Aphthasol
Hydroxyzine in the treatment of interstitial cystitis.

Theoharides TC.

Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, Massachusetts.

Hydroxyzine is a piperazine, tricyclic, H1-receptor antagonist with unique properties, especially the inhibition of mast cell and neuronal secretion. Preliminary results indicate is has an unusual ability to reduce interstitial cystitis symptoms. The long history, lack of major side effects, wide availability, low cost, and apparent effectiveness of hydroxyzine compel presentation of these preliminary results.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8284834&dopt=Abstract hydroxyzine Atarax



Aphthasol
Comparative studies on the in vitro drug dissolution profiles for hydroxyzine hydrochloride tablets.

Loucas SP, Maager P, Mehl B.

Department of Pharmacy, Mount Sinai Hospital Medical Center, New York, NY 10029.

OBJECTIVE: A significant practical problem in the standardization of dissolution testing is addressed. In vitro releasing characteristics of hydroxyzine hydrochloride tablets are presented to further the documentation of bioequivalency criteria. DESIGN: The assessment model compares the official United States Pharmacopeia disintegration approach for dissolution analysis with that of the Food and Drug Administration's recommended rotating paddle technique for inducing aqueous disruption of the solid oral dosage form. RESULTS: The rationale and significance of the study focuses attention on the variation in release of the active ingredient observed relative to the four formulation strengths. With differences in the extent of dissolution noted and official standards in mind, emphasis is placed on the development of an alternate test protocol. CONCLUSIONS: Dissolution data derived via ultraviolet spectrophotometry revealed statistically significant differences in the amount of hydroxyzine hydrochloride being released from its coated structure, the extent of which was found to be dependent on the acid nature of the simulated gastric dissolution medium used and intensity of mixing action employed.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8431611&dopt=Abstract hydroxyzine Atarax



Aphthasol
Effect of hydroxyzine and meperidine on arterial blood gases in patients with chronic obstructive pulmonary disease.

Zsigmond EK, Flynn K, Shively JG.

Department of Anesthesiology, University of Michigan Medical Center, Ann Arbor.

Hydroxyzine is frequently used to tranquilize chronic obstructive pulmonary disease patients, who may be concomitantly receiving narcotic analgesics. Therefore, its effect alone and in combination with meperidine on arterial blood gases and ventilation at rest were evaluated in 44 patient volunteers, who gave informed consent. Hydroxyzine, 1.5 mg/kg i.v. caused no significant decrease in PaO2 and pH, no increase in PaCO2 at 5, 10, 20, 30 and 60 min post-infusion (n = 13, mean age = 63.4 years). Meperidine, 1.5 mg/kg i.v. caused a significant (p < 0.001) reduction in PaO2 for 20 min with concomitant increase in PaCO2 (n = 14; mean age = 49.4 years). The combination of the same doses of hydroxyzine with meperidine i.v. caused no greater decrease in PaO2 or in pH or increase in PaCO2 than did meperidine alone (n = 17; mean age = 52.6 years), indicating no greater ventilatory depression with the combination than with meperidine alone. The lack of significant pH decreases at 30 and 60 min further corroborates no potentiation of meperidine by hydroxyzine. In conclusion, hydroxyzine, even when given through the i.v. route in excess of the maximum i.m. therapeutic dose, caused no changes in PaO2, PaCO2 or pH in chronic obstructive pulmonary disease patients. Therefore, its i.m. administration resulting in lower blood levels than i.v., is not likely to cause ventilatory depression. Furthermore, hydroxyzine caused no potentiation of the ventilatory depression induced by meperidine, hence hydroxyzine may be safely employed in combination with meperidine.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8468109&dopt=Abstract hydroxyzine Atarax



Aphthasol
Hydroxyzine inhibits experimental allergic encephalomyelitis (EAE) and associated brain mast cell activation.

Dimitriadou V, Pang X, Theoharides TC.

Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA.

Experimental allergic encephalomyelitis (EAE) has been used as an animal model for the human demyelinating disease multiple sclerosis (MS). In acute MS or EAE, early disruption in the integrity of the blood-brain-barrier (BBB) precedes brain infiltration by inflammatory cells or any clinical evidence of disease. BBB permeability could be affected by vasoactive mediators and cytokines released from perivascular brain mast cells. We investigated the number and degree of activation of brain mast cells in EAE and the effect of the heterocyclic histamine-1 receptor antagonist hydroxyzine, a piperazine compound known to also block mast cells. Acute EAE was induced in Lewis rats by immunization with whole guinea pig spinal cord homogenate and complete Freund's adjuvant (CFA). A second group of animals were treated orally with hydroxyzine for one day before immunization and then continuously for 14 days. Control rats were treated with CFA or hydroxyzine alone. The clinical progression of EAE was assessed on days 10, 12 and 14 after immunization. The number of metachromatic mast cells and the degree of degranulation was assessed in the thalamus with light microscopy. At day 14, there was a three-fold increase in the number of brain mast cells with EAE, as compared to controls. These cells were positive for the immunoglobulin E binding protein (FcepsilonRI), while those from control rats were not. Over 40% of all thalamic mast cells studied in EAE showed partial staining or extruded secretory granule indicative of secretion. Hydroxyzine treatment inhibited (p<0.05) the progression and severity of EAE by 50% and the extent of mast cell degranulation by 70% (p<0.05). These findings indicate that brain mast cells are associated with EAE development and that inhibition of their activation correlates positively with the clinical outcome.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10884588&dopt=Abstract hydroxyzine Atarax



Aphthasol
Conscious sedation of pediatric dental patients using chloral hydrate, hydroxyzine, and nitrous oxide--a retrospective study of 382 sedations.

Needleman HL, Joshi A, Griffith DG.

Harvard School of Dental Medicine, Boston, Massachusetts, USA.

This retrospective study assessed the effectiveness and safety of chloral hydrate (55 mg/kg), hydroxyzine (1 mg/kg), and nitrous oxide in the sedation of 336 uncooperative pediatric dental patients over 382 sedation sessions, and identified variables associated with effectiveness including: sex, weight, age, and preoperative behavior of the patient; route and combinations of the sedative drugs; and sex of the operating and monitoring dentists. The operating and monitoring dentists rated the sedation session as either effective or ineffective and also as either heavy, moderate, light or poor. The mean age of the children was 2.6 years and mean weight was 14.1 kg. Seventy-four percent of the sedation sessions were deemed effective. Boys had more effective sessions (80.6%) than girls (65.1%) (P = 0.001). Also, the percentage of sedations rated as effective increased as the preoperative behavior was more positively rated (P = 0.001). Oral regimen of chloral hydrate alone or in combination with oral hydroxyzine was more effective (75.5%) than rectal administration of chloral hydrate alone (65.7%) (P = 0.09). There was no significant difference in effectiveness when chloral hydrate was administered orally alone or in combination with oral hydroxyzine. Sedation sessions rated effective had longer operative times, included more sextants of treatment, were more likely to include restorative treatment, and were less likely to include extractions than the ineffective sedations. Vomiting was the only complication reported, occurring in 8.1% of the sedations. Vomiting did not vary significantly with either route of administration or inclusion of hydroxyzine in the oral regimen. Pulse rates were significantly higher for children in the ineffective sedation sessions. This sedative drug regimen was deemed safe and effective for treating young and uncooperative pediatric dental patients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8786908&dopt=Abstract hydroxyzine Atarax