Aphthasol
Hydroxyzine prevents isolation-induced vocalization in guinea pig pups: comparison with chlorpheniramine and immepip.

Lamberty Y, Gower AJ.

Psychopharmacology Unit, Preclinical CNS Research, Chemin du Foriest, UCB Pharma S.A., B-1420, Braine l'Alleud, Belgium. yves.lamberty ucb-group.com

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.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15388291&dopt=Abstract hydroxyzine Atarax



Aphthasol
Premedications and peribulbar analgesia--a prospective audit.

van den Berg AA.

Dept. of Anesthesia Medical School University of Texas at Houston, 6431 Fannin MSD 5.020, Houston 77030, Texas, USA. antonvdb2000 yahoo.com

PURPOSE: After peribulbar block analgesia (PBA) instituted in the preoperative anesthetic room, patients are often anxious, developing increased heart rate (HR) and blood pressure (BP) upon their arrival to the operating room and during subsequent surgery. The efficacy of premedication in attenuating these stress responses has not been examined. A prospective audit was undertaken to examine the relationship between the premedication schedules most commonly prescribed at the King Khaled Eye Specialist Hospital and increases in HR and BP during surgery in response to the stress of surgery, and the requirements for intravenous (IV) benzodiazepine, opioid or NSAID medication to treat these increases, or any complaint of pain or positional discomfort on the operating table, respectively. METHODS: The preoperative and intraoperative anesthesia course of 1,064 patients > or = 50 years of age who underwent ocular surgery under PBA was prospectively examined. The following data were recorded: (i) patient characteristics, state of health or disease, medications and premedications; (ii) heart rate (HR), systolic arterial pressure (SAP), and diastolic arterial pressure (DAP) at 0600 hrs before surgery (baseline), on admission to the operating room, maximum and minimum values of HR, SAP and DAP recorded at the start of, and during, surgery; and (iii) all instances of benzodiazepine, opioid or NSAID drug administration during surgery, according to standard protocols. RESULTS: Five premedication schedules were identified: Group 1 hydroxyzine po alone (n = 302); Group 2 hydroxyzine, paracetamol with codeine (Revacod), diclofenac po (N = 173); Group 3 hydroxyzine, diclofenac, ranitidine po (N = 94); Group 4 hydroxyzine, cimetidine or ranitidine po, morphine or pethidine IM (N = 340); and Group 5 lorazepam (nocte), hydroxyzine, diclofenac, ranitidinepo, morphine or meperidine IM (N = 155). The five groups of patients were comparable for age, sex, weight and health. Healthy, diseased (with concurrent hypertension, diabetes, ischemic heart disease) and all patients in each premedication group had similar baseline HR, SAP and DAP. In the operating room, the maximum and minimum mean HR in each group was similar, except that more patients in Group 1 developed SAP exceeding 160 mmHg and DAP exceeding 90 mmHg than in Group 5 (p<0.002 and <0.0005, respectively). The requirements for medication at the commencement of, and during, surgery in the five groups to treat increases in HR/BP, eye pain and positional discomfort on the operating table were similar. CONCLUSION: Each of the five premedication schedules described appear to confer similar effects on cardiovascular changes in anticipation of, and during, surgery, except that those given the lightest premedication, Group 1, showed greater increases in BP at the start of surgery than did those given the heaviest premedication, Group 5. The requirements in the operating room for IV medication were similar in the five premedication groups, and no greater benefit was discernible for any one of the five premedication schedules on the objective features assessed. These data suggest that simple oral premedication of hydroxyzine, with or without an H2 receptor antagonist and NSAID, may suffice as premedication in middle-aged to elderly patients undergoing anterior segment surgery.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15449745&dopt=Abstract hydroxyzine Atarax



Aphthasol
[Atarax in treatment of anxiety in outpatient clinic]

[Article in Russian]

Bobrov AE, Babin AG, Gladyshev OA, Belianchikova MA, Piatnitskii NIu, Bakalova EA, Abolmasova OB.

