Drugs Used to Treat Parkinsonism
parkinsonism is a disorder of the nervous system in which voluntary movement is disturbed, involuntary movements occur and the tone of muscles is altered. Voluntary movements become slow and shaky (tremor) and muscles become stiff (rigidity). The group of signs and symptoms produced are usually referred to as the 'Parkinsin's syndrome' or simply as 'parkinsomism'. There are several causes and the severity of the disorders varies between patients. A not infrequent cause these days is the long-term use of anti-psychotic drugs.
To function properly, centres in the brain responsible for controlling movement are kept in balance by two nerve transmitter systems, acetylcholine and dopermin. These two systems in the brain are often referred to as the cholinergic system and Doperminergic system respectively. In parkinsonism the doperminegic system appears to be defective so that the control mechanisms of movement become unbalanced and the cholinergic system dominates. Producing the abnormal movements and rigidity seen in parkinsonism. Chemical suppression of this dominance may,therefore be applied by the use of drugs which bock ir interfere with the action of acetylcholine (e.g. by the use of anticholinergic drugs). Alternatively, drugs which increase the effect of the doperminergic system will have beneficial effects ( e.g. the use of levopoda).
The main aim of treatment in parkinsonism has been treated with anticholinergic is to try to improve both the difficulty in starting movements and the slowness of movement (bradykinsia), and to reduce tremor and muscle rigidity.
For over a century parkinsonism has been with anticholinergic drugs. Atropine was the first to be used and since then many atropine-like drugs have been used. Antihistamines have also been used (such as promethazine and diphenhydramine) but these may have helped because they produce mild antichoinergic effects. Many other drugs have been claimed to be of benefit in treating patients suffering from parkinsonism but the real advance was the discovery of levopoda and other drugs that improve the dopaminergic system.
Anticholinergic Drugs
There is a choice of anticholinergic drugs available for the treatment of parkinsonism. These include benzhexol ( Artane, Broflex), benztropine (Cgentin), biperiden (Akineton), orphenadrine( Biorphen, Disipal) and procyclidine ( Arpicoin, Kemadrin).
The anticholinergic drug's effects in parkinsonism are limited. Muscle rigidity and tremors may be helped but bradykinesia (slowness of movement), one of the most disturbing effects of parkinsonism, is unaffected by them. They dry up the mouth and may help reduce dribbling.
Antichoinergic drugs are useful in patients with mild early symptoms of parkinsonism who may improve on these drugs before they need to take levodopa. Patients with post-encephalitic parkinsonism appear to respond better to anticholinergic drugs than patients with idiopathic parkinsonism. They are also useful for reducing drug-induced parkinsonism in patients receiving anti-psychotic drugs. Tardive dyskinesia is not improved by anti-choinergic drugs and may be made worse. The choice of drug is not critical and they may be taken before food if dry mouth is a problem or after food if they produce stomach upsets.
Different people respond differently to any one of the anticholinergic drugs: therefore if one drug does not work it is worth tying another.
Dopaminergic Drugs
Levodopa ( Brocadopa, in Madopar, in Sinemet) is the chemical forerunner ( precursor) of dopamine. It improves some of the worst feartures of parkinsonism difficulty in starting movement and slowness of movement. This is often impressive, resulting in improvement in walking, eating and talking. The rigidity is also helped and other effects of parkinsonism such as difficulty in balancing, drooling of saliva from the mouth and involuntary eye movements may also improve slowly. Shaking is less frequently improved.
