Antiparkinson Drugs

Definition

Antiparkinson drugs are medicines that relieve the symptoms of Parkinson's disease and other forms of parkinsonism.

Purpose

Antiparkinson drugs are used to treat symptoms of parkinsonism, a group of disorders that share four main symptoms: tremor or trembling in the hands, arms, legs, jaw, and face; stiffness or rigidity of the arms, legs, and trunk; slowness of movement (bradykinesia); and poor balance and coordination. Parkinson's disease is the most common form of parkinsonism and is seen more frequently with advancing age. Other forms of the disorder may result from viral infections, environmental toxins, carbon monoxide poisoning, and the effects of treatment with antipsychotic drugs.

The immediate cause of Parkinson's disease or Parkinsonian-like syndrome is the lack of the neurotransmitter dopamine in the brain. Drug therapy may take several forms, including replacement of dopamine, inhibition of dopamine metabolism to increase the effects of the dopamine already present, or sensitization of dopamine receptors. Drugs may be used singly or in combination.

Description

Levodopa (Larodopa) is the mainstay of Parkinson's treatment. The drug crosses the blood-brain barrier, and is converted to dopamine. The drug may be administered alone, or in combination with carbidopa (Lodosyn) which inhibits the enzyme responsible for the destruction of levodopa. The limitation of levodopa or levodopa-carbidopa therapy is that after approximately two years of treatment, the drugs cease to work reliably. This has been termed the "on-off phenomenon." Additional treatment strategies have been developed to retard the progression of Parkinsonism, or to find alternative approaches to treatment.

Anticholinergic drugs reduce some of the symptoms of Parkinsonism, and reduce the reuptake of dopamine, thereby sustaining the activity of the natural neurohormone. They may be effective in all stages of the disease. All drugs with anticholinergic properties, the naturally occurring belladonna alkaloids (atropine, scopolamine, hyoscyamine), some antihistamines with anticholinergic properties, and synthetics such as benztropin (Cogentin), procyclidine (Kemadrin) and biperiden (Akineton) are members of this group. Although the anticholinergic drugs have only limited activity against Parkinson's disease, they are useful in the early stages, and may be adjuncts to levodopa as the disease progresses.

Amantadine (Symmetrel), was developed for prevention of influenza virus infection, but has anti-Parkinsonian properties. Its mechanism of action is not known.

Bromocriptine (Parlodel) is a prolactin inhibitor, which is used for a variety of indications including amenorrhea/galactorrhea, female infertility, and acromegaly. It appears to work by direct stimulation of the dopamine receptors. Bromocriptine is used as a late adjunct to levodopa therapy, and may permit reduction in levodopa dosage. Pergolide (Permax) is similar to bromocriptine, but has not been studied as extensively in Parkinson's disease.

Entacapone (Comtan) appears to act by maintaining levels of dopamine through enzyme inhibition. It is used as an adjunct to levodopa was the patient is beginning to experience the on-off effect. Tolcapone (Tasmar) is a similar agent, but has demonstrated the potential for inducing severe liver failure. As such, tolcapone is reserved for cases where all other adjunctive therapies have failed or are contraindicated.

Selegeline (Carbex, Eldepryl) is a selective monoamine oxidase B (MAO-B) inhibitor, however its mechanism of action in Parkinsonism is unclear, since other drugs with MAO-B inhibition have failed to show similar anti-Parkinsonian effects. Selegeline is used primarily as an adjunct to levodopa, although some studies have indicated that the drug may be useful in the early stages of Parkinsonism, and may delay the progression of the disease.

Pramipexole (Mirapex) and ropinirole (Requip) are believed to act by direct stimulation of the dopamine receptors in the brain. They may be used alone in early Parkison's disease, or as adjuncts to levodopa in advanced stages.

Recommended dosage

Dosages of anti-Parkinsonian medications must be highly individualized. All doses must be carefully titrated. Consult specific references.

KEY TERMS

Anorexia— Lack or loss of appetite.

Anticholigerginc— An agent that blocks the parasympathetic nerves and their actions.

Bradykinesia— Extremely slow movement.

Bruxism— Compulsive grinding or clenching of the teeth, especially at night.

