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Research has shown that dietary protein antago- from the blood and may help lower the competition can also cause and urine discoloration. ments). nizes the clinical effectiveness of the levodopa- between amino acids and levodopa thereby increas- combination. Dietary protein causes a ing Sinemet's effectiveness. COMT Inhibitor and Levodopa: AGENTS large peak in the concentration of certain amino Carbidopa-Levodopa- (Stalevo®) (Artane®, Cogentin®) acids; when the blood amino acid levels are high, SUMMARY levodopa uptake into the brain is slow and inad- A combination tablet of carbidopa, levodopa and These drugs include (Artane) and equate. The pharmacological management of Parkinson's entacapone is available and marketed as Stalevo. benztropine (Cogentin). Anticholinergic agents disease is complex and dynamic; there is no one Stalevo is indicated for treatment of idiopathic PD exert their effect in PD by correcting the imbalance Meals high in fat can also be a problem. A high-fat right strategy for what drugs to use at what stage to substitute for immediate-release (IR) created from decreased and unabated meal can take as long as two hours to clear the of the disease. However, it has been shown in vari- carbidopa-levodopa and entacapone previously cholinergic input. In addition to suppressing stomach. If Sinemet is in the stomach too, it will ous studies that starting early will administered as individual products and to replace central cholinergic activity, these agents may also also take two hours to clear, shortening its useful give better long-term motor results. The current IR carbidopa-levodopa when patients experience inhibit the reuptake and storage of dopamine at lifespan. Therefore, it is best to take Sinemet 30 to trend is to initiate symptomatic therapy with a the signs and symptoms of end-of-dose “wearing- the central dopamine receptors, thereby prolonging 60 minutes before eating a meal or 45 minutes or other levodopa sparing agent off.” Stalevo simplifies treatment by providing the action of dopamine. They were the standard after the meal to decrease interference between such as or and supplement three medications in one tablet, which reduces the antiparkinsonian treatment until the late 1960's, absorption of Sinemet and off proteins in the food. with levodopa when clinical features are no longer number of tablets patients need to take daily. An when newer drugs were developed. Anticholin- satisfactory. As PD progresses a combination of additional advantage is Stalevo 50 and 100mg ergics are most effective for reducing tremor, and levodopa therapy, dopamine agonists, MAO-B tablets are smaller for patients with swallowing usually provide minimal benefit with regard to Studies have further demonstrated that patients and/or COMT inhibitors are often used. Amanta- difficulties. The most common side effects of the bradykinesia and rigidity. In addition, tremor may who experience "on-off" fluctuations or who don't dine and anticholinergic agents are also occasion- combination product are and or may not improve with anticholinergic agents respond to levodopa-carbidopa therapy can benefit ally used. The optimal effect of is which can often be managed with alteration in the and a given patient may respond to one anticholin- by adjusting their protein intake. Specifically, further obtained when used in conjunction with drug dosing schedule. Other common side effects ergic but not others. Their use is often limited by high-protein foods should be eaten only in the exercise, speech therapy, counseling, diet, support include diarrhea, urine discoloration, abdominal side effects such as dry mouth, constipation, evening; this allows better mobility during the day. groups and other nonpharmacologic therapies. pain, dizziness, constipation, fatigue, pain and memory impairment, confusion and Another suggestion is to eat meals that consist of a hallucinations. and they are less well tolerated by older patients ratio of seven parts of carbohydrate to one part The enclosed pamphlet “Medications Approved for and those with dementia. Therefore, the prescrib- protein. A high ratio of carbohydrate to protein the Treatment of Parkinson’s Disease in the USA” ing of is often confined to younger causes a large amount of insulin to be released into provides a summation of the PD medications, along (Symmetrel®) patients with tremor as the primary symptom. the blood. Insulin removes some of the amino acids with their mode of action and common side effects.