A major problem with levodopa is that it is rapidly metabolized in the body into dopamine which cannot cross the blood- brain barrier whereas levodopa can. When given in high dosage sufficient levodopa enters the brain, where it is converted in to dopamine. However, adverse effects of levodopa are doserelated. Carbidopa and benserazide block levodopa metabolism in the body by inhibiting the enzyme dopa-decarboxylase but do not enter the brain. They cannot therefore interfere with levodopa, the metabolism of levodopa outside the brain. When these are given along with levodopa, the metabolism of levodopa outside the brain is blocked and the blood evel of levodopa increases. An effective treatment, therefore, is to give a dose of levodopa and carbidopa o beserazide together. This enables the dose of levodopa to be reduced. When giving cabidopa or benserazide and levodopa separately there is a isk that too high a dose of levodopa may be given. Therefore a fixed-dose preparation is used, e.g. carbidopa and levodopa ( Co-careldopa, Sinemet) o benserazide and levodopa ( Co-beneldopa, Madopar). This also ensures the appropriate dose of each.
During the first 6-18 months of treatment with levodopa there may be a slow improvement which is maintained for further two years. Unfortunatly, after several months of treatment there may be variations in response, with attacks of weakness lasting for a few hours. Theses 'on/off' effects are a problem but can be treated by decreasing the interval between doses or by adding other drugs to the treatment. The duration of benefit after each dose of evodopa may decrease overtime ('end of dose' effect) and this may be helped by giving modified release preparations.
Amantadine (Symmetrel) is an antiviral drug used to treat influenza. In parkinsonism it is thought to work by increasing the concentration of dopamine in the brain. It produces mild imporvement of slowness of movement, tremor and rigidity. Only a few patients benefit and its effects are short-lived. Combination with levodopa, particularly in patients who are unable to tolerate full doses of levodopa.
Bromocriptine ( Parodel) stimulates dopamine receptors. It produces similar effects to levodopa but has a long duration of action which may be useful if taken at bedtime. It is reserved for patients in whom levodopa no longer works may cause movement disorders and confusion.
Selegiline ( Centrapyl, Edepryl, Vivepryl) is a monoamine oxidase (B) inhibitor which blocks the enzyme that breaks down dopermine. It is generally used when the effects of levodopa begin to wear off. It does not produce the adverse in previously untreated patients and when given with levodopa it may help to reduce the wearing-off effects ( end-of-dose effects) that may occur between doses with levodopa. It enables the dose of levodopa to be reduced.
Lysuride ( Revanil, pergolide ( Celace) and ropinirole ( Requip) are selective dopamine stimulants. They can be used with levodopa to reduce the fluctuations in response and end of dose effects which may occur with levodopa. They enable the dose of levodopa to be reduced.
Apomorphine ( Britaject) is a power stimulator of dopamine receptors and may be beneficial in patients whe experience 'on/off' effects with levodopa. The anti-vomiting drug domperidone should be given to prevent vomiting during treatment and for 3 days before treatment starts.
The main aim of treatment in parkinsonism has been treated with anticholinergic is to try to improve both the difficulty in starting movements and the slowness of movement (bradykinsia), and to reduce tremor and muscle rigidity.
For over a century parkinsonism has been with anticholinergic drugs. Atropine was the first to be used and since then many atropine-like drugs have been used. Antihistamines have also been used (such as promethazine and diphenhydramine) but these may have helped because they produce mild antichoinergic effects. Many other drugs have been claimed to be of benefit in treating patients suffering from parkinsonism but the real advance was the discovery of levopoda and other drugs that improve the dopaminergic system.
Anticholinergic Drugs
There is a choice of anticholinergic drugs available for the treatment of parkinsonism. These include benzhexol ( Artane, Broflex), benztropine (Cgentin), biperiden (Akineton), orphenadrine( Biorphen, Disipal) and procyclidine ( Arpicoin, Kemadrin).
The anticholinergic drug's effects in parkinsonism are limited. Muscle rigidity and tremors may be helped but bradykinesia (slowness of movement), one of the most disturbing effects of parkinsonism, is unaffected by them. They dry up the mouth and may help reduce dribbling.
