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.

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.

Assessment of the effects of 2 sedation regimens on cardiopulmonary parameters in pediatric dental patients: a retrospective study.

PURPOSE: The purpose of this study was to evaluate the cardiopulmonary effects of 2 sedation regimens during treatment: (1) oral meperidine and hydroxyzine with nitrous oxide (N2O); and (2) oral diazepam and hydroxyzine, submucosal meperidine, and N2O. Nitrous oxide was tapered to oxygen (O2) only 10 minutes following submucosal meperidine administration. METHODS: Sixty-two children were evaluated who met the following criteria: (1) history of uncooperative behavior; (2) ASA I or II; (3) nothing to eat or drink after midnight the night before the appointment; (4) an initial/recall exam prior to the sedation appointment; and (4) patients who met the American Academy of Pediatric Dentistry guidelines for sedation. Regimens I and II included 32 and 30 patients, respectively. A single clinician treated all patients. A Criticare monitor recorded the following at 5-minute intervals: (1) O2 saturation; (2) respiratory rate; (3) heart rate; (4) systolic and diastolic blood pressures; (5) end tidal carbon dioxide concentration; and (6) mean arterial blood pressure. RESULTS: The t test indicated significant differences between the 2 regimens for: (1) heart rate; (2) systolic blood pressure; and (3) diastolic blood pressure (regimen II had higher values). Using the general linear model, no significant differences were found. All cardiopulmonary parameters were within normal limits. CONCLUSION: Regimens I and II had similar cardiopulmonary effects.

A prospective study of 2 sedation regimens in children: chloral hydrate, meperidine, and hydroxyzine versus midazolam, meperidine, and hydroxyzine.

The aim of this study was to compare both the behavioral and physiological effects of 2 drug regimens in children: chloral hydrate (CH), meperidine (M), and hydroxyzine (H) (regimen A) versus midazolam (MZ), M, and H (regimen B). Patients between 24 and 54 months of age were examined by crossover study design. Behavior was analyzed objectively by the North Carolina Behavior Rating System and subjectively through an operator and monitor success scale. Physiological data were recorded every 5 minutes and at critical points throughout the appointment. Sixteen patients completed this study. No significant differences in behavior were noted by the North Carolina Behavior Rating System or the operator and monitor success scale. A quiet or annoyed behavior was observed 93% and 90% of the time for regimen A and regimen B, respectively. Using the operator and monitor success scale, 63% of regimen A and 56% of regimen B sedations were successful. No statistically significant differences were noted in any of the physiological parameters between the 2 regimens. Ten episodes of hemoglobin desaturation were detected with regimen A sedations. There were no differences between the sedative drug regimens CH/M/H and MZ/M/H for behavioral outcomes or physiological parameters.

Role of endocytosis in the action of ether lipids on WEHI-3B, HL60, and FDCP-mix A4 cells.

We investigated the effect of a number of platelet activating factor antagonists on cell killing by 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphoryl choline (ET-18-OCH3). Of six platelet activating factor antagonists tested, four were found to protect WEHI-3B leukemic cells against cell death induced by ET-18-OCH3. Certain other compounds, not platelet activating factor antagonists, had similar protective effects. The protective compounds were all lipophilic weak bases. We describe experiments that indicate that these compounds protect by inhibition of endocytic uptake of ET-18-OCH3. Sensitive cells showed rapid endocytic uptake, whereas in resistant cells, uptake was slow. Uptake of ET-18-OCH3 could be suppressed by inhibitors of endocytosis such as chloroquine, monensin, and vinblastine. We conclude that one of the principal determinants of sensitivity or resistance to ether lipids may be the rate at which cells take them up by endocytosis.

The pharmacokinetics and pharmacodynamics of hydroxyzine in patients with primary biliary cirrhosis.

