The Effects of Pharmacological Treatment of Nightmares: A Systematic Literature Review and Meta-Analysis of Placebo-Controlled, Randomized Clinical Trials.

Nightmares are highly prevalent and distressing for the sufferer, which underlines the need for well-documented treatments. A comprehensive literature review and meta-analysis of the effects of different pharmacological placebo-controlled randomized clinical trials, covering the period up to 1 December 2022, was performed. Searches were conducted in PubMed, Embase, Web of Science, PsychInfo, Cinahl, and Google Scholar, resulting in the identification of 1762 articles, of which 14 met the inclusion criteria: pharmacological intervention of nightmares, based on a placebo-controlled randomized trial published in a European language, reporting outcomes either/or in terms of nightmare frequency, nightmare distress, or nightmare intensity, and reporting sufficient information enabling calculation of effect sizes. Most studies involved the effect of the α1-adrenergic antagonist prazosin in samples of veterans or soldiers suffering from posttraumatic stress disorder. Other medications used were hydroxyzine, clonazepam, cyproheptadine, nabilone, and doxazosin. The vast majority of studies were conducted in the USA. The studies comprised a total of 830 participants. The Clinician-Administered PTSD Scale was the most frequently used outcome measure. The results showed an overall effect size of Hedges' g = 0.50 (0.42 after adjustment for publication bias). The synthetic cannabinoid nabilone (one study) showed the highest effect size (g = 1.86), followed by the histamine H1-antagonist hydroxyzine (one study), and prazosin (10 studies), with effect sizes of g = 1.17 and g = 0.54, respectively. Findings and limitations are discussed, and recommendations for future studies are provided.

Association of QT-Prolonging Medication Use in CKD with Electrocardiographic Manifestations.

BACKGROUND AND OBJECTIVES: Several drugs used in CKD can prolong electrocardiographic conduction. We examined the use of electrocardiogram QT-prolonging medications in predialysis CKD and their association with QT duration. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In total, 3252 Chronic Renal Insufficiency Cohort participants with at least one study electrocardiogram between 2003 and 2011 were included. QT-prolonging medications used in 100 or more visits (n=16,451 visits) along with diuretics and proton pump inhibitors, given their potential for electrolyte disturbances, were examined for QT interval prolongation. RESULTS: Mean QT interval corrected for heart rate was at 414±21 (±SD) milliseconds and prolonged (≥450 milliseconds) in 4.6% of electrocardiograms. QT interval corrected for heart rate was inversely related to serum potassium and calcium. Medications classified as QT prolonging were taken at 76% of visits, with two or more of these taken at 33% of visits. Of 30 medications examined, eight were associated with statistically significant QT interval corrected for heart rate prolongation after adjustment for comorbidities, potassium, and calcium, including amiodarone (+10±2 milliseconds), metolazone (+7±2 milliseconds), fluoxetine (+4±1 milliseconds), citalopram (+4±1 milliseconds), hydroxyzine (+4±1 milliseconds), escitalopram (+3±2 milliseconds), venlafaxine (+3±1 milliseconds), and furosemide (+3±0 milliseconds). Potassium-depleting diuretics were associated with minimal decrements in potassium (between 0.1 and 0.3 mEq/L) and smaller changes in calcium. Diuretics associated with a change in QT interval corrected for heart rate before adjustment for potassium and calcium were metolazone (+8±3 milliseconds), furosemide (+4±1 milliseconds), and spironolactone (-3±3 milliseconds). Most of the QT prolongation associated with metolazone and furosemide, but not spironolactone, remained after adjustment for potassium and calcium. Proton pump inhibitors were not associated with QT prolongation. CONCLUSIONS: Use of medications associated with QT prolongation is common in CKD; the safety implications of these findings should be considered in these high-risk patients. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2017_08_09_CJASNPodcast_17_09_b.mp3.

Identification of compounds that suppress Toxoplasma gondii tachyzoites and bradyzoites.