50 patients (10 men, 40 women) with generalized anxiety (29), disorders of adaptation (15), somatoformed disorders (6), diagnosed according to ICD-10, were treated by atarax. Mean age of the patients was 42.4 years, average duration of the disease-1.9 years. Evaluation of efficiency was performed according to "Global Clinic Impression" scale, Hamilton rating scale for anxiety and depression (HAM-A and HAM-D) as well as according to FARD scale for anxiety. The patients were examined both before the treatment and on 14 and 28 days of treatment. According to "Global Clinical Impression" scale excellent and good results were observed in 66% of the patients. Unsatisfactory results were found in 10% of the cases. Reduction of the total HAM-A scores by 50% and more was observed in 48% of the patients. The same decrease was observed in 58% of the patients according to HAM-D scale and in 54% of the patients according to FARD scale. Following side-effects were noted: transitory sleepiness (36% of the cases), weakness (18%), headache (6%), changes of both appetite (6%) and body mass (6%), slight mucosa dryness (2%). In one case skin allergic reaction in form of urticaria bullosa took place and the therapy was interrupted.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9532714&dopt=Abstract hydroxyzine Atarax



Aphthasol
Hydroxyzine inhibits neurogenic bladder mast cell activation.

Minogiannis P, El-Mansoury M, Betances JA, Sant GR, Theoharides TC.

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

OBJECTIVES: Increased numbers of activated mast cells have been documented close to substance P (SP) containing nerve endings in the bladders of patients with interstitial cystitis (IC), a painful, sterile bladder disorder occurring primarily in females. Many of these patients also suffer from allergies, but common antihistamines do not help. In line with the fact that IC symptoms worsen under stress, we recently showed that bladder mast cells could be activated by the stable acetylcholine (Ach) analogue carbachol and by immobilization stress. Preliminary data from open label studies indicated that the heterocyclic histamine-1 receptor antagonist (H-1r alpha) hydroxyzine reduces IC symptoms. We, therefore, investigated whether hydroxyzine could inhibit carbachol-induced bladder mast cell activation. METHODS: Bladder pieces from male Sprague-Dawley rats were perfused with 10(-5) M carbachol, 10(-5) M SP, or 100 microg/ml compound 48/80 (C48/80), with or without preincubation with the designated concentrations of the H-1r alpha. Mast cell activation was assessed by release of exogenous 3H-serotonin and morphological evidence of secretion by light microscopy. RESULTS: Carbachol at 10(-5) M triggered rat bladder mast cell serotonin release which represented a 65% increase over control. Equimolar concentrations of SP caused a 32% increase, while C48/80 had no effect. The heterocyclic piperazine H-1r alpha hydroxyzine reduced carbachol-induced serotonin release by 25% at 10(-6) M and 34% at 10(-5) M, both of which were statistically significant (P < 0.05). On the contrary, the well known H-1r alpha diphenhydramine had no inhibitory effect, while the mixed H-1r alpha and 5-hydroxytryptamine-receptor antagonist (5-HTr alpha) azatadine actually caused an 11% increase. CONCLUSION: Hydroxyzine reduced carbachol-induced serotonin release from rat bladder in vitro through a mechanism which was unrelated to its H-1 receptor antagonistic properties. The ability of hydroxyzine to inhibit bladder mast cell activation by neurogenic stimuli along with its anticholinergic, anxiolytic and analgesic properties, may explain the clinical efficacy of this drug in reducing IC symptoms. Other, nonsedating, hydroxyzine analogues able to inhibit bladder mast cell activation may provide potentially new therapeutic approaches for IC.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9839659&dopt=Abstract hydroxyzine Atarax



Aphthasol
Substance P provokes cutaneous erythema and edema through a histamine-independent pathway.

Cappugi P, Tsampau D, Lotti T.

Department of Dermatology I, University of Florence, Italy.

Substance P is a neuropeptide (contained in/and released from the A delta and C nerve fibers of the skin), which provokes erythema, edema, and pruritus after intradermal injection. Local pretreatment with capsaicin produces decreased substance P-dependent erythema, with edema similar to that observed before pretreatment with capsaicin. We injected histamine and in a parallel experiment, substance P in five volunteers before and after local treatment with capsaicin, with 48/80, after 5 days of hydroxyzine. The injection of SP provoked erythema centered by a wheal. After treatment with 48/80, SP provoked increased erythema and a wheal. After hydroxyzine treatment, the injection of histamine produced no erythema or edema in four of the five subjects, while SP provoked erythema in all five subjects and edema similar to that observed before treatment with hydroxyzine. These data support the hypothesis that substance P provokes erythema and edema both with histamine-dependent and histamine-independent pathways.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1373708&dopt=Abstract hydroxyzine Atarax