In the brain there are two chemical messengers (messengers): Dopamine (Dopamine) and Acetylcholine (acetylcholine), which 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 and in some patients tremors. These signs of Parkinson's do not appear until about 50 percent 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.

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 exercise and rest, as temporary measures for an interim period.

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.

In this article, the type of drug appears as a title. The names of the drugs will appear in the generic oil as well as 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.

Medicines are available

Levodopa

The drug levodopa has been used to treat the symptoms of Parkinson's disease since the 60s. Levodopa is a natural amino acid, which the brain turns into dopamine, and therefore it replaces the missing chemical substance and comes in its place. The most common levodopa drugs in Israel, Levobore, Dupikar and Sinemat, also contain another substance that prevents levodopa from turning into dopamine, before it reaches the brain.

In Israel, Levopper contains levodopa and benserazide and Duficare and Sinemat contain levodopa and carbidopa). Usually, 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.

Controlled-release levodopa

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 type preparations, it is possible that it will be necessary to increase the amount of levodopa required up to 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.

Levodopa in suspension

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.

Low concentration levodopa

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.

The existing lobodopa preparations

Madhufar - contains levodopa plus benzrazide equivalent to Levophor in Israel.

Name of the product in Europe

levodopa (mg)
Benzerazid (mg)
The name of the preparation in Israel
Madhufar 62.5
50
12.5
NO
Madhufar 125
100
25
For the bopper plus 125
Madhufar 250
200
50
For the bopper plus 250
Medofar 62.5 in suspension
50
12.5
NO
Medofar 125 in suspension
100
25
NO
Medupar CR
100
25
NO

Sinemat - contains levodopa plus carbidopa.

Name of the product in Europe

levodopa (mg)
Carbidopa (mg)
The name of the preparation in Israel
Cinemat LS
50
12.5
NO
Cinemat 110
100
10
NO
Cinemat 275
250
25
Dupiker
Cinemat Plus
100
25
NO
Half Cinemat CR
100
25
NO
Cinemat CR
200
50
Cinemat CR

Advantages

Most people are able to tolerate Dupiker, Sinemat, or Lebopper, and most feel significant improvement for many years, especially when it comes to stiffness and slowness of movement.

Disadvantages

In the first days of taking the above-mentioned drugs, certain feelings of nausea and vomiting are common. However, they are usually mild and pass as the body adapts to the drug. Involuntary movements (dyskinesias). There is a small percentage of people who are unable to tolerate these drugs 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.

Over time, these drugs may become less reliable, 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 effect of the next one begins to take effect.

Over time, the involuntary movements (dyskinesias) may be more and more annoying, and there may be sudden transitions from states of "ON" and the ability to move to states of "OFF" and the lack of ability to move.

These long-term effects can sometimes be improved by changing the type or amount of duficar, cinnamate, or levobuterol, or the frequency 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 who sometimes recommend eating low-protein meals during the day and postponing the protein-rich meal until the evening.

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.

Dopamine Agonists 

When taken orally 

Generic name

The commercial name in Israel 
Bromocriptine
Bromocriptine
Perlodel, Prilak
Parlodel, Parilac
Cabergoline
cabergoline
Cabser
Cabaser
Lizoride
Lisuride
Dupergin
Dopergin
Pargolide
Pergolide
Pargolide
Pergolide
Rupinrol
Ropinirole
Requip
requip
Pramipexole
Pramipexole
There is no land
- 

The above-mentioned drugs are called dopamine agonists, because they directly stimulate those parts of the brain where dopamine works. In varying degrees, their activity is more prolonged than that of levodopa, and for some patients they may be more suitable than dupikar, sinemat or levoboper.

Dopamine agonists can be taken without the addition of other drugs, but until recently it was common for them to be given together with dupikar, sinemat or levobufer, in order to reduce the fluctuations in the functioning of Parkinson's patients, whose responses to levodopa treatment begin to undergo fluctuations.

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 control of the signs of the disease during the day can be more effective and prolonged than is generally accepted when using levodopa. Most dopamine agonists are taken several times during the day, except for cabergoline which can be taken once a day as a single dose, due to its prolonged effect time.

Disadvantages 

When dopamine agonists are taken alone, they are generally considered less effective than the standard preparations of levodopa (Dupicare, Sinemat or Levobufer), especially in the advanced stages of the disease.

