PubMed · 13752555
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L H KENT, J H SLADE. 1960. Immunochemically-active cross-linked polystyrene preparations.. https://doi.org/10.1042/bj0770012
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Antidopaminergic gastrointestinal prokinetics (bromopride, clebopride, domperidone, levosulpiride and metoclopramide) have been exploited clinically for the management of motor disorders of the upper gastrointestinal tract, including functional dyspepsia, gastric stasis of various origins and emesis. The prokinetic effect of these drugs is mediated through the blockade of enteric (neuronal and muscular) inhibitory D2 receptors. The pharmacological profiles of the marketed compounds differ in terms of their molecular structure, affinity at D2 receptors, ability to interact with other receptor systems [5-hydroxytryptamine-3 (5-HT3) and 5-HT4 receptors for metoclopramide; 5-HT4 receptors for levosulpiride) and ability to permeate the blood-brain barrier (compared with the other compounds, domperidone does not easily cross the barrier). It has been suggested that the serotonergic (5-HT4) component of some antidopaminergic prokinetics may enhance their therapeutic efficacy in gastrointestinal disorders, such as functional dyspepsia and diabetic gastroparesis. The antagonism of central D2 receptors may lead to both therapeutic (e.g. anti-emetic effect due to D2 receptor blockade in the area postrema) and adverse (including hyperprolactinaemia and extrapyramidal dystonic reactions) effects. As the pituitary (as well as the area postrema) is outside the blood-brain barrier, hyperprolactinaemia is a side-effect occurring with all antidopaminergic prokinetics, although to different extents. Extrapyramidal reactions are most commonly observed with compounds crossing the blood-brain barrier, although with some differences amongst the various agents. Prokinetics with a high dissociation constant compared with that of dopamine at the D2 receptor (i.e. compounds that bind loosely to D2 receptors in the nigrostriatal pathway) elicit fewer extrapyramidal signs and symptoms. A knowledge of central and peripheral D2 receptor pharmacology can help the clinician to choose between the antidopaminergic prokinetics to obtain a more favourable risk/benefit ratio.
Crystals of dimenhydrinate as a model drug were used for crystal coating, a method that can be applied to increase the flowability of a material and facilitate the tablet making. An increase in particle size was observed during the film coating. The change in shape of the coated particles was also examined. Some physicochemical parameters changed during coating, e.g. the surface free energy parameters and the wetting of the samples. The amount of coating material (and therefore the coating time) influenced several parameters (the shape of the particles, the flow properties and surface free energy parameters, compressibility and compactibility). Several parameters of prepared tablet (porosity, breaking hardness) were examined. Accordingly, coating of the crystals can be performed in order to enhance the handling of a material with insufficient properties for tablet making.
In December 2001, the FDA required a "black box warning" suggesting that unexpected cardiovascular deaths could occur at normal therapeutic doses of droperidol. We reviewed data from 270 MedWatch reports, including 99 reports of death, submitted between November 1, 1997, and January 10, 2002. We further reviewed primary reports of deaths and cardiovascular adverse events associated with < or = 10 mg of droperidol. There were 99 death reports representing 89 patients, with a specified dose in 66 cases. Among 74 (83%) foreign fatality reports, 57 included a known dose (> or = 50 mg in 29 cases [49%] and < or = 2.5 mg in only 3 cases [5%]). Of the 15 (17%) U.S. cases, 9 included a specified dose (< or = 2.5 mg in 5 cases and 5-10 mg in 4 cases). Cardiovascular deaths after therapeutic doses (< or = 2.5 mg) of droperidol are rare. Mandatory electrocardiographic screening appears unnecessary.