Carbon monoxide— A colorless, odorless, highly poisonous gas.

Central nervous system— The brain and spinal cord.

Chronic— A word used to describe a long-lasting condition. Chronic conditions often develop gradually and involve slow changes.

Hallucination— A false or distorted perception of objects, sounds, or events that seems real. Hallucinations usually result from drugs or mental disorders.

Heat stroke— A severe condition caused by prolonged exposure to high heat. Heat stroke interferes with the body's temperature regulating abilities and can lead to collapse and coma.

Parkinsonism— A group of conditions that all have these typical symptoms in common: tremor, rigidity, slow movement, and poor balance and coordination.

Pregnancy category— A system of classifying drugs according to their established risks for use during pregnancy. Category A: Controlled human studies have demonstrated no fetal risk. Category B: Animal studies indicate no fetal risk, but no human studies; or adverse effects in animals, but not in well-controlled human studies. Category C: No adequate human or animal studies; or adverse fetal effects in animal studies, but no available human data. Category D: Evidence of fetal risk, but benefits outweigh risks. Category X: Evidence of fetal risk. Risks outweigh any benefits.

Seizure— A sudden attack, spasm, or convulsion.

Spasm— Sudden, involuntary tensing of a muscle or a group of muscles.

Tremor— Shakiness or trembling.

Precautions

There are a large number of drugs and drug classes used to treat Parkinson's disease, and individual references should be consulted.

The anticholinergics have a large number of adverse effects, all related to their primary mode of activity. Their cardiovascular effects include tachycardia, palpitations, hypotension, postural hypotension, and mild bradycardia. They may also cause a wide range of central nervous system effects, including disorientation, confusion, memory loss, hallucinations, psychoses, agitation, nervousness, delusions, delirium, paranoia, euphoria, excitement, lightheadedness, dizziness, headache, listlessness, depression, drowsiness, weakness, and giddiness. Dry mouth, dry eyes and gastrointestinal distress are common problems. Sedation has been reported with some drugs in this group, but this may be beneficial in patients who suffer from insomnia. Pregnancy risk factor is C. Because anticholinergic drugs may inhibit milk production, their use during breastfeeding is not recommended. Patients should be warned that anticholinergic medications will inhibit perspiration, and so exercise during periods of high temperature should be avoided.

Levodopa has a large number of adverse effects. Anorexia, loss of appetite, occurs in roughly half the patients using this drug. Symptoms of gastrointestinal upset, such as nausea and vomiting, have been reported in 80% of cases. Other reported effects include increased hand tremor; headache; dizziness; numbness; weakness and faintness; bruxism; confusion; insomnia; nightmares; hallucinations and delusions; agitation and anxiety; malaise; fatigue and euphoria. Levodopa has not been listed under the pregnancy risk factor schedules, but should be used with caution. Breastfeeding is not recommended.

Amantadine is generally well tolerated, but may cause dizziness and nausea. It is classified as pregnancy schedule C. Since amantadine is excreted in breast milk, breastfeeding while taking amantidine is not recommended.

Pergolide and bromocriptine have been generally well tolerated. Orthostatic hypotension are common problems, and patients must be instructed to risk slowly from bed. This problem can be minimized by low initial doses with small dose increments. Hallucinations may be a problem. Bromocriptine has not been evaluated for pregnancy risk, while pergolide is category B. Since both drugs may inhibit lactation, breastfeeding while taking these drugs is not recommended.

Pramipexole and ropinirole cause orthostatic hypotension, hallucinations and dizziness. The two drugs are in pregnancy category C. In animals, ropinirole has been shown to have adverse effects on embryo-fetal development, including teratogenic effects, decreased fetal body weight, increased fetal death and digital malformation. Because these drugs inhibit prolactin secretion, they should not be taken while breastfeeding.

Side effects

The most common side effects are associated with the central nervous system, and include dizziness, lightheadedness, mood changes and hallucinations. Gastrointestinal problems, including nausea and vomiting, are also common.

Interactions

All anti-Parkinsonian regimens should be carefully reviewed for possible drug interactions. Note that combination therapy with anti-Parkinsonian drugs is, in itself, use of additive and potentiating interactions between drugs, and so careful dose adjustment is needed whenever a drug is added or withdrawn.

