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Parkinson's Disease

 


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Condition
Parkinson's disease

Class
Central Nervous System

Description
Parkinson's disease is a progressive neurological condition affecting parts of the brain that control movement. As a result, every day tasks such as talking, walking, writing and balance become more difficult.

Parkinson's disease is a relatively common condition, affecting about 120,000 people in the UK. Around 10,000 new patients are diagnosed each year. Signs of Parkinson's disease start to appear usually after the age of 50, although in some people the disease can appear earlier. Men are more likely to be affected than women.

Sometimes, the term parkinsonism is used to describe conditions that have similar symptoms to Parkinson's disease.

Causes
Parkinson's disease occurs as the result of the loss of nerve cells in a part of the brain called the substantia nigra. These nerve cells normally secrete a chemical called dopamine which is responsible for transmitting signals associated with muscular activity between the substantia nigra and another part of the brain called the corpus striatum. Low dopamine levels result in an inability to control the body's movements properly.

In addition to controlling movement, dopamine is involved in other areas of the brain that control other activities. Loss of dopamine in these areas is thought to be the cause of the psychological symptoms associated with Parkinson's disease such as depression, changes in behaviour, slowed reactions, changes in sensation and sleep disturbances.

Although it is known that a lack of dopamine is responsible for the symptoms of Parkinson's disease, it is not known what causes the loss of nerve cells in the substantia nigra. Doctors currently believe that genetic, environmental and natural ageing factors set off a chain of events that causes the nerve cells to die. The process continues unnoticed for years. It is only when dopamine falls to 20-40% of normal levels that symptoms appear.

Symptoms of parkinsonism (as distinct from Parkinson's disease) may result from environmental toxins such as pesticides, drugs, genetic mutation, head trauma or other medical disorders.

Symptoms
Parkinson's disease affects people in different ways. The symptoms and the speed at which the disease develops vary.

The main symptoms of Parkinson's disease are:
Tremor - the arms and legs show a shaking movement. The tremor usually first appears on one side of the body and is most noticeable when the limb is not being used. Tremor decreases when the limb is moved.

Rigidity - muscle tone increases and leads to stiffness. Increased limb stiffness, together with the resting tremor produces a ratchet or cogwheel type movement when someone (other than the person affected) tries to move the limb. The person may have difficulty getting out of a chair or rolling over in bed.

Bradykinesia - slowness of movement. The person finds it difficult to start and to stop movements. Parkinson's disease patients walk with a characteristic fast shuffle. They find it difficult to start walking but, once started, they find it difficult to stop or change direction.

Loss of balance - people find it difficult to maintain the body's posture, and they may lose balance, stumble and fall.

Other symptoms that develop largely as a result of loss of muscle control include difficulties with swallowing, speech, writing and blinking, muscle pain, drooling and urinary incontinence. Other symptoms can include depression, sleep disturbances, fatigue, pain, dementia and memory problems.

Treatment
Although there is currently no cure, medicines can help to manage many of the symptoms of Parkinson's disease and improve the person's quality of life.

There are three main ways in which drugs work to control the symptoms of Parkinson's disease:

  • Increase the level of dopamine in the brain
  • Mimic or copy the way that dopamine works in the brain
  • Inhibit or block the action of other chemicals that oppose dopamine


As the drugs work in different ways, different types of drug are often used together to improve control of symptoms while possibly reducing the risks of side effects.

Drugs that increase the level of dopamine in the brain
Levodopa or L-dopa - It is not possible to give dopamine itself to replace the transmitter that has been lost because dopamine is not able to pass into the brain from the blood stream. The building block of dopamine, called levodopa or L-dopa, has to be given instead. Levodopa is able to pass into the brain where it is converted into dopamine, restoring the depleted transmitter.

Many people get considerable relief with levodopa, especially from stiffness and slowness of movement. After two or more years, people may get trouble with side effects, one of which is known as dyskinesia. Dyskinesias are uncontrollable wriggling or writhing movements, although often painless they may interfere with daily life. The person may also experience ‘end of dose' deterioration where the effects of one dose wear off before the next dose is due. People also get fluctuations in mobility, so called ‘on/off' fluctuations, where the person suddenly swings from being mobile (on) to being immobile (off).

Enzyme inhibitors - The effect of levodopa can be increased by drugs that inhibit the enzymes that break down levodopa or dopamine. There are three types of enzyme inhibitor - decarboxylase inhibitors, COMT inhibitors and MAO-B inhibitors.

