists are: ① directly stimulate the postsynaptic DR in the striatum, and do not rely on DDC to convert L-dopa into DA to exert its effect; ② the plasma half-life is longer (compared to compound DOPA); ③ it may have a protective effect on the substantia nigra DA neurons. The combination of early DR agonists and compound dopa can not only improve the efficacy and reduce the dosage of compound dopa, but also reduce or avoid symptom fluctuations or movement disorders.

Indications: For patients in the late stage of PD who experience symptom fluctuations or movement disorders when treated with compound dopa, the addition of DR agonists can alleviate or eliminate the symptoms and reduce the dosage of compound dopa. In the later stages of the disease, due to the lack of DDC in the nigrostriatal DA system, exogenous L-dopa cannot be decarboxylated and converted into DA. The use of compound dopa is completely ineffective, but DR agonists may be effective. The efficacy of DA receptor agonists alone is poor, and it is generally recommended to use them in combination with the compound L-dopa. It can be used alone for early patients with a young age of onset. The dose should be started at a small level and gradually increased until satisfactory therapeutic effect is achieved without side effects. The side effects are similar to those of compound L-dopa, with a low incidence of symptom fluctuations and movement disorders, and a higher incidence of orthostatic hypotension and psychiatric symptoms.

Commonly used preparations: mainly bromocriptine and pergolide.

① Bromocriptine: Activates D2 receptors, starts with 0.625 mg/d, increases by 0.625 mg every 3 to 5 days, usually the therapeutic dose is 7.5 to 15 mg/d, taken in 3 divided doses; side effects are similar to levodopa, illusions and hallucinations are common, it is contraindicated for patients with a history of mental illness, relative contraindications include recent myocardial infarction, severe peripheral vascular disease, and active peptic ulcer, etc.

② Pergolide: Activates both D1 and D2 receptors, starts with 0.025 mg/d, increases by 0.025 mg every 5 days, generally effective dose is 0.375-1.5 mg/d, maximum does not exceed 2.0 mg/d, reaches peak plasma concentration in 1-3 hours, has a longer half-life (average 30 hours), has slightly stronger anti-PD effect than bromocriptine, and has a longer duration of action. When bromocriptine is ineffective, switching to pergolide may be effective.

③Tasuda sustained-release tablets

SR): The chemical component is piribedil, which is a selective D2/D3 dopamine receptor agonist. The dosage is 150-250 mg/d. It has an agonist effect on the D3R of the midbrain-cortex and limbic lobe pathways, has a significant effect on improving tremor, and also has an effect on rigidity and hypokinesia.

④ Lisuride: It has a strong selective D2R agonist effect and a very weak effect on D1R. It starts with a small dose, 0.05-0.1 mg/d, and gradually increases the dose. The average effective dose is 2.4-4.8 mg/d. According to the action-dose ratio, it is 10-20 times stronger than bromocriptine, with a short half-life (average 2.2h) and a short duration of action. It is water-soluble and can be applied by intravenous or subcutaneous infusion pump. It has an obvious "on-off" phenomenon when used for compound dopa treatment.

⑤ Apomorphine: D1 and D2R agonist, can significantly reduce the "off" state, has obvious therapeutic effects on symptom fluctuations, especially the "on-off" phenomenon and dystonia. It takes effect 5 to 15 minutes after pen injection, and the effective action time is 60 minutes. Each dose is 0.5 to 2 mg, and it can be used multiple times a day. Portable micropump subcutaneous continuous infusion method can enable patients to maintain good motor function every day; it can also be administered through the nasal cavity, but long-term use may irritate the nasal mucosa.

⑥ Cabergoline (cabaser): It has the longest half-life (70h) and the longest duration of action among all DR agonists. It is suitable for patients with symptom fluctuations and movement disorders caused by long-term use of compound dopa in the late stage of PD. The effective dose is 2-10mg/d, with an average of 4mg/d. It only needs to be taken once a day, which is more convenient.

⑦ Pramipexole (0.125 mg, 3 times/d, gradually increased to 0.5-1.0 mg, 3 times/d) and ropinirole (0.25 mg, 3 times/d, gradually increased to 2-4 mg, 3 times/d) are both non-ergot derivatives and have no ergot side effects. They are used for early or progressive PD. The incidence of symptom fluctuations and movement disorders is low, and confusion, hallucinations and orthostatic hypotension are common.

