Xiao Liu is now afraid of his father going out on the street because his Parkinson’s disease seems to be “out of control”. I do not know is the drug failure, or the condition is serious, the original take a dose of drugs can be controlled for several hours after taking three or four times a day, the symptoms are basically under control, but now need more and more large amount of medication, the drug effect of the time is getting shorter and shorter. Sometimes, before the next dose, the symptoms worsened; sometimes, there will be a sudden failure of the drug, just like the lights were suddenly turned off. Sometimes, this “sudden turn off” happens when crossing the street. Neighbors have told Liu, see his father walked to the middle of the road, suddenly can not open step, had to watch the vehicles whizzing by, but completely unable to move half a step, passers-by look intuitively alarmed! Xiao Liu’s father appeared, is common in the late stages of Parkinson’s disease, “end of the dose phenomenon” (the next dose of medication before the aggravation) and “switch phenomenon” (the drug suddenly fails). Some patients, even if they obediently follow the doctor’s instructions to take medication, will still experience these situations after a few years. Is it drug failure or disease progression? Disease progression, “hovering between hell and heaven” For some time, many people believe that the appearance of the switch phenomenon is a toxic side effect of levodopa, but in recent years, studies have found that levodopa in therapeutic doses does not have neurotoxic effects, but rather neuroprotective effects, the emergence of the “magic “The “switch” is mainly due to the progression of the disease and the reduction of nerve cells in the brain. In the early stage of the disease, there are more nerve cells left in the brain, and these cells can secrete dopamine, and when the concentration of levodopa in the blood is relatively high, it can be stored first and then released when needed. If the patient can take the medication on time, the effect can be “seamless”. However, as the disease progresses, the number of nerve cells in the brain decreases, the “access” function of dopamine decreases, and the buffer is lost. The concentration of the drug in the brain fluctuates with the concentration in the blood, and the patient’s symptoms fluctuate with it, and the patient “hovers between heaven and hell” every day. The patient’s symptoms also fluctuate, “hovering between heaven and hell every day. So, do we just watch the switch go out of control and do nothing about it? CDS, a bottom-up reform Although fewer and fewer nerve cells are secreting dopamine, thankfully, the nerve cells at the next level below these nerve cells (this is how the nervous system conducts up and down) are still normal, and the fluctuation phenomenon can be overcome if these nerve cells are continuously stimulated with dopamine. How to make these neurons continuously stimulated with dopamine is what doctors call “CDS” (continuous dopaminergic stimulation). There are various ways of doing this. For example, continuous drug delivery: continuous intravenous drug delivery or continuous enteral drug delivery (through percutaneous gastrostomy, implantation of an intestinal tube with an external micropump containing levodopa to achieve “continuous dopamine stimulation”. Alternatively, long-acting dopamine agonists can be given intravenously or subcutaneously. These drugs are not dopamine, but they “look” like dopamine and also stimulate the dopamine receptors, acting as dopamine. These methods are effective, but are either cumbersome, invasive, or expensive, and are usually practiced in hospitalized patients with severe symptoms. Entacapone: a good drug, but a “lone voice” The “switch phenomenon”, in addition to the reduction of neurons, there is another reason for the emergence of the levodopa drug itself: the presence of a short period of time in the bloodstream. After absorption into the bloodstream, about one to one and a half hours, half of the levodopa is metabolized, and the effect of the drug can not be sustained. From this point on, there is another way to do the CDS described above, and that is to prolong the time that dopamine is in the bloodstream. There is a drug called entacapone that inhibits the activity of the enzyme that causes levodopa to be degraded in the blood, thus greatly extending the time that levodopa is present in the blood, so that it maintains a certain concentration, which leads to the continued production of dopamine in the brain, and thus prolongs the “on” period of levodopa’s short “off” period, and also reduces the “on” period of levodopa. “period, can also reduce the daily dose of levodopa. The use of this drug in foreign countries has been very common, some people will use a diagnosis, but due to the price is still relatively expensive, so the domestic or more in the emergence of “switch out of control”, it is recommended to use. It is worth pointing out that . Although this drug is good, it can not replace the role of levodopa, so it is not effective when used alone, and must be taken at the same time with methyldopa or resting…. In any case, the treatment of Parkinson’s disease is a dynamic process, different stages of the disease have different therapeutic strategies, sometimes, the side effects of the drug and the manifestation of the disease is very similar, the doctor only rely on the description of the family is very difficult to make a correct judgment, it is recommended that the patient should be their own regular review to the hospital, and adjust the medication in a timely manner.