Decarboxylase inhibitors act by blocking the enzyme responsible for the breakdown of levodopa. When a decarboxylase inhibitor is given with levodopa it prevents the levodopa from being converted into dopamine before it can pass into the brain. This helps reduce side effects and increases the effect of levodopa. Decarboxylase inhibitors include drugs such as benserazide and carbidopa.

COMT inhibitors act by blocking catechol-o-methyltransferase, another enzyme that breaks down levodopa. COMT inhibitors prolong the action of levodopa, improving ‘end of dose' deterioration, increasing the daily ‘on' time and reducing the ‘off' time. COMT inhibitors include entacapone and tolcapone.

MAO-B inhibitors act by blocking monoamine oxidase-B, the enzyme that breaks down dopamine in the brain. MAO-B inhibitors may be used alone in newly diagnosed patients who still have some dopamine remaining in the brain, or in combination with levodopa. MAO-B inhibitors include rasagiline and selegiline.

Drugs that copy the way that dopamine acts in the brain
Dopamine agonists - These drugs stimulate the areas of the brain where dopamine usually acts. They produce a longer lasting effect than levodopa and provide good control of ‘on/off' fluctuations and are less likely to produce dyskinesia. Dopamine agonists may be used alone to relieve symptoms early on in Parkinson's disease or later on in combination with levodopa to reduce side effects. Dopamine agonists include apomorphine, bromocriptine, cabergoline, pergolide, pramipexole, ropinirole and rotigotine. Another drug, amantadine, is thought to act by stimulating the release of dopamine in the brain, possibly through an action on receptors called glutamate receptors.

Drugs that block transmitters that oppose dopamine
Anticholinergics - The corpus striatum includes another type of nerve, called cholinergic nerves that normally oppose the action of dopamine. When dopamine is depleted, the excess cholinergic nerves exaggerate the symptoms of Parkinson's disease. Anticholinergic drugs block the activity of the cholinergic nerves and so help restore the balance. Anticholinergics are better at controlling tremor than they are at controlling stiffness. They may be particularly useful in reducing saliva production when salivation is a problem, and in helping to control urinary incontinence. Anticholinergics include orphenadrine, procyclidine and trihexyphenidyl.

When to see your pharmacist
Your pharmacist is part of a healthcare team and will be able to put you in touch with the right people who should be able to help with all aspects of managing Parkinson's disease.

If you are receiving treatment for Parkinson's disease and there is anything that you do not understand about your treatment, or you are worried about side effects, talk to your pharmacist. In some cases it can be difficult to distinguish between a side effect of the drug and the progression of the disease.

Even if you do not have Parkinson's disease, but you develop symptoms of parkinsonism while taking other medicines, for example medicines to control schizophrenia, let your pharmacist know as it may be a side effect of this type of drug.

When to see your doctor
If you think you or a relative has one of the main symptoms of Parkinson's disease it is important to go and see your doctor. If Parkinson's disease is suspected, NHS guidelines state that you should be referred to a specialist within 6 weeks, or within 2 weeks if you have complex problems. This will ensure that you get expert care right from the start. Thereafter you should have access to specialist nursing care, physiotherapy, occupational therapy and speech therapy.

Living with Parkinson's disease
Receiving a diagnosis of Parkinson's disease can come as a shock. You and your family are likely to have many questions about the disease, its treatment and how it will affect you. Talk to your specialist, your doctor and nurse about anything you do not understand, they are there to help you. If you have access to a computer, look up the Parkinson's UK's website (see below), it carries plenty of practical information to help you understand and cope with your condition. If you think it will help, join your local Parkinson's UK network to meet people who are similarly affected by the disease.

When it comes to treatment, ask your specialist to explain the options available and work together to find a treatment which is right for you and your lifestyle. If you subsequently find that your medicines are difficult to take or you find it difficult to remember when to take them, ask your doctor or pharmacist if there are alternatives.

Try to eat a balanced diet. If you are losing weight or gaining weight, if shopping for groceries is difficult ask your doctor or nurse to put you in contact with a dietician who will draw up a dietary plan, or with a carer who can help with your shopping.

Try to remain active. Regular exercise will help reduce muscle and joint stiffness, create a general sense of well-being and reduce long-term problems. If you are experiencing severe difficulty with movement ask your doctor to refer you to a physiotherapist trained in the management of people with Parkinson's disease.

Further information
Parkinson's UK is a charity leading research work to find a cure for the disease and providing help and support for people affected by Parkinson's disease. The charity's website covers details of its comprehensive activities and services including downloadable information on all manner of topics about the disease and its treatment and about practical issues such as driving and financial matters.

Helpline: 0808 800 0303
www.parkinsons.org.uk

altFunded and edited by Boehringer Ingelheim


Reviewed on 12 April 2011


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