Hydroxyzine, a potent H1-receptor antagonist often used for relief of pruritus in patients with hepatic dysfunction, was studied in eight patients, mean age 53.4 +/- SD 11.2 years, with primary biliary cirrhosis. The patients ingested a single dose of hydroxyzine, 0.7 mg/kg (mean dose 43.9 +/- 6.6 mg). Before the dose, then hourly for 6 hours, every 2 hours from 6-12 hours, at 24 hours, and every 24 hours for 6 days, serum hydroxyzine and cetirizine were measured and an intradermal injection of 0.01 mL of a 0.1 mg/mL solution of histamine phosphate was performed. Wheals and flares were traced at 10 minutes and the areas were calculated. Mean peak hydroxyzine levels of 116.5 +/- 60.6 ng/mL occurred at 2.3 +/- 0.7 hours and mean peak cetirizine levels of 500.4 +/- 302.0 ng/mL occurred at 4.8 +/- 2.8 hours. The mean serum elimination half-life of hydroxyzine was 36.6 +/- 13.1 hours, and the mean serum elimination half-life of cetirizine was 25.0 +/- 8.2 hours. The mean hydroxyzine clearance rate was 8.65 +/- 7.46 mL/min/kg, and the mean volume of distribution was 22.7 +/- 13.3 L/kg. The mean wheal area was suppressed (P less than 0.01) from 1 to 120 hours, with maximal suppression from 2 to 48 hours. The mean flare area was suppressed from 1 to 144 hours, with maximal suppression from 3 to 24 hours (P less than 0.01). All patients became sleepy from 0.5 to 6 hours. Blurred vision, dizziness and dry mouth each occurred in two patients. Hydroxyzine elimination is impaired in patients with primary biliary cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Problems of medication with the pediatric patient.

During the course of dental treatment, when it is necessary to prescribe pharmacologic agents for the pediatric patient, a drug should be selected that is not only effective but also available in a readily acceptable form. Dosages should be considered carefully. Rather than attempting to adjust adult recommendations, established guidelines for children should be utilized. Manufacturer's doses should be followed when available. If a child frustrates efforts toward treatment and does not respond to nonpharmacotherapeutic management approaches, premedication should be considered. The practitioner should have a thorough medical history before deciding to employ outpatient sedation. This history can be helpful in selecting the most appropriate regimen. Very young children and severely compromised patients are not good candidates for sedation and are best treated under general anesthesia. Narcotic analgesics are rarely indicated for control of pain following dental treatment in children. Nonnarcotic preparations are very effective and will suffice for most procedures. Because prolonged bleeding has been demonstrated, aspirin should be used with caution in surgical cases. Oral administration is recommended for most dental infections requiring antibiotics. In instances when severe infection is encountered, the parenteral route is suggested. A narrow-spectrum, bactericidal agent is preferred; barring allergy, penicillin is the usual drug of choice. When antibiotic prophylaxis is indicated, adherence to American Heart Association guidelines is strongly encouraged.

Anxiolytic activity of chloral hydrate and hydroxyzine.

The combination of chloral hydrate and hydroxyzine is given frequently to anxious pediatric dental patients. In order to observe and quantify the anxiolytic effects of these drugs given alone and in combination, highly explorative male C57/black mice were tested using the light/dark test box after injecting subhypnotic doses for increased transitions between the light and dark side of the test box. Fifty-one mice were subjected individually to a 10-min test in the box for dose responses following the i.p. administration of 32-, 64-, and 132-mg/kg doses of chloral hydrate; 1-, 4-, 7-, and 10-mg/kg doses of hydroxyzine; or a combination of each of these doses of hydroxyzine and chloral hydrate. The automated test box recorded the number of times a mouse crossed between the two chambers. Doses of chloral hydrate 132 mg/kg and hydroxyzine 1 mg/kg resulted in significantly increased transitions. None of the combinations studied produced significantly increased transitions when compared with the effective doses identified for each individual drug. The paradigm did not support the hypothesis that the anxiolytic effects of chloral hydrate and hydroxyzine are additive or synergistic.

The evaluation of child behavior during dental examination and treatment using predmedication and placebo.

