Aphthasol
[Effects of co-administration of an antidepressant and an anxiolytic drug in the "learned helplessness" paradigm: importance of hydroxyzine]

[Article in French]

Martin P, Guillou N, Lacroix P, Billardon M.

AMC Research Group, Paris.

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.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9035982&dopt=Abstract hydroxyzine Atarax



Aphthasol
Prospective controlled study of hydroxyzine and cetirizine in pregnancy.

Einarson A, Bailey B, Jung G, Spizzirri D, Baillie M, Koren G.

Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada.

BACKGROUND: Hydroxyzine has been used for many years for the treatment of allergic symptoms. Cetirizine, an active metabolite of hydroxyzine, has become very popular for the treatment of allergy symptoms because of its efficacy without the sedating effects of the parent compound. Little is known about the safety of hydroxyzine use during pregnancy, and there are no published reports on the effects of cetirizine on pregnancy outcome. OBJECTIVE: To determine whether hydroxyzine and cetirizine are associated with any increased risk of malformations in humans. METHODS: All pregnant women counseled by the Motherisk Program in Toronto on the use of hydroxyzine or cetirizine during their pregnancies were enrolled in a prospective, controlled, observational study. The control group consisted of pregnant women matched for age, smoking, and alcohol consumption who were counseled for non-teratogenic drug. RESULTS: One hundred twenty women were followed after exposure to either hydroxyzine or cetirizine during pregnancy. Of these, 53 were exposed to hydroxyzine during organogenesis and 39 to cetirizine. There were no significant differences found between the hydroxyzine or cetirizine groups and the control groups in the pregnancy outcome: rate of livebirths, spontaneous or therapeutic abortion, or stillbirth. There was also no difference in the rates of major or minor anomalies, mean birth weight, mode of delivery, gestational age, or presence of neonatal distress. CONCLUSIONS: The use of hydroxyzine and cetirizine does not appear to be associated with increased teratogenic risk.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9048526&dopt=Abstract hydroxyzine Atarax



Aphthasol
Distribution of antihistamines into the CSF following intranasal delivery.

Chou KJ, Donovan MD.

College of Pharmacy, University of Iowa, Iowa City 52242, USA.

The preferential absorption of certain drug compounds from the nasal cavity into the cerebrospinal fluid (CSF) raises questions regarding the transport processes controlling drug disposition following intranasal delivery. The disposition characteristics of several structurally similar antihistamine compounds, hydroxyzine, chlorpheniramine, triprolidine, and chlorcyclizine, into the CSF following nasal administration were studied using the rat as an animal model. The antihistamines were administered either intranasally or intra-arterially, and serial CSF and plasma samples were collected from the cisterna magna and the femoral artery, respectively. The drug levels in CSF and plasma were assayed by HPLC. Hydroxyzine concentrations in plasma and CSF were found to be significantly greater than most of the other compounds tested. In addition, hydroxyzine also showed the most rapid systemic absorption following nasal administration. Interestingly, the hydroxyzine levels in CSF following intranasal administration were significantly higher than those following intra-arterial administration. The AUC ratios between CSF and plasma for hydroxyzine after intranasal and intra-arterial administration were 4.0 and 0.4, respectively. The AUC ratios for triprolidine, the other antihistamine with measurable CSF concentrations, were 0.5 and 0.7, respectively. The distribution of antihistamines from the nasal membrane into the CSF appears to be controlled by a combination of their molecular properties. It also appears that the intranasal delivery of drugs with optimal physicochemical characteristics can result in an improved CNS bioavailability compared to those achieved from an equivalent parenteral dose.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9158881&dopt=Abstract hydroxyzine Atarax



Aphthasol
Influence of combined administration of ethyl alcohol with caffeine and hydroxyzine on cardiac minute volume and stroke volume in rabbits.

Czarnecka E, Darzynkiewicz-Czernik D, Mazur M, Polakowski P.

The effect of combined administration of ethyl alcohol with caffeine and hydroxyzine on cardiac volume and vascular resistance was studied. Combined administration of these compounds diminished cardiac stroke volume and minute output and increased general vascular resistance. Simultaneous administration of ethanol with caffeine and hydroxyzine exerts an unfavorable effect on haemodynamics of circulatory system.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1214515&dopt=Abstract hydroxyzine Atarax



Aphthasol
An allergist looks at urticaria.

Beakey JF.

Some etiologic possibilities which must be considered are foods, drugs, infection, inhalant sensitivity, psychic factors, physical agents, underlying connective tissue disease or neoplasm, insect bite or stings and genetic abnormalities. A painstaking history and a complete physical examination are, of course, mandatory. These are followed by appropriate studies for whatever etiologic factors are suggested by the history and physical examination. Certain routine or more sophisticated studies might be indicated including a complete blood count, urinalysis, stools for ova and parasites, antinuclear antibody titer, complete complement, sedimentation rate, sinus, chest and dental X rays and any other specified test depending on where the clues lead. O'Loughlin described a practical approach in the use of laboratory studies for the diagnosis of chronic urticaria. Skin tests can be helpful especially for inhalants, but food tests are usually not reliable in the diagnosis of chronic urticaria. The acute urticaria reaction to a food is clinically obvious and this type of patient does not usually seek medical attention or need extensive investigation. Treatment includes a few basic medications. Hydroxyzine (Atarax, Vistaril), which combines tranquilizer and antihistamine action, is frequently effective. Cyproheptadine HCL (Periactin) both a serotonin and histamine antagonist with anticholinergic effect, is also helpful--especially in combination with hydroxyzine. Antihistamines, ephedrine, epinephrine, aminophyllin and occasionally corticosteroids are helpful. Immunotherapy with inhalants is occasionally indicated. Eliminating possible offending foods, dyes or drugs has been previously discussed. Anti-candidal therapy and low yeast diet is effective when indicated. The final aspect of the investigation and treatment process might best be described as "patient support"--patience on the part of the physician. It should be realized that in 75% of the cases of chronic urticaria, no convincing etiology is found. It should also be realized that urticaria all too frequently "settles down" due as much to the natural course as to the careful ministrations of the physician.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=138566&dopt=Abstract hydroxyzine Atarax