Some patients with Parkinson's disease are unable to continue taking dopamine agonists because of side effects, which include nausea, vomiting, confusion, hallucinations, drowsiness and dizziness, which are often associated with low blood pressure.

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 effect or even worse, but this usually disappears with increasing the dose.

by subcutaneous injection 

Generic name 

The commercial name in Israel 

Apomorphine
Apomorphine
Not yet registered in Israel

Apomorphine is an injectable dopamine agonist, because it breaks down in the gastrointestinal tract when administered orally. There are Parkinson's patients with motor fluctuations who enter severe OFF states, despite all efforts to adjust the medications they take. In these cases, apomorphine injections can be used as a "rescue drug", and quickly get rid of the difficult situation. Apomorphine acts directly on the same sites in the brain where dopamine is active.

Since apomorphine can only be 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. These can be performed in day care settings, or at the hospital, or under hospitalization. Most patients can be satisfied with normal self-injection or with special auto-injectors, but some patients need continuous administration of apomorphine given by subcutaneous injection using a pump. The portable, battery-operated pump, with an automatic piston injects the drug continuously through a tube to a needle inserted daily in another part of the body under the skin.

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.

Disadvantages 

Apomorphine can only help those Parkinson's patients who respond to Duficar, Sinemat, or Levofar. 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).

A wound can develop in the injection areas, and when this happens you must contact your doctor or a nurse specializing in Parkinson's disease.

Amantadine (Amantadine)

Generic name 

The commercial name in Israel 
Adamantamine sulfate
1-Adamantanamine Sulphate
P.K. March

A-Perkin
PK-Merz
A-parkin

Amantadine hydrochloride
Amantadine hydrochloride
Pritrel
Paritrel 

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.

Advantages 

It has only few side effects. Sometimes it may help reduce the 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 (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 swelling of the ankles and vein drawing in the skin, and can also contribute to confusion or memory disturbances.

Anticholinergics

Generic name 

The commercial name in Israel 
trihexyphenidyl
Trihexyphenidyl
Arten

detail
artane
Partane
benztropine
Benztropine
Cogentin
Cogentin
Bifridan
Biperids
Dekint
Dekinet
Procyclidine
Procyclidine
Kamdrin
Kemadrin
Orphendrine
Orphenadrine
Disciple
Disciple 

These are old drugs, now given less frequently, 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. 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 an acute problem of salivation.

Disadvantages 

The common side effects are: confusion, memory loss, dry mouth, constipation, blurred vision and difficulty urinating may occur. 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.

COMT Inhibitors

Generic name 

The commercial name in Israel 
Antiphone
Entacapone
Comtan
Comtan
payphone
Tolcapone
Tesmer (marketing discontinued)
tasmar 

Medicines of the type of COMT enzyme inhibitors are new medicines that work by blocking the enzyme called COMT - Catechol-O-Methyl Transferase, which breaks down levodopa.

As a result, they slow down the destruction of levodopa in the body. COMT-inhibiting drugs are therefore given, only together with levodopa, to prolong the duration of levodopa's activity and thereby reduce the symptoms of Parkinson's disease.

Advantages 

One of the advantages of drugs of the type of COMT inhibitors is their possible contribution to reducing the fluctuations that appear in function after the first years of treatment. These drugs should also decrease the dose and frequency of levodopa doses needed, and may increase the duration

The ON. 

 Disadvantages 

The side effects of these preparations, as reported, include an increase in involuntary movements (dyskinesias), states of confusion, nausea, vomiting as well as changes in the color of urine. In some cases, diarrhea can be a real problem, to the point of stopping the use of the drug. The use of Tesmer requires blood tests once a month, to check the activity levels of the liver enzymes. Marketing of the drug Tesmar was stopped in Israel after reports of deaths in patients as a result of liver damage.
The drug Comtan was recently approved for use in Israel, and it does not harm liver functions.

The enzyme inhibitors (MAO-B (Mono Amine Oxidase Type-B).

Selegiline (Selegiline)  

Generic name 
The commercial name in Israel 
Selegiline
Selegiline HCL
Selegiline

Yomax
Selegiline
Jumex

Selegin slows down the breakdown of dopamine in the brain. 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 Segilin significantly changes the course of the disease.

