Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We present a review of the recent literature and personal experience with apomorphine in patients with Parkinson's disease. Apomorphine is a potent D1 and D2 dopaminergic agonist. It has a rapid and short duration effect after subcutaneous administration at doses ranging from 15 to 180 micrograms/kg. Plasma maximal concentration is reached in 8-16 minutes, with a plasma half life of 34-70 minutes. Bioavailability is close to 100%. Repeated injections in patients show post-stimulative hyposensitivity. Apomorphine test appears very useful for the differential diagnosis between idiopathic Parkinson's disease and other Parkinson plus syndromes, and as a predictive test for dopaminergic responsiveness. Appropriate doses are able to alleviate akinesia, rigidity and tremor. Recent therapeutic trials have demonstrated the high interest of intermittent multiple subcutaneous apomorphine injections to cut the "off" motor phases in fluctuating parkinsonian patients under chronic levodopa treatment. In some cases, continuous apomorphine subcutaneous infusion with a portable pump may be required, particularly when levodopa treatment is temporarily interrupted, as after abdominal surgery. During long-term treatment, the apomorphine dose able to relieve akinesia remains stable. Peripheral side effects such as nausea and hypotension may be prevented by the co-administration of domperidone, a peripheral dopaminergic antagonist. Cutaneous fibrous nodules and psychiatric symptoms may occur, but usually at high dosages with continuous infusion. Local allergic effects have limited the use of other routes of administration, such as intranasal, sublingual, and rectal routes. Apomorphine is also used as a pharmacological tool for clinical research with the aim of a better understanding of the pathophysiology of Parkinson's disease.
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PMID:Apomorphine in patients with Parkinson's disease. 766 39

28 patients suffering from idiopathic Parkinson's disease received subcutaneous apomorphine for the treatment of painful dystonia and of off-phases of long duration. After a mean period of 12.4 months 20 patients still used apomorphine. In this time the mean dose per injection had fallen from 2.5 mg to 2.1 mg and the mean number of daily applications from 2.6 to 2.2. Most patients considered dystonias and off-phases to respond satisfactorily to apomorphine. However, in most cases the treatment effect was impaired by side effects, especially nausea.
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PMID:[Apomorphine as adjuvant treatment in idiopathic Parkinson syndrome]. 770 89

The main clinical features, pathophysiology and underlying mechanisms of drug-induced parkinsonism are reviewed. The clinical manifestations of drug-induced parkinsonism are often indistinguishable from idiopathic Parkinson's disease. However, some subtle differences may exist: for example drug-induced parkinsonism is often associated with tardive dyskinesias, bilateral symptoms and the absence of resting tremor, etc. Besides toxins (eg manganese, carbon monoxide or MPTP), many drugs are known to produce parkinsonism: dopamine blocking drugs (true neuroleptics used as antipsychotics: phenothiazines, butyrophenones, thioxanthenes but also sulpiride, "hidden" neuroleptics prescribed as anti-nausea or anti-vomiting drugs (such as metoclopramide and other benzamide derivatives), dopamine depleting drugs (reserpine, tetrabenazine), alpha-methyldopa, calcium channel blockers (flunarizine, cinnarizine, etc). The putative role of other drugs (eg fluoxetine, lithium, amiodarone) as well as the therapeutic management of this side effect are reviewed.
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PMID:Drug-induced parkinsonism: a review. 785 36

GI motility changes little--if at all--with age in healthy patients. However, a variety of diseases, including diabetes and Parkinson's disease, may cause autonomic neuropathy that is manifest as a motility disorder in the GI tract. Autonomic neuropathy can cause dysmotility in the esophagus, stomach, and gut. Symptoms are often nonspecific, including difficulty in swallowing, nausea, vomiting, heartburn, indigestion, diarrhea, and constipation. Nonpharmacologic treatment includes management of underlying diseases, avoidance of anticholinergic medications, and dietary changes. Agents with prokinetic action are the therapy of choice when drug treatment is indicated.
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PMID:GI motility disorders: diagnostic workup and use of prokinetic therapy. 790 Nov 29