This antiviral agent has mild antiparkinson effects Medication Dosing and Administration and is thought to act by causing a release of dopamine from intact dopamine neurons remain- All medication used in the treatment of Parkin- ing in the . It may also inhibit son's disease should be introduced slowly to mini- dopamine reuptake, stimulate dopamine receptors, mize the appearance of adverse effects. They must exert an anticholinergic effect and block NMDA also be administered on time. Fluctuations of 30 (N-methyl-D-aspartate) receptors. Amantadine is minutes to an hour might be acceptable for other used mainly in the early stages of the disease (first agents but not Parkinson's medications. ly 6 to 12 months) as a means of controlling the symp- Reprinted Feb. 2013 toms of PD, thereby lengthening the amount of Even a slight fluctuation in schedule can result in time the patient can remain functional without the an exacerbation of symptoms and diminished qual- addition of levodopa. It seems to have only a mini- ity of life for some patients. Worse yet, the appear- mal effect on tremor and modest effect on rigidity ance of these symptoms could mistakenly convince and bradykinesia which may not be long lasting. caregivers that a patient needs more medication (f) Amantadine is also utilized in later stages of the and that could lead to unwarranted increases in disease for symptoms of “wearing off” or to possibly dosage. reduce (abnormal involuntary move- makes taking medicines correctly and at the right methyltransferase (COMT). This is time challenging. extended-release is responsible for the of levodopa, an important once daily treatment option. dopamine, other ( and noradrenaline), and their metabolites. When MAO-B Inhibitors: Selegiline (Eldepryl®), administered with levodopa and carbidopa, these Selegiline ODT (Zelapar®), Rasagiline agents increase the availability of levodopa for (Azilect®) delivery to the brain. In addition, COMT inhibitors decrease levodopa clearance, prolonging the half- Selegiline and rasagiline slow the metabolism of life and increasing levodopa without dopamine through the blockade of monoamine affecting peak levodopa plasma concentration. Tol- oxidase (MAO)-B. MAO-B is an enzyme located in capone and entacapone are indicated as adjunct to the brain which metabolizes dopamine to an inac- levodopa and carbidopa for the treatment of the tive product. By inhibiting dopamine degradation signs and symptoms of idiopathic Parkinson's in the brain selegiline and rasagiline may prolong disease. Both and entacapone have no the duration of the dopamine effect. They are used antiparkinsonian effect when administered in the as monotherapy in the early phase of the disease or absence of levodopa. Because of the risk of poten- in combination with levodopa, or in the later stages tially fatal, acute fulminant failure, tolcapone of the disease (in fluctuating patients). Rasagiline should ordinarily be used in patients with Parkin- parts of the gastrointenstinal tract. is approximately five to ten times more potent than son's disease on levodopa/carbidopa who are expe- At the end of April 2008, it was temporarily with- selegiline. Selegiline orally disintegrating tablets riencing symptom fluctuations and are not drawn from the US Market because of problems (ODT), are a once-daily adjunct therapy for responding satisfactorily to or are not appropriate related to crystallization of the drug, which caused Parkinson’s disease patients being treated with candidates for other adjunctive therapies. Because unreliable drug delivery. These problems have levodopa/carbidopa who exhibit deterioration in of the risk of liver injury and because tolcapone, since been solved by the company. The FDA reap- the quality of their response to this therapy. The when it is effective, provides an observable symp- proved its use and Neupro was made available in formulation is a fast-dissolving dosage form in a tomatic benefit, the patient who fails to show the US market in July 2012. unique freeze-dried tablet that does not require substantial clinical benefit within 3 weeks of initia- Ropinirole extended-release was FDA approved in water to aid swallowing. When the tablet is put tion of treatment, should be withdrawn from tolca- June 2008. It is the only oral once-daily dopamine into the mouth, the freeze-dried structure disinte- pone. Liver function must be monitored closely agonist for the treatment of the signs and symp- grates instantaneously and releases selegiline, especially for the first six months. The drug must toms of PD. It may be taken alone or in combina- which dissolves in the saliva and is absorbed be discontinued if liver enzyme levels are twice the tion with levodopa. The tablets are composed of an directly into the systemic circulation through the upper level or if clinical signs and symptoms innovative tri-layer formulation that allows a oral mucosa. More active drug is delivered at a suggest the onset of liver failure. steady rate of