Parkinson's drugs and treatments
Unfortunately, there are still no drugs and/or treatments that cure Parkinson's disease, but there are a variety of drugs and treatments that dramatically alleviate the symptoms of the disease. Therefore, when you discuss the course of treatment with your doctor, you should decide how much the symptoms affect your quality of life and adjust the treatment individually according to personal priority according to what is important to you in your daily life (for example, a singer and a makeup artist will have the same type of needs - because Parkinson's can affect On fine motor skills and the voice, and also different treatments have different consequences - such as deep brain stimulation that may disrupt the quality of the voice and speech). Since no two patients react in the same way to any drug, one must be patient and patient until finding the exact and most correct dosage, timing and combination For you And also the right advanced treatment (pump or surgery) and at the right time for you. Even after finding the right dose, the relief of symptoms can be only partial.
In the early stages of Parkinson's disease there is a tendency to start the treatment on "low fire" and save the "heavy firing of the guns" for the later stages. This is due to the reason of delaying the onset of the complications of levodopa treatment: wearing off and dyskinesias.
The logic behind such a method is to avoid the complications of levodopa treatment (wearing off and dyskinesias). At the same time, (1) other drugs also have side effects, even more and (2) there is no proof at the level of a clinical trial that this method really works. That is why it is important not to wait too long when starting drug treatment that contains levodopa in order to maintain optimal function and a good quality of life.
Another strategy is to start levodopa (which is considered the most potent treatment and according to the cannon metamorphosis, levodopa is considered the cannon). But start with the lowest dose and increase the dose over the years slowly and carefully. The side effects of the other drugs that do not have levodopa are sometimes very problematic, so even with these drugs you have to be very careful with the doses and strive to reach the lowest dose necessary - and also be aggressive enough in the treatment to allow you to function as much as possible.
According to the US National Institutes of Health (NIH)
"The surgical treatment of Parkinson's disease was common in the past. After the discovery of Levodopa, surgical treatment was limited to a few cases. In one of the procedures called Cryothalamotomy, a very cooled metallic probe is inserted into the thalamus (a "relay station" located deep in the brain) in order to destroy the area responsible for creating the tremor. This medical procedure and similar ones are being brought back to use in patients who suffer from severe tremors or patients whose disease affects only one side of their body. Researchers have also answered the question with a surgical procedure called pallidotomy, which treats/damages a part of the brain called the globus pallidus. Studies have shown that pallidotomy improves Symptoms of tremor, stiffness and slowness of movement, probably by the interruption of the nerve course between the Globus Pallidus and the Striatum or the Thalamus."
Since there is still no cure for Parkinson's, drug treatment is done to try and control the symptoms of the disease. There are no perfect drugs to treat Parkinson's, although there are many promising developments in this field. When a person has only mild signs of illness, the attending physician in consultation with the patient may come to a general decision, that the best option is to postpone the drug treatment until a later stage, and in the meantime put the emphasis on a healthy lifestyle, including physical training, stress reduction, relaxation and relaxation exercises , a healthy diet, making sure to have good sleeping habits and continuing to be cooperative in society (work, family, hobbies, volunteering in the community and activity in various communities such as, of course, the branches of the Parkinson's Association.
According to the hypothesis of dopamine-acetylcholine balance, there are two chemical messengers in the brain: Dopamine and Acetylcholine that work in balance to transmit messages between nerve cells and between muscles. These messages allow us to perform a variety of coordinated movements.
In Parkinson's patients, this balance is disturbed due to the loss of some of the dopamine-producing cells. The result is manifested in muscle stiffness, slowness of movement, difficulty in starting movements, a tendency to make smaller movements and in some patients tremors. These signs of Parkinson's do not appear until about 50 percent or more of the dopamine has been lost, and the dopamine level will continue to decline slowly for many years. However, every Parkinson's patient is different, and the rate and nature of the development of Parkinson's disease will be very different in different people.
The main goal of drug treatment in Parkinson's disease is to restore the balance between dopamine and acetylcholine. This can be achieved by increasing the level of dopamine reaching the brain, stimulating the parts of the brain where dopamine works, or by blocking the action of acetylcholine. In most people newly diagnosed with Parkinson's disease, considerable improvement can be achieved by cautiously starting one or more of the antiparkinsonian drugs. At the same time, the "anticholinergic burden" which causes cognitive decline and other problems such as confusion and hallucinations must be taken into account. Of course, anticholinergic drugs have a high anticholinergic load, but this is also a problem with other drugs, including antidepressants.
When old drugs are no longer protected by a patent, they can be "copied" and produced at a lower cost as generic versions. The generic versions are supposed to be subject to the same strict quality requirements as the original drugs. Sometimes a Parkinson's patient is prescribed a generic version of the original drug. This drug may look different from the original drug and have a different name, but in all respects it is the same drug and there is no reason to worry. It is important to check that the active ingredient and the dosage are equal. If there is a change in symptoms (which could be due to less or more effectiveness of TL) it is important to report to the attending physician.
In this article, the type of drug appears as a title. The names of the drugs will appear in the generic oil (usually the name of the active ingredient) and also in the commercial oil, as they are marketed in Israel. At the end of the booklet there is a dictionary that clarifies the technical terms in alphabetical order. All technical terms appear in the text in bold letters.
This page partially presents the medications and treatments currently given to Parkinson's patients. We do our best to update the page to include as many medications and treatments as possible.
