Continuous dopaminergic stimulation

The Parkinson's-Reversing Breakthrough

Treatment Options for Parkinson Disease

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Natural dopamine is released constantly without significant day-night (diurnal) variations. Dopamine replacement therapy should ideally replicate this, but the short duration of levodopa when given orally does not fulfil this need. Oral DAs have a longer duration of action, and help to smooth out the motor fluctuations inherent to levodopa therapy. Longer-acting oral DAs (e.g. ropinirole prolonged release) allow once-daily dosing, while transdermal, subcutaneous, and enteral routes (levodopa as Duodopa) offer more constant delivery (67, 68).

Allowing a small drop in overnight levels may prevent the development of tolerance (i.e. increasing doses required for the same effect) but the clinical significance of this is not certain. The way the patient times their medication influences plasma (and brain) levels and may contribute to motor fluctuations.

Nasogastric test infusion

Pump and cassette

Gastric port PEG

Nasogastric test infusion

Pump and cassette

Gastric port PEG

Duodopa Pump Dutch

67 24-hour profile of antiparkinson therapy. Steady delivery of antiparkinson therapy fulfils the requirements of the continuous dopamine stimulation hypothesis. Avoiding fluctuating drug levels by infusions such as apomorphine and Duodopa, can help reduce motor fluctuations in late-stage disease. Longer-acting oral agents or transdermal delivery may prove helpful in a similar way However; there remains a need for a long-acting agent with the efficacy of levodopa.

68 Duodopa infusion. An intestinal infusion of levodopa in the form of Duodopa as a concentrated gel, requires insertion of a percutaneous gastrostomy tube (yellow line) with the tip placed at the junction of the duodenum and jejunum. Treatment is typically given during the waking day and this smooths out the fluctuations inherent in oral therapy in advanced disease.

Avoid frequent peaks and

Constant dose delivery achieved by rotigotine (transdermal patch)

troughs typical of standard oral

Steady daytime delivery achieved by apomorphine infusion; Duodopa; once daily drugs, e.g. rasagiline, cabergoline; long-acting oral non-ergot DAs, e.g. ropinirole prolonged release.

therapy

8 am

24 hours

CHAPTER 5

Nonmotor features of Parkinson's disease

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