absorption with fewer fluctuations in lower dose compared to conventional selegiline. There is no evidence of liver dysfunction in patients ropinirole concentration over 24 hours compared to The once daily tablet should be taken in the morn- treated with entacapone. Entacapone is recom- immediate-release ropinirole given three times ing before breakfast and without liquid; food or mended for PD patients experiencing the signs and daily. Switching from the previous ropinirole liquids should be avoided for five minutes before symptoms of “wearing-off,” i.e., slowness, tremor, immediate-release formulation can take place and after the ODT. Both selegiline ODT and rasa- rigidity that begin to reappear between levodopa overnight. The initial switching dose of ropinirole giline do not produce similar metabolites as doses, usually near the end of the dosing cycle. extended-release should most closely match the conventional selegiline and may have fewer side Because entacapone is almost completely metabo- total daily dose of immediate-release ropinirole. In effects. lized prior to , it should be used with general, similar types of adverse reactions are seen caution in patients with hepatic impairment. The with ropinirole extended-release and immediate- COMT Inhibitors: Tolcapone (Tasmar®), most common side effects observed with the COMT release ropinirole. Individuals with Parkinson’s Entacapone (Comtan®) inhibitors are in nature, for example, disease often require multiple doses of one or more dyskinesias, nausea, hallucinations and hypoten- medications to control their symptoms, which Tolcapone and entacapone are selective and revers- sion. These side effects can usually be reduced or ible inhibitors of the enzyme -O- eliminated by decreasing the levodopa dose. They makes taking medicines correctly and at the right methyltransferase (COMT). This enzyme is time challenging. Ropinirole extended-release is responsible for the metabolism of levodopa, an important once daily treatment option. dopamine, other catecholamines (adrenaline and noradrenaline), and their metabolites. When MAO-B Inhibitors: Selegiline (Eldepryl®), administered with levodopa and carbidopa, these Selegiline ODT (Zelapar®), Rasagiline agents increase the availability of levodopa for (Azilect®) delivery to the brain. In addition, COMT inhibitors decrease levodopa clearance, prolonging the half- Selegiline and rasagiline slow the metabolism of life and increasing levodopa bioavailability without dopamine through the blockade of monoamine affecting peak levodopa plasma concentration. Tol- oxidase (MAO)-B. MAO-B is an enzyme located in capone and entacapone are indicated as adjunct to the brain which metabolizes dopamine to an inac- levodopa and carbidopa for the treatment of the tive product. By inhibiting dopamine degradation signs and symptoms of idiopathic Parkinson's in the brain selegiline and rasagiline may prolong disease. Both tolcapone and entacapone have no the duration of the dopamine effect. They are used antiparkinsonian effect when administered in the as monotherapy in the early phase of the disease or absence of levodopa. Because of the risk of poten- in combination with levodopa, or in the later stages tially fatal, acute fulminant liver failure, tolcapone of the disease (in fluctuating patients). Rasagiline should ordinarily be used in patients with Parkin- parts of the gastrointenstinal tract. is approximately five to ten times more potent than son's disease on levodopa/carbidopa who are expe- At the end of April 2008, it was temporarily with- selegiline. Selegiline orally disintegrating tablets riencing symptom fluctuations and are not drawn from the US Market because of problems (ODT), are a once-daily adjunct therapy for responding satisfactorily to or are not appropriate related to crystallization of the drug, which caused Parkinson’s disease patients being treated with candidates for other adjunctive therapies. Because unreliable drug delivery. These problems have levodopa/carbidopa who exhibit deterioration in of the risk of liver injury and because tolcapone, since been solved by the company. The FDA reap- the quality of their response to this therapy. The when it is effective, provides an observable symp- proved its use and Neupro was made available in formulation is a fast-dissolving dosage form in a tomatic benefit, the patient who fails to show the US market in July 2012. unique freeze-dried tablet that does not require substantial clinical benefit within 3 weeks of initia- Ropinirole extended-release was FDA approved in water to aid swallowing. When the tablet is put tion of treatment, should be withdrawn from tolca- June 2008. It is the only oral once-daily dopamine into the mouth, the freeze-dried structure disinte- pone. Liver function must be monitored closely agonist for the treatment of the signs and symp- grates instantaneously and releases selegiline, especially for the first six months. The drug must toms of PD. It may be taken alone or in