Drug treatment for toxoplasmosis is problematic, because current drugs cannot eradicate latent infection with Toxoplasma gondii and can cause bone marrow toxicity. Because latent infection remains after treatment, relapse of infection is a problem in both infections in immunocompromised patients and in congenitally infected patients. To identify lead compounds for novel drugs against Toxoplasma gondii, we screened a chemical compound library for anti-Toxoplasma activity, host cell cytotoxicity, and effect on bradyzoites. Of 878 compounds screened, 83 demonstrated >90% parasite growth inhibition. After excluding compounds that affected host cell viability, we further characterized two compounds, tanshinone IIA and hydroxyzine, which had IC50 values for parasite growth of 2.5 µM and 1.0 µM, respectively, and had no effect on host cell viability at 25 µM. Both tanshinone IIA and hydroxyzine inhibited parasite replication after invasion and both reduced the number of in vitro-induced bradyzoites, whereas, pyrimethamine, the current therapy, had no effect on bradyzoites. Both tanshinone IIA and hydroxyzine are potent lead compounds for further medicinal chemistry. The method presented for evaluating compounds for bradyzoite efficacy represents a new approach to the development of anti-Toxoplasma drugs to eliminate latency and treat acute infection.

Serotonergic Synergy in the Pharmacotherapy of Acute Posttraumatic Stress Disorder Exacerbation: A Case Report.

OBJECTIVE: Posttraumatic stress disorder (PTSD) is often associated with acute panic, dissociation, suicidality, and aggression. However, pharmacologic interventions for such acute exacerbations are understudied. In this article, we report a case of combat-related PTSD with severe panic, suicidality, and agitation which responded favorably to a combination of ziprasidone, propranolol, and hydroxyzine. METHODS: An extensive literature search did not reveal any use of this combination, and there were few studies about each medication individually, with regard to PTSD. We reviewed current literature to provide potential explanations for the case. RESULTS: Our case report describes a novel medication regimen which was used to treat an acute PTSD exacerbation. We explore possible biochemical explanations examining the pharmacologic profiles of ziprasidone, propranolol, and hydroxyzine. CONCLUSION: These medications each have relatively rapid onset and unique serotonergic activities. Given the role of serotonin in fear conditioning and traumatic memory consolidation, these treatments could be of significant benefit for PTSD patients, especially in the acute setting. We believe the treatments warrant further research to determine whether they are potential alternatives for anxiolytics like benzodiazepines, which are frequently used clinically but have evidence of risks in and little efficacy for PTSD.

Focal transient CNS vessel leak provides a tissue niche for sequential immune cell accumulation during the asymptomatic phase of EAE induction.

Peripheral immune cells are critical to the pathogenesis of neurodegenerative diseases including multiple sclerosis (MS) (Hendriks et al., 2005; Kasper and Shoemaker, 2010). However, the precise sequence of tissue events during the early asymptomatic induction phase of experimental autoimmune encephalomyelitis (EAE) pathogenesis remains poorly defined. Due to the spatial-temporal constrains of traditional methods used to study this disease, most studies had been performed in the spine during peak clinical disease; thus the debate continues as to whether tissue changes such as vessel disruption represent a cause or a byproduct of EAE pathophysiology in the cortex. Here, we provide dynamic, high-resolution information on the evolving structural and cellular processes within the gray matter of the mouse cortex during the first 12 asymptomatic days of EAE induction. We observed that transient focal vessel disruptions precede microglia activation, followed by infiltration of and directed interaction between circulating dendritic cells and T cells. Histamine antagonist minimizes but not completely ameliorates blood vessel leaks. Histamine H1 receptor blockade prevents early microglia function, resulting in subsequent reduction in immune cell accumulation, disease incidence and clinical severity.

Bilastine vs. hydroxyzine: occupation of brain histamine H1 -receptors evaluated by positron emission tomography in healthy volunteers.