We describe our clinical experience in the evaluation of gastrointestinal symptoms in patients with Parkinson's disease. Dysphagia, heartburn, medication-related nausea, and constipation were the predominant symptoms. Although all of the patients localized their dysphagia to the oropharynx and although oropharyngeal dysfunction was common, evaluation revealed significant dysfunction in either the esophageal body or lower esophageal sphincter in many--gastroesophageal reflux-related disease being especially common. Studies of anorectal sphincter and pelvic floor function in those patients with constipation demonstrated a high incidence of abnormal external anal sphincter dysfunction. We conclude, first, that dysphagia in patients with Parkinson's disease should not be assumed to result solely from oropharyngeal dysfunction but deserves detailed evaluation and, second, that constipation in Parkinson's disease is commonly consequent on anorectal sphincter and pelvic floor dysfunction.
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PMID:Gastrointestinal dysfunction in Parkinson's disease. A report of clinical experience at a single center. 793 Apr 24

In a recent study we identified abnormal salivation, dysphagia, nausea, constipation, and defecatory dysfunction as those gastrointestinal (GI) symptoms associated with Parkinson disease (PD) and characterized their relationship to PD severity and therapy. In this study, we re-evaluated these symptoms and their relationship to parameters of PD 18 months later. Sixty-six percent of the original participants responded. Over the 18 months, 68% of originally untreated PD subjects commenced anti-PD therapy. Abnormal salivation, dysphagia, nausea, constipation, and defecatory dysfunction were again identified as those GI symptoms more common in PD. Constipation increased both in severity and frequency. Comparison of GI symptom scores and parameters of PD dysfunction failed to reveal significant progression of either GI symptomatology or PD dysfunction, or the development of new GI symptoms over the 18-month period. This study validates our GI dysfunction assessment system and confirms abnormal salivation, dysphagia, nausea, constipation, and defecatory function as those GI symptoms truly associated with PD. A direct relationship between PD and its related GI symptoms is again supported.
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PMID:Gastrointestinal symptoms in Parkinson disease: 18-month follow-up study. 809 49

Apomorphine is a D1 and D2 dopamine receptor agonist with anti-parkinsonian properties qualitatively similar to those seen with L-dopa. It was first used in the treatment of Parkinson's disease by Schwab in the 1950s but owing to its short duration of action, the need for parenteral administration, and adverse reactions including nausea, vomiting, postural hypotension and sedation, it was not widely prescribed. In the early 1970s, Cotzias confirmed its potent anti-parkinsonian effects and that some of its secondary effects were diametrically opposite to those seen with L-dopa. The advent of peripheral dopamine receptor antagonist drugs, which counteract the unwanted effects of apomorphine, and the development of new drug delivery systems including insulin pens and ambulatory mini pumps have led to the resurrection of apomorphine for the treatment of Parkinson's disease. Over the last five years in Europe, the drug has proved to be a major advance in the treatment of refractory "on-off" oscillations in Parkinson's disease. It has also been used as a diagnostic test for dopaminergic responsiveness in Parkinson syndromes and tremors of uncertain aetiology. The drug has also proved particularly useful in dealing with certain "off-period" disabilities, including pain, bladder dysfunction, dystonia and gastro-intestinal symptoms. Continuous steady state infusion of apomorphine by mini-pump may reduce the severity of "on" phase dyskinesias over time. The drug has also proved useful in the clinical pharmacological investigation of the pathophysiology of the motor response to dopaminergic drugs in Parkinson's disease and the occurrence of involuntary movement sequences. Neuropsychiatric side-effects are relatively infrequent when compared with ergolene dopamine agonists.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dopamine agonists in Parkinson's disease: a look at apomorphine. 850 Jul 83

