Pramipexole Levodopa

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. 

Maintenance treatment - Pramipexole is effective and well tolerated over a dosage range of 1.5 to 4.5 mg/day administered in equally divided doses 3 times/day with or without concomitant levodopa ( 800 mg/day). When pramipexole is used in combination with levodopa, consider a reduction of the levodopa dosage. 

Pramipexole is not an ergot derivative, but it has preferential affinity for the D3 family of receptors. It is effective as monotherapy for mild parkinsonism and is also helpful in patients with advanced disease, permitting the dose of levodopa to be reduced and smoothing out response fluctuations. Pramipexole may ameliorate affective symptoms. A possible neuroprotective effect has been suggested by its ability to scavenge hydrogen peroxide and enhance neurotrophic activity in mesencephalic dopaminergic cell cultures. 

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. 

This patient had taken ecstasy 10 times during the year before, the last time about 3 months before the onset of symptoms. Apart from marijuana, he denied using other substances. He was treated with maximal tolerable doses of levodopa and pramipexole, without improvement. The authors reported that they had no explanation for this patient s symptoms, other than the use of ecstasy. They felt that the parkinsonian symptoms most closely resembled MPTP-induced parkinsonism. They further postulated that this could be a delayed neurotoxic effect of ecstasy in the substantia nigra and striatum and could have occurred as a result of neuronal damage by free radicals. 

DOPAMINERGICS PARACETAMOL Amantadine, bromocriptine, levodopa, pergolide, pramipexole and selegiline may slow the onset of action of intermittent-dose paracetamol Anticholinergic effects delay gastric emptying and absorption Warn patients that the action of paracetamol may be delayed. This will not be the case when paracetamol is taken regularly... 

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). 

Parkinson Study Group (2000) Pramipexole vs. levodopa as inidal heatment for Parkuison s disease A randomized con Rolled Rial. JAMA 284 1931-1938. 

It should be noted that the patient was and apparently still is taking pramipexole and amantadine in addition to levodopa. 

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. 

Pramipexole is a non-ergot dopamine agonist similar to bromocriptine, used in the management of Parkinson s disease as an adjunct to levodopa. 

Worsened dyskinesia is the most common outcome in patients with advanced disease taking concomitant levodopa therapy. In a systematic review of four randomized, placebo-controlled trials of pramipexole in 669 patients with idiopathic Parkinson s disease and long-term complications of levodopa therapy, there were no significant changes in a dyskinesia rating scale, but dyskinesia as an adverse event was reported more often with pramipexole... 

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. 

Antiparkinsonian agents Bromocriptine Dopamine Entacapone Levodopa Peroxide Pramipexole Rasagiline derivatives Lasdostigil m30... 

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