Ropinirole Levodopa

Bromocriptine (Parlodel) (Azilect) Carbidopa/Levodopa Ropinirole (Requip)... 

Great caution must be exercised in the use of this drug (or drugs from the same class) in parkinsonian patients who have prostatic hypertrophy or obstructive gastrointestinal disease (A) Benztropine Carbidopa Levodopa Ropinirole Selegiline... 

C2H3CIO 75-36-5) see Acebutolol Acetiamine Acetylcholine chloride L-Alanine Benfurodil hemisuccinate . Chlorprothixene Flumetasone Ibuprofen lotalamic acid loxitalamic acid Levodopa Methestrol dipropionate Midecamycin acetate Naproxen Nimesulide Paclitaxel Paramethasone Phensuximide Retinol Rocuronium bromide Rofecoxib Ropinirole Tazarotene Thiopropazate Tiracizine Vecuronium bromide... 

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... 

The most important alternatives to levodopa therapy are direct-acting dopamine receptor agonists, such as ropinirole,pramipexole, or pergolide (Fig. 46-5). A number of studies have shown that use of these agents may help to delay the need for use of levodopa/carbidopa. This has... 

Dopamine-Boosting Medications. Levodopa/carbidopa (Sinemet), bromocriptine (Parlodel), pramipexole (Mirapex), and ropinirole (Requip) increase dopamine nenrotransmission in the brain by one or another mechanism. These medications do not reliably induce sleep, and in some patients are activating. They are certainly not true sedative-hypnotics. They are most often used by neurologists to treat Parkinson s disease. 

Dopamine receptor agonists. Deficient dopaminergic transmission in the striatum can be compensated by ergot derivatives (bromocriptine p. 114], lisu-ride, cabergoline, and pergolide) and nonergot compounds (ropinirole, prami-pexole). These agonists stimulate dopamine receptors (D2, D3, and D sub-types), have lower clinical efficacy than levodopa, and share its main adverse effects. 

When ropinirole is administered as adjunct therapy to levodopa, the concurrent dose of levodopa may be decreased gradually as tolerated. Discontinue ropinirole gradually over a 7-day period. Decrease the frequency of administration from 3 times/day to twice/day for 4 days. For the remaining 3 days, decrease the frequency to once/day prior to complete withdrawal of ropinirole. 

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. 

Whone AL, Watts RL, Stoessl AJ, et al. Slower progression of Parkinson s disease with ropinirole versus levodopa the REAL-PET study. Ann Neurol 2003 54 93-101. 

Another nonergoline derivative, ropinirole (now available in a generic preparation) is a relatively pure D2 receptor agonist that is effective as monotherapy in patients with mild disease and as a means of smoothing the response to levodopa in patients with more advanced disease and response fluctuations. It is introduced at 0.25 mg three times daily, and the... 

Dopamine agonists Bromocriptine Cabergoline Pergolide Pramipexole Ropinirole Directly stimulates dopamine receptors in basal ganglia. May produce fewer side effects (dyskinesias, fluctuations in response) than levodopa preliminary evidence suggests that early use may also delay the progression of Parkinson disease. 

The following are new, non-ergot dopamine agonists that have been approved for the treatment of Parkinson s disease. Pramipexole and ropinirole are effective as first-line and adjunctive therapy, whereas tolcapone should only be used as an adjunct in patients on levodopa/carbidopa. 

A 38-year-old man developed Parkinsonism that progressed to Hoehn and Yahr stage 5 within 4 years of onset (44). Treatment with ropinirole resulted in further deterioration, levodopa was not tolerated, and subthalamic nucleus stimulation provided only partial relief. The patient reluctantly reported heavy use of ecstasy through most of his twenties and thirties. He had a family history of Parkinsonism, but other investigations to determine the underlying cause, such as urine copper and heavy metals, were non-contributory. 

Pramipexole has been shown to be safe and effective when used as monotherapy early in PD (Parkinson Study Group, 1997, 2000) and in mild to moderate PD (Shannon et al., 1997). Ropinirole has also been shown to be effective in early PD (Rascol et al., 1998 Korczyn et al., 1999). In later stages of PD, dopamine agonists are usually prescribed with levodopa to achieve optimal therapeutic effects and to help moderate the motor fluctuations associated with levodopa (Pinter et al., 1999). Possible side effects of all dopamine agonists include nausea, peripheral edema, somnolence and hallucinations. Pramipexole has also been associated with compulsive behavior (Driver-Dunckley etal., 2003). 

Rascol O, Brooks DJ, Brunt ER, Korczyn AD, Poewe WH, Stocchi F (1998) Ropinirole in die heatment of early Parkinson s disease A 6 mondi uiteiim report of a 5 year levodopa conholled study. Mov Disord 13 39 5. 

Some remarkable case reports have previously been published (SEDA-25, 169) and reports continue to appear, supplemented by prospective studies and other analyses. For instance, 11 studies involving ropinirole or pramipexole in a total of 2066 patients have been reviewed (24). Four of these (two each with ropinirole and pramipexole) were placebo-controUed. The pooled relative risk of somnolence was 4.98 compared with placebo there was a non-significant trend for greater somnolence with ropinirole, but the confidence intervals were much wider than with pramipexole. In the other studies levodopa alone was compared with levodopa plus the newer drugs the relative risk was 2.06 compared with levodopa alone. It must be borne in mind that somnolence and sleep attacks may be separate phenomena, although this is controversial. 

Overall, the current evidence suggests that sedation is a class effect of all dopaminergic drugs, including levodopa. It may be more severe with the newer synthetic agents pramipexole and ropinirole, but this cannot yet be stated with certainty. The existence of discrete sleep attacks also remains controversial, although on balance one would conclude that they can occur. 

Two women in New York, aged 66 and 68 years, took pramipexole 15 and 3.5 mg/day (11). Both developed progressive hair loss 2-12 months later. When pramipexole was withdrawn, there was partial regrowth of hair. Ropinirole and levodopa did not provoke hair loss in these women. 

Supraventricular extra beats have rarely been reported after low doses of ropinirole and have also been reported after pergolide and levodopa (1). Symptomatic postural hypotension has occurred after even low oral doses of ropinirole (2-5), related to peripheral dopaminergic activity. Hypotensive effects occur within 3 minutes of standing, usually between 2 and 4 hours after an oral dose, associated with nonspecific malaise (2). Dizziness occurred in up to 40% of patients in clinical trials. Related symptoms include faintness, malaise, and yawning (2). Bradycardia has occasionally accompanied postural hypotension (4). Syncope has been reported. 

Vidailhet MJ, Bonnet AM, Belal S, Dubois B, Marie C, Agid Y. Ropinirole without levodopa in Parkinson s disease. Lancet 1990 336(8710) 316-17. 

Rascol O, Brooks DJ, Korczyn AD, et al. A five-year study of the incidence of dyskinesia in patients with early Parkinson s disease who were treated with ropinirole or levodopa. N Engl J Med 2000 342 1491. 

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