Parkinson’s Disease Initial Medication Considerations A 69-year-old male, retired bus driver, complains of progressive tremor in the right hand for 3 years, slow gait, and difficulty turning over, fastening buttons, and using cutlery while sleeping. How to use medication? What are the initial medications included for patients with Parkinson’s disease? Parkinson’s disease is a progressive neurodegenerative disorder characterized by tremor, bradykinesia, bradykinesia, and a range of non-motor symptoms including sleep disturbances, decreased sense of smell, bladder and bowel abnormalities, fatigue, dementia, and other neuropsychiatric symptoms. While there is no cure for this disease, viable treatments can control motor symptoms and improve quality of life for patients. A subset of the class of drugs has been approved for use as monotherapy in early Parkinson’s disease, as well as adjunctive therapy in the later stages of the disease: Levodopa is the pioneer of the dopamine class of drugs, and has been used as the primary drug for decades. Dopamine agonists stimulate dopamine secretion by directly binding to dopamine post prominent receptors in the striatum. This class of drugs includes: 1. Non-ergot dopamine agonists (the oral drugs pramipexole and ropinirole, as well as transdermally administered rotigotine); 2. Ergot-derived dopamine agonists (cabergoline, bromocriptine, and pegfilgrastim): the use of this class of drugs requires the detection of cardiac valvular and retroperitoneal fibrosis, which is why the National Institutes of Health and the Guidelines for Excellence in Nursing recommend the use of non ergot dopamine receptor agonists. B-type monoamine oxidase inhibitors (rasagiline and silagiline) selectively inhibit B-type monoamine oxidase, which metabolizes dopamine and increases its availability. How do they work? 1, levodopa Compared with other drugs, levodopa can play a superior role in motor function, activities of daily living and quality of life are improved. In a randomized controlled trial that included 361 untreated patients using levodopa (150mg, 300mg, 600mg per day) or placebo for 40 weeks, the levodopa group’s overall Unified Parkinson’s disease rating scale (UPDRS) score was significantly better than placebo. superior to placebo. A recent large open randomized trial (PD MED) showed that in patients with early Parkinson’s disease, levodopa showed a small benefit in improving quality of life compared to dopamine agonists and monoamine oxidase inhibitors. While this result did not minimize a clinically meaningful difference, this small benefit was seen at seven years of follow-up as well. In addition, dopamine agonist and monoamine oxidase inhibitor therapies were more likely to add other treatments than levodopa therapy. 2, Dopamine agonists The role of this class of drugs in improving motor symptoms has been demonstrated in randomized controlled trials and systematic reviews comparing their efficacy with that of placebo. In a randomized, double-blind, placebo-controlled trial early in the course of the disease, the non-ergot dopamine agonist pramipexole (immediate- and extended-release formulations) significantly reduced the adjusted mean of UPDRS motor and activities of daily living at 33 weeks compared with placebo. In a multicenter extension study of a randomized controlled trial, patients completed a 12-month study cycle of monotherapy with ropinirole, without combined levodopa dosing, with good efficacy and lower mean UPDRS scores compared with the control group. In another randomized controlled trial, response was better with rotigotine compared to placebo. 3, B-type monoamine oxidase inhibitors A systematic analysis of the use of B-type monoamine oxidase inhibitors in early Parkinson’s disease showed a statistically significant smaller improvement in UUPDRS motor scores compared with placebo. However, in other systematic analyses, patients on monoamine oxidase inhibitors often required combination therapy compared with patients on levodopa and dopamine agonists. How effective are they compared with other drugs? Amantadine, anticholinergics, and beta-blockers have been used in the past to treat patients in the early stages of the disease. However, these are not recommended as first-line medications due to the availability of other, more effective treatments. In addition, anticholinergics can cause neuropsychiatric complications. When both oral and transdermal medications are not effective, further Parkinson’s disease treatment options include catecholamine transferase inhibitors, deep brain stimulation, apomorphine, and the application of intrajejunal levodopa gel. These therapies are not recounted here. How safe are these medications? Common side effects of several drugs are as follows: 1. Levodopa Sedation, nausea and vomiting are less common and are dose-related; dyskinesia and fluctuations in motor symptoms (including fading phenomena and unpredictable on/off fluctuations) occur at a 40% incidence after 5 years of treatment, with a higher risk in Parkinson’s patients with younger onset of the disease (90% over 5 years) and a higher risk for those with longer disease progression and higher levodopa doses. higher risk in those with longer disease progression and higher levodopa doses. Compared to placebo, the number needed to harm (NNH) for adverse events at 42 weeks was 1,380 (150 mg), 94 (300 mg), and 8 (600 mg); impulse control disorders (hypersexuality, pathological gambling, excessive shopping, and overeating) may be present, especially at higher doses; other impulse control disorders, including Meaningless repetitive movements and dopamine dysregulation syndrome (overdose of dopamine impulses). 