AIM: A close correlation exists between positron emission tomography (PET)-determined histamine H1 -receptor occupancy (H1 RO) and the incidence of sedation. Antihistamines with H1 RO <20% are classified as non-sedating. The objective was to compare the H1 RO of bilastine, a second generation antihistamine, with that of hydroxyzine. METHODS: This randomized, double-blind, crossover study used PET imaging with [(11) C]-doxepin to evaluate H1 RO in 12 healthy males (mean age 26.2 years), after single oral administration of bilastine (20 mg), hydroxyzine (25 mg) or placebo. Binding potentials and H1 ROs were calculated in five cerebral cortex regions of interest: frontal, occipital, parietal, temporal, insula. Plasma bilastine concentrations, subjective sedation (visual analogue scale), objective psychomotor performance (digital symbol substitution test), physiological variables and safety (adverse events, AEs), were also evaluated. RESULTS: The mean binding potential of all five regions of interest (total binding potential) was significantly greater with bilastine than hydroxyzine (mean value 0.26 vs. 0.13, P < 0.01; mean difference and 95% CI -0.130 [-0.155, 0.105]). There was no significant difference between bilastine and placebo. Overall H1 RO by bilastine was significantly lower than that by hydroxyzine (mean value -3.92% vs. 53.95%, P < 0.01; mean difference and 95% CI 57.870% [42.664%, 73.075%]). There was no significant linear relationship between individual bilastine plasma concentrations and total binding potential values. No significant between-treatment differences were observed for sedation and psychomotor performance. Twenty-six non-serious AEs were reported. Sleepiness or sedation was not reported with bilastine but appeared in some subjects with hydroxyzine. CONCLUSIONS: A single oral dose of bilastine 20 mg had minimal H1 RO, was not associated with subjective sedation or objective impairment of psychomotor performance and was devoid of treatment-related sedative AEs, thus satisfying relevant subjective, objective and PET criteria as a non-sedating antihistamine.

The conventional antihistamine drug cyproheptadine lacks QT-interval-prolonging action in halothane-anesthetized guinea pigs: comparison with hydroxyzine.

Antihistamines are known to belong to the chemical class that may induce long QT syndrome. Among them, cyproheptadine has been shown to exert multifaceted actions on the ventricular repolarization phase; namely, shortening of the action potential duration at supra-therapeutic concentrations of 2 - 8 µM and prolongation of the QT interval at ≥ 10 µM. Since information is limited regarding the in vivo electrophysiological effects of cyproheptadine, we assessed it using the halothane-anesthetized guinea-pig model, which was compared with effects of another antihistamine drug, hydroxyzine. Sub-therapeutic to therapeutic doses of hydroxyzine at 1 and 10 mg/kg, i.v. prolonged the QT interval and duration of monophasic action potential, whereas therapeutic to supra-therapeutic doses of cyproheptadine at 0.1 and 1 mg/kg, i.v. hardly affected the indices of ventricular repolarization. These results suggest that cyproheptadine may be categorized into antihistamines with little effect on the ventricular repolarization.

Psychomotor and subjective effects of bilastine, hydroxyzine, and cetirizine, in combination with alcohol: a randomized, double-blind, crossover, and positive-controlled and placebo-controlled Phase I clinical trials.

OBJECTIVE: The aim of this study was to compare the effects of concomitant administration of alcohol and bilastine versus alcohol alone on the central nervous system. METHODS: Twenty-four healthy young volunteers of both sexes participated in a randomized, double-blind, double-dummy, crossover, and positive-controlled and placebo-controlled clinical trials. At 1-week intervals, subjects received six different treatments: (i) placebo; (ii) alcohol 0.8 g/kg alone (ALC); (iii) ALC in combination with: bilastine 20 mg (B20 + A); (iv) bilastine 80 mg (B80 + A); (v) cetirizine 10 mg (CET + A); and (vi) hydroxyzine 25 mg (HYD + A). Psychomotor performance tests (fine motor, finger tapping, nystagmus, critical flicker-fusion frequency, temporal estimation, 'd2' cancellation, and simple reaction time) and subjective self-reports (drunkenness, drowsiness, mental slowness, clumsiness, anger, attentiveness, competence, happiness, hostility, interest, and extroversion) were carried out at baseline and multiple points thereafter. RESULTS: All active treatments induced a significant psychomotor impairment. The greatest and most lasting impairment was observed with HYD + A followed by B80 + A and CET + A. In contrast, objective measures showed less impairment with B20 + A and ALC, both with a similar magnitude. Self-reports showed a subjective perception of performance impairment in all active treatments. CONCLUSION: Concomitant administration of bilastine (at therapeutic dose) and alcohol does not produce greater central nervous system depressant effects than ACL alone.