Parkinson's drugs
Anticholinergics
Parkinson's patients were mainly treated with these drugs before levodopa was introduced. They may help control tremors but their usefulness is limited due to the side effects. They are especially helpful in reducing motor signs of Parkinson's disease: rigid slowness and tremors that have developed as a result of taking psychiatric drugs of the neuroleptic type. Anticholinergics seem to work by blocking another chemical in the brain - Acetylcholine whose effects increase when the dopamine level drops. Only about half of the patients receiving anticholinergics respond to them, usually for a short period and with only a 30% effect. Although not as effective as Levodopa or Bromocriptine, they may have a medicinal effect. Common side effects include dry mouth, constipation, urinary retention/retention, hallucinations, memory loss, blurred vision, changes in mental activity, and confusion. Therefore, great caution is needed at the older age and at higher doses.
Amantadine is an antiviral drug that helps reduce the symptoms of Parkinson's disease. It is usually used only in the early stages of the disease or in combination with an anticholinergic drug or Levodopa. After several months, the effect of Amantadine wears off in half or a third of the patients who use it. Its effect can return after taking a short break from the drug. Amantadine has several side effects, such as mottled skin, leg swelling, confusion, blurred vision, and depression. A big advantage of Amantadine is that it may reduce the intensity of dyskinesias. The treatment can be administered intravenously. This is done as an inpatient or day hospital over several consecutive days. There are anecdotal reports of improvement but high-level evidence is lacking.
Oral medications
Without a doubt, the drug Levodopa, also called L-dopa, is the crowning glory of modern-day treatment.
L-dopa is a natural amino acid found naturally in plants and animals. Nerve cells can use Levodopa to produce dopamine and replenish its depleting supply in the brain. The most common Levodopa drugs in Israel, Levopar, Dufikar and Sinemat, also contain an additional substance that prevents Levodopa from turning into dopamine, before it reaches the brain and reduces the side effects of dopamine (mainly nausea).
In Israel, Levopar contains levodopa and benserazide and Duficar and Cinnamate contain levodopa and carbidopa. Usually, the drug treatment for Parkinson's patients begins with a low dose, which is gradually increased, until the attending physician and the patient are satisfied with the response achieved.
Dopamine cannot be given directly because it does not cross the blood-brain barrier (the extensive network of blood vessels and cells that filter the blood when it reaches the brain). Patients usually receive Levodopa in combination with Carbidopa, which delays the conversion of Levodopa into dopamine until it reaches the brain, thus preventing or reducing some of the side effects that often accompany Levodopa treatment. Carbidopa also reduces the amount of Levodopa required.
Although levodopa helps at least 75% of Parkinson's cases, not all symptoms respond equally to the drug. Slowness of movement and stiffness respond best, while shaking is only marginally reduced. Balance problems and other symptoms may not be affected at all.
Because a high-protein diet can interfere with levodopa absorption, some doctors recommend that patients taking this drug limit their protein intake to dinner only.
Levodopa is such an effective drug that some people forget that they have Parkinson's, but it does not cure the disease. Although Levadopa can reduce symptoms, it cannot replace lost nerve cells and cannot stop the progression of the disease.
Side effects of the drug- Levodopa
The most common side effects are nausea, vomiting, low blood pressure, involuntary movements and restlessness. In rare cases, patients may suffer from confusion. Nausea and vomiting are greatly reduced by taking Carbidopa in combination with Levodopa, which also increases the effectiveness of a lower dose. There is also a Slow Release Formula for this drug, which gives a longer-term effect to patients who take it.
involuntary movements (Dyskinesias) Such as convulsions, shaking of the head and sharp and sudden movements usually appear in patients who have taken large doses of Levodopa over time. These movements can be light or sharp as well as very fast or very slow. The only effective way to control these movements, caused by the drug, is to reduce the dose of Levodopa or use drugs that block dopamine. These drugs usually cause a reappearance of symptoms of the disease.
When using Levodopa for a long time, other disturbing problems can appear. Patients can notice the onset of more pronounced symptoms even before the first dose of medication has been taken in the morning and they can sense when the effect of the medication begins to wear off (muscle spasms are common in these cases). The symptoms gradually begin to return. The duration of the effect of each drug dose is shortened - the wear-off effect. Another potential problem is sudden, unexpected changes in movements from normal to parkinsonian movements and back, which can occur several times a day. These effects probably indicate that the patient's response to the drug is changing or that the disease is progressing.
These two drugs mimic the role of dopamine in the brain and cause neurons to respond as they would to dopamine. They can be taken separately or together with Levodopa already in the early stages of the disease in order to prolong the response to Levodopa in patients who experience wear-out effects or sudden changes in the type of movements (as described above in the Levodopa side effects section). These drugs are generally less effective than levodopa in controlling stiffness and slowness of movement. Their side effects may include paranoia, hallucinations, confusion, involuntary movements, nightmares, nausea and vomiting.
Selegiline also known asdeprenyl, has become the most common drug for the treatment of Parkinson's. Studies supported by the US National Research Institutes have shown that this drug delays the need to use Levodopa for a year or more. When the Selegiline preparation is given together with Levodopa, it seems to increase and prolong the response time to Levodopa, and thus can reduce the erosion fluctuations (which were described in the Levodopa side effects section). Animal studies have shown that selegiline protects the dopamine-producing neurons from the toxic effect of MPTP. Selegiline inhibits or prevents the action of the MAO-B enzyme, which changes dopamine in the brain's metabolic process, and inhibits the breakdown of dopamine. The natural and the dopamine created from the Levodopa. Dopamine is thus stored in the surviving neurons in the brain. Some, but not all, doctors prefer to start selegiline in all Parkinson's patients because of the drug's possible protective effect. Selegiline is an easy drug to take, although its side effects may include nausea, orthostatic hypotension, or insomnia (when taken late at night). Toxic reactions also occurred in patients who took Selegiline with Fluoxetine (an antidepressant) and with Meperidine (a sedative and pain reliever).
