Personal studies in allergic eye diseases reviewed in this paper indicate that: 1. An increased number and an abnormal distribution of eosinophils is present in conjunctival biopsies of patients with vernal keratoconjunctivitis (VKC). 2. Eosinophil and eosinophil products, such as ECP, are also increased in tears of VKC patients and, in hay fever conjunctivitis, accumulate during the late-phase of allergic reaction following specific allergen challenge. 3. Circulating eosinophils of VKC patients show a typical activation phenotypic profile which is associated with increased serum level of eosinophil cationic protein and eosinophil-derived neurotoxin/protein X. A clinical study of the modulatory effect of cetirizine on the early and late phase of the allergic reaction as well as on the eosinophil activation and tissue recruitment following conjunctival allergen challenge is reported as an example of the need to evaluate eosinophil functions when investigating anti-allergic drugs. Drugs modulating various aspects of eosinophil function could play a primary role in the treatment of allergic eye disease.
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The antihistamines astemizole and cetirizine were compared for the treatment of grass pollen hayfever in 158 patients who received either astemizole (10 mg od) or cetirizine (10 mg od) for a four week period in a randomised double-blind, double-dummy, parallel group, comparative assessment. Patients visited their general practitioner (GP) on three occasions and at each visit the GP made an assessment of the severity of individual hayfever symptoms. Patients recorded daily throughout the study the severity of their hayfever symptoms and their level of daytime sedation on visual analogue scales in a diary card. The primary measure of efficacy was the overall symptom visual analogue scores recorded daily by the patients. The results demonstrate that these two antihistamines are equally effective treatments for hayfever, in terms of magnitude of symptom relief, speed of onset of symptom improvement and lack of sedative effect.
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Anyone talks about the taste using different taste scale. Since how to feel the taste is different from one to other people, we sometimes lead to inconsistency when speaking about the taste of food. The present study aims at development of electronic tongue (taste sensor) and electronic nose (odor sensor). There are two important properties about the taste sensor. One, each sensor electrode (lipid/polymer membrane) is specific to each taste. Another is that the sensor can measure the aftertaste such as richness, which is the aftertaste of umami. In the case of, e.g., bitterness electrode (BT0), it responds well to bitter taste substances such as quinine, cetirizine, hydroxyzine and bromhexine. For other taste qualities, on the other hand, it shows no response. A taste sensor is now sold by Intelligent Sensor Technology, Inc., and utilized in pharmaceutical and food companies. An electronic nose to detect lingering scent is composed of surface plasmon resonance (SPR) sensor, which is a sensing device with high sensitivity, and antigen-antibody interaction. A self-assembled monolayer was constructed on the reception surface of SPR device. The experimental result on benzaldehyde, a typical peach flavor, shows the sensor sensitivity 4 ppb, which is superior to the human sensitivity of about 350 ppb. Our developed taste sensor and electronic nose play the role of gustatory and olfactory senses, respectively.
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Changes in heart rate (HR), systolic arterial pressure (SAP) and diastolic arterial pressure (DAP) occur in anticipation of, and following, injection of a peribulbar local analgesic agent. We examined these changes in two groups of awake patients given a pre-medication of either hydroxyzine 1.0 mg/kg alone (control) or hydroxyzine 1.0 mg/kg with morphine 0.05 mg/kg.
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Histamine H1 receptor (H1R) antagonists often have sedative side effects, which are caused by the blockade of the neural transmission of the histaminergic neurons. We examined the brain H1R occupancy (H1RO) and the subjective sleepiness of levocetirizine, a new second-generation antihistamine, comparing fexofenadine, another non-sedating antihistamine, as a negative active control.
The present study was performed to study the participation of histamine H(3) receptors in nasal symptoms using Sch 50971, a potent and selective agonist of the H(3) receptor. Repeated topical application of antigen caused an increase in sneezing and nasal rubbing in sensitized mice. Oral administration of Sch 50971 and imetit, specific H(3)-receptor agonists, resulted in an inhibition of nasal symptoms induced by an antigen similar to an H(1)-receptor antagonist, cetirizine. Furthermore, simultaneous use of H(3)-receptor agonists, Sch 50971 or imetit, and an H(1)-receptor antagonist, cetirizine, caused a significant inhibitory effect on nasal symptoms at doses that showed no effect when used separately. The number of eosinophils in the nasal mucosa of mice sensitized with antigen was significantly decreased by cetirizine; however, Sch 50971 and imetit had no effect on eosinophil infiltration. These results clearly indicate that H(3) receptors are involved in the etiology of nasal allergy, and the stimulation of H(3) receptors may be useful as a novel therapeutic approach in nasal allergy.