Antiparkinson drugs

Definition

Antiparkinson drugs are medicines used to reduce the symptoms of Parkinson's disease .

Purpose

Parkinson's disease (PD) is a neurodegenerative disorder that affects movement. In PD, cells in a part of the brain called the substantia nigra die off. The normal function of these cells is to regulate the action of other cells in other brain regions by releasing a chemical called dopamine. When substantia nigra cells release dopamine, the dopamine attaches to dopamine receptors on the other cells, which influences them in various ways depending on the specific type of cell. The actions of these cells work in concert with other systems that influence movement. When all cells are working properly together, the end result is controlled, fluid movement.

When substantia nigra cells die off, however, as they do in PD, less dopamine is available for release. Consequently, the cells that depend on receiving dopamine are not properly regulated. The result is an imbalance in movement control that causes slowed movements, stiffness, and tremor—the classic signs of PD.

Antiparkinson drugs attempt to restore the balance through one of several mechanisms, depending on drug type. The most effective drugs, called dopaminergic drugs, replace dopamine, or mimic its action in the brain. Another group of drugs delays the breakdown of dopamine, thus increasing the level in the brain. Other drugs act on the other systems that influence movement, preventing them from being too active.

Description

Levodopa

Levodopa, also called L-dopa, is the most widely prescribed antiparkinson medication; almost all PD patients eventually receive levodopa. It is a chemical related to dopamine, and it is converted into dopamine within the brain. Dopamine itself cannot cross the barrier between the bloodstream and the brain, while levodopa can. This chemical form of dopamine works in the place of the natural dopamine that is lost due to the disease process.

Levodopa is chemically similar to amino acids, a type of molecule the body needs and absorbs from foods high in protein. In the digestive system, a carrier picks up the levodopa and transports it into the bloodstream. The same transport process occurs between blood and brain. Meals high in protein may interfere with absorption of levodopa from the digestive tract or from the blood into the brain. Patients may be advised to avoid high-protein meals too close to the time they take levodopa.

Once in the bloodstream, levodopa can be converted to dopamine. This is a problem because, as noted, dopamine cannot be taken into the brain. Additionally, dopamine in the periphery (that is, outside the brain) causes nausea, vomiting, and other adverse effects. To minimize these side effects, levodopa is always given with another drug that inhibits its conversion to dopamine in the periphery. In the United States, this drug is carbidopa. Levodopa and carbidopa are available in a single tablet, with doses adjusted for maximum benefit. However, it should be noted that peripheral dopamine is not always undesirable: it has important metabolic functions, including maintaining blood pressure.

Within the brain, levodopa is taken up by remaining substantia nigra cells, converted to dopamine, and released normally. The extra dopamine provided by the levodopa allows the brain to maintain normal movements, even in the face of dying substantia nigra cells. There are limitations because, as the disease progresses and more cells die, it becomes difficult for the few remaining cells to maintain normal function, even with extra dopamine.

Recommended dosage

Levodopa treatment is usually started when the patient's symptoms begin to interfere with daily living or the ability to work. Initial dosage is typically 200–600 mg of levodopa per day, taken in tablets with carbidopa. This amount of drug is contained in 2–6 tablets, which are taken at regular intervals during the day. The dose is adjusted to the point at which symptoms are well controlled. As the disease progresses, the dose is increased.

Precautions

Levodopa itself is not well tolerated, which is why it is combined with carbidopa. Carbidopa decreases peripheral metabolism of levodopa, which allows for lower doses of levodopa and less-severe side effects. The combination is a safe and well-tolerated medication for patients with Parkinson's disease. Levodopa may cause orthostatic hypotension , or low blood pressure upon standing. Patients with low blood pressure or who are susceptible to ortho-static hypotension should be cautious when starting treatment or increasing the dose.

Levodopa can cause sudden and unexpected extreme drowsiness, which some physicians term "sleep attacks." Currently, no reliable predictive criteria have been developed to determine which patients are susceptible. Patients starting levodopa should be aware of this possibility, and discuss with their physician how best to modify their activities (such as driving) to guard against injury in the event of such an incident.

