Parkinsonism 

The correct choice of pharmaceutical interventions for Parkinsonism management results in a better patient outcome and reduced occurrence of motor complications. This guideline outlines the efficacy and the adverse effects of the available class of drugs for pharmacotherapy of parkinsonism. Parkinsonism is characterized by tremor, bradykinesia, rigidity and postural instability. Treatment strategies of parkinsonism depend on the patient’s age, disease stage, most troublesome symptoms, the balance between efficacy, and other factors. However, it is important to base treatment decisions on the best available data for each intervention. Practical guideline for the adjustment of initial therapy in patients without motor complications Patients not on dopaminergic therapy: If a patient has started on an MAO-B inhibitor, anticholinergic, amantadine or a combination of these, a stage will come when there is a requirement for adding levodopa or a dopamine agonist. Patients on dopaminergic therapy: If on dopamine agonist therapy: Increase the dose. Switch between agonists Add levodopa If on levodopa: Increase the dose Add an agonist Add a COMT inhibitor Patients with disabling tremor: If significant tremor persists, use the following: Anticholinergics Clozapine Beta-blockers Deep brain stimulation Class of drugs for therapeutic interventions of parkinsonism Anticholinergics Anticholinergics were the first drugs for the treatment of Parkinson’s disease. Monotherapy with these drugs is effective in improving motor function. Anticholinergics such as Biperiden is as effective as apomorphine for parkinsonian tremor and have a small motor effect. Adjunctive therapy of benztropine/bornaprine in levodopa-treated patients has minor effect on PD symptoms. However, the clinical use of anticholinergics is limited by cognitive and neuropsychiatric side effects. Amantadine Amantadine blocks NMDA glutamate receptors and may have an anticholinergic effect and release presynaptic dopamine stores. Monotherapy with amantadine results in improvement of parkinsonism. The addition of amantadine to anticholinergics is also efficacious. It has been found that Amantadine is beneficial as an adjunct to levodopa. Side effects of amantadine include dizziness, anxiety, insomnia, vomiting, edema, headache, nightmares, ataxia, confusion/agitation, constipation/diarrhea, anorexia, xerostomia, and livedo reticularis. Levodopa Levodopa acts through conversion to dopamine and is routinely combined with a decarboxylase inhibitor (benserazide/carbidopa). Levodopa is highly effective and reduces UPDRS score. Its symptomatic effect has been proved better than ropinirole, pramipexole, pergolide, lisuride, and cabergoline. Supplementation of levodopa to other antiparkinsonian medications is common clinical practice to improve symptomatic control. Shortening of dose intervals and reducing individual doses of levetova may postpone the emergence of motor complications. Adverse effects of these drugs include neuropsychiatric complications, gastrointestinal and cardiovascular dysfunction. MAO-B inhibitors Selegiline and rasagiline inhibit monoamine oxidase isoenzyme type B, preventing the breakdown of dopamine. Unlike oral selegiline, buccal selegiline and rasagiline are not metabolized to amphetamine. Clinical trials with rasagiline in early PD showed a modest benefit. No consistent beneficial effect was demonstrated in studies for the addition of selegiline to other antiparkinsonian therapies in nonfluctuating patients. So, combination therapies are not beneficial. Selegiline has no effect in preventing motor complications. Dopaminergic adverse reactions, the serotonine syndrome may occur with MAO-B inhibitors as common side effects. COMT inhibitors Catechol-O-methyltransferase inhibitors reduce the metabolism of levodopa, extending its plasma half-life and prolonging its action. Levodopa/carbidopa/entacapone combination is better than monotherapy with levodopa/carbidopa alone in patients. COMT inhibitors induce dopaminergic reactions. Diarrhea occurs in 3–5% of patients 2–3 months after initiation and may require discontinuation. Tolcapone can rarely increase liver enzymes. Dopamine agonists Of the 10 dopamine agonists available for PD, five are ergot derivatives (bromocriptine, cabergoline, dihydroergocryptine, lisuride, pergolide) and five are non-ergot (apomorphine, piribedil, pramipexole, ropinirole, rotigotine). Apart from apomorphine and rotigotine, which are used via the subcutaneous or transdermal routes, respectively, all other agonists are used orally. Dihydroergocryptine, pergolide, pramipexole, Ropinirole, piribedil, and rotigotine are effective in early PD. Although Levodopa is more efficacious than any oral dopamine agonist, the addition of the agonists to Levodopa-treated patients results in improvement in parkinsonism. Early agonist use can reduce the incidence of motor complications (better than Levodopa). Complications with dopamine agonists are hallucinations, somnolence and leg edema. The risk of pleuropulmonary/ retroperitoneal and heart valve fibrosis is greater with ergot agonists. Multiple pharmacological interventions are available for the management of parkinsonism. However, the best treatment decision depends on the combination of the efficacy and the adverse complications of the drugs.

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