combina- which dissolves in the saliva and is absorbed be discontinued if liver enzyme levels are twice the tion with levodopa. The tablets are composed of an directly into the systemic circulation through the upper level or if clinical signs and symptoms innovative tri-layer formulation that allows a oral mucosa. More active drug is delivered at a suggest the onset of liver failure. steady rate of absorption with fewer fluctuations in lower dose compared to conventional selegiline. There is no evidence of liver dysfunction in patients ropinirole concentration over 24 hours compared to The once daily tablet should be taken in the morn- treated with entacapone. Entacapone is recom- immediate-release ropinirole given three times ing before breakfast and without liquid; food or mended for PD patients experiencing the signs and daily. Switching from the previous ropinirole liquids should be avoided for five minutes before symptoms of “wearing-off,” i.e., slowness, tremor, immediate-release formulation can take place and after the ODT. Both selegiline ODT and rasa- rigidity that begin to reappear between levodopa overnight. The initial switching dose of ropinirole giline do not produce similar metabolites as doses, usually near the end of the dosing cycle. extended-release should most closely match the conventional selegiline and may have fewer side Because entacapone is almost completely metabo- total daily dose of immediate-release ropinirole. In effects. lized prior to excretion, it should be used with general, similar types of adverse reactions are seen caution in patients with hepatic impairment. The with ropinirole extended-release and immediate- COMT Inhibitors: Tolcapone (Tasmar®), most common side effects observed with the COMT release ropinirole. Individuals with Parkinson’s Entacapone (Comtan®) inhibitors are dopaminergic in nature, for example, disease often require multiple doses of one or more dyskinesias, nausea, hallucinations and hypoten- medications to control their symptoms, which Tolcapone and entacapone are selective and revers- sion. These side effects can usually be reduced or ible inhibitors of the enzyme catechol-O- eliminated by decreasing the levodopa dose. They makes taking medicines correctly and at the right methyltransferase (COMT). This enzyme is time challenging. Ropinirole extended-release is responsible for the metabolism of levodopa, an important once daily treatment option. dopamine, other catecholamines (adrenaline and noradrenaline), and their metabolites. When MAO-B Inhibitors: Selegiline (Eldepryl®), administered with levodopa and carbidopa, these Selegiline ODT (Zelapar®), Rasagiline agents increase the availability of levodopa for (Azilect®) delivery to the brain. In addition, COMT inhibitors decrease levodopa clearance, prolonging the half- Selegiline and rasagiline slow the metabolism of life and increasing levodopa bioavailability without dopamine through the blockade of monoamine affecting peak levodopa plasma concentration. Tol- oxidase (MAO)-B. MAO-B is an enzyme located in capone and entacapone are indicated as adjunct to the brain which metabolizes dopamine to an inac- levodopa and carbidopa for the treatment of the tive product. By inhibiting dopamine degradation signs and symptoms of idiopathic Parkinson's in the brain selegiline and rasagiline may prolong disease. Both tolcapone and entacapone have no the duration of the dopamine effect. They are used antiparkinsonian effect when administered in the as monotherapy in the early phase of the disease or absence of levodopa. Because of the risk of poten- in combination with levodopa, or in the later stages tially fatal, acute fulminant liver failure, tolcapone of the disease (in fluctuating patients). Rasagiline should ordinarily be used in patients with Parkin- parts of the gastrointenstinal tract. is approximately five to ten times more potent than son's disease on levodopa/carbidopa who are expe- At the end of April 2008, it was temporarily with- selegiline. Selegiline orally disintegrating tablets riencing symptom fluctuations and are not drawn from the US Market because of problems (ODT), are a once-daily adjunct therapy for responding satisfactorily to or are not appropriate related to crystallization of the drug, which caused Parkinson’s disease patients being treated with candidates for other adjunctive therapies. Because unreliable drug delivery. These problems have levodopa/carbidopa who exhibit deterioration in of the risk of liver injury and because tolcapone, since been solved by the company. The FDA reap- the quality of their response to this therapy. The when it is effective, provides an observable symp- proved its use and Neupro was made available in formulation is a fast-dissolving dosage form in a tomatic benefit, the patient who fails to show the US market in July 2012. unique freeze-dried tablet that does not require substantial clinical benefit within 3 weeks of initia- Ropinirole extended-release was FDA approved in