Patients who have had myocardial infarction (heart attack) or other heart abnormalities should be monitored carefully when beginning levodopa treatment.

Side effects

Early on in the disease, levodopa can cause nausea, vomiting, orthostatic hypotension, and drowsiness. Nausea and vomiting typically stop being problems within several months of treatment.

Long-term use of levodopa in PD often leads to dyskinesias, or unwanted and uncontrolled movements. Dyskinesias appear as writhing, shaking, or twitching movements that may involve a small or large part of the body. Early in the disease, lowering the dose of levopoda can help control dyskinesias, but later on, the lower dose leads to significant loss of movement. Balancing the control of symptoms with the control of dyskinesias is a difficult and frustrating challenge for both patient and physician.

Long-term levodopa use can also lead to psychotic symptoms, including hallucinations, vivid and disturbing dreams, paranoia, and confusion.

Interactions

Patients who are taking drugs called nonselective MAO (monoamine oxidase) inhibitors should discontinue these drugs at least two weeks before beginning levodopa. MAO inhibitors are used to treat depression . A selective MAO-B inhibitor, such as selegiline, may be taken, and indeed is often prescribed for use in Parkinson's disease.

Description

Dopamine agonists

Dopamine agonists are drugs that mimic the effect of dopamine by stimulating the same cells as dopamine. They have several theoretical advantages over levodopa in the treatment of PD: dopamine agonists do not require uptake and release by substantia nigra cells; they do not compete with amino acids for transport, and so high-protein meals are not a problem; and the effect of an individual dose lasts longer.

One of the most significant advantages of the dopamine agonists is their ability to delay the onset of dyskinesias when used instead of levodopa at the start of disease. Patients who take a dopamine agonist instead of levodopa for the first 1–2 years tend to develop dyskinesias many months later than those who begin on levodopa. On the other hand, dopamine agonists are not quite as effective as levodopa at controlling other PD symptoms, and may cause more confusion in elderly patients. For this reason, common advice for elderly patients is to begin on levodopa, with the expectation that dyskinesias are less likely to be a serious problem within the treatment timeframe, while younger patients should begin on a dopamine agonist to delay dyskinesias within a much longer timeframe of treatment.

Dopamine agonists prescribed for PD in the United States include pramipexole, ropinirole, pergolide, and bromocriptine. Approval of another, apomorphine, was expected in early 2004. Unlike the others, apomorphine is injected and has a very short duration of action. It is intended for intermittent (not continuous) use as a treatment for emergent symptoms while waiting for the effect of other medications to begin.

Recommended dosage

There are half a dozen dopamine agonists available in oral forms for treatment of PD. The individual dosage and schedule for each vary. In each case, a low dose is used to begin with, with a gradual adjustment over several weeks to achieve the optimum level of symptomatic benefit.

Precautions

Like levodopa, the dopamine agonists may cause sudden and unpredictable episodes of extreme drowsiness.

Side effects

Long-term use of dopamine agonists can cause nausea, vomiting, orthostatic hypotension, and psychotic symptoms, including hallucinations, vivid and disturbing dreams, paranoia, and confusion. While the risk for developing dyskinesias is lower with dopamine agonists, their long-term use does lead to this complication in many patients.

Description

COMT inhibitors

COMT (Catechol-O-Methyl Transferase ) inhibitors restrict the action of an enzyme that converts levodopa to dopamine in the periphery (outside the brain). This allows more of the levodopa to reach the brain. In this way, a COMT inhibitor increases the effectiveness of a dose of levodopa. A COMT inhibitor cannot be used by itself, but must be administered with levodopa.

Recommended dosage

There are two COMT inhibitors approved for use in PD. Entacapone is dosed at 200 mg with each dose of levodopa. Tolcapone is dosed at either 100 or 200 mg three times per day.

Precautions

Tolcapone has been associated with liver damage in a small number of patients, which has led to death in three patients. Tolcapone is only approved for use by patients for whom other therapies are not providing adequate relief of symptoms.

COMT inhibitors increase the effectiveness of levodopa, as well as levodopa's side effects. Consequently, the same precautions apply for use of COMT inhibitors as for levodopa.

