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)

Domperidone is a dopamine antagonist that has recently been released in Canada. Unlike metoclopramide hydrochloride, the other available dopamine antagonist, it does not readily enter the central nervous system. Domperidone acts as both an antiemetic and an upper gastrointestinal tract prokinetic agent. It is rapidly absorbed after oral administration, and few side effects have been reported. Domperidone has been approved for use in Canada for the symptomatic management of upper gastrointestinal tract motility disorders and to prevent gastrointestinal symptoms associated with the use of dopamine agonist agents in Parkinson's disease. The pharmacologic features, indications and side effects of domperidone are reviewed.
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PMID:Domperidone, a new dopamine antagonist. 352 96

We studied the effects of bromocriptine therapy (mean dosage, 56.0 mg daily) for 12 months in five patients with both Parkinson's disease and hypertension. Therapy improved neurologic manifestations and reduced both supine and standing systolic blood pressures and standing diastolic blood pressure with no consistent change in heart rate. Transient episodes of orthostatic hypotension appeared in two cases. Domperidone (60 mg daily for 1 month) did not abolish the antihypertensive effect of bromocriptine, suggesting that central dopaminergic or alpha-adrenolytic mechanisms are involved in this effect. Bromocriptine may be useful in the treatment of hypertension in patients with Parkinson's disease.
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PMID:Parkinson's disease and hypertension: chronic bromocriptine treatment. 405 53

To study the absorption of levodopa and interaction with the extracerebral dopamine antagonist domperidone, 15 patients with idiopathic Parkinson's disease were given levodopa 500 mg p.o., alone, and with domperidone pre-treatment. Domperidone pretreatment (10, 20, 40 mg, p.o., i.v. or i.m.) caused a mean 12% increase in peak plasma levodopa concentration, which occurred a mean of 10 min earlier than when levodopa was given alone. Parkinsonian disability scores were improved and peak clinical response occurred 16 min earlier with domperidone than without. Domperidone slightly increases the immediate bioavailability (over 4 h) and anti-parkinsonian response to a given dose of levodopa.
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PMID:Domperidone and levodopa in Parkinson's disease. 652 36

Gastrointestinal (GI) motility disorders are frequent in patients with Parkinson's disease, manifesting mainly as dysphagia, disorders of gastric emptying and constipation. The most likely causes of these disorders are cerebral degeneration and degeneration of the myenteric plexus. Although the effect of antiparkinsonian medication is largely overestimated, it certainly has an influence and should be adapted accordingly in patients with GI motility disorders. In particular, anticholinergic drugs should be avoided, and anamnesis, clinical examination and, if necessary, diagnostic tests performed. Domperidone, a peripheral dopamine antagonist, is the drug of choice for motility disorders of the upper GI tract, although cisapride is an alternative. In the lower GI tract, conservative therapeutic options should be used in the first instance. The administration of cisapride leads to a marked temporary improvement in symptoms in lower GI disorders, while rare forms of anism (involuntary dystonic contraction of the anal sphincter) may be treated with botulinum toxin.
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PMID:Gastrointestinal motility problems in patients with Parkinson's disease. Effects of antiparkinsonian treatment and guidelines for management. 910 86

This study investigated whether domperidone could improve gastrointestinal symptoms in patients with Parkinson's disease who were receiving levodopa therapy. A total of 11 patients were studied. Following a baseline gastric emptying test, patients were treated with a starting dose of domperidone 20 mg p.o. q.i.d. A follow-up gastric emptying test was repeated at least 4 months after starting domperidone therapy. At the beginning and at each 3-month follow-up visit, symptoms of nausea, vomiting, anorexia, abdominal bloating, heartburn, regurgitation, dysphagia, and constipation were evaluated and scored on a scale of 0-3. The overall mean follow-up period was 3 years. Compared with their baseline evaluation, patients experienced a significant improvement in all symptoms (p < 0.05) except dysphagia and constipation. Gastric emptying of an isotope-labeled solid meal was significantly faster, with a baseline result of 60.2 +/- 6.4% retention of isotope 2 h after the meal compared with 37.0 +/- 2.2% retention during domperidone therapy (p < 0.05). Patients' global assessment of Parkinson's disease remained stable or improved. Serum prolactin was elevated in all patients after domperidone therapy (p < 0.05). Domperidone therapy significantly reduces upper gastrointestinal symptoms and accelerates gastric emptying of a solid meal, but does not interfere with response to antiparkinsonism treatment.
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PMID:Effect of chronic oral domperidone therapy on gastrointestinal symptoms and gastric emptying in patients with Parkinson's disease. 939 20

