Used in Parkinsonism Other Movement Disorders

Drugs Used in Parkinsonism Other Movement Disorders 

Pathophysiology Parkinsonism is a common movement disorder that involves dysfunction in the basal ganglia and associated brain structures. Signs (mnemonic RAFT) include rigidity of skeletal muscles, akinesia (or bradykinesia), flat facies, and tremor at rest. 

DRUGS USED IN PARKINSONISM OTHER MOVEMENT DISORDERS / 253 

Strategies of drug treatment of parkinsonism involve increasing dopamine activity in the brain or decreasing muscarinic choUneigic activity in the brain (or both). 

Mechanisms Because dopamine has low bioavaUability and does not readily cross the blood-brain barrier, its precursor, t-dopa (levodopa), is used. This amino acid is converted to dopamine by the enzyme aromatic L-amino acid decarboxylase (DOPA decarboxylase), which is present in many body tissues, including the brain. Levodopa is usually given with carhidopa, a drug that does not cross the blood-brain barrier but inhibits DOPA decarboxylase in peripheral tissues. With this combination, lower doses of levodopa are effective, and there are fewer peripheral side effects. 

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As described in Chapter 28 Pharmacologic Management of Parkinsonism Other Movement Disorders, the treatment of Parkinson s disease is often an exercise in polypharmacy, since no single agent is fully effective over the course of the disease. Most antimuscarinic drugs promoted for this application (see Table 28-1) were developed before levodopa became available. Their use is accompanied by all of the adverse effects described below, but the drugs remain useful as adjunctive therapy in some patients. 

Antimuscarinic drugs used in parkinsonism are listed in Chapter 28 Pharmacologic Management of Parkinsonism Other Movement Disorders. 

From the evidence available to date, the reversible, short-acting MAO inhibitor moclobemide, which is available in several countries (but not the USA), appears to be relatively free of this interaction. (The selective MAO-B inhibitor selegiline loses selectivity at antidepressant dosage. Because its action is on the enzyme that metabolizes dopamine, it is most useful in the treatment of Parkinson s disease [Chapter 28 Pharmacologic Management of Parkinsonism Other Movement Disorders].)... 

Cabergoline, bromocriptine, and pergolide have been used in Parkinson s disease to improve motor function and reduce levodopa requirements as discussed in Chapter 28 Pharmacologic Management of Parkinsonism Other Movement Disorders. Cabergoline has also been effective in restless legs syndrome. 

Antipsychotics also have a troublesome side effect burden that includes an often-irreversible movement disorder known as tardive dyskinesia (TD). Other side effects include so-called parkinsonism, dystonic reactions (i.e., abrupt onset of muscle spasms), akathisia (an uncomfortable sense of motoric restlessness), sedation, weight gain, dizziness, dry mouth, and constipation among others. These side effects, in particular the risk for TD, limit the usefulness of antipsychotics in the treatment of ADHD, and at this time the typical antipsychotics cannot be considered a reasonable monotherapy in uncomplicated ADHD. 

Nicotine is most often used in replacement therapy for tobacco addiction, but also has some potential uses to treat other conditions. It has been helpful in stopping bleeding in ulcerative colitis. Nicotine gum is being tested in conjunction with Tourette syndrome where it has been seen to lessen the severity and frequency of tics. Nicotine may reduce tremors in Parkinson s patients because it increases dopamine levels, which are reduced in these patients. It also improves attention in Alzheimer s patients. Nicotine is being studied for its effect on dystonias (movement disorders), chronic pain syndrome, sleep apnea, ulcers, attention deficit disorder, obesity, and chronic inflammatory skin disorders as well. 

The authors concluded that the citalopram had probably precipitated latent Parkinson s disease. Citalopram is the most highly selective SSRI and, in anecdotal accounts, has been implicated somewhat less often than other SSRIs in extrapyramidal movement disorders. However, this case, together with another report of citalopram-induced worsening of pre-existing Parkinson s disease (12), suggests that it should be used with caution in patients with this disorder. 

Despite certain severe side effects, the drug lev-odopa (1-dopa) is currently used as the most effective medication in the treatment of Parkinson disease. Some of the adverse side effects are disorders of the digestive system, hemorrhage, disturbances in heart rhythm, depression, confusion, possible psychotic reactions, and delirious episodes. The extent of these reactions appears to be dependent on the amount of medication used. In some patients the mask-like facial expression gives way to distorted facial expressions, and other unusual body movements may result from the use of the drug. 

Nervous system Tetrabenazine inhibits vesicular monoamine transporter 2, leading to depletion of dopamine and other monoamines in the central nervous system. In a retrospective chart review, 448 patients who had used tetrabenazine between 1997 and 2004 (mean age at onset of the movement disorder, 43 years 42% men) were treated for a variety of hyperkinesias, including tardive dyskinesia (n = 149), dystonia (n = 132), chorea (n = 98), tics (n = 92), and myoclonus (n = 19) [68"]. They took treatment for a mean of 2.3 years and efficacy was sustained in most cases. Common adverse effects included drowsiness (25%), parkinsonism (15%), depression (7.6%), and akathisia (7.6%). Although it has repeatedly been observed that tetrabenazine alleviates hyperkinetic movements, it can worsen parkinsonism [69 ]. 

One of the most successful commercially available implantable microelectrode arrays is the deep-brain stimulator. Deep-brain stimulation (DBS) uses chronically implanted electrodes to treat neurological conditions such as movement disorders. Electrodes deliver high-frequency electrical stimulation to targeted regions of the brain to treat symptoms of Parkinson s disease. Implantable visual prostheses promise to restore vision by providing stimulation at the retina, optic nerve, or visual cortex. Cochlear implants include an electrode array implanted in the inner ear to stimulate the auditory nerve. Other commercially available implantable neural interfaces include neurostimulation systems for treatment of chronic pain or urinary control. 

Later, the disease does not respond to the drug and doses are required to be given in combination with carbidopa. Levodopa is effective in relieving bradykinesia and other disorderly voluntary movements. Parkinson s disease is not a hereditary disease. Drugs such as levodopa, carbidopa, benserazide, bromocriptine, pergolide, selegiline, and amantadine are used as therapeutic agents.61... 

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