Side effects

COMT inhibitors can cause diarrhea. They also can increase the severity of levodopa's side effects, including orthostatic hypotension, hallucinations, and dyskinesias.

Description

MAO-B inhibitors

MAO-B inhibitors restrict the action of monoamine oxidase B, an enzyme that breaks down levodopa in the brain. Thus, an MAO-B inhibitor prolongs the effectiveness of dopamine, as well as a dose of levodopa. The only MAO-B inhibitor in widespread use for Parkinson's disease is selegiline, also called deprenyl.

Selegiline is often used in the early stages of PD, before other drugs, based on its mild symptomatic benefit. It is also often prescribed based on the possibility it may be neuroprotective—that is, it may help slow the death of neurons (brain cells) in the substantia nigra. While some experiments have suggested this may be true, others have shown no effect, and as of late 2003, there was no widespread consensus that selegiline had any effect in PD other than on symptoms.

Recommended dosage

Selegiline is usually prescribed at 5 mg twice daily.

Precautions

At doses higher than those used in PD, selegiline in combination with certain foods can lead to dangerously high blood pressure. These foods include aged cheeses, fermented beverages such as beer or wine, and smoked or pickled meats. This effect is also seen very rarely in patients taking the recommended dose for PD.

Selegiline should not be used with meperidine. Use with other narcotics should only be with the express approval of the patient's physician.

Side effects

Selegiline can cause side effects similar to levodopa, and when taken with levodopa, may worsen those effects. No reports of sudden drowsiness have been published for PD patients on selegiline alone.

Interactions

Interaction between selegiline and certain kinds of antidepressants is possible, and patients should consult with their physician before combining these two types of medications.

Description

Amantadine

Amantadine is prescribed for two different purposes in PD. It has a mild symptomatic effect in early PD, and is often prescribed before levodopa for that reason. It also reduces dyskinesias, and may be prescribed late in the disease once this symptom develops.

Recommended dosage

Amantadine is dosed at 200–300 mg per day.

Precautions

Patients with kidney disease or reduced kidney function require a much lower dose of amantadine.

Side effects

Amantadine can cause side effects similar to levodopa, including hallucinations, confusion, and orthostatic hypotension. Amantadine can also cause mottled skin and swelling in the peripheral tissues such as the legs.

Description

Anticholinergics

Anticholinergics were the first class of antiparkinson medications developed, but are used much less now than in the past, due to the availability of improved drugs. Anticholinergics suppress activity of the acetylcholine system in the brain, which is relatively overactive in PD. They are mainly effective against tremor and rigidity, and less so against slowed movements.

Recommended dosage

Different anticholinergics are dosed at different levels and frequencies. A dose is chosen that maximizes benefits and minimizes side effects. The dose is gradually increased to avoid worsening side effects.

Side effects

Anticholinergics can cause significant confusion, delirium , and hallucinations, especially in older patients. For this reason, they are seldom used in this group. They can also cause constipation and urinary retention.

Resources

PERIODICAL

Olanow, C. W., R. L. Watts, and W. C. Koller, eds. "An Algorithm (Decision Tree) for the Management of Parkinson's Disease (2001): Treatment Guidelines." Neurology 56, Supplement 5 (June 12, 2001): S1–S88.

WEBSITE

Parkinson's Disease: Etiology, Diagnosis and Management—Version 2.2. November 6, 2003 (March 2, 2004). <http://www.mdvu.org/multimedia/slides/parv2.2/>.

ORGANIZATIONS

National Parkinson Foundation. 1501 N.W. 9th Avenue, Miami, FL 33136-1494. (800) 327-4545. [email protected]. <http://www.parkinson.org>.

Richard Robinson

Antiparkinson Drugs

Definition

Antiparkinson drugs are medicines that relieve the symptoms of Parkinson's disease and other forms of parkinsonism.

Purpose

Antiparkinson drugs are used to treat symptoms of parkinsonism, a group of disorders that share four main symptoms: tremor or trembling in the hands, arms, legs, jaw, and face; stiffness or rigidity of the arms, legs, and trunk; slowness of movement (bradykinesia); and poor balance and coordination. Parkinson's disease is the most common form of parkinsonism and is seen more frequently with advancing age. Other forms of the disorder may result from viral infections, environmental toxins, carbon monoxide poisoning, and the effects of treatment with antipsychotic drugs.