Researchers are still trying to find answers to questions about the use of selegiline, such as how long the drug remains effective and whether there are negative effects with long-term use. Evaluating the long-term effects will help determine the value of the drug for all stages of the disease.
Except for Sinemat CR, all the drugs now containing levodopa are basically immediate release of levodopa. In order to reduce the symptoms of wearing off and dyskinesias, many new drugs that act on the dopaminergic system in a different way or that allow slow release or continuous administration have come to the market and are under development.
In all preparations of this type, the letters CR (Controlled Release) appear after the name of the medicine. The CR preparations release the drug over 4 to 6 hours and the result may be less fluctuations in levodopa levels in the blood. When switching from using standard preparations to CR preparations, it is customary to increase the amount of levodopa required by 30 percent. With the transition from standard preparations to CR preparations, the total amount of daily levodopa received by the patient changes. The switch to CR type drugs extends by 30%-50% the time interval between taking doses of the drug.
CR type preparations can be used when a Parkinson's patient taking standard levodopa suffers from problems such as wearing off, or involuntary movements (dyskinesia). These medications can be taken before bed to reduce stiffness and the inability to move in bed during the night.
Sinemet CR must not be crushed or chewed. The pill must be swallowed in its original form, to fully benefit from the slow release action of the drug. Together, this is because in Israel there is no 100 mg dose of Sinemat. Your doctor may recommend that you cut the pill in half and take half a pill each time.
Madopar, the drug equivalent in Europe to Levopar, has a form that creates a suspension in water (Madopar) dispersible). The tablet can be swallowed whole or dissolved in water or orange juice. The absorption of the suspension is faster, and the drug can be used in cases where rapid absorption is preferred, such as, for example, in the morning, or during difficult and painful OFF times. The suspension is also convenient to use, when the patient has difficulty swallowing tablets or capsules. It is important to note that this is not a substance that dissolves in water, but only creates a suspension that requires good mixing before drinking. Despite its importance in quickly alleviating the symptoms of the disease, the drug cannot be obtained in Israel.
There is no equivalent preparation of Dupicer in suspension on the market, but you can crush normal tablets of Dupicer or open the capsules of the Halbofer and mix the powder with liquids or with a spoonful of yogurt. This may make it easier to swallow them and may also speed up their rate of absorption. Of course, activity as a doe only after the approval of the attending physician.
Cinemat is also marketed as LS. The letters LS mean Low Strength, meaning a low concentration of levodopa.
In the Cinnamate preparation, the substance carbidopa is the ingredient that prevents levodopa from breaking down, before it reaches the brain. The substance carbidopa is the inhibitor of the carboxylase enzyme responsible for breaking down levodopa.
The required dose of carbidopa is usually 70-100 mg per day. People who take a lower dose than this are more likely to suffer from nausea and vomiting.
The Sinemat LS preparation contains more carbidopa in relation to levodopa, a ratio of 4:1, compared to the usual preparations such as Duficare, where the ratio of the amounts of carbidopa to levodopa is 10:1. These amounts are similar to the ratio between levodopa and benzarazide in the Levopress preparations.
This preparation can be used in the early stages of Parkinson's disease, when a small amount of levodopa is needed, and it is still necessary to give an appropriate dose of carbidopa, or in the late stages of the disease when the involuntary movements appear and a larger number of small doses of the drug are needed. The drug is not marketed in Israel, but as mentioned before, your doctor may recommend taking half a regular Cinemat CR pill (Levodopa dose 200 mg). Another option for a low dose of Levodopa is to take a pill of Duficar (each pill 250 mg Levodopa) ) or Stalvo 50 (dose levodopa 50 mg each pill).
It is possible to give Budopa continuously in order to achieve a better balance over the day with less dyskinesias and less OFF states. Now it is possible through an intestinal pump (through PEG), see drugs in infusion through the digestive system. In addition to this, two pharmaceutical companies are developing a subcutaneous pump system for levodopa or levodopa.
Advantages
Most people are able to carry Dupiker, Sinemat, Lebopper or Stalvo, and most feel significant improvement for many years, especially when it comes to stiffness and slowness of movement. Other symptoms that may improve: tremors, pain, quality of sleep, facial expressions, quality and strength of speech and sometimes also mood.
Disadvantages
In the first days of taking the above-mentioned medications, certain feelings of nausea and vomiting are common. However, they are usually mild and pass as the body adapts to the medication. There is a small percentage of people who are unable to tolerate these medications at all, and this is because of severe nausea and vomiting or other side effects , such as confusion, false visions (hallucinations), mood swings or psychological changes. There are also people who develop dyskinesias (excessive movements / involuntary movements) with low doses of levodopa. It is important to separate and distinguish between dyskinesias (can appear in any part of the body: face , head, limbs, torso) and between the OFF state (then the symptoms of Parkinson's get worse - stiffness, tremors, tremors and sometimes also limb deformities called dystonia). If there is any doubt, you can take a picture and show it to the attending physician.
Over time, the response to these drugs may become less reliable and less stable, and those who take them may experience increasing periods of time in which the effect of the last dose taken wears off, before it is time to take the next one, or before the next one takes effect. After her, she begins to act. In addition to this, you can also notice that the time to ON (time to on) is getting longer, that is, the time until the ball starts to have an effect is getting longer.