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In period A, an adequate response was obtained in 64.7% (33/51). Nine patients each with inadequate response were randomized to either the drug-change or dose-increase groups. A significant improvement was observed in the severity of wheal and itching in the dose-increase group in period B. The QOL was significantly improved in all sub-scales of Skindex-16.
Cetirizine, an effective, minimally sedating, second-generation H1-antihistamine is widely used orally to treat allergic skin disorders. This study was performed to assess the peripheral H1-antihistaminic activity and extent of systemic absorption of cetirizine from liposomes applied to the skin. Cetirizine was incorporated into small unilamellar vesicles (SUV) and multilamellar vesicles (MLV) prepared using L-alpha-phosphatidylcholine hydrogenated (HPC), and into Glaxal Base (GB) as the control. In a randomized, crossover study, each formulation, containing 10 mg of cetirizine, was applied to the depilated backs of 6 rabbits (3.08 +/- 0.05 kg). Histamine-induced wheal tests and blood sampling were performed before cetirizine application and at designated times for up to 24 hours afterwards. Compared with baseline, histamine-induced wheal formation was suppressed by cetirizine in SUV only at 24 hours, in MLV from 0.5 to 24 hours, and in GB from 0.5 to 8 hours (P < or = .05). Wheal suppression by cetirizine in SUV at 24 hours (91.7% +/- 5.2%) and in MLV from 1 to 24 hours (93.8% +/- 2.2% to 76.2% +/- 6.5%) was greater than in GB (36.5% +/- 7.4% to 60.6% +/- 14.2%) from 1 to 24 hours (P < or = .05). Faster onset, as well as greater and more persistent suppression was obtained from cetirizine in MLV. Plasma cetirizine concentrations from MLV (area under the curve [AUC] of 221.2 +/- 42.3 ng x hr/mL) were lower than from GB (AUC of 248.3 +/- 34.6 ng.hr/mL). In this model, cetirizine from MLV had excellent topical H(1)-antihistamine activity, while systemic exposure was reduced, compared with cetirizine from GB.
To elucidate the possible role of substance P in the pathogenesis of acute gastric mucosal damage, rats were treated intragastrically with 1.0 mL 96% ethanol, 0.6N HCl, or 25% NaCl, with or without IP coadministration of substance P, senktide, or septide (1 mumol/L per 100 g). All three peptides were found to double the mean lesion area when compared with that induced by ethanol, whereas substance P antagonist (1 mumol/L per 100 g) prevented the expansion of damage extent. The increased damage was associated with increased gastric mucosal levels of platelet activating factor, leukotriene B4, and leukotriene C4. Substance P antagonists also reduced by half the extent of the gastric damage induced by ethanol when administered by itself. WEB 2086 (platelet-activating factor antagonist; Boehringer Ingelheim KG, Germany), hydroxyzine (H1 blocker), and cimetidine (H2 blocker) reduced lesion area by 50%, but only in rats treated with both substance P and ethanol. Ketotifen (mast-cell stabilizer) (100 micrograms/100 g), administered orally 30 minutes before damage induction, totally abolished the extent of the damage induced by either ethanol or the coadministration of ethanol and peptides in the surface epithelium of the entire mucosa. The protective effect of ketotifen was accompanied by significant reduction in mucosal generation of platelet-activating factor, leukotriene C4, and leukotriene B4. Similar mucosal protection was afforded by ketotifen against damage induced by 0.6N HCl, 25% NaCl, or indomethacin. Therefore, it is suggested that substance P is involved in the pathogenesis of acute ethanol-induced gastric mucosal damage. The effective mucosal protection provided by ketotifen indicates the important role of mast cells and their mediators in the pathogenesis of acute gastric mucosal damage and may have therapeutic implications.