The immediate cause of Parkinson's disease or parkinsonian-like syndrome is the lack of the neurotransmitter dopamine in the brain. Drug therapy may take several forms, including replacement of dopamine, inhibition of dopamine metabolism to increase the effects of the dopamine already present, or sensitization of dopamine receptors. Drugs may be used singly or in combination.

Description

Levodopa (Larodopa) is the mainstay of Parkinson's treatment. The drug crosses the bloodbrain barrier, and is converted to dopamine. The drug may be administered alone, or in combination with carbidopa (Lodosyn) which inhibits the enzyme responsible for the destruction of levodopa. The limitation of levodopa or levodopa-carbidopa therapy is that after approximately two years of treatment, the drugs cease to work reliably. This has been termed the "on-off phenomenon." Additional treatment strategies have been developed to retard the progression of Parkinsonism, or to find alternative approaches to treatment.

Anticholinergic drugs reduce some of the symptoms of Parkinsonism, and reduce the reuptake of dopamine, thereby sustaining the activity of the natural neurohormone. They may be effective in all stages of the disease. All drugs with anticholinergic properties, the naturally occurring belladonna alkaloids (atropine, scopolamine, hyoscyamine), some antihistamines with anticholinergic properties, and synthetics such as benztropin (Cogentin), procyclidine (Kemadrin) and biperiden (Akineton) are members of this group. Although the anticholinergic drugs have only limited activity against Parkinson's disease, they are useful in the early stages, and may be adjuncts to levodopa as the disease progresses.

Amantadine (Symmetrel), was developed for prevention of influenza virus infection, but has antiparkinsonian properties. Its mechanism of action is not known.

Bromocriptine (Parlodel) is a prolactin inhibitor, which is used for a variety of indications including amenorrhea/galactorrhea, female infertility, and acromegaly. It appears to work by direct stimulation of the dopamine receptors. Bromocriptine is used as a late adjunct to levodopa therapy, and may permit reduction in levodopa dosage. Pergolide (Permax) is similar to bromocriptine, but has not been studied as extensively in Parkinson's disease.

Entacapone (Comtan) appears to act by maintaining levels of dopamine through enzyme inhibition. It is used as an adjunct to levodopa was the patient is beginning to experience the on-off effect. Tolcapone (Tasmar) is a similar agent, but has demonstrated the potential for inducing severe liver failure. As such, tolcapone is reserved for cases where all other adjunctive therapies have failed or are contraindicated.

Selegeline (Carbex, Eldepryl) is a selective monoamine oxidase B (MAO-B) inhibitor, however its mechanism of action in Parkinsonism is unclear, since other drugs with MAO-B inhibition have failed to show similar anti-parkinsonian effects. Selegeline is used primarily as an adjunct to levodopa, although some studies have indicated that the drug may be useful in the early stages of Parkinsonism, and may delay the progression of the disease.

Pramipexole (Mirapex) and ropinirole (Requip) are believed to act by direct stimulation of the dopamine receptors in the brain. They may be used alone in early Parkison's disease, or as adjuncts to levodopa in advanced stages.

Recommended dosage

Dosages of anti-parkinsonian medications must be highly individualized. All doses must be carefully titrated. Consult specific references.

Precautions

There are a large number of drugs and drug classes used to treat Parkinson's disease, and individual references should be consulted. The most common side effects are associated with the central nervous system, and include dizziness, lightheadedness, mood changes and hallucinations. Gastrointestinal problems, including nausea and vomiting, are also common.

The anticholinergics have a large number of adverse effects, all related to their primary mode of activity. Their cardiovascular effects include tachycardia, palpitations, hypotension, postural hypotension, and mild bradycardia. They may also cause a wide range of central nervous system effects, including disorientation, confusion, memory loss, hallucinations, psychoses, agitation, nervousness, delusions, delirium, paranoia, euphoria, excitement, lightheadedness, dizziness, headache, listlessness, depression, drowsiness, weakness, and giddiness. Dry mouth, dry eyes and gastrointestinal distress are common problems. Sedation has been reported with some drugs in this group, but this may be beneficial in patients who suffer from insomnia. Pregnancy risk factor is C. Because anticholinergic drugs may inhibit milk production, their use during breastfeeding is not recommended. Patients should be warned that anticholinergic medications will inhibit perspiration, and so exercise during periods of high temperature should be avoided.