Over time, the involuntary movements (dyskinesias) may be more and more annoying (the movements are annoying in many aspects: social, this can be embarrassing and even make people shut up at home and avoid social events, functional: the ability to perform simple daily tasks may be impaired as a result of controlled balletic movements, instability in walking: Rapid movements of the limbs, especially the legs, can interfere with walking and be a component of instability in walking, and pain: because of the many movements, there is accompanying pain in the limbs and often in the back. When there are many hours in the day with dyskinesia, there is also a risk of weight loss in light of the increased energy consumption as a result of excessive movements. Regarding an unstable response to the treatment, there are situations of unexpected OFF situations during the period that is supposed to be good (that is, after the pill has started to take effect but still far from the next one) and there are also situations of a complete lack of response to a pill (which is called dose failure).
These long-term effects can sometimes be improved by changing the type or amount of duficar, cinnamate, or levobuffer, or the frequency (number of doses) with which the drug is taken. If after all this there is no improvement to a sufficient degree, other types of medication can be tried.
Among the patients with Parkinson's disease there are those for whom the protein in the food may interfere with the absorption of levodopa in the intestines, and this is because both levodopa and the proteins are produced from amino acids.
As a result, a smaller amount of the drug may reach the brain, and thus the drug may be less effective if taken together with or immediately after a protein-rich meal. In cases where a problem arises with proteins and levodopa, there are doctors and dietitians (nutritionists) who sometimes recommend eating low-protein meals during the day and postponing the protein-rich meal until the evening. It is important to maintain a time span between taking medicine with levodopa until a meal of half an hour to an hour and after eating wait as long as possible until taking a dose of medicine with levodopa.
Recently there is evidence that even meals rich in fats can slow down the rate of drug clearance from the stomach and thus contribute to "OFF" states.
One way or another, it is important that any change in the diet be made in consultation with the attending physician and under the supervision of a dietician.
to Bopar/Medopar - Contains levodopa with the addition of benserazid, equivalent to Levophor in Israel. Sometimes in pharmacies in Israel, the prescription of Lebuper will be applied, to Medupar or vice versa.
Levofar/Medofar 125: Levodopa 100 mg | Benserazid 25 mg
Levofar/Medofar 250: Levodopa 200 mg | Benserazid 50 mg
Cinemat - Contains levodopa plus carbidopa.
Cinemat CR 200: levodopa 200 mg | carbidopa 50 mg
Duficar - Contains levodopa plus carbidopa.
Dupicar 250: Levodopa 250 mg | Carbidopa 25 mg
Stalbo - Contains levodopa plus carbidopa.
Stalvo 50: Levodopa 50 mg | Carbidopa 12.5 mg | Antecofone 200 mg
Stalvo 75: Levodopa 75 mg | Carbidopa 18.75 mg | Antecofone 200 mg
Stalvo 100: Levodopa 100 mg | Carbidopa 25 mg | Antecofone 200 mg
Stalvo 125: Levodopa 125 mg | Carbidopa 31.25 mg | Antecofone 200 mg
Stalvo 150: Levodopa 150 mg | Carbidopa 37.5 mg | Antecofone 200 mg
Stalvo 175: Levodopa 175 mg | Carbidopa 43.75 mg | Antecofone 200 mg
Stalvo 200: Levodopa 200 mg | Carbidopa 50 mg | Antecofone 200 mg
Dopamine agonists
The above-mentioned drugs are called dopamine agonists, because they directly stimulate those parts of the brain where dopamine works and bind to dopamine receptors in the same way that dopamine itself binds. In varying degrees, their activity is more prolonged than that of levodopa, and for some patients they may be more suitable than Dupicer, Sinemat or Levoper. The choice between treatment with levodopa or other drugs is individual. A common rule of thumb is to start agonists when the disease is still at the beginning and there are no cognitive problems or fear of other side effects. Agonists can cause
According to a recently developed approach, the treatment of the disease can be started with the administration of a dopamine agonist only, before levodopa, because of the advantages of dopamine agonists that will be detailed below.
It was found that dopamine agonists cause fewer long-term side effects, such as involuntary movements (dyskinesia). In light of these findings relating to all dopamine agonists, an approach is being developed to administer dopamine agonists before levodopa, mainly in the young patient population.
If in the early stages of Parkinson's disease one can be satisfied with only a dopamine agonist, the long-term problems associated with the use of levodopa can sometimes be postponed for several years.
יadvantages
The advantages are that it sometimes has a good effect on the mood. Another advantage is that it is possible to maintain lower doses of levodopa over the years and thus also (hopefully) postpone and reduce the complications of levodopa treatment mentioned above (wearing off) and dyskinesias.
In recent years, it has been possible to prescribe pramipexone or ropinorole in the form of extended release (ER) and thus take it only once a day and there is no need to worry about taking it on an empty stomach or worrying about waiting half an hour before eating proteins.
Disadvantages
Dopamine agonists are considered to be less effective than the standard preparations of levodopa (Dupicare, Sinemat or Levopress), especially in the advanced stages of the disease. In addition to this, there are also more side effects, especially in the elderly or at high doses, such as forgetfulness, confusion and difficulty concentrating, hallucinations, drowsiness. More side effects: (1) nausea and vomiting, (2) ) Dizziness after getting up from sitting or lying down and even passing out, (3) excessive sleepiness, (4) sleep attacks, (5) edema in the legs, (6) impulse control disorders.
Some patients with Parkinson's disease are unable to continue taking dopamine agonists because of side effects, which include nausea, vomiting, and dizziness, which are often associated with low blood pressure (more precisely, blood pressure that drops after getting up from sitting or lying down).
Starting to give dopamine agonists to a Parkinson's patient requires caution, while gradually and slowly increasing the dose until the desired response is achieved. Low doses may cause no or even worse effect. Excessive sleepiness and sleep attacks (which may impair the ability to drive safely) but they usually disappear once you get used to the drug. Affective disorders are a sensitive issue and sometimes because of the sensitivity the problem is hidden and it is not talked about until the situation is serious. For people who have a tendency to this (perhaps genetic or perhaps personality from before the disease) or after reaching high doses of agonists, impulse control disorders may appear, which can be reflected in extravagance, over-engagement in hobbies, over-use of computers, tendency to disassemble and assemble things, increased desire for foods Sweets, increased desire to shop or increased sexual drive.
