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. Antiparkinson Drugs Brand Name (GenericName) Possible Common Side Effects Include: Artane (trihexyphenidylhydrochloride) Dry mouth, nervousness, blurred vision,nausea Benadryl (diephenhydra-mine hydrochloride) Dizziness, sleepiness, upset stomach,decreased coordination Cogentin (benztropinemesylate) Constipation, dry mouth, nausea andvomiting, rash Eldepryl (selegilinehydrochloride) Abdominal and back pain, drowsiness,decreased coordination Parlodel (bromocriptinemesylate) Constipation, decreased blood pressure,abdominal cramps Sinemet CR Involuntary body movements, confusion,nausea, hallucinations 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. 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.