water to aid swallowing. When the tablet is put tion of treatment, should be withdrawn from tolca- June 2008. It is the only oral once-daily dopamine into the mouth, the freeze-dried structure disinte- pone. Liver function must be monitored closely agonist for the treatment of the signs and symp- grates instantaneously and releases selegiline, especially for the first six months. The drug must toms of PD. It may be taken alone or in combina- which dissolves in the saliva and is absorbed be discontinued if liver enzyme levels are twice the tion with levodopa. The tablets are composed of an directly into the systemic circulation through the upper level or if clinical signs and symptoms innovative tri-layer formulation that allows a oral mucosa. More active drug is delivered at a suggest the onset of liver failure. steady rate of absorption with fewer fluctuations in lower dose compared to conventional selegiline. There is no evidence of liver dysfunction in patients ropinirole concentration over 24 hours compared to The once daily tablet should be taken in the morn- treated with entacapone. Entacapone is recom- immediate-release ropinirole given three times ing before breakfast and without liquid; food or mended for PD patients experiencing the signs and daily. Switching from the previous ropinirole liquids should be avoided for five minutes before symptoms of “wearing-off,” i.e., slowness, tremor, immediate-release formulation can take place and after the ODT. Both selegiline ODT and rasa- rigidity that begin to reappear between levodopa overnight. The initial switching dose of ropinirole giline do not produce similar metabolites as doses, usually near the end of the dosing cycle. extended-release should most closely match the conventional selegiline and may have fewer side Because entacapone is almost completely metabo- total daily dose of immediate-release ropinirole. In effects. lized prior to excretion, it should be used with general, similar types of adverse reactions are seen caution in patients with hepatic impairment. The with ropinirole extended-release and immediate- COMT Inhibitors: Tolcapone (Tasmar®), most common side effects observed with the COMT release ropinirole. Individuals with Parkinson’s Entacapone (Comtan®) inhibitors are dopaminergic in nature, for example, disease often require multiple doses of one or more dyskinesias, nausea, hallucinations and hypoten- medications to control their symptoms, which Tolcapone and entacapone are selective and revers- sion. These side effects can usually be reduced or ible inhibitors of the enzyme catechol-O- eliminated by decreasing the levodopa dose. They Research has shown that dietary protein antago- from the blood and may help lower the competition can also cause diarrhea and urine discoloration. ments). nizes the clinical effectiveness of the levodopa- between amino acids and levodopa thereby increas- carbidopa combination. Dietary protein causes a ing Sinemet's effectiveness. COMT Inhibitor and Levodopa: ANTICHOLINERGIC AGENTS large peak in the concentration of certain amino Carbidopa-Levodopa-Entacapone (Stalevo®) (Artane®, Cogentin®) acids; when the blood amino acid levels are high, SUMMARY levodopa uptake into the brain is slow and inad- A combination tablet of carbidopa, levodopa and These drugs include trihexyphenidyl (Artane) and equate. The pharmacological management of Parkinson's entacapone is available and marketed as Stalevo. benztropine (Cogentin). Anticholinergic agents disease is complex and dynamic; there is no one Stalevo is indicated for treatment of idiopathic PD exert their effect in PD by correcting the imbalance Meals high in fat can also be a problem. A high-fat right strategy for what drugs to use at what stage to substitute for immediate-release (IR) created from decreased dopamine and unabated meal can take as long as two hours to clear the of the disease. However, it has been shown in vari- carbidopa-levodopa and entacapone previously cholinergic input. In addition to suppressing stomach. If Sinemet is in the stomach too, it will ous studies that starting medications early will administered as individual products and to replace central cholinergic activity, these agents may also also take two hours to clear, shortening its useful give better long-term motor results. The current IR carbidopa-levodopa when patients experience inhibit the reuptake and storage of dopamine at lifespan. Therefore, it is best to take Sinemet 30 to trend is to initiate symptomatic therapy with a the signs and symptoms of end-of-dose “wearing- the central dopamine receptors, thereby prolonging 60 minutes before eating a meal or 45 minutes dopamine agonist or other levodopa sparing agent off.” Stalevo simplifies treatment by providing the action of dopamine. They were the standard after the meal to decrease interference between such as rasagiline or selegiline and supplement three medications in one tablet, which reduces the antiparkinsonian treatment until the late 1960's, absorption