It is important to be closely monitored in order to adjust the dosages, timings and combinations of drugs because over the years the nature of the disease changes and the side effect of drug treatment can appear after years.
It is also important to be aware of the phenomenon of dopamine agonist withdrawal syndrome - the syndrome of withdrawing from dopamine agonists. Studies that examined why people after deep brain surgery went into apathy and depression despite a marked improvement in motor symptoms and found that there is a correlation in changes in medication. In fact, patients with high doses of dopamine agonists before surgery who after surgery lowered their dose a lot and quickly were at increased risk of these symptoms. Note that although less common, this can also happen with a rapid decrease in medication with levodopa. It is common to treat apathy and impulsivity as a spectrum. So it is easy to understand how too rapid changes in dopamine agonist medication can cause impulsivity (with an increase) and apathy (with a decrease).
Medicines by injection or continuous subcutaneous infusion
First of all, despite the name, this drug has nothing to do with mirapium or other narcotics. Apomorphine is an injectable dopamine agonist, because it breaks down in the gastrointestinal tract when administered orally. It is actually a very potent and effective treatment, on the same level even as levodopa. A big advantage comes from the fact that because of the subcutaneous administration, the drug reaches the blood circulation in a very short time, sometimes even minutes. And this is in contrast to oral treatment, which has to undergo absorption in the digestive system. When you add to this problems with the motility of the digestive system among Parkinson's patients, then the time until the oral pills take effect is even longer. There are Parkinson's patients with motor fluctuations who enter severe OFF states and severe dyskinesias, despite all efforts to adjust the medications they take, it is not possible to achieve balance. As the dose increases, there are more dyskinesias and difficulty. As the dose decreases, there are more OFF states. In these cases, apomorphine injections can be used as a "rescue therapy" and quickly get rid of the difficult situation.
Since apomorphine is given by injection, it is imperative that Parkinson's patients, or their caregivers, be able to handle this task, which usually requires practice and instruction. For the purpose of practice and training, deciding on the correct dosage and checking for the presence or absence of side effects (mainly a drop in blood pressure while standing) it is customary to titrate in a hospital outpatient clinic. There are several options for injecting: (1) normal self-injection by the patient or by the patient's partner or (2) with special automatic injectors. When dealing with severe fluctuations, a large number of injections are necessary. For these patients, continuous treatment using a small pump device is A good solution. The portable pump, powered by batteries, with an automatic piston continuously injects the drug through a tube to a needle that is inserted daily in a different place in the body under the skin. The pump is on the belt and is invisible to those around. It should be noted that since it is a dopamine agonist, so are all the mentioned side effects Above under "dopamine agonists" also apply in the case of subcutaneous apomorphine.
Advantages
Apomorphine works very quickly and reliably, so that patients who must be active at specific times, can continue to engage in their usual activities. It can bring great relief to people who experience sharp fluctuations in their mobility and long and difficult OFF periods. Another advantage is that you can adjust the rate individually and even give additions in additional short doses in case of a sudden OFF situation.
Disadvantages
Apomorphine can only help those Parkinson's patients who respond to levodopa (ie Dupicer, Cinmet, Levopress or Stalvo). Apomorphine causes nausea mainly at the beginning of the treatment, and therefore the drug motilium (domperidone) should also be taken during the first treatment period, which works directly against nausea and vomiting.
In rare cases, apomorphine can cause worsening of the involuntary movements (dyskinesias).
Skin lesions / nodules can develop in the injection areas, and when this happens you must contact the attending physician or a nurse specializing in Parkinson's disease.
Trade name: PK-Merz, Paritrel
Dosage: 100 mg each pill, up to 3 times a day.
amantadine An antiviral drug that helps reduce the symptoms of Parkinson's disease. This drug works differently than the drugs discussed so far. Its main beneficial effect is to increase the release of dopamine and allow it to stay longer at its site of action. Amantadine can be given as a single treatment (monotherapy), but can also be taken with other antiparkinsonian drugs.
It is usually used only in the early stages of the disease or in combination with an anticholinergic drug or Levodopa. After several months, the effect of Amantadine wears off in half or a third of the patients who use it. Its effect can return after taking a short break from the drug. Amantadine has several side effects, such as mottled skin, edema, confusion, blurred vision, and depression.
Advantages
It may help reduce involuntary movements (dyskinesias). Amantadine is marketed in capsules and syrup. And yes, it is an anti-parkinsonian preparation that exists in liquid form and can be instilled intravenously. In light of this, in cases where it is not possible to administer drugs to the digestive system (for example, after intestinal surgery), it is common to administer amantadine intravenously.
Disadvantages
It has a weak effect, it only helps some Parkinson's patients and its effect may be short-term. Often causes edema in the legs and venous drawing in the skin (livedo reticularis), and can also contribute to confusion or memory disorders.
Generic name: Trihexyphenidyl
Trade name: Artane, Partane
Generic name: Benztropine
Trade name: Cogentin
Generic name: Biperiden
Trade name: Dekinet
Generic name: Procyclidine
Trade name: Kemadrin
Orphendrine
Orphenadrine
Disciple
Disciple
Anticholinergics Parkinson's patients were mainly treated with these drugs before levodopa was introduced. Their usefulness is limited, but they may help control tremors and stiffness. They are especially helpful in reducing Parkinson's that developed as a result of taking medication. Anticholinergics seem to work by blocking another chemical in the brain - Acetylcholine whose effects increase when the dopamine level drops. Only about half of the patients receiving anticholinergics respond to them, usually for a short period and with only a 30% effect. Although not as effective as Levodopa or Bromochriptine, they may have a medicinal effect. Common side effects include dry mouth, constipation, urinary retention/retention, hallucinations, memory loss, blurred vision, changes in mental activity, and confusion.