Chloral hydrate and/or hydroxyzine for sedation in pediatric EEG recording.

PURPOSE: To evaluate and compare the success of chloral hydrate (CH) and hydroxyzine on sedation and assess the changes of these drugs on sleep EEG recordings. METHOD: Three hundred and forty-one patients (mean age: 60.92±53.81months) that were uncooperative with the EEG setup or referred for sleep EEG were enrolled in the study. Patients, partially sleep-deprived the night before, were firstly tried to fall on sleep without any medication, the patients who could not sleep spontaneously were randomly divided in two groups of hydroxyzine and chloral hydrate. RESULTS: In 147 (43%) of cases, CH was given for sedation. In 112 (32%) hydroxyzine and in 8% of cases CH and hydroxyzine were given. 17% of children had spontaneous sleep. The doses of drugs prescribed were as follows: hydroxyzine 1.43±0.74mg/kg CH 38±14.73mg/kg. The time to go on a sleep was 34.68±30.75min in hydroxyzine and 32.34±26.83min in CH group (p>0.05). Eighty-nine percent of cases who were sedated with CH and 89.6% of cases who sedated with hydroxyzine were able to sleep (p>0.05). The background rhythm was faster with CH compared to hydroxyzine (p<0.05). There were no association between the occurrence of fast background rhythm and the doses of CH. CONCLUSION: The study described the clinical practice of sedation with CH and hydroxyzine on EEG recording. Data suggest that CH with low doses and hydroxyzine is equally effective for sleep induction, but the side effects of CH on the sleep EEG is much more prominent.

Microencapsulation of hydroxyzine HCl by thermal phase separation: in vitro release enhancement and in vivo pharmacodynamic evaluation.

The systemic effect of hydroxyzine hydrochloride following its oral administration or topical application is associated with non compliant anticholinergic effect. Subsequently, the present study aims to prepare microcapsules loaded with hydroxyzine hydrochloride enabling its controlled release into the skin and reducing the side effect of its systemic absorption. The microcapsules were prepared by thermal phase separation method using ethyl cellulose/cyclohexane. Optimization of the formulation parameters was carried out by: (1) varying the type and the concentration of the coacervation inducer with microcapsules prepared with three different core: wall ratios, (2) by using ethyl cellulose with two different viscosities, (3) and by the addition of pore inducers such as pregelatinized starch and sucrose in order to enhance the drug release. Microcapsules of 99% encapsulation efficiency were prepared using 1% w/v polyisobutylene, and 1:0.1 core: wall ratio. The highest percent of drug is released after 9 h from microcapsules prepared using 1:0.1 core :wall ratio. Almost 100% drug was released after 3 h, from the same microcapsules prepared with pregelatinized starch that acts as a core coated with the drug. The pharmacodynamic effect of the chosen preparation was tested on the shaved back of histamine sensitized rabbits. Histopathological studies were driven for the detection of the healing of inflamed tissues.

Analysis of benzodiazepine withdrawal program managed by primary care nurses in Spain.