The purpose of this study were to determine the association of scores on the North Carolina Behavior Rating Scale (NCBRS) to those of the Frankl scale during restorative visits; and to quantify and compare rated behavior of children during an oral examination and restorative visits involving either a placebo or a combination of chloral hydrate (CH) and hydroxyzine. Fifteen patients 21-37 months old participated in this institutionally approved study. The study was a double-blind, crossover design. Following an examination using a mirror, explorer, and prophylaxis cup, the child received either a placebo or a combination of chloral hydrate (CH) and hydroxyzine. Fifteen patients 21-37 months old participated in this institutionally approved study. The study was a double-blind, crossover design. Following an this institutionally approved study. The study was a double-blind, crossover design. Following an examination using a mirror, explorer, and prophylaxis cup, the child received either a placebo or a combination of chloral hydrate and hydroxyzine. The sequence was reversed at the next appointment. All exam and treatment visits were videotaped and analyzed using the NCBRS. In addition, all treatment visits were rated with the Frankl scale. The data were analyzed using a repeated ANOVA and correlation coefficients. The results showed a high interrater reliability (> 86% agreement) and a significant correlation between the NCBRS and Frankl scale (P < 0.001). No significant difference was found for the amount of disruptive behavior among oral examination, placebo, and medication visits (P < or = 0.097), although a consistent decrease in mean disruptive behavior for that order of visits was observed most frequently.(ABSTRACT TRUNCATED AT 250 WORDS)

IV sedation in pediatric dentistry: an alternative to general anesthesia.

This prospective study was conducted to determine the sedative effects of IV ketamine and fentanyl on vital signs and behavior. Twenty-seven children, classified as ASA I, with a mean age of 34 months, were studied. The dosages of IV ketamine and fentanyl given were 0.5 mg/kg and 0.5 mcg/kg, respectively, approximately every 15-20 min. The pulse rate averaged 125 throughout the case. Blood pressure averaged 112/64. The respiration rate averaged 22 breaths per min. Mean behavior composite scores were 1.9 at the initial examination and 3.3 during treatment. One child vomited during treatment. Post-treatment complications were discomfort in 19% (5), nausea in 22% (6), and vomiting in 15% (4) of the patients. We concluded that IV sedation of precooperative healthy pediatric patients with ketamine, fentanyl, and nitrous oxide/oxygen appears to be a safe and effective sedation modality with minimal side effects when administered and monitored by a qualified anesthetist, offering the practitioner an alternative to general anesthesia.

The effects of nitrous oxide on behavior and physiological parameters during conscious sedation with a moderate dose of chloral hydrate and hydroxyzine.

The purpose of this study was to determine differences in heart rate (HR), blood pressure (BP), peripheral oxygen saturation (pO2), expired CO2 (CO2), and behavior (using two scales) comparing nitrous oxide/oxygen (N2O) with oxygen (O2) alone in 20 children (mean age 45 +/- 5.1 months) sedated with chloral hydrate (CH) and hydroxyzine in a double-blind crossover design. Administration of CH (40 mg/kg) and hydroxyzine (2 mg/kg) was held constant for each patient visit; however, N2O (50%) was administered during one visit and O2 (100%) at the other in a randomly determined manner. Physiologic and behavioral parameters were collected during eight specific procedural events (e.g., administration of local anesthesia). Data were analyzed with a repeated-measures ANOVA, one-way ANOVA, t-test, Kruskal Wallis ANOVA, and descriptive statistics. There was no statistically significant difference in any physiologic or behavioral parameter as a function of inhalation agent. However, significant differences were found for certain physiological parameters (i.e., HR [F = 5.41, P < 0.001], pO2 [F = 6.04, P < 0.001], and CO2 [F = 2.33, P < 0.027]) and all behavioral measures (% crying [F = 2.82, P < 0.008], % quiet [F = 5.38, P < 0.001], % movement [F = 3.88, P < 0.001], and % struggle [F = 2.83, P < 0.007]) of one scale (Ohio State University Behavioral Rating Scale [OSUBRS]) as a function of procedural events. Although no statistically significant differences were attributable to inhalation agent, evidence suggests that N2O resulted in less crying and struggling and more quiet behaviors than O2. Significant correlations existed between sub-categories of the two behavioral rating scales, suggesting some association between the scales. One may conclude from the results of this study that moderate doses of CH and hydroxyzine in combination with nitrous oxide are not associated with any significant potentiation effects on physiologic parameters compared with the same oral agents with oxygen alone. Certain procedural events (e.g., administration of local anesthesia) do result in patient responses that affect specific behaviors and physiology. Although the effects of N2O may not be statistically significant, generally it produces an attenuation in physiological and behavioral responses as measured under the conditions of this study.