As mentioned, these are old drugs, which are given less frequently today, and which can have a mild effect on the symptoms of Parkinson's by blocking the action of the neurotransmitter acetylcholine.
The anticholinergic drugs are usually given in the early stages of the disease alone or in combination with levodopa or amantadine.
Advantages
They can help young people in the early stages of Parkinson's disease, when the symptoms are still weak and when tremors are the main concern. It was found that these drugs have a special effect on tremors. The anticholinergic drugs can also be used to reduce saliva production, when there is a serious problem of excessive salivation.
Disadvantages
The common side effects are: confusion, memory loss, dry mouth, constipation, blurred vision and difficulty urinating may occur. All side effects occur precisely because of the anticholinergic mechanism of action. These preparations are not usually given to elderly Parkinson's patients, as they have a high risk of confusion and memory impairment, as well as in men, for fear of worsening the difficulty in urinating due to prostate problems. In fact, these considerations greatly limit the use of these drugs. Furthermore, in any situation of cognitive complaints / hallucinations or delusions it is important to treat all medications and try to stop or replace medications with "anticholinergic load".
Generic name: Selegiline
Commercial name: Jumex
Selegin slows down the breakdown of dopamine in the brain by inhibiting the MAO-B enzyme that breaks down dopamine. It is used to prolong the effect of a dose of levodopa (Dupicare, Levopress), or to reduce the amount of Dupicer or Levopress needed. It may also reduce the fluctuations in the degree of effectiveness of drugs, which some patients with Parkinson's disease feel, after the first years.
Many doctors start the treatment of a newly diagnosed Parkinson's patient with the drug selegiline as a single treatment without the addition of another drug. Selegiline may slightly improve symptoms and delay the need for levodopa. As of today, there is no evidence that selegiline significantly changes the course of the disease.
Advantages
By itself, selegiline has very few side effects.
Disadvantages
The great majority have no side effects at all. At the same time, the effect of the treatment on the symptoms is relatively weak. One of the side effects that you should be aware of is a drop in blood pressure when standing up from sitting or lying down, called orthostatic hypotension.
Generic name: Rasagaline
Trade name: Azilect
Similar to selegeline, this preparation is also a monoamine oxidase enzyme inhibitor, selective (type B) and irreversible. The method of treatment with the preparation is convenient, with the administration of the medicine once a day, without the need to monitor the doses.
Azilact can be used as a single drug treatment in the early stages of Parkinson's disease. The reason why side effects are relatively rare and according to the clinical trial was evidence that this drug can slow down the progression of the disease, although the effect is weak. There is no other drug treatment that has been proven to affect the progression of the disease.
As in the case of selegeline, rasageleine may also cause orthostatism.
Medicines by infusion through the digestive system
In order to reduce the non-physiological increases and decreases of levodopa levels in the blood (and consequently in the brain) and to reach a more superficial and more physiological curve, continuous dopaminergic stimulation is necessary. Basically, the thought of treating with agonists was in this direction, but due to lesser effectiveness, it is always necessary to combine treatment with levodopa later in the course of the disease (and also to prevent disorders of impulse regulation or to allow a lowering of the dose of agonists when problems with impulse regulation appear). So in the end it is a very common problem: almost 50% of patients of levodopa patients begin to suffer from wearing off or dyskinesias within 5 to XNUMX years of treatment. There are methods of oral or subcutaneous drug treatment (by injection or instillation) to reduce these effects. But in all of these methods (even deep brain stimulation surgery) there is still a need for further medical treatment with oral levodopa preparations, so in most cases it is only possible to reduce the severity of wearing off and dyskinesias.
The innovation of intestinal levodopa gel is that levodopa can be administered continuously. The main disadvantages are that (1) you have to undergo an invasive procedure: performing a PEG (gastrostomy) and usually also an initial titration before infusing the treatment through a probe and (2) you also have to "carry" the gel in a cassette during the day.
new drugs
The Xadego label is for Parkinson's patients with motor fluctuations in an intermediate to advanced stage as an adjunct to stable drug-only treatment.
Xedago is a MAOB-I that acts as an inhibitor of MAOB activity and thus prevents the breakdown of dopamine. The activity of Xadago is reversible, and very specific. Xedago has another mechanism of action that regulates levels of glutamate. This mechanism of action is unique to Xadego and does not exist in other MAOB-I.
Glutamate plays a role in both motor and non-motor symptoms in Parkinson's.
In the clinical studies it was seen that the use of Casdago significantly improved motor symptoms and increased the "good ON time" which was defined as ON time without dyskinesias or without disturbing dyskinesias by about an hour and a half a day.
Studies have looked at the effect of Xadego on non-motor symptoms. It was found that Xadego also had an effect on pain, and the study showed a 26.2% decrease in the number of painkillers taken by the patients while using Xadego compared to patients who took a placebo. Also in the tests that examined the change in the quality of life of the patients, a significant improvement was found in the patients who received Casdago compared to placebo.
The side effect profile in the studies was good and without a big difference between the placebo group and the group receiving Casdago. The side effects that were higher than the placebo group were dyskinesias and falls.
Xedago is given PO to Parkinson's patients in combination with a stable dose of levodopa, once a day and is available in two doses - 50 mg and 100 mg.