BACKGROUND: Benzodiazepine (BZD), the long-term treatment of which is harmful for cognitive function, is widely prescribed by General Practitioners in Spain. Based on studies performed in other countries we designed a nurse-led BZD withdrawal program adapted to Spanish Primary Care working conditions. RESULTS: A pseudo-experimental (before-after) study took place in two Primary Care Centres in Barcelona. From a sample of 1150 patients, 79 were identified. They were over 44 years old and had been daily users of BZD for a period exceeding six months. Out of the target group 51 patients agreed to participate. BZD dosage was reduced every 2-4 weeks by 25% of the initial dose with the optional support of Hydroxyzine or Valerian. The rating measurements were: reduction of BZD prescription, demographic variables, the Short-Form Health Survey (SF-12) to measure quality of life, the Medical Outcomes Study (MOS) Sleep Scale, and the Goldberg Depression and Anxiety Scale.By the end of the six-month intervention, 80.4% of the patients had discontinued BZD and 64% maintained abstinence at one year. An improvement in all parameters of the Goldberg scale (p <0.05) and in the mental component of SF-12 at 3.3 points (p = 0.024), as well as in most components of the MOS scale, was observed in the group that had discontinued BZD. No significant differences in these scales before and after the intervention were observed in the group that had not discontinued. CONCLUSIONS: At one year approximately 2/3 of the patients had ceased taking BZD. They showed an overall improvement in depression and anxiety scales, and in the mental component of the quality of life scale. There was no apparent reduction in the sleep quality indicators in most of the analysed components. Nurses in a Primary Care setting can successfully implement a BZD withdrawal program.

Dexmedetomidine and hydroxyzine synergistically potentiate the hypnotic activity of propofol in mice.

PURPOSE: Investigation into the characteristics of anesthetic interactions may provide clues to anesthesia mechanisms. Dexmedetomidine, an α(2)-adrenergic receptor agonist, has become a popular sedative in intensive care, and hydroxyzine, a histamine receptor antagonist, is well known as a tranquilizing premedication for anesthesia. However, no experimental or pharmacological evaluation has been reported concerning their combination with propofol. Thus, we studied their combined effect with a hypnotic dose of propofol in ddY mice. METHODS: Male adult mice were intravenously administered either dexmedetomidine (30 µg/kg) or hydroxyzine (5 mg/kg) with propofol (3.75-10 mg/kg) to induce hypnosis, defined as a loss of the righting reflex (LRR). Other mice were intravenously administered propofol, dexmedetomidine (300 µg/kg), or hydroxyzine (50 mg/kg) alone, and subsequent behavioral changes were observed. The 50% effective dose (ED(50)) for LRR was calculated, and the duration of LRR was determined. RESULTS: The hypnotic dose of propofol was 9.95 ± 1.04 mg/kg (ED(50) ± SEM) without combination. Dexmedetomidine and hydroxyzine reduced the ED(50) of propofol to 5.32 ± 0.57 and 5.63 ± 0.57 mg/kg, respectively. Coadministration of dexmedetomidine significantly extended LRR duration compared with propofol alone, whereas hydroxyzine significantly shortened LRR duration. A maximal dose of dexmedetomidine or hydroxyzine alone did not induce hypnosis. CONCLUSIONS: Dexmedetomidine and hydroxyzine demonstrated no hypnotic action alone; however, their coadministration potentiated the hypnotic activity of propofol. Although reduction in the dose of propofol was similar, only dexmedetomidine prolonged the duration of hypnosis.

Effects of the histamine H(1) receptor antagonist hydroxyzine on hERG K(+) channels and cardiac action potential duration.

AIM: To investigate the effects of hydroxyzine on human ether-a-go-go-related gene (hERG) channels to determine the electrolphysiological basis for its proarrhythmic effects. METHODS: hERG channels were expressed in Xenopus oocytes and HEK293 cells, and the effects of hydroxyzine on the channels were examined using two-microelectrode voltage-clamp and patch-clamp techniques, respectively. The effects of hydroxyzine on action potential duration were examined in guinea pig ventricular myocytes using current clamp. RESULTS: Hydroxyzine (0.2 and 2 µmol/L) significantly increased the action potential duration at 90% repolarization (APD(90)) in both concentration- and time-dependent manners. Hydroxyzine (0.03-3 µmol/L) blocked both the steady-state and tail hERG currents. The block was voltage-dependent, and the values of IC(50) for blocking the steady-state and tail currents at +20 mV was 0.18±0.02 µmol/L and 0.16±0.01 µmol/L, respectively, in HEK293 cells. Hydroxyzine (5 µmol/L) affected both the activated and the inactivated states of the channels, but not the closed state. The S6 domain mutation Y652A attenuated the blocking of hERG current by ~6-fold. CONCLUSION: The results suggest that hydroxyzine could block hERG channels and prolong APD. The tyrosine at position 652 in the channel may be responsible for the proarrhythmic effects of hydroxyzine.