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A review of 33 patients in whom repeat chemonucleolysis was performed in the period between 1979 and 1983 indicates satisfactory results in 24 patients for a 73% success rate. Immediate sensitivity reactions (anaphylaxis) were seen in three patients and all were successfully managed by appropriate medical therapy. The last 12 patients were pretreated with histamine1 antagonists (hydroxyzine) and histamine2 antagonists (cimetidine). In this group there was not a single anaphylactic reaction. According to these results, repeat chemonucleolysis is a viable alternative to laminectomy and discectomy for patients suffering from recurrent lumbar disc herniations that are refractory to conservative therapy. The increased risk of sensitivity to the enzyme can be minimized by pretreatment with histamine blockers.
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This multicenter, randomized, double-blind, parallel-group, 2-week comparative study was conducted during the 2004 fall allergy season in patients with moderate to severe SAR. After a 1-week placebo lead-in period, patients were randomized to receive azelastine nasal spray 2 sprays per nostril twice daily plus placebo tablets or cetirizine 10-mg tablets once daily plus a placebo saline nasal spray for the 2-week double-blind treatment period. The primary efficacy variables were (1) change from baseline to day 14 in the 12-hour reflective total nasal symptom score (TNSS), which combines scores for rhinorrhea, sneezing, itchy nose, and nasal congestion, and (2) onset of action, based on the instantaneous TNSS over 4 hours after the first dose of study drug. During the double-blind treatment period, patients recorded their symptom scores on diary cards twice daily (morning and evening). Patients aged > or =18 years also completed the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) at baseline and on day 14.
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Whereas benzodiazepines are routinely coadministered with tricyclic antidepressants, in patients undergoing treatment for depressive disorders, little information is known about the combination of benzodiazepines with other antidepressants such as specific serotonin reuptake inhibitors (SSRI's), and combination with other anxiolytic drugs. On the other hand, it is known that benzodiazepines decrease the serotoninergic transmission. The present study was undertaken to evaluate the effect of concomittant administration of anxiolytic drugs such as benzodiazepines (diazepam, lorazepam) or diphenylmethane derivative (hydroxyzine) with specific serotonin reuptake inhibitors, (fluvoxamine, fluoxetine, indalpine) on the ability of antidepressant drugs to reverse helpless behavior in this test. Our results show that: daily injection of diazepam (0.25-2 mg/kg), lorazepam (0.06-0.25 mg/kg) or hydroxyzine (8.32 mg/kg) failed to reverse the behavioral deficit in rat. In contrast fluvoxamine: 4 mg/kg/day; fluoxetine: 4 mg/kg/day; indalpine: 1 mg/kg/day significantly reverse the helpless behavior in this test; the reversal of helpless behavior by fluvoxamine or indalpine was dose-dependently antagonized by daily coadministration of diazepam or lorazepam; in contrast, the reversal of helpless behavior by fluvoxamine or fluoxetine was not modified by daily coadministration of hydroxyzine (8 mg/kg). In conclusion, it may be suggested that combined benzodiazepine-specific serotonin reuptake inhibitors, should be avoided. We suggest that anxiolytic drugs such as hydroxyzine might be better in coadministration with antidepressants, particularly with specific serotonin reuptake inhibitors.
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To introduce cetirizine, a nonsedating antihistamine, and discuss its mechanism of action, chemistry, clinical and comparative trials, and adverse effects.
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The main purpose of this study was to evaluate the diagnostic value of patch testing in establishing an aetiological diagnosis in fixed drug eruptions.
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Cerebrospinal fluid (CSF) HVA, MHPG, 5-HIAA, cAMP and cGMP concentrations were measured in schizophrenic patients with tardive dyskinesia before and after a three-week administration of oxypertine (n = 4), hydroxyzine pamoate (n = 4) or placebo (n = 4). The oxypertine administration resulted in a reduction of the CSF HVA concentration and an elevation of the MHPG and cAMP concentrations, associated with a clinical improvement in tardive dyskinesia. The hydroxyzine administration reduced the CSF 5-HIAA concentration in all the patients and the CSF HVA concentration in two of four patients with a clinical improvement. A reduction in the CSF HVA concentration associated with possible therapeutic effects of oxypertine or hydroxyzine may suggest the normalization of a hyperdopaminergic state. Discussions were held that functional disorders of not only the dopaminergic system but the norepinephrinergic and serotoninergic systems may relate to the pathogenesis of tardive dyskinesia.