You should start with a dose of 50 mg per day, if necessary, the dose can be increased to 100 mg per day, and this is based on clinical judgment. Studies have shown a clinical advantage at the 100 mg dose in some symptoms.
- Xadago (Safinamide) SmPC, Zambon SpA
- Fox SH, Drugs 2013
- Caccia C. et al., Neurology 2006, 67
- Borgohain R. et al., Mov Disord 2014, Vol. 29, N. 2
- Borgohain R. et al., Mov Disord 2014, Vol. 29, N. 10
- Schapira AH, et al., JAMA Neurol 2017, Vol. Feb 1;74(2):216-224
There is no perfect cure for Parkinson's disease. This is the reason why research must continue to look for new drugs for the disease. After all the laboratory tests on new substances have been completed, the doctors are involved in a clinical trial of the new drugs on Parkinson's patients.
Those among the patients who are considered suitable for a trial with a particular drug must always receive information (oral and written), and it is necessary for them to have enough time to talk with the attending physician and their family members about the reasons and considerations for and against, before they decide to take part or not to take part in the trial. A patient may enter a clinical study with a new drug only after signing a consent form. It is also important to understand that at any given moment, even after signing and even receiving the research treatment, there is a right to withdraw from the study and withdraw consent.
None of those involved in research must put any kind of pressure on patients to take part in, or continue to participate in, drug trials.
There are clinical trials in the world and in Israel with a wide variety of indications for Parkinson's patients for all stages of the disease, for personal treatment according to the genetic status, with the administration of drugs through pumps or through injection into the spinal fluid, stem cells and more.
Although there is no clinical trial that can prove and characterize which patients with Parkinson's can benefit from treatment with medical cannabis and which problems there are more and more reports from the field (among patients, among doctors with experience, clinical articles and also academic articles including animal models) which support the potential of medical cannabis. Decreased mood, pain, and difficulty sleeping are all symptoms that greatly affect the quality of life of people who are dealing with Parkinson's disease. Unfortunately, most of the pharmaceutical solutions are problematic and even dangerous among the community of people dealing with Parkinson's. See the "Drugs to Avoid" section to understand where there might be a place for medical cannabis treatment.
Cannabis is currently defined as a dangerous name but you can get a recommendation for this treatment from your doctor and there are doctors who have undergone training who can approve requests for medical cannabis and even write the prescription (along with granting a license) directly to the patients.
Since cannabis prescription is not defined as a drug, we have put it here in a separate section. It is not in the medicine basket and a medical cannabis license is required (from the medical cannabis unit, Ministry of Health). On the other hand there are many aspects that are similar to standard drug treatment for Parkinson's. (1) This is a symptomatic treatment, we mean a treatment that relieves symptoms but cures and does not slow down the progression of the disease, (2) accurate and continuous balancing and titration is necessary in order to arrive at a therapeutic treatment plan, (3) there are several ways of administering oil through the mouth including cooking , you will flower by smoking or you will flower by vaping.
Medications to avoid
It is very common for people to have additional medical problems on top of Parkinson's disease. Although usually the drugs given for other problems do not pose a problem, it is important that the attending physician considers the interaction of the different types of drugs with the drugs given for Parkinson's disease. For example: Laxatives or antihypertensives can usually be taken without a problem.
However, there are drugs that can cause the appearance of parkinson-like symptoms (parkinsonism secondary to drug treatment). Generally, Parkinson's patients should avoid them, unless they are specifically recommended by a Parkinson's specialist. At the top of the list is neuroleptic treatment (also known as antipsychotic). As soon as there is concern about parkinsonian signs secondary to this type of drug treatment, the doctor who prescribed the treatment should be consulted in order to consider reducing the screening and/or switching to one treatment. Of all the drug treatments of the type of neuroleptics, the drugs that cause less parkinsonian symptoms are quetiapine (Seroquel) or clozapine (Leponex). Another option (when it comes to parkinsonism secondary to drug treatment without a diagnosis of Parkinson's disease) is to add anticholinergic treatment.
Because of the risk of aggravation of the motor symptoms and other side effects (drowsiness, fogginess of thought) they try as much as possible not to prescribe such drugs to Parkinson's patients. Sometimes there is even an aggravation of the mental symptoms (restlessness, tantrums, hallucinations and delusions) - a phenomenon called a paradoxical reaction. Such a problem is more common when it comes to a disease similar to Parkinson's called dementia of the Lewy body type.
There are other drugs on the list of drugs to be careful of because of the risk of worsening parkinsonian signs: Tetrabenazine (Xenazine), Metoclopramide (Pramin), Cinnarizine (Stunarone), Sulpiride (Modal), and Valproic acid (Valproic acid) Depalept). Other medications that can cause thalassemia especially when it comes to more severe Parkinson's or older age include: pregabalin Pregabalin (Lyrica), sleeping pills - except melatonin Melatonin (Circadin), tranquilizers, pain relievers with opiates (including codeine, Percocet), anti-nausea drugs - with the exception of Domperidone (Motilium). Parkinson's patients who take Rasagaline (Azilect) are often told to avoid other drugs that affect the serotonergic system, for example SSRI antidepressants. This is a syndrome Very rare but dangerous. Although Resagelin is defined as a preparation of the type of monoamine oxidase enzyme inhibitors (MAOIs), there are actually two types, MAOI-A and MAOI-B. The problem is more common with MAOI-A and Resagelin is an MAOI - B. The risk is essentially only theoretical and there are no reports of this syndrome. Of course, you should consult with the attending physician.
If you are taking an MAOI-A type antidepressant (although not widely used), you should stop this treatment two weeks before starting drug treatment containing levodopa because of the risk of a dangerous phenomenon of very high blood pressure. Of course you should consult your doctor.
