Dopamine agonists: When levodopa responsiveness is lost dopamine agonists are used. Bromocriptine is a D2 agonist with mixed agonist and antagonist effects at D: receptors. Lisuride and Pergolide are more potent and act mainly at D2 receptors. Apomorphine is an agonist at both D! and D2 receptors given by continuous infusion or intermittent injection and is effective in shortening periods of prolonged immobility (freezing).
Dopamine agonists may produce postural hypotension and confusion. Selegiline: the enzymes monoamine oxidase (MAO) A and B play a key role in the breakdown of dopamine. This drug is an MAO-B inhibitor. Its usage results in increased dopamine levels. A recent randomised study has suggested a neuroprotective as well as symptomatic effect.
Amantidine, an antiviral drug, may help rigidity. The mode of action is not known.
Advances in drug treatment in recent years have reduced the need for stereotactic surgery (see page 370), but in patients with intractable tremor this is still of benefit. A stereotactic lesion is made in the globus pallidus or ventrolateral nucleus of the thalamus (contralateral to the tremor). Pallidotomy relieves contralateral dyskinesia. Human fetal and medullary transplantation: experimental evidence shows that transplantation to the striatum of tissue capable of synthesising and releasing dopamine reverses the motor symptoms of Parkinson's disease. Despite much publicity, this treatment remains experimental.
Regime of Treatment (Drug therapy becomes more complex as disease progresses)
EARLY-- FLUCTUATIONS — LOSS OF -- AKINETIC -- END II
TREATMENT (ON/OFF) DOPAMINE 'FREEZING' STAGE
AT DIAGNOSIS RESPONSIVENESS DISEASE
Reduce dose and give more frequently
Reduce dose and give more frequently i amantadine i anticholinergics
Introduce controlled-release preparations i amantadine i anticholinergics
Introduce controlled-release preparations
Additional measures Nausea: -
Peak dose dyskinesia: End dose dyskinesia: -
— domperidone (peripheral dopamine antagonist)
— tilt bed head, elastic stockings + mineralocorticoid
— lower levodopa dose
— add dopamine agonist
Nocturnal pain/immobility: - add controlled-release levodopa at night
Confusion I aggravated - add clozapine (cortical dopamine antagonist)
dementia: if no help reduce levodopa and/or dopamine agonist
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