An individualized approach to the hypertensive patient with renal disease: six illustrative case studies.
The best experimental conditions for a selective binding of 3H-apomorphine to dopamine receptors on cryostat sections were first selected by liquid scintillation quantification of the bound radioactivity. In the corpus striatum, a specific binding occurred with a half-maximal saturation concentration of about 1 nM and a maximal capacity of 180 fmol/mg of slice protein, both values in agreement with previous binding data on either membranes or slices incubated in a physiological medium. Inhibition with domperidone was clearly biphasic, indicating two classes of sites corresponding to the D-2 and D-3 sites as previously defined on membranes. When 3H-apomorphine was used at low concentrations (0.8-1.5 nM), a condition ensuring a preferential labelling of D-2 sites, rather well contrasted autoradiographic pictures were generated. The major dopaminergic projection fields in telencephalon (caudate-putamen, nucleus accumbens, olfactory tubercles) were visualised as well as other catecholaminergic regions such as the superficial gray layer of superior colliculi. Within the striatum, differences in density of these sites were observed in three perpendicular planes and confirmed by a computer densitometric image analysis. Labelling of areas of origin of the cerebral dopaminergic neurons in substantia nigra or ventral tegmental area were also observed. When a higher concentration of 3H-apomorphine (3.5 nM) was used in the presence of domperidone, another, but autoradiographically less distinct subclass of sites (D-3 sites) was demonstrated.
There have been reports of transient psychosis in women medicated for gynecologic conditions.
There is increased awareness about risks and benefits of using domperidone to treat gastroparesis.
Itopride has good efficacy in terms of global patients assessment, postprandial fullness, and early satiety in the treatment of patients with FD and shows a low rate of adverse reactions. Itopride can greatly improve FD syndromes-score.
The resocializing and activating properties of halopemide were investigated in an open study and a double-blind study in 20 patients who had been hospitalized on account of various psychiatric disorders. The results of the open study showed a significant improvement in contact and activity, regardless of the nosological characteristics. There was no significant difference in therapeutic effect between the single (2 X 10 mg/day) and the double (2 X 20 mg/day) dose. The patients were more approachable, sought contact with their surroundings and showed a greater interest in their work. However, these results were not confirmed by the double-blind study, which for these target symptoms showed no significant difference between the placebo phase and halopemide phase. Two factors that might explain the discrepancy between the results of the open study and the double-blind study are postulated: the difference in experimental methods and the short duration of the study phases.
Levodopa-induced dyskinesias result in considerable functional impairment for patients and formidable therapeutic challenges for physicians. A practical method of treating such dyskinesias is first to classify the levodopa dyskinesias according to their temporal profile after drug administration, namely, into predictable (interdose, biphasic and 'off-period') and unpredictable ('on-off') dyskinesias. Treatment of each type of dyskinesia requires a different and relatively specific therapeutic strategy. With progression of Parkinson's disease, the threshold for interdose dyskinesia lowers, while the threshold for antiparkinsonian efficacy is unchanged; therefore, the strategy is to maintain levodopa concentrations between these 2 thresholds and avoid high concentrations. Frequent small doses of liquid levodopa preparations may be indicated. Clozapine appears to increase the threshold for dyskinesia. However, its usefulness is limited primarily by dose-related sedation and by dose-unrelated agranulocytosis. Buspirone and fluoxetine may have specific antidyskinetic benefit. Surgical treatment may aid selected patients, although criteria for selection are not fully established. The biphasic dyskinesias occur just before and just after an oral dose of levodopa. They result when levodopa concentrations fall below or rise above the threshold for therapeutic efficacy; therefore, the strategy is to maintain concentrations as nearly constant as possible above that threshold. Dopamine agonists such as subcutaneous apomorphine combined with domperidone may be particularly helpful. Thalamic stimulation can also benefit selected patients. 'Off-period' dyskinesias occur at times of predicted low concentrations of levodopa. The treatment strategy is to provide sufficient levodopa or dopaminergic stimulation during those intervals. Dopamine agonists (e.g. bromocriptine at night) may help the characteristic early foot dystonia. Anticholinergic agents may also help. The unpredictable ('on-off') dyskinesias are first analysed to establish a pattern of response. Then, on the basis of that pattern, they are treated by maintaining levodopa concentrations or dopaminergic tone during the periods that would ordinarily be 'off.' Administration of liquid levodopa preparations, addition of dopaminergic agents, restriction of treatment during the morning hours as well as restriction of the majority of dietary protein in the evening meal may provide a period of predictable good function early in the day. Clozapine, even early in treatment, appears to reduce the incidence of these dyskinesias. Rescue with apomorphine during a malignant prolonged 'off' phase is particularly valuable.