of Sinemet and off proteins in the food. with levodopa when clinical features are no longer number of tablets patients need to take daily. An when newer drugs were developed. Anticholin- satisfactory. As PD progresses a combination of additional advantage is Stalevo 50 and 100mg ergics are most effective for reducing tremor, and levodopa therapy, dopamine agonists, MAO-B tablets are smaller for patients with swallowing usually provide minimal benefit with regard to Studies have further demonstrated that patients and/or COMT inhibitors are often used. Amanta- difficulties. The most common side effects of the bradykinesia and rigidity. In addition, tremor may who experience "on-off" fluctuations or who don't dine and anticholinergic agents are also occasion- combination product are nausea and dyskinesia or may not improve with anticholinergic agents respond to levodopa-carbidopa therapy can benefit ally used. The optimal effect of medication is which can often be managed with alteration in the and a given patient may respond to one anticholin- by adjusting their protein intake. Specifically, further obtained when used in conjunction with drug dosing schedule. Other common side effects ergic but not others. Their use is often limited by high-protein foods should be eaten only in the exercise, speech therapy, counseling, diet, support include diarrhea, urine discoloration, abdominal side effects such as dry mouth, constipation, evening; this allows better mobility during the day. groups and other nonpharmacologic therapies. pain, dizziness, constipation, fatigue, pain and memory impairment, confusion and hallucinations Another suggestion is to eat meals that consist of a hallucinations. and they are less well tolerated by older patients ratio of seven parts of carbohydrate to one part The enclosed pamphlet “Medications Approved for and those with dementia. Therefore, the prescrib- protein. A high ratio of carbohydrate to protein the Treatment of Parkinson’s Disease in the USA” AMANTADINE ing of anticholinergics is often confined to younger causes a large amount of insulin to be released into provides a summation of the PD medications, along (Symmetrel®) patients with tremor as the primary symptom. the blood. Insulin removes some of the amino acids with their mode of action and common side effects.

This antiviral agent has mild antiparkinson effects Medication Dosing and Administration and is thought to act by causing a release of dopamine from intact dopamine neurons remain- All medication used in the treatment of Parkin- ing in the substantia nigra. It may also inhibit son's disease should be introduced slowly to mini- dopamine reuptake, stimulate dopamine receptors, mize the appearance of adverse effects. They must exert an anticholinergic effect and block NMDA also be administered on time. Fluctuations of 30 (N-methyl-D-aspartate) receptors. Amantadine is minutes to an hour might be acceptable for other used mainly in the early stages of the disease (first agents but not Parkinson's medications. ly 6 to 12 months) as a means of controlling the symp- Reprinted Feb. 2013 toms of PD, thereby lengthening the amount of Even a slight fluctuation in schedule can result in time the patient can remain functional without the an exacerbation of symptoms and diminished qual- addition of levodopa. It seems to have only a mini- ity of life for some patients. Worse yet, the appear- mal effect on tremor and modest effect on rigidity ance of these symptoms could mistakenly convince and bradykinesia which may not be long lasting. caregivers that a patient needs more medication (f) Amantadine is also utilized in later stages of the and that could lead to unwarranted increases in disease for symptoms of “wearing off” or to possibly dosage. reduce dyskinesias (abnormal involuntary move- Research has shown that dietary protein antago- from the blood and may help lower the competition can also cause diarrhea and urine discoloration. ments). nizes the clinical effectiveness of the levodopa- between amino acids and levodopa thereby increas- carbidopa combination. Dietary protein causes a ing Sinemet's effectiveness. COMT Inhibitor and Levodopa: ANTICHOLINERGIC AGENTS large peak in the concentration of certain amino Carbidopa-Levodopa-Entacapone (Stalevo®) (Artane®, Cogentin®) acids; when the blood amino acid levels are high, SUMMARY levodopa uptake into the brain is slow and inad- A combination tablet of carbidopa, levodopa and These drugs include trihexyphenidyl (Artane) and equate. The pharmacological management of Parkinson's entacapone is available and marketed as Stalevo. benztropine (Cogentin). Anticholinergic agents disease is complex and dynamic; there is no one Stalevo is indicated for treatment of idiopathic PD exert their effect in PD by correcting the imbalance Meals high in fat can also be a problem. A high-fat right strategy for what drugs to use at what stage to substitute for immediate-release (IR) created from decreased dopamine and