Levodopa Dopamine agonists

Parkinsonian patients receiving the dopamine precursor, levodopa or dopamine receptor agonists, such as bromocriptine and apomoiphine may experience nausea and vomiting due to stimulation of dopamine D2 receptors in the CTZ. 

Figure 15.5 Counteracting the emetic effect of (a) levodopa and (b) a dopamine agonist in the therapy of PD.

A number of azetidine-based compounds have been disclosed in patent applications from Aventis Pharma for CBi-modulated treatment of diseases such as obesity, Parkinson s disease, schizophrenia, respiratory and neurological diseases [330-334]. Compound (556) was specifically claimed for use in two formulation patent applications [330, 331] for a stable semi-solid composition and oral emulsion composition, respectively. The optional coadministration of an agent that activates norepinephrinergic and se-rotoninergic neurotransmission (for example, sibutramine) or dopaminergic neurotransmission was also claimed for the treatment of obesity. The optional use of a dopamine agonist (for example, levodopa) was claimed... 

Opioids, benzodiazepines, barbiturates, corticosteroids, dopamine agonists (e.g., amantadine, bromocriptine, levodopa, pergolide, pramipexole, ropinirole), H2-receptor antagonists, anticholinergics (e.g., diphenhydramine, trihexylphenidyl), P-adrenergic blockers, clonidine, methyldopa, carbamazepine, phenytoin, baclofen, cyclobenzaprine, lithium, antidepressants (e.g., tricyclic antidepressants, selective serotonin reuptake inhibitors), and interleukin-2... 

Dopamine agonists are useful as initial therapy, as they can delay the need to start levodopa and can decrease the risk of developing motor fluctuations by two- to threefold during the first 4 to 5 years of treatment. After a few years, dopamine agonists inadequately control the patient s symptoms and levodopa needs to be started. In advanced disease, dopamine agonists can be added to levodopa because they have a longer duration of action, minimize fluctuations in dopamine blood concentrations, decrease off-time, improve wearing-off symptoms, allow a reduction in levodopa dose, and improve ADLs.1-3,16,22,23,26... 

Bromocriptine is a dopamine agonist acting by direct stimulation of the dopamine receptors. In Parkinson s disease, it is reserved for use in patients who are intolerant to levodopa or in whom levodopa alone is not sufficient. Orphenadrine is an antimuscarinic indicated in Parkinson s disease. Antimuscarinics tend to be more effective than levodopa in targeting tremor rather than rigidity and bradykinesia. Moclobemide is an antidepressant referred to as a reversible monoamine oxidase inhibitor (RIAAA) type A. 

In medical practice, four types of dopaminergic drags are used, and they can be characterized as dopamine precursors (levodopa), dopamine-releasing drugs (amantadine), dopamine receptor agonists (bromocriptine), and dopamine inactivation inhibitors (selegiline). 

Antihypertensives, diuretics, antipsychotics, tricyclic antidepressants, levodopa, dopamine agonists, a-blockers Corticosteroids NSAIDs, anticoagulants -Blockers (non-selective)... 

The antihistamine diphenhydramine (Benadry/), because it has anticholinergic properties, is used for mild parkinsonism and with the elderly, who may not be able to tolerate the more potent anticholinergics, levodopa, or the dopamine agonists. 

Geriatric Considerations - Summary Ropinirole is a nonergot dopamine agonist which directly stimulates dopamine Dj receptors. It can be used in combination with levodopa or as monotherapy. If discontinued, ropinirole should be slowly tapered because abrupt discontinuation can cause confusion, hallucinations, and a condition similar to neuroleptic malignant syndrome. 

Levodopa, which is converted to dopamine in the body, and dopamine agonists with central actions are of considerable value in the treatment of Parkinson s disease and prolactinemia. These agents are discussed in Chapters 28 and 37. 

There is no evidence that one agonist is superior to another individual patients, however, may respond to one but not another of these agents. Apomorphine is a potent dopamine agonist but is discussed separately in a later section in this chapter because it is used primarily as a rescue drug for patients with disabling response fluctuations to levodopa. 

Levodopa or dopamine agonists produce diverse dyskinesias as a dose-related phenomenon in patients with Parkinson s disease dose reduction reverses them. Chorea may also develop in patients receiving phenytoin, carbamazepine, amphetamines, lithium, and oral contraceptives, and it resolves with discontinuance of the offending medication. Dystonia has resulted from administration of dopaminergic agents, lithium, serotonin reuptake inhibitors, carbamazepine, and metoclopramide and postural tremor from theophylline, caffeine, lithium, valproic acid, thyroid hormone, tricyclic antidepressants, and isoproterenol. 

Dopamine agonists suppress prolactin release very effectively in patients with hyperprolactinemia. GH release is reduced in patients with acromegaly, although not as effectively. Cabergoline and bromocriptine are also used in Parkinson s disease to improve motor function and reduce levodopa requirements (see Chapter 28). Newer, nonergot D2 agonists... 

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