Antichoinergic drugs are useful in patients with mild early symptoms of parkinsonism who may improve on these drugs before they need to take levodopa. Patients with post-encephalitic parkinsonism appear to respond better to anticholinergic drugs than patients with idiopathic parkinsonism. They are also useful for reducing drug-induced parkinsonism in patients receiving anti-psychotic drugs. Tardive dyskinesia is not improved by anti-choinergic drugs and may be made worse. The choice of drug is not critical and they may be taken before food if dry mouth is a problem or after food if they produce stomach upsets.
Different people respond differently to any one of the anticholinergic drugs: therefore if one drug does not work it is worth tying another.
Dopaminergic Drugs
Levodopa ( Brocadopa, in Madopar, in Sinemet) is the chemical forerunner ( precursor) of dopamine. It improves some of the worst feartures of parkinsonism difficulty in starting movement and slowness of movement. This is often impressive, resulting in improvement in walking, eating and talking. The rigidity is also helped and other effects of parkinsonism such as difficulty in balancing, drooling of saliva from the mouth and involuntary eye movements may also improve slowly. Shaking is less frequently improved.
A major problem with levodopa is that it is rapidly metabolized in the body into dopamine which cannot cross the blood- brain barrier whereas levodopa can. When given in high dosage sufficient levodopa enters the brain, where it is converted in to dopamine. However, adverse effects of levodopa are doserelated. Carbidopa and benserazide block levodopa metabolism in the body by inhibiting the enzyme dopa-decarboxylase but do not enter the brain. They cannot therefore interfere with levodopa, the metabolism of levodopa outside the brain. When these are given along with levodopa, the metabolism of levodopa outside the brain is blocked and the blood evel of levodopa increases. An effective treatment, therefore, is to give a dose of levodopa and carbidopa o beserazide together. This enables the dose of levodopa to be reduced. When giving cabidopa or benserazide and levodopa separately there is a isk that too high a dose of levodopa may be given. Therefore a fixed-dose preparation is used, e.g. carbidopa and levodopa ( Co-careldopa, Sinemet) o benserazide and levodopa ( Co-beneldopa, Madopar). This also ensures the appropriate dose of each.
During the first 6-18 months of treatment with levodopa there may be a slow improvement which is maintained for further two years. Unfortunatly, after several months of treatment there may be variations in response, with attacks of weakness lasting for a few hours. Theses 'on/off' effects are a problem but can be treated by decreasing the interval between doses or by adding other drugs to the treatment. The duration of benefit after each dose of evodopa may decrease overtime ('end of dose' effect) and this may be helped by giving modified release preparations.
Amantadine (Symmetrel) is an antiviral drug used to treat influenza. In parkinsonism it is thought to work by increasing the concentration of dopamine in the brain. It produces mild imporvement of slowness of movement, tremor and rigidity. Only a few patients benefit and its effects are short-lived. Combination with levodopa, particularly in patients who are unable to tolerate full doses of levodopa.
Bromocriptine ( Parodel) stimulates dopamine receptors. It produces similar effects to levodopa but has a long duration of action which may be useful if taken at bedtime. It is reserved for patients in whom levodopa no longer works may cause movement disorders and confusion.
Selegiline ( Centrapyl, Edepryl, Vivepryl) is a monoamine oxidase (B) inhibitor which blocks the enzyme that breaks down dopermine. It is generally used when the effects of levodopa begin to wear off. It does not produce the adverse in previously untreated patients and when given with levodopa it may help to reduce the wearing-off effects ( end-of-dose effects) that may occur between doses with levodopa. It enables the dose of levodopa to be reduced.
Lysuride ( Revanil, pergolide ( Celace) and ropinirole ( Requip) are selective dopamine stimulants. They can be used with levodopa to reduce the fluctuations in response and end of dose effects which may occur with levodopa. They enable the dose of levodopa to be reduced.
Apomorphine ( Britaject) is a power stimulator of dopamine receptors and may be beneficial in patients whe experience 'on/off' effects with levodopa. The anti-vomiting drug domperidone should be given to prevent vomiting during treatment and for 3 days before treatment starts.
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