I. Commonly used drugs for the treatment of Parkinson’s disease.
The principle of medication for Parkinson’s disease is to achieve effective improvement of symptoms and quality of life. It is advisable to start with small doses and gradually increase the dosage to achieve satisfactory results with the smallest dose. The medication should follow the general principles while also emphasizing individualization. The best treatment plan should be adopted according to the patient’s condition, age, occupation and economic conditions. Drug treatment should not only control the symptoms, but also try to avoid the occurrence of drug side effects, and try to make the patient’s clinical symptoms can be controlled for a longer period of time from a long-term perspective.
1, anticholinergic drugs: mainly by inhibiting the activity of acetylcholine in the brain, corresponding to improve the dopamine effect. Clinically used is benzhexol hydrochloride, 1-2mg, three times a day. It is mainly indicated for patients with significant tremor and younger age.
The main adverse effects include dry mouth, blurred vision, constipation, difficulty in urination, and affects intelligence, and in severe cases, hallucinations and delusions.
2, amantadine: can promote the synthesis and release of dopamine in the nerve endings and prevent its reabsorption. 50-100mg, 2-3 times a day, the last time should be taken before 4pm.
Adverse reactions include restless legs, blurred vision, reticular cyanosis of the lower extremities, ankle edema, etc., which are relatively uncommon.
Use with caution in patients with renal insufficiency, epilepsy, severe gastric ulcer, liver disease, and forbidden for lactating women.
3.Monoamine oxidase B (MAO-B) inhibitor: By irreversibly inhibiting MAO-B in the brain, it blocks the degradation of dopamine and relatively increases the dopamine content for therapeutic purposes.MAO-B inhibitor can be used as monotherapy for new-onset, young patients with Parkinson’s disease or as an adjunct to compound levodopa for patients with intermediate to advanced disease.
It may have neuroprotective effects, so early use is recommended in principle.
The domestic MAO-B inhibitors include Silegiline (Sigfranc, Midolby, Kingspin), which is used at 2.5-5mg twice daily.
Use with caution in cases of gastric ulcer;
Do not combine with 5-hydroxytryptamine reuptake inhibitors (SSRI), which may cause cardiac side effects.
4, DR agonist: can directly stimulate dopamine receptors and play a role, is the first choice for early Parkinson’s disease patients, can also be used in combination with compound levodopa for the treatment of patients in the middle and late stages. MAO-B inhibitors or DR agonists are preferred in young patients at the beginning of the disease course, and the long half-life of these drugs can reduce or delay the occurrence of motor complications. Agonists should all start with a small dose and gradually increase the amount of non-ergot DR agonists currently in clinical use.
(1) Piribedil extended-release tablets (Tamsulosin): initial dose of 50 mg once daily, increasing to 50 mg twice daily in the second week, effective dose of 150 mg daily, maximum of 250 mg daily.
(2) Pramipexole (Senflor): initial dose of 0.125mg three times daily, increasing by 0.125mg weekly, general effective dose of 0.50-0.75mg three times daily, maximum dose not to exceed 4.5mg daily. the incidence of symptom fluctuation and allodynia is low with agonists, but the incidence of postural hypotension and psychiatric symptoms is high.
Common side effects include gastrointestinal symptoms, drowsiness, hallucinations, etc.
5.Compound levodopa (including levodopa/benserazide and levodopa/carbidopa): levodopa is a precursor of dopamine. Peripherally supplemented levodopa can cross the blood-brain barrier and be converted to dopamine in the brain by decarboxylation of dopa decarboxylase, thus playing a role in replacement therapy. These drugs are the most basic and effective drugs for the treatment of Parkinson’s disease, and are effective in tremor, rigidity, and motor retardation. The initial dose of 62.5-125mg is given 2-3 times a day, and the dose is gradually increased until the treatment is satisfactory and no side effects occur. The dose should be taken one hour before or one and a half hours after a meal. Older patients can use it as early as possible, and monoamine oxidase B inhibitors or dopamine agonists should be preferred, especially in young patients with Parkinson’s disease, and then consider adding compound levodopa when the above drugs cannot control the symptoms well.
