Parkinson Disease Treatment

Parkinson Disease Treatment

The goal of medical treatment in Parkinson disease is to control signs and symptoms for as long as possible, while the adverse effects of drugs should be minimized. Medical treatment for Parkinson disease include levodopa, dopamine agonists, anticholinergic medication and other therapeutic agents.

Levodopa

Levodopa is considered the most effective drug for Parkinson disease. Is a precursor of dopamine. The indication of using this drug is represented by the biochemical imbalance produced by depletion of dopamine in the nuhcleus striatum. Levodopa can be combined with peripheral dopa decarboxylase inhibitor such as carbidopa or benserazide, in order to prevent its fast destruction and to achieve a better control of the symptoms with a low doses of levodopa.

Levodopa relieves disease symptoms, but with prolonged use of the drug and the disease progression will appear  the wearing off phenomenon (a gradually decrease in the efficiency of the drug before the administration of the next dose).

Levodopa adverse effects are important,  being represented by involuntary movements, labial dyskinesia, lingual, trunk, neck and limbs dystonia, grimacing and head movements. May also occur orthostatic hypotension, depression and the possibility of worsening a preexisting depression. Other adverse effects are represented by hyperexcitability and aggression.

Parkinson Disease Treatment

Secondary phenomena usually occur at high doses of levodopa, after a long term therapy. If adverse effects appear at low doses, combination with other dopaminergic agents such as amantadine or bromocriptine is recommended. It is believed that long-term evolution of Parkinson disease is not influenced by treatment with levodapa, even administered from the early stages of the disease. Degeneration of substantia ningra cells progresses and after years of  Parkinson disease evolution, drug efficiency is decreasing and in 80% of patients will appear dyskinesias and fluctuations in drug response or on-off phenomenon.  On-off phenomenon is a state in which patient passes within a few minutes from a state of relative mobility to a complete immobility, akinesia, hypotonia, which may last from 30 minutes to several hours, state that is not modified by the next dose of levodopa. The cause is unknown, although it was observed that off phenomena are correlated with low plasma levels of levodopa concentration.

Inhibitors of catechol-O-methyl transferase (COMT)

Inhibitors of catechol-O-methyl transferase (COMT), represented by tolcapone and entacapone are adjuncts for levodopa treatment. Are recommended in patients with Parkinson disease who present wearing off phenomena, in order to prolong the response to levodopa.

Dopamine agonists

Bromocriptine is an ergotamine derivative that stimulates dopamine receptors. It is used in combination with levodopa in Parkinson disease cases associated with dyskinesias or on-off phenomena and allows lower levodopa doses. As side effects were reported nausea, vomiting, hypotension, confusional states and hallucinations.

Pergolide or lisuride is also a ergotamine derivative used as an adjunct drug to cases that do not respond satisfactorily to levodopa. Pramipexole and ropinirole are other dopamine receptor agonist that directly stimulates dopamine receptors. Adverse effects of these drugs are represented by nausea, vomiting, hypotension, hallucinations.

Anticholinergic medication

Are used for a longtime as initial therapy for Parkinson disease in order to counteract the predominance of cholinergic system induced by dopamine deficiency. Synthetic anticholinergics are represented by artane, cogentin and biperiden, being useful in tremor control. Side effects are represented by dry mouth, blurred vision (mydriasis), dizziness, constipation, urinary retention, worsening of an untreated glaucoma, confusional states and hallucinations.

Amantadine

It is an antiviral agent that stimulates dopamine release in the striatum nucleus neurons and also present anticholinergic effects. It is useful in controlling hypokinezia, rigidity and tremor, the beneficial effects of the drug appear immediately after initiation of therapy. It is recommended to be administrated on newly diagnosed cases or on patients who present intolerance on effective doses of levodopa. Amantadine may be associated with levodopa or anticholinergic treatment. Side effects are represented by lower limb edema, congestive heart failure, livedo reticularis, urinary retention and visual hallucinations.

Parkinson Disease Treatment

Selegiline

Is an monoamine oxidase B  inhibitor (IMAO-B), being used in early forms of Parkinson disease. It inhibits the metabolic degradation of intracerebral dopamine. Selegiline can be associated with levodopa treatment, but should not be associated with antidepressant medication. Selegiline also have neuroprotective effect.

Surgical Treatment

Surgery in Parkinson’s disease has two objectives: to suppress certain clinical signs, especially tremor and compensate dopamine deficiency. Surgical options are sterotactic interventions and consists of ablation procedures and chronic stimulation of certain brain structures: the ventral intermediate thalamic nucleus, subthalamic nucleus and globus pallidus.

Pallidototmy (globus pallidus surgical removal) was practiced for dyskinesias and motor fluctuations induced by medical treatment. Thalamotomy (thalamus surgical removal), after certain statistics, improved tremor and reduced rigidity in 90% of patients and has little effect on bradykinesia, rigidity, motor fluctuations or dyskinesia. Bilateral thalamic interventions have a high incidence of speech disorders (dysarthria) and are not recommended.

Neural transplantation could represent a potential treatment for Parkinson disease and consist of  implantation in putamen and caudate nucleus of autologous adrenal medullary cells or of fetal porcine adrenal medullary cells. Investigations on the usefulness of these methods are still in progress.