Levodopa has a large number of adverse effects. Anorexia, loss of appetite, occurs in roughly half the patients using this drug. Symptoms of gastrointestinal upset, such as nausea and vomiting, have been reported in 80% of cases. Other reported effects include increased hand tremor, headache, dizziness, numbness, weakness and faintness, bruxism, confusion, insomnia, nightmares, hallucinations and delusions, agitation and anxiety, malaise, fatigue, and euphoria. Levodopa has not been listed under the pregnancy risk factor schedules, but should be used with caution. Breastfeeding is not recommended.

Amantadine is generally well tolerated, but may cause dizziness and nausea. It is classified as pregnancy schedule C. Since amantadine is excreted in breast milk, breastfeeding while taking amantidine is not recommended.

Pergolide and bromocriptine have been generally well tolerated. Orthostatic hypotension are common problems, and patients must be instructed to risk slowly from bed. This problem can be minimized by low initial doses with small dose increments. Hallucinations may be a problem. Bromocriptine has not been evaluated for pregnancy risk, while pergolide is category B. Since both drugs may inhibit lactation, breastfeeding while taking these drugs is not recommended.

Pramipexole and ropinirole cause orthostatic hypotension, hallucinations and dizziness. The two drugs are in pregnancy category C. In animals, ropinirole has been shown to have adverse effects on embryo-fetal development, including teratogenic effects, decreased fetal body weight, increased fetal death and digital malformation. Because these drugs inhibit prolactin secretion, they should not be taken while breastfeeding.

Interactions

All anti-parkinsonian regimens should be carefully reviewed for possible drug interactions. Note that combination therapy with anti-parkinsonian drugs is, in itself, use of additive and potentiating interactions between drugs, and so careful dose adjustment is needed whenever a drug is added or withdrawn.

KEY TERMS

Anorexia— Lack or loss of appetite.

Anticholigerginc— An agent that blocks the parasympathetic nerves and their actions.

Bradykinesia— Extremely slow movement.

Bruxism— Compulsive grinding or clenching of the teeth, especially at night.

Carbon monoxide— A colorless, odorless, highly poisonous gas.

Central nervous system— The brain, spinal cord and nerves throughout the body.

Chronic— A word used to describe a long-lasting condition. Chronic conditions often develop gradually and involve slow changes.

Hallucination— A false or distorted perception of objects, sounds, or events that seems real. Hallucinations usually result from drugs or mental disorders.

Heat stroke— A severe condition caused by prolonged exposure to high heat. Heat stroke interferes with the body's temperature regulating abilities and can lead to collapse and coma.

Parkinsonism— A group of conditions that all have these typical symptoms in common: tremor, rigidity, slow movement, and poor balance and coordination.

Pregnancy category— A system of classifying drugs according to their established risks for use during pregnancy. Category A: Controlled human studies have demonstrated no fetal risk. Category B: Animal studies indicate no fetal risk, but no human studies; or adverse effects in animals, but not in well-controlled human studies. Category C: No adequate human or animal studies; or adverse fetal effects in animal studies, but no available human data. Category D: Evidence of fetal risk, but benefits outweigh risks. Category X: Evidence of fetal risk. Risks outweigh any benefits.

Seizure— A sudden attack, spasm, or convulsion.

Spasm— Sudden, involuntary tensing of a muscle or a group of muscles.

Tremor— Shakiness or trembling.

Resources

ORGANIZATIONS

American Parkinson Disease Association. 60 Bay Street, Suite 401, Staten Island, NY 10301. (800) 223-2732.

National Institute of Neurological Disorders and Stroke. P.O. Box 5801, Bethesda, MD 20824. (800) 352-9424.

National Parkinson Foundation, Inc. 1501 N.W. 9th Avenue, Miami, FL 33136-1494. (800) 327-4545.