(5) Monoamine oxidase B (MAO-B) inhibitors: inhibit the decomposition of DA in neurons and increase the DA content in the brain. The combined use of compound L-dopa has a synergistic effect, reducing the dosage of L-dopa by about 1/4, delaying the switching phenomenon, and having a neuroprotective effect. Commonly used selegiline, also known as deprenyl, 2.5-5 mg, twice a day, preferably in the morning and afternoon. Taking it in the evening may cause insomnia. Side effects include dry mouth, poor appetite and orthostatic hypotension. It should be used with caution in patients with gastric ulcer. Lazabemide (Ro19-6327) is also a MAO-B inhibitor, but there are few reports on its clinical application.

(6) Catechol-O-methyltransferase (COMT) inhibitors: inhibit the peripheral metabolism of L-dopa, maintain a stable plasma concentration of L-dopa, accelerate its passage through the BBB, prevent the degradation of DA in brain glial cells, and increase the DA content in the brain. Combination with Madopar or Sinimetinib can enhance the efficacy of the latter and reduce symptom fluctuations. It is ineffective when used alone. Side effects may include diarrhea, headache, sweating, dry mouth, elevated transaminase levels, abdominal pain, lighter urine color, etc. Liver function must be monitored during medication.

4. Commonly used preparations:

① Tolcapone: also known as tasmar, 100-200 mg orally, 3 times/d. Side effects include diarrhea, confusion, movement disorders and elevated transaminase, etc. Attention should be paid to liver toxicity; it has peripheral and central COMT inhibitory effects. Clinical trials have shown that 69 cases of PD with reduced efficacy of compound dopa were treated with tolcapone 100-150 mg 3 times/d for 6 months, with an effective rate of 98.5%, no obvious toxic side effects, and can be used in combination with compound dopa and MAO-B inhibitors.

② Entacapone: also known as comtan, is a peripheral COMT inhibitor, 100-200 mg orally, 5 times/d is appropriate. Unlike tocopone, there has been no report of severe liver damage so far.

(7) Excitatory amino acid (EAA) receptor antagonists and release inhibitors: EAA can damage substantia nigra cells, and inhibitors have neuroprotective effects and can enhance the effects of L-dopa. However, there are currently no reports of effective clinical treatment.

(8) Iron chelators: The concentration of Fe2 in the substantia nigra of PD patients is significantly increased, and the ferritin content is significantly decreased. Administration of iron chelators can reduce Fe2

concentration, reducing oxidation reactions. Currently, 21-aminosteroids (21-aminosteroide) are commonly used. They can bind to Fe2 through the blood-brain barrier, inhibit lipid peroxidation, and have a protective effect on substantia nigra cells.

(9) Neurotrophic factors

Factors): They play an important role in the development, differentiation and survival of neurons. Neurotrophic factors that selectively act on DA neurons are helpful in the prevention and treatment of PD. Neurotrophic factors include acidic and alkaline fibroblast growth factors (aFGF, bFGF), epithelial growth factor (EGF), ciliary neurotrophic factor (CNTF), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and Neurturin. GDNF and Neurturin have strong specificity for midbrain DA neurons.

(10) Traditional Chinese medicine or acupuncture has a certain auxiliary effect in the treatment of PD and needs to be used in combination with Western medicine. The effect of using them alone is not ideal.

5. Rehabilitation

Providing patients with training and guidance in language, eating, walking and various daily life activities is very important for improving their quality of life. Bedridden patients in the late stage should receive enhanced care to reduce the occurrence of complications. Rehabilitation includes voice and intonation training, facial muscle training, hand, limb and trunk training, respiratory muscle relaxation training, gait and balance training, posture recovery training, etc.

In the above article, we introduced the treatment methods of Parkinson's disease. Although Parkinson's disease is difficult to treat and the recovery time takes a long time, we still have ways to treat Parkinson's disease. The above article introduces several methods of treating Parkinson's disease. I hope it will be useful to everyone.