Medical management There are no known disease-modifying agents for the treatment of PD. The cornerstone of management continues to be symptom management through levodopa therapy. Medical management also incorporates surgical procedures and referral to rehabilitation therapies. Pharmacological management Dopaminergic drugs improve motor function, reduce both the morbidity and mortality of PD, and improve quality of life (Armstrong & Okun, 2020). Levodopa was first developed in the 1960s, and when combined with carbidopa, it is the most clinically effective medication for managing the symptoms of PD. The brand names for carbidopa-levodopa are Sinemet ® , Atamet ® , and Parcopa ® . When levodopa is combined with carbidopa, it is better able to cross the blood-brain barrier and is turned into dopamine within the nerve cell. It alleviates bradykinesia and rigidity but has only minimal effect on reducing tremor. Common side effects include orthostatic hypotension, dyskinesias, hallucinations, and sleepiness. Although early symptoms of PD respond well to levodopa or carbidopa- levodopa, late-occurring motor and nonmotor symptoms respond poorly to this medication. Over time, the death of neurons in the basal ganglia leads to the need for higher and higher doses of dopaminergic drugs to obtain symptomatic relief. Because dopamine is active systemically, these higher doses lead to undesired secondary effects. One such secondary effect is dyskinesia (abnormal involuntary movement), which typically occurs at peak dose. Patients often report that they are not troubled by the dyskinesias and would rather have the dyskinesias than be Table 2: Pharmacologic Management of Parkinson’s Disease Dopamine agonists Directly stimulate dopamine receptors.
hypokinetic or experience “freezing.” Another secondary effect, increased motor fluctuations, becomes problematic later in the disease. Known as an on-off phenomenon, these fluctuations in motor performance occur as the level of active drugs in the system ramp up and then fall off. Overall, levodopa-carbidopa has been well tolerated and effective. However, its use in treating younger patients for longer periods poses an increased risk of long-term complications. Therefore levodopa-sparing strategies, which use agents such as dopamine agonists to optimize endogenous dopamine use and uptake, are being instituted early in treatment (Armstrong & Okun, 2020). Medications such as Eldepryl ® and Deprenyl ® act to optimize endogenous dopamine by slowing down its reuptake; the dopamine agonists Requip ® , Mirapex ® , and Neupro ® mimic dopamine in the brain and activate the dopamine receptors. Other medications, such as catechol-O-methyltransferase (COMT) inhibitors and anticholinergics, are used for symptomatic relief. COMT inhibitors potentiate levodopa by preventing its degradation by COMT. Anticholinergic medications reduce overactivity of acetylcholine and thus inhibit dopamine reuptake in the striatum of the basal ganglia. This medication is good for reducing tremor activity and is typically used in younger individuals. Monoamine oxidase B (MAO-B) inhibitors inhibit MAO-B, which degrades dopamine after it is released. Use of these medications lengthens the time in which dopamine remains active in the brain. Glutamate antagonists are known as dopamine agonists because they lead to the release of dopamine and decrease dopamine reuptake. A full listing of common medications used for the treatment of PD and their actions is provided in Table 2.
Pramipexole (Mirapex ® ), ropinirole (Requip ® ), apomorpine (Upima ® ). Entacapone (Comtan ® ), LD and entacapone (Stalevo ® ), tolcapone (Tasmar ® ). Trihexyphenidyl HCl (Artane ® ) and benztropine mesylate (Cogentin ® ), procyclidine hydrochloride (Kemadrin ® ). Selegiline hydrochloride (Eldepryl ® ), rasagiline (Azilect ® ).
COMT inhibitors
Potentiates levodopa: prevents its degradation by COMT. Reduce overactivity of acetylcholine; inhibit dopamine reuptake in the striatum; good for tremors; used in younger individuals.
Anticholinergics
MAO-B inhibitors
Inhibits MAO-B that degrades dopamine.
COMT = catechol-O-methyltransferase; MAO-B = Monoamine oxidase B Note . From Western Schools, 2018. Surgical intervention
carbidopa; and (3) unilateral implantation often fails to mitigate gait and balance problems. Pallidotomy surgery permanently destroys the overactive globus pallidus internus to eliminate rigidity and significantly reduce contra-lateral tremor, bradykinesia, and balance problems. An invasive surgery with the potential for life-threatening side effects, pallidotomy surgery has been used only rarely since the advent of deep brain stimulation procedures. However, because pallidotomy surgeries were performed in the recent past, therapists may treat individuals who, having had a pallidotomy, are now unable to benefit from additional symptom relief through deep brain stimulation. Thalamotomy surgery destroys part of the ventrolateral thalamic nucleus to relieve contralateral tremors. Destruction of this small area of the thalamus enhances the benefit of medication for the treatment of tremors and helps to lessen tremors. Because this surgical procedure addresses only tremor, it is rarely used to treat individuals with PD. It would be used only in individuals whose primary disability was because of tremor; in PD, the disability is usually due to bradykinesia and postural instability along with some individuals also being significantly affected by the presence of tremors. The advent of deep brain stimulation has further lessened the use of thalamotomy in treating PD.
There are three common surgical procedures that can be used to treat the symptoms of PD: deep brain stimulation, pallidotomy, and thalamotomy. Deep brain stimulation involves placing electrodes in the brain that are connected by wires to an impulse generator implanted under the skin of the chest, below the collarbone. It is unclear whether the stimulation suppresses or activates cells. This procedure is indicated when a person is still responsive to dopaminergic medications, yet continues to have disabling symptoms or motor fluctuations despite taking medications. For example, individuals may experience prolonged “off” times during the day that prevent them from being able to walk or stand. Because the procedure reduces parkinsonian symptoms (tremors, rigidity, bradykinesia), individuals can take less carbidopa-levodopa. Decreasing their dopamine therapy can help those who have difficulty with significant dyskinesias, a side effect of the medication that can develop over time. The impulse generators (stimulators) typically last 3 to 5 years before requiring replacement. There are some limitations to deep brain stimulation: (1) most patients must still take medications; (2) the amount of reduction in symptoms is never better than what can be achieved with levodopa-
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