[Examination of the influence of selected drugs administered orally on amount of saliva excreted and pocket fluid as well as on patients' feeling during stomatological treatment]. / Badania wpluwu wybranych leków podawanych doustnie na ilosc wydzielanej sliny i plynu kieszonkowego oraz na odczucia pacjentów podczas leczenia stomatologicznego.

The influence of pyralgin, acenol, hydroxizinum and scopolan administered orally on the amount of the saliva excreted and pocket fluid as well as one the patients' feeling during stomatological treatment has been examined by the dual blind test method. The examinations haven't proved any significant influence of these drugs on the excretion of the saliva and pocket fluid of a statistical importance; these drugs, however, have reduced the painfulness of the operations depending on hard dental tissues processing. Among the drugs applied Pyralgin has proved to be the most useful drug for patients premedication before stomatological treatment.

Monitoring of sedated pediatric dental patients.

The results of this study showed that children sedated with 50 mg/kg chloral hydrate and 25 mg hydroxyzine in conjunction with 40 percent nitrous oxide and 60 percent oxygen may have respiratory difficulties which are not detected by the traditional monitoring of blood pressure, pulse, respiratory rate and skin color. The use of a pulse oximeter that noninvasively measures oxygen saturation of hemoglobin (SaO2) allowed earlier detection of respiratory distress, when correction was a relatively simple matter of readjusting head position. This combination of sedative agents was effective in managing two-thirds of the patients originally classified in a behavioral category of definitely negative. No children sedated with only 40 percent nitrous oxide and 60 percent oxygen exhibited respiratory problems, and over 80 percent of the patients classified in behavioral category of negative were managed effectively with this technique.

Prolongation of simple and choice reaction times in a double-blind comparison of twice-daily hydroxyzine versus terfenadine.

Newer, nonsedating antihistamines provide a therapeutic alternative for the patient with allergy whose work is impaired by the side effects of traditional H1 antihistamines. To assess the differential effect of these antihistamines on reaction times and subjective symptoms, we compared terfenadine, 60 mg twice daily, to hydroxyzine, 25 mg twice daily, in a double-blind, placebo-controlled, crossover study of 16 healthy, asymptomatic adults. Simple reaction time and choice reaction time were measured with a computer-based, eye-hand, reaction-time testing apparatus. Reaction times and symptom scores were assessed 90 minutes after the fourth and tenth doses of each drug. Hydroxyzine, but not terfenadine, significantly prolonged both simple and choice reaction time (p less than or equal to 0.0001). However, decision time, the time to process one bit of spatial information, was not prolonged by either antihistamine. Therefore, hydroxyzine prolonged the interpretation and response to stimuli of the central nervous system without increasing single-bit processing time. Although terfenadine was not different from placebo for any symptom assessed, hydroxyzine produced significant drowsiness (p = 0.001), dry mouth (p = 0.022), and irritability (p = 0.021). During the 5 days of hydroxyzine administration, neither objective nor subjective symptoms demonstrated the development of tolerance. No correlation was found between subjective symptoms and prolongation of reaction times by hydroxyzine, suggesting that side effect symptoms of traditional antihistamines are unreliable predictors of objective performance. Terfenadine provides a promising therapeutic alternative to traditional antihistamines for individuals performing critical tasks.