Orthostatic hypotension is common in elderly patients, and is now considered to be an important prognostic factor for cognitive decline and mortality. In patients with Parkinson's disease, the prevalence of symptomatic orthostatic hypotension may be as high as 20%. Two factors could explain this high prevalence. First, dopaminergic drugs may induce or worsen orthostatic hypotension. Secondly, Parkinson's disease is a cause of primary autonomic failure with an involvement of the peripheral autonomic system as shown by the ubiquitous distribution of Lewy bodies and reduced iobenguane [metaiodobenzylguanidine (MIBG)] cardiac uptake. These pathological and pharmacological characteristics clearly differentiate autonomic failure of Parkinson's disease from multiple system atrophy. If autonomic abnormalities appear to be present from the first stage of the disease, early onset (within the first year) of symptomatic orthostatic hypotension in the course of parkinsonism can be considered as an exclusion criteria for idiopathic Parkinson's disease. No specific clinical trials have evaluated the effects of antihypotensive drugs in patients with Parkinson's disease and thus no specific therapeutic strategy can be recommended. The management of orthostatic hypotension in patients with Parkinson's disease should always start with patient education and nonpharmacological treatment. Drug therapy should be reserved for symptomatic patients who do not get benefit from nonpharmacological management. Among the available drugs, alpha1-adrenergic agonists (mainly midodrine) or plasma volume expanders (mainly fludrocortisone) are the most frequently used. There are also some drugs that are currently investigational such as yohimbine and droxidopa. Other drugs such as desmopressin or octreotide may be of interest in some situations. Domperidone is widely used in patients with parkinsonism with no proven effect on orthostatic hypotension.
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PMID:Orthostatic hypotension in patients with Parkinson's disease: pathophysiology and management. 1148 43

We examined basal and reflex salivary flow rate and composition in 46 patients with Parkinson's disease (PD), both in off and on conditions, compared to 13 age-matched controls without underlying disease or treatment affecting autonomic function. Whole saliva was collected 12 hours after withdrawal of dopaminergic drugs and at the peak of levodopa-induced motor improvement. Twenty-three of the 46 PD patients had received domperidone a week before the study. Basal salivary flow rate was significantly lower in PD patients in the off state compared to controls (P<0.005). Levodopa increased salivary flow rate (P<0.05) both in the domperidone-pretreated and untreated groups. Citric acid stimulated salivary flow rate in both the off and on states in PD patients. This effect was higher in the domperidone-pretreated patients. Salivary concentration of sodium, chloride, and amylase was higher in PD patients than in controls and was not affected by levodopa or domperidone treatment. Levodopa stimulates both basal and reflex salivary flow rate in PD. The mechanism appears to be central, as the effect is not blocked by domperidone. Domperidone may have a peripheral effect that potentiates reflex salivary secretion. Salivary composition is abnormal in PD and is not affected by levodopa treatment.
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PMID:Quantitative study of salivary secretion in Parkinson's disease. 1641 45