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The effect of patient recognition of tranquilizing agents on patient requests for tranquilizers during detoxification treatment was evaluated. A total of 120 subjects, all patients at a detoxification unit, were randomly assigned to four groups: diazepam 10 mg in its commercially available form, diazepam 10 mg masked in opaque capsules, hydroxyzine pamoate 50 mg in its commercially available form, and hydroxyzine pamoate 50 mg masked in opaque capsules. Tranquilizers were administered only on patient request, and the time and date of each request were recorded. Subjects were interviewed about previous tranquilizer use and recognition of tranquilizing agents. They also completed a state-trait anxiety inventory. Patient records were reviewed to obtain basic demographic data. Although requests and recognition were higher in those subjects in the diazepam groups, the differences between the two groups were not significant. However, there was a positive relationship between requests for diazepam among those who recognized their medications, and administering the medications in opaque capsules significantly reduced the number of requests for both drugs. Anxiety scores and previous drug therapy were found to be significantly related to recognition and the average number of requests. There was a positive relationship between recognition of and requests for a tranquilizer. Clinicians should consider giving patients with a tendency to abuse drugs nonidentifiable dosage forms.
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Solid-phase extraction (SPE) was carried out to analyse the PhACs in the influent and effluent samples. Ultrasonic solvent extraction was used before SPE for PhACs analysis in sludge samples. PhAC extracts were analysed by LC-MS. Solid-phase microextraction of liquid and sludge samples was used for the analysis of musks, which were detected by GC-MS. The fluxes of the most abundant compounds (13 PhACs and 5 musks) out of 79 compounds studied were used to perform the mass balance on the WWTP.
The present pharmacological study was conducted to investigate a possible role of the brain histaminergic system in vocalization induced in guinea pig pups by maternal separation and isolation in an unfamiliar environment. The effects of drugs acting at histamine receptors were determined after intraperitoneal injection, comprising hydroxyzine and chlorpheniramine, both histamine H1 antagonists, and the H3 agonist, immepip. A range of psychoactive drugs known to be active in this paradigm was also tested for comparison. Hydroxyzine, 4.3 to 14.3 mg/kg, dose-dependently suppressed vocalization but neither chlorpheniramine, 2 to 16 mg/kg, nor immepip, 5 to 20 mg/kg, was active. All reference drugs, fluoxetine, 5 and 10 mg/kg, imipramine, 16 and 32 mg/kg, and chlordiazepoxide, 5 and 10 mg/kg, were shown to be active. The present data indicate that, consistent with known anxiolytic effects in man, the antihistamine hydroxyzine proved effective in suppressing maternal-separation-induced vocalization in guinea pig pups. However, in view of the lack of effect of either chlorpheniramine or immepip, it is proposed that additional nonhistaminergic effects are involved in the tranquilizing action of hydroxyzine.
1. Enzymic and ion-exchange chromatographic analyses were used to measure adenosine triphosphate (ATP), diphosphate (ADP) and monophosphate (AMP) in brain extracts from rats treated with a wide range of centrally acting drugs. Phosphocreatine (PC) was assayed by the acid molybdate method.2. An anaesthetic dose of phenobarbitone caused an increase in brain levels of ATP and PC, and a reduction in ADP and AMP. A convulsant dose of leptazol gave rise to precisely opposite effects. Subanaesthetic (hypnotic) and subconvulsive doses of the two drugs, respectively, produced no alterations in brain nucleotide levels.3. Among the psychotropic drugs, dexamphetamine, LSD and hydroxyzine, at the doses used, caused no changes in brain levels of the adenine nucleotides. Iproniazid and imipramine caused slight increases in the ATP level and ATP / ADP ratio, respectively. Chlorpromazine failed to give rise to any effect in the nucleotides 3 hr after administration, but produced a rise in brain ATP after 6 hr. Reserpine, on the other hand, caused a fall in the ATP/ADP ratio 6 hr after injection.4. These results indicate that some psychotropic drugs can cause small changes in the rat brain ATP/ADP ratio but do not support claims by certain workers that such changes correlate closely with the behavioural effects of these drugs.
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Antihistamine activity of NCX 1512 and NCX 1514 was investigated in vitro in the guinea pig ileum, in tracheal rings (GPTR) and lung parenchymal strips (GPLP) of the guinea-pig. The NO-releasing capacity was investigated in vascular preparations; the isolated rabbit and guinea-pig aorta and guinea-pig pulmonary artery. Kinetics of NO release were assessed in a rat whole blood assay.