2, Dopamine agonists Compared with placebo or levodopa: nausea (NNH=9), somnolence (NNH=8), edema (NNH=9), dizziness (NNH=15), vomiting (NNH=34), hallucinations (NNH=22), hypotension (NNH=48); impulse control disorders: compared with patients who have not used dopamine agonists for 6 months, NNH=10 3. B-type monoamine oxidase inhibitors Dopaminergic drug side effects, such as nausea and vomiting, are less common side effects compared to dopamine agonists. What are all the precautions to be taken? Common precautions and drug interactions are listed in the table below. In addition, there are reports of melanoma associated with the use of levodopa and rasagiline. A meta-analysis showed a link between Parkinson’s disease and melanoma, with some cases of melanoma occurring before or after the diagnosis of Parkinson’s disease. These results suggest that it is more likely that there is a link between the two diseases themselves rather than an effect caused by the medications. Medication during Pregnancy and Breastfeeding There is limited data on the safety of medication during pregnancy and breastfeeding, due to the fact that patients with Parkinson’s disease are usually well past their childbearing years before the onset of the disease. Therefore, the use of dopamine agonists needs to be weighed against the pros and cons and should only be used if the benefit of the medication is sufficiently great. A series of reports have indicated that levodopa produces persistent patent foramen ovale, entropian foot, and nasal deformities. Breastfeeding should be avoided with levodopa and dopamine agonists; the drugs inhibit lactation and are secreted in breast milk. The use of B-type monoamine oxidase inhibitors should be avoided during pregnancy and breastfeeding due to limited safety-related data. How can I monitor and adjust my medication? A number of factors need to be taken into account, such as age, side effects of the medication, severity of cognitive and motor deficits, and the patient’s preference for the initial therapeutic agent. Patients should be informed of and monitored for these side effects (especially motor complications and impulse control disorders) and the dose should be adjusted as appropriate (see above for side effects). If nausea and vomiting are significant, domperidone is recommended as an antiemetic. 1, levodopa Levodopa is suitable for patients with severe motor system disorders, and compared with other drugs, its effect on the motor system is more obvious. Levodopa is also the first-line treatment for elderly patients (>60 years), especially those with cognitive impairment, as dopamine agonists increase the risk of neuropsychiatric complications. Start the medication with Co-careldopa tablets 25mg/100mg (carbidopa/levodopa) or Co-beneldopa capsules 25mg/100mg three times daily with meals. Slowly increase the dosage every few years to 400-500mg daily in 4-5 doses. Smaller doses of levodopa can be given at shorter intervals to minimize motor system complications. As the disease progresses, a double dose (200 mg levodopa) can be used in the morning for a total daily dose of 600 mg (8 to 9 mg/kg). Levodopa controlled-release tablets are poorly absorbed and do not delay motor system complications. In later stages of the disease, a combination of dopamine agonists, B-type monoamine oxidase inhibitors, or catecholamine transferase inhibitors may be needed for better symptom control. 2.Dopamine agonists This class of drugs can be used as initial therapeutic agents in younger patients and those with milder symptoms to delay the use of levodopa and therefore motor system complications. Long-acting dopamine agonists provide more sustained dopaminergic stimulation and can be used in patients who experience periods of non-responsiveness at night or in the morning. Rotigotine transdermal patches can be used when oral administration is not possible. Increase the dose according to the clinical response, and if the dose is increased in time without symptom control, switch to another dopamine agonist or add a B-type monoamine oxidase inhibitor, and finally consider levodopa. 3.B-type monoamine oxidase inhibitor For young patients and mildly ill patients, this drug (once daily) is the first-line drug. The use of rasagiline requires monitoring of liver function in patients with hepatic impairment. If liver function worsens, discontinue use. The patient at the beginning of the article was clinically diagnosed with primary Parkinson’s disease. Initial use of levodopa (Co-careldopa tablets 25mg/100mg) three times daily for two months resulted in significant improvement in finger sensitivity and other motor symptoms. Medication Points for Physicians 1, First-line therapeutic agents for Parkinson’s disease include levodopa, non-ergot dopamine agonists, and B-type monoamine oxidase inhibitors. 2, Consider starting levodopa therapy in all (except younger) patients, especially those with severe motor symptoms (due to its excellent performance in terms of benefit in motor symptoms) or cognitive impairment (due to its fewer neuropsychiatric side effects than dopamine agonists). 3, need to monitor motor system complications (dyskinesia, fluctuating motor symptoms), impulsive behavior, and adjust the dose accordingly. 4, Do not stop the drug abruptly, which may cause malignant hyperthermia (Parkinsonian hyperthermia syndrome). Some reminders for Parkinson’s disease patients and caregivers 1, do not suddenly stop taking the drug, which can cause life-threatening consequences; 2, in the use of Parkinson’s disease medication if there is severe drowsiness, please inform your doctor; if the symptoms are very serious, please avoid driving and heavy machinery operation; 3, if the drug’s effect began to weaken or effective time is getting shorter and shorter, or the appearance of body movement abnormalities, please inform the If you notice any change in impulsive behavior after taking the drug, such as hypersexuality, gambling, shopping, or overeating, report it to your doctor.