In the treatment of Parkinson's disease, levodopa, DCI, MAO-B inhibitor, COMT inhibitors, dopamine receptor agonists, amantadine, anticholinergics have been applied and new drugs are being developed. Levodopa is still the golden standard in the treatment of Parkinson's disease. The study on levodopa bioavailability showed 3-4 times differences in individual patients. Drug-food interactions are prominent in levodopa. Low protein food increased levodopa bioavailability and improved no ON or delayed ON in the treatment of Parkinson's disease. Vitamine C or magnesium did not alter the bioavailability of levodopa. The bioavailability of levodopa between the levodopa/carbidioa (100/12.5) group and the levodopa/benserazide (100/25) group was studied in patients with Parkinson's disease by population PK study. C(max) of levodopa in levodeopa/benserazide group was twice as high as in levodopa/carbidopa group. Domperidone, a dopamine receptor antagonist applied as an antiemetic inceases vowel movement. The effect of domperidone on levodopa bioavailability was studied, and the combination of domperidone with levodopa increased AUC of levodopa. Clarythromycin or grape fruit juice inhibits both of CYP3A4 and P-glycoprotein which work on metabolism and absorption of drugs. Coadministration of clarythromycin with ergot alkaloids such as cabergoline or bromocriptine increased the AUC up to 2-3 times. Amantadine is excreted through kidney without being metabolized and renal function is the most important factor in the blood concentration of amantadine. In elder women with the body weight of 50 kg or less, creatinine clearance is less than 50 ml/min even though the serum creatinine is within the normal range. Selegiline is metabolized through CYP2D6 and 3A4. Coadministration of qunidine, cimetidine, maclorides, antifungals, grape fruit juice increase the bioavailability of selegiline and may augment the antiparkinsonian effect.
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PMID:[Inter- and intraindividual pharmacokinetic variations in the treatment of Parkinson's disease]. 1644 56

Apomorphine, a non-ergot derivative, is a potent, directly acting dopamine receptor agonist with high affinity to D4, lower to D2, D3, D5, the lowest to D1-like dopamine receptors as well as to serotonin and adrenoreceptors. Subcutaneous apomorphine is currently used in Parkinson's disease as an add-on to levodopa therapy or monotherapy for management of sudden, unexpected and refractory to levodopa-induced off state and fluctuation in advanced stage of illness. Many clinical trials have shown markedly (about 50-72%) reduced time of off phases. Other indications include the challenge test for determining the dopaminergic responsiveness. Apomorphine is used subcutaneously either as intermittent rescue injections or continuous infusions. Several other routes - transdermal, sublingual, intranasal, rectal and intravenous infusion - have been tried. Oral administration is not recommended. Apomorphine has rapid onset of antiparkinsonian action, qualitatively comparable to that of levodopa, short duration of action and stable efficacy with usually mild adverse events similar to other dopamine agonists. Domperidone or trimethobenzamide should be introduced before starting apomorphine treatment to reduce occurrence of peripheral adverse events (nausea, vomiting, orthostatic hypotension). Dyskinesias, sleep disturbances, hallucinations, delusion, oedema and yawning can occur, but some side effects are connected only with a specific route (for example skin nodules appearing during subcutaneous administration). Despite its long history, apomorphine is registered and used in only a few countries. Apomorphine warrants wider application in treatment of advanced Parkinson disease but the high cost of the drug, the necessity of concomitant treatment for prevention of side effects and subcutaneous administration restrict its use.
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PMID:[Apomorphine in off state--clinical experience]. 1794 58

Duloxetine is a serotonin and norepinephrine reuptake inhibitor that possesses antidepressant and pain-relieving properties. Compared with other antidepressants, it has a high affinity for both norepinephrine and serotonin reuptake transporters, which are relatively balanced. Analgesic onset has been observed within the first week of administration in randomized controlled trials and is likely obtained by enhancing the tone of the descending pain inhibition pathways of the central nervous system. Randomized trials have documented significant analgesic effects for managing chronic pain associated with fibromyalgia and diabetic peripheral neuropathic pain. Studies have also suggested that pain associated with major depressive disorder can be reduced with this medication. Modest effects for headache, osteoarthritic pain, and pain secondary to Parkinson disease have also been documented, but data are obtained from single-blinded or open-label trials that require further corroboration with larger randomized studies. Duloxetine has not yet been directly compared with other antidepressants or anticonvulsants for the treatment of pain syndromes.
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PMID:Duloxetine: a review of its pharmacology and use in chronic pain management. 2092 42


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