If there is difficulty urinating secondary to an enlarged prostate, one should be careful of drops in blood pressure when lying down or sitting, especially if you are receiving or have been advised to take an alpha blocker treatment - such as Tamsulosin (Omnic). If you have urinary incontinence and have received anticholinergic drug treatment such as Vezikar, Tobiaz, Detrositol, Spazmax and Novitropen, you should also consult about this because it may cause confusion, forgetfulness and even hallucinations, another option is Mirabegron (Betmiga) which also helps the bladder Irritable but works in a different mechanism, so it might be better for Parkinson's patients.
Advanced treatments
tips
Ask the doctor treating you to come back and explain to you once more, what you did not understand from his words. Write down the most important messages and/or make sure it is written in a summary letter. Make sure you have someone else in the meeting who can help ask the important questions and also help you remember what was said.
Report to your doctor all the effects of the treatment, good and bad. You should write the things down in advance, so that they are not forgotten during the visit. Many times there are recommendations in the drug treatment from the previous visit - it is important to report first of all what was done and the suspensions for better or for worse. You need to update on all medical changes since the previous visit - related to the disease and not related. Sometimes there will be things that you think are unrelated and actually there is a connection. Even in my direction there may be things that are difficult to know whether it is related to Parkinson's or not and that you need to make an inquiry in different directions in addition (for example fatigue - you need to rule out anemia, weight loss - you need to do a gastro examination, urination disorder - you need a PSA and urological test, slowness of walking - you need an orthopedic examination and more').
Ask your doctor for advice if you are concerned about any aspect of your life that may be affected by Parkinson's disease or the Parkinson's disease medications you are taking.
Keep a diary or graph, when you start using a new drug, or when there is a change in the dose of the drugs you receive. If you are tired or dizzy, especially after getting up from lying down or sitting, measure and record your blood pressure while lying down as well as standing up and come with the list/table. If you have a symptom tracker or another digital tool (perhaps a Fitbit or a pedometer from your smart watch or smartphone) then bring Also statistics from there... you might even have a trend of improvement if you manage to stick with your exercise program and/or the change in treatment was helpful.
State the amount and timing of taking the medication, the duration of the ON/OFF periods, or the involuntary movements - when you take the medication, how long after taking each pill you feel relief, and anything unusual that you experience. These records can be very helpful to your doctor when he is planning your new medication regimen.
If you forget to take a certain dose on time, take it immediately as soon as you remember, but under no circumstances take a double dose. If you felt aggravation that day after you forgot a dose (and even if not) note it because it can indicate the existence of wearing off / motor fluctuations.
Be sure to keep your medicines out of the reach of children, and store them at normal room temperature (between 15 and 25 degrees Celsius), unless otherwise written on the medicine. For example: apomorphine marketed in glass ampoules must be kept in the refrigerator, but on the other hand, apomorphine in automatic syringes must be kept at room temperature and not in the refrigerator.
Remember, unexpected dizziness can be a sign of low blood pressure. If you feel dizzy or light-headed, especially if it happens after getting up from lying down or sitting, it is advisable to have your blood pressure checked, both sitting and standing. Bring the list of measurements if you document the date, time and position (lying / sitting / standing).
Remember, your pharmacists can also give you advice, as well as help you prepare the medicines when necessary. There are solutions to help you remember to take the right medicines at the right times, from "lo-tech" such as a medicine box with markings and compartments for the days of the week to "hi-tech" such as smartphone apps (like medical safe).
Do not assume that the treatment you receive, the dosage or the timing of taking your medication, must be the same as those received by other Parkinson's patients.
Do not assume that you will experience serious (or even not serious) side effects - you won't! It is true that sometimes it is quite scary to read the list of side effects in the drug list, but of course everything that appears does not always happen to everyone, these are things that were reported mainly during the clinical trial and there was a reasonable circumstantial connection to the drug treatment. The advantage of knowing what can happen is that side effects can be identified more quickly. But if there is anything that worries you, report it to your doctor. Note that if side effects are suspected, you will inform your attending physician. It's a shame to suffer side effects when there is no benefit, if there is a benefit then you have to come to a decision, sometimes it's a certain trade-off. Pay attention to any change in symptoms or new symptoms, they may be side effects. For example, there are medications that can cause swelling in the legs, a drop in blood pressure, confusion, hallucinations, a change in impulse control such as a desire for sweets and money laundering, dry mouth and more. Sometimes the treatment has to be stopped or changed and it is always advisable to start and change each treatment gradually and carefully.
Do not make significant changes in your medication dosage quickly. Changes that are too rapid may cause side effects - especially reducing the dose of the medication (explained above under levodopa and dopamine agonists). The doctor treating you will certainly suggest trying different times to find the set of medications that will suit you, while maintaining the daily amount of medications prescribed for you.
The consulting doctor's note:
Any change or adjustment of medications is desirable, to be done slowly and carefully to avoid complications and side effects. Many times you will receive from your doctor a plan for increasing the dosage or changing the medication that takes many weeks to reach the goal - so that the changes are made gently and there will be enough time for the body to get used to the change
The author of the article, Dr. Simon Israeli Koren, is an employee of Neuroderm Ltd.
This article and the contents presented in it are for informational purposes only and should not be considered medical advice, a recommendation or a substitute for any treatment or a recommendation for any product or preparation. If the reader or any other party has a medical problem, he must contact a doctor for treatment or medical advice.
Professional medical advice should not be ignored and the search for medical treatment should not be delayed or postponed due to the information presented in this article. If you believe that you are in a medical emergency, you should immediately contact the attending physician or the local emergency center in order to receive treatment or medical advice.