Bispectral index monitoring of sedation depth in pediatric dental patients.

The bispectral index (BIS) monitor records electroencephalogram waveforms and provides an objective measure of the hypnotic effect of a sedative drug on brain activity. The aim of this pilot study was to use the BIS monitor to evaluate the depth of procedural sedation in pediatric dental patients and to assess if the BIS monitor readings correlate with a validated pediatric sedation scale, the University of Michigan Sedation Scale (UMSS), in determining the level of sedation in these patients. Thirty-five pediatric dental patients requiring sedation were studied prospectively. A baseline BIS reading was obtained and during the procedure an independent observer recorded the BIS every 5 minutes. The operator, who was blinded to the BIS results, determined the UMSS scale at the same 5-minute interval. The patients were monitored postoperatively for 1 hour. There was a significant but moderate correlation between BIS values and UMSS scores (Spearman's rank correlation r  =  -0.574, P < .0001). Percentage of agreement and kappa coefficient using all the observations were also calculated. The percentage of agreement was 37.8%, the kappa coefficient was 0.18 (P < .0001), and the weighted kappa coefficient 0.26 (P < .0001). A lack of correlation was noted between the deeper levels of UMSS sedation scores and BIS values. This study demonstrated a significant correlation between BIS values and the UMSS score in pediatric dental patients undergoing mild to moderate sedation. Based on our results, it appears that the BIS monitor may be useful during mild or moderate sedations to establish the level of sedation objectively without the need to stimulate the patient.

Short-term effects of morning versus evening dose of hydroxyzine 50 mg on cognition in healthy volunteers.

It is well known that the sedative properties of antihistamines can differ considerably between individual drugs. Several factors have been suggested to determine the presence, absence, and/or magnitude of sedation by antihistamines. Research has suggested that the sedative effects caused by central H1 blockade partly depend on the availability of histamine competing for the same receptor and that this competition is affected by a mechanism related to sleep. Consequently, the present study was designed to compare the effects of evening and morning doses of the first-generation antihistamine hydroxyzine on cognition. It was expected that the sedative effect of hydroxyzine would be apparent in the evening after an evening dose but would be smaller in the morning after a morning dose owing to the greater release of histamine shortly after awakening. Eighteen participants (9 females) participated in a placebo-controlled, randomized, double-blind 3-way crossover design. Performance was assessed using several psychomotor tests: that is, divided attention task, critical tracking task, stop signal task, the attention network test, and the experimental attention switch task. Results demonstrated that evening doses of hydroxyzine impaired performance on the divided attention and the attention network test. Impairment after morning doses was generally larger in magnitude and affected performance measures in all tasks. It is concluded that hydroxyzine-induced impairment at tmax is more prominent after morning doses compared with evening doses and that the present study could not present direct evidence to substantiate the hypothesis that histamine availability inversely affects the magnitude of antihistamine impairment.

Acute and subchronic effects of bilastine (20 and 40 mg) and hydroxyzine (50 mg) on actual driving performance in healthy volunteers.