unabated meal can take as long as two hours to clear the of the disease. However, it has been shown in vari- carbidopa-levodopa and entacapone previously cholinergic input. In addition to suppressing stomach. If Sinemet is in the stomach too, it will ous studies that starting medications early will administered as individual products and to replace central cholinergic activity, these agents may also also take two hours to clear, shortening its useful give better long-term motor results. The current IR carbidopa-levodopa when patients experience inhibit the reuptake and storage of dopamine at lifespan. Therefore, it is best to take Sinemet 30 to trend is to initiate symptomatic therapy with a the signs and symptoms of end-of-dose “wearing- the central dopamine receptors, thereby prolonging 60 minutes before eating a meal or 45 minutes dopamine agonist or other levodopa sparing agent off.” Stalevo simplifies treatment by providing the action of dopamine. They were the standard after the meal to decrease interference between such as rasagiline or selegiline and supplement three medications in one tablet, which reduces the antiparkinsonian treatment until the late 1960's, absorption of Sinemet and off proteins in the food. with levodopa when clinical features are no longer number of tablets patients need to take daily. An when newer drugs were developed. Anticholin- satisfactory. As PD progresses a combination of additional advantage is Stalevo 50 and 100mg ergics are most effective for reducing tremor, and levodopa therapy, dopamine agonists, MAO-B tablets are smaller for patients with swallowing usually provide minimal benefit with regard to Studies have further demonstrated that patients and/or COMT inhibitors are often used. Amanta- difficulties. The most common side effects of the bradykinesia and rigidity. In addition, tremor may who experience "on-off" fluctuations or who don't dine and anticholinergic agents are also occasion- combination product are nausea and dyskinesia or may not improve with anticholinergic agents respond to levodopa-carbidopa therapy can benefit ally used. The optimal effect of medication is which can often be managed with alteration in the and a given patient may respond to one anticholin- by adjusting their protein intake. Specifically, further obtained when used in conjunction with drug dosing schedule. Other common side effects ergic but not others. Their use is often limited by high-protein foods should be eaten only in the exercise, speech therapy, counseling, diet, support include diarrhea, urine discoloration, abdominal side effects such as dry mouth, constipation, evening; this allows better mobility during the day. groups and other nonpharmacologic therapies. pain, dizziness, constipation, fatigue, pain and memory impairment, confusion and hallucinations Another suggestion is to eat meals that consist of a hallucinations. and they are less well tolerated by older patients ratio of seven parts of carbohydrate to one part The enclosed pamphlet “Medications Approved for and those with dementia. Therefore, the prescrib- protein. A high ratio of carbohydrate to protein the Treatment of Parkinson’s Disease in the USA” AMANTADINE ing of anticholinergics is often confined to younger causes a large amount of insulin to be released into provides a summation of the PD medications, along (Symmetrel®) patients with tremor as the primary symptom. the blood. Insulin removes some of the amino acids with their mode of action and common side effects.

This antiviral agent has mild antiparkinson effects Medication Dosing and Administration and is thought to act by causing a release of dopamine from intact dopamine neurons remain- All medication used in the treatment of Parkin- ing in the substantia nigra. It may also inhibit son's disease should be introduced slowly to mini- dopamine reuptake, stimulate dopamine receptors, mize the appearance of adverse effects. They must exert an anticholinergic effect and block NMDA also be administered on time. Fluctuations of 30 (N-methyl-D-aspartate) receptors. Amantadine is minutes to an hour might be acceptable for other used mainly in the early stages of the disease (first agents but not Parkinson's medications. ly 6 to 12 months) as a means of controlling the symp- Reprinted Feb. 2013 toms of PD, thereby lengthening the amount of Even a slight fluctuation in schedule can result in time the patient can remain functional without the an exacerbation of symptoms and diminished qual- addition of levodopa. It seems to have only a mini- ity of life for some patients. Worse yet, the appear- mal effect on tremor and modest effect on rigidity ance of these symptoms could mistakenly convince and bradykinesia which may not be long lasting. caregivers that a patient needs more medication (f) Amantadine is also utilized in later stages of the and that could lead to unwarranted increases in disease for symptoms of “wearing off” or to possibly dosage. reduce dyskinesias (abnormal involuntary move-