The D2 dopamine agonist piribedil is not widely used in the treatment of Parkinson's disease because it was thought to be effective mainly on parkinsonian tremor and to produce a high incidence of peripheral side effects, particular nausea. In this study, we used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated primates to reevaluate the antiparkinsonian ability of piribedil after its oral administration in the presence or absence of domperidone pretreatment. Adult common marmosets (Callithrix jacchus) were treated with the nigral toxin MPTP to induce a parkinsonian syndrome characterised primarily by bradykinesia and other motor deficits. Oral administration of a solution of piribedil [1-(3,4-methylenedioxybenzyl)-4-(2-pyrimidinyl)piperazine] produced a dose-related reversal of all MPTP locomotor and behavioural deficits. However, this effect was short lived and associated with unwanted effects, particular nausea and retching, which clearly hindered locomotion. In contrast, after pretreatment with the peripheral dopamine antagonist domperidone, administration of piribedil did not induce nausea or retching in MPTP-treated marmosets. In these animals, piribedil caused a more marked and longer lasting enhancement of locomotor activity and a further reduction in behavioural deficits than that observed after administration of piribedil alone. In addition, piribedil induced increased vigilance and awareness. These data show that piribedil can reverse akinesia and rigidity in MPTP-treated primates. In addition, they show the drug to be effective without peripheral side effects when used in conjunction with domperidone. These data indicate that piribedil should be an effective monotherapy for Parkinson's disease.
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PMID:An appraisal of the antiparkinsonian activity of piribedil in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated common marmosets. 868 81

Fifteen Thai patients with Parkinson's disease (7 females, 8 males) were enrolled in an open label trial of pergolide (a new dopamine agonist) to evaluate its safety and efficacy. Inpatients and outpatients from Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand from 1992 to 1994 were included in the study with a total duration of 18 weeks. Both de novo patients and patients who were being treated with levodopa without dopamine agonist and were obtaining a less than optimal response at both visit 1 and visit 2 were all enrolled in this study. At entry into the study, 3 patients had Hoehn and Yahr stage I, 7 patients at stage II, 3 patients at stage III, and 2 patients at stage IV. Pergolide dosage was gradually built up until an optimal dosage was achieved. The average dose of pergolide during the study was 0.94 mg/day (range 0.075 to 8 mg/day). All patients completed the study and no patients dropped out. Two patients (13.33 per cent) experienced nausea (on 0.4 mg/day and 0.075 mg/day), two patients (13.33 per cent) experienced sleepiness (0.50 mg/day and 0.075 mg/day) and one patient (6.67 per cent) unsteadiness on walking (0.50 mg/day). There was one patient who required pergolide up to 8 mg/day which is higher than the recommended dosage (5 mg/day) but this patient experienced no adverse effects and his disabled dyskinesic was abolished. Our study demonstrated the good toleration and efficacy of pergolide treatment for Thai patients with Parkinson's disease. This new dopamine agonist stimulates both D1 and D2 receptors in comparison to other dopamine agonists (bromocriptine and lisuride) which stimulate only D2 receptors.
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PMID:An open label trial of pergolide in Thai patients with Parkinson's disease. 870 4

Eleven patients with levodopa-related motor fluctuations were scored before and after intranasal apomorphine monotherapy, and the motor responses were compared with those with levodopa/carbidopa in this openlabel study. Oral trimethobenzamide was used to prevent apomorphine-induced nausea. Three measures of motor performance were employed: (a) the Unified Parkinson's Disease Rating Scale (UPDRS) motor battery; (b) a timed hand-tapping test; and (c) the Webster's step-seconds test. The magnitude of the motor-score improvement after apomorphine administration was very similar to that after the usual doses of levodopa/carbidopa in the 10 patients completing the study; this was true for all three outcome measures. A major advantage of apomorphine was the rapid onset of clinical response, which typically occurred in < 10 min, as well as the ease of administration. Major side effects, beyond those experienced with levodopa/carbidopa, were limited to nausea and vomiting (three patients) and orthostatic hypotension (one patient); however, only a single patient dropped out of the study as a consequence. These results indicate that intranasal apomorphine is effective in rapidly relieving parkinsonian "off" states and that, for most patients, trimethobenzamide is an effective and well-tolerated antiemetic for use with apomorphine.
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PMID:Intranasal apomorphine rescue therapy for parkinsonian "off" periods. 872 38


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