Bilastine is a new second-generation H1 antagonist. Although bilastine has been demonstrated to produce little or no performance impairment in laboratory tests, it cannot be excluded that it produces impairments in real-life performance such as driving. This study aims to assess the effects of two doses of bilastine (20 and 40 mg) on actual driving after single and repeated administration. Hydroxyzine 50 mg was included as an active control. Twenty-two participants (11 females, 11 males) were tested in a placebo-controlled, randomized, double-blind, four-way cross-over design. Participants were treated with once-daily doses for eight consecutive days. On day 1 and 8 of each treatment period participants performed an actual highway driving test. The primary variable was standard deviation of lateral position (SDLP), a measure of weaving. Results demonstrated that hydroxyzine significantly increased SDLP on days 1 and 8 of treatment. Bilastine did not affect SDLP. It is concluded that hydroxyzine produces severe driving impairment after single doses and that this impairment only partly mitigates over time due to a lack of complete tolerance. Bilastine did not produce any driving impairment after single and repeated doses and can be safely used in traffic in doses up to 40 mg.

The effects of single dose anxiolytic medication on the CO2 models of anxiety: differentiation of subjective and objective measures.

This was a double blind, placebo-controlled, 4-way cross-over study in 12 healthy volunteer subjects of the acute effects of three drugs each of which are used in the clinic to treat some forms of anxiety: propranolol 40 mg, hydroxyzine 25 mg, flupentixol 0.5 mg and placebo. Each test session consisted of inhalation of air for 20 min, 10-min rest, inhalation of CO2 7.5% for 20 min, 10-min rest, followed by a single vital capacity inhalation of 35% CO2. The CO2 7.5% was administered at peak drug effect. Subjective effects were measured using Visual Analogue Scales (VAS), the Panic Symptom Inventory and the Generalised Anxiety Disorder Assessment inventory. Twelve subjects participated (eight men), with a mean age of 25.9 years. The expected subjective effects of CO2 were seen and these were significantly different from effects of peak air. However, there were no statistically significant differences between the drugs or between drugs and placebo, indeed there was a trend for some VAS anxiety scores to be higher than placebo in the drug groups. There were some significant differences in cardiovascular responses to CO2, with propranolol significantly decreasing heart rate and flupentixol increasing blood pressure when compared with placebo. The lack of subjective anxiolytic actions of the three drugs contrasts with our previous findings with acute benzodiazepines and chronic selective serotonin reuptake inhibitor administration. It may be that prolonged treatment with these agents would be required to show anxiolytic effects, although it may also be that their efficacy is insufficient to be demonstrated in this model. The lack of anxiolytic actions of propranolol, despite a significant reduction in heart rate, is a further support for a central action of CO2 to produce anxiety.

Effects of dexamethasone and hydroxyzine treatment on intradermal testing and allergen-specific IgE serum testing results in horses.

To determine whether dexamethasone or hydroxyzine affect intradermal testing (IDT) and allergen-specific IgE serum testing (ASIST) results in horses, these tests were performed serially in five horses without signs of atopic dermatitis before and after treatment with the drugs. IDT consisted of saline, histamine (1:100,000 w/v) and eight commercial extracts; results were evaluated as subjective scores by comparison to saline (0) and histamine (4) and as objective measurement of wheal diameter (mm). After baseline testing, dexamethasone (20 mg) was administered intramuscularly daily for 7 days. Testing was repeated 3-4 h, 7 days, and 14 days after the final dose of dexamethasone. Hydroxyzine (500 mg) was subsequently administered orally twice daily for 7 days. Testing was performed 3-4 h, 3 days, and 7 days after the final dose of hydroxyzine. No differences were found between pre- and post-treatment subjective IDT scores for either drug. However, wheal diameter for histamine and house dust, dust mite mix, and black ant extracts decreased (P < 0.05) at all times post-injection for IDT performed 3-4 h after the final dose of both medications. Wheal diameter returned to pre-treatment levels 14 days after discontinuation of dexamethasone and 7 days after discontinuation of hydroxyzine. No significant changes in ASIST results were found. In conclusion, treatment of horses with dexamethasone or hydroxyzine for 7 days had no effect on ASIST results but did decrease IDT wheal diameters. Based on findings of this study, withdrawal times of 14 and 7 days for dexamethasone and hydroxyzine, respectively, prior to IDT can be recommended.