The standard tablets of compound levodopa are commonly used in China: methyldopa and benadryl. There is another foreign preparation: diffusible dobutamine (madopar dispersible), which is characterized by easy dissolution in water, easy oral administration, fast absorption and onset of action, and the duration of action is similar to that of standard tablets. It is indicated for patients with morning stiffness, postprandial shutdown, and dysphagia.
Adverse reactions include peripheral symptoms such as nausea, vomiting, hypotension, arrhythmia; central ones include symptom fluctuation, allodynia and psychiatric symptoms. Use with caution in patients with active peptic ulcers, narrow-angle glaucoma, psychiatric patients are prohibited.
6. Catechol-oxo- methyltransferase (COMT) inhibitors: reduce the metabolism of levodopa in the periphery by inhibiting COMT enzyme, thus increasing the amount of levodopa in the brain. The commonly used COMT inhibitor is entacapone (Kodan), 100-200 mg per dose, the same number of doses as levodopa, and the combination of the two can enhance the efficacy and improve the fluctuation of symptoms to reduce the “off period”. Entacapone needs to be taken together with levodopa to be effective and is not effective alone.
Adverse effects include diarrhea, headache, excessive sweating, dry mouth, elevated aminotransferase, abdominal pain, and yellowing of urine. Tor
Tolcapone has the potential to cause hepatic impairment and should be monitored closely, especially during the first 3 months of use.
II. Principles of drug therapy for Parkinson’s disease
1. Protective therapy: In principle, Parkinson’s disease should be treated with protective therapy as soon as it is diagnosed in order to slow down the progression of the disease and improve the patient’s symptoms. It has been reported that treatment with Silegiline + vitamin E can delay the disease progression for about 9 months and postpone the use of levodopa, but further confirmation is needed.
2.Symptomatic treatment
Early Parkinson’s disease treatment (Hoehn-Yahr l-2 level)
(1) When to start medication: When the disease is mild in the early stage and has no obvious effect on daily life or work yet, medication can be suspended, and patients should be encouraged to insist on work and participate in social activities, and psychological guidance and functional exercise can be carried out. If the disease affects the patient’s daily life or ability to work, or if the patient requires early control of symptoms, symptomatic treatment should be started.
(2) Preferred drug principle.
Patients in early old age (<65 years) without mental retardation may choose.
(i) non-ergot dopamine receptor (dr) agonists.
(ii) mao-b inhibitors.
③amantadine, or anticholinergics if tremor is significant and other anti-pd drugs are ineffective.
(iv) Compound levodopa + catechol-oxygen-position-methyltransferase (comt) inhibitors.
⑤ compounded levodopa; generally added when ①, ② and ③ regimens are not effective. However, if the work requires significant improvement of motor symptoms or cognitive impairment, regimens ④ or ⑤ may be preferred, or regimens ①, ② or ③ may be used in small doses in combination with a small dose of levodopa.
Patients ≥65 years of age or with mental retardation: compound levodopa is preferred, and DR agonists, MAO-B or COMT inhibitors can be added if necessary. Benzedrine has a high number of side effects and should not be used if possible, especially in elderly male patients, except when there is severe tremor that significantly affects the patient’s ability to perform activities of daily living and is ineffective with other drugs.
Mid-stage Parkinson’s disease treatment (Hoehn-Yahr class III)
Patients who are treated with DR agonists, MAO-B inhibitors or amantadine/anticholinergic drugs in the early stage should be treated with the addition of levodopa in the middle stage when the original drugs cannot control the symptoms well; patients who are treated with low-dose levodopa in the early stage should be treated with a higher dose or the addition of DR agonists, MAO-B inhibitors, amantadine, or anti-cholinergic drugs in the middle stage when the symptoms are not well controlled. -B inhibitors, amantadine, or COMT inhibitors.
Treatment of advanced Parkinson’s disease (Hoehn-Yahr class IV-V)
Patients with advanced Parkinson’s disease have complex clinical manifestations and more difficult therapeutic management due to the progression of the disease itself and the emergence of motor complications. Therefore, early treatment countermeasures are particularly important. A reasonable treatment plan should be formulated at the beginning of treatment, taking into account the actual situation of the patient, in order to delay the appearance of motor complications as much as possible and extend the time window for effective treatment of patients. The treatment of late stage patients should continue to improve motor symptoms, but also deal with some concomitant motor and non-motor complications.