Advantages 

By itself, selegiline has very few side effects.

Disadvantages 

When selegiline is taken together with duficare and buprenorphine, side effects of levodopa, such as involuntary movements (dyskinesias), hallucinations (hallucinations) or very vivid dreams

(vivid dreaming), may sometimes appear or worsen. To reduce the risk of side effects, the dose of levodopa must be lowered. Selegiline acts as a mild stimulant, so it is often given as a single dose, which should be taken in the morning, not in the evening, because it can interfere with sleep.

 

Rasagiline (Azilect. Rasagiline (Azilect

Generic name 
The commercial name in Israel 
Azilect
azilect

A new drug from Teva containing 1 mg of rasagiline, a selective (type B) and irreversible monoamine oxidase enzyme inhibitor. The way of treating the drug is convenient, with the administration of the drug 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, and as an additional treatment to levodopa in the intermediate and advanced stages of Parkinson's disease.

Azilect as a single drug treatment significantly improves the motor symptoms and quality of life of the patients.

As a combined treatment with levodopa for advanced disease, Azilect significantly improves the OFF/ON balance (reduces the amount of time in a day when, despite medication, the patient's ability to move is very limited), and increases the patient's ability to function.

Azilact is a safe and well-tolerated product at any age, and shows a low rate of side effects in all stages of the disease.

Clinical trials of new drugs

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 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.

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.

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 antidepressants can usually be taken without a problem.

However, there are drugs that can cause the appearance of Parkinson-like symptoms. Generally, Parkinson's patients should avoid them, unless they are specifically recommended by a Parkinson's specialist.

Preparations of the type of monoamine oxidase A inhibitors (MOAIs), are one of the two main types of antidepressant preparations. They do not make Parkinson's disease worse, but they should not be given together with levodopa, as they can have opposing effects on the function of the heart and blood pressure.

Do not give drugs from this group with selegiline (Umax).

New antipsychotic drugs have been introduced, such as Clozapine and Olanzapine, which are less likely to worsen Parkinson's symptoms.

Some of the above medicines contain more than one active ingredient, when sometimes one ingredient may have an adverse effect. Therefore, we advise people to report to their doctor all the medicines they are taking, including those bought without a doctor's prescription.

These drugs are listed in the following table:

Medications that Parkinson's patients must consult a neurologist before taking 

Generic name
The commercial name in Israel 

The medicine to treat b 
Metoclopramide
Fermin
Pramin
Nausea/vomiting
Perphenazine
Paraffin
Perphenan
psychosis
Flupenthixol
Fluenzaxol
Fluanhol
Depression, psychosis, mania
Chlorpromazine
Tractyl
Taroctyl
Thinking disorders, psychosis, severe restlessness
Fluphenazine
polite,

Saditan,

choosen
Modecate, Sediten, Selecten
Thinking disorders, psychosis, restlessness
Haloperidol
the lodol,

the reduction,

looper,

Prickett
Halodol, Halidol, Haloper, Pericate
Thinking disorders, psychosis, severe restlessness
Pimozide
Orp Forte
Orap Forte
Thinking disorders, psychosis, involuntary movements, Tic disorder
Sulpiride
model
Modal
Disturbances in thinking, restlessness, dizziness
Thioridazine
Melril,
Ridzin
Melleril, Ridazin
Confusion, disorientation, disturbances in thinking, restlessness 

 

The only anti-nausea drug that does not worsen the symptoms of Parkinson's disease is Motilium (domperidone).

Do's and don'ts

 Made

Ask the doctor treating you to come back and explain to you once more, what you did not understand from his words.

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.
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. Note the amount and timing of taking the medication, the duration of the ON/OFF periods, or the involuntary movements, 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 remember this, only when it is time to take the next dose, skip the forgotten dose.
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 it is advisable that your blood pressure be checked, both in a sitting position and in a standing position.
Consult your doctor if you have Parkinson's disease and think you may be pregnant.
Remember, your pharmacists can also give you advice, as well as help you prepare the medicines when necessary.

Do not do

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 side effects - you will not! But if there is anything that worries you, report it to your doctor.
Do not make significant changes in your medication dosage quickly. Too rapid changes may cause side effects. 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.