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We studied the hypotensive effect of three carrageenans and of dextran sulphate in Brown Norway (BN) rats. The plasma of these BN rats is devoid of high molecular weight kininogen and poor in plasma prekallikrein. The hypotensive effect in BN rats was greatly reduced in comparison with the effects in normal rats. It was proportional to the thrombocytopenia induced by the sulphated polysaccharides and absent in rats made thrombopenic by antiplatelet serum. The hypotensive effect in BN rats was reduced by bromophenacyl bromide, mepacrine, aspirin, methysergide, promethazine and CCI 17810, and was unchanged after the administration of cobra venom factor, heparin, amino caproic acid, chloroquine, dexamethazone, lidocaine, propranolol, indomethacin, phenidone, imidazol, adenosine and cyproheptadine. The thrombopenic effect was reduced by methysergide and CCI 17810 and was not modified by bromophenacyl bromide and chloroquine.
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The inhibitory effect of orally administered dexchlorfeniramine (4 mg/day), cyproheptadine (8 mg/day), astemizole (20 mg/day), loratadine (40 mg/day) and terfenadine (120 mg/day) on the size of histamine-induced weals was tested by skin prick test with histamine in an open study including 23 healthy individuals. The antihistamines were administered for 2 days in the nationally recommended therapeutic doses. For all drugs the maximal weal suppression with the dosage chosen was recorded the day after the last dosage, being 29% (for dexchlorfeniramine), 72% (for cyproheptadine), 50% (for astemizole), 62% (for loratadine), and 56% (for terfenadine) of the baseline value. For the drugs in the same order the duration of the inhibitory effect of the drugs after the last dose administered was between 3-4, 7-11, 17-28, 4-7, and 4-7 days, respectively.
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To determine the effect of coadministration of food on the bioavailability of oral desloratadine.
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This study in children shows that prophylactically given loratadine decreases significantly the whealing and pruritus caused by mosquito bites and also reduces the size of the 24-h bite lesions. Therefore, the therapeutic profile of loratadine extends from immediate to delayed allergic symptoms in mosquito-bite-sensitive children.
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A PMSS in CIU patients evaluated the tolerability and efficacy of desloratadine in clinical practice. At Visit 1 (baseline), demographic and CIU history were recorded and patients/physicians rated the severity of CIU symptoms, interference with sleep/daily activities and the general state of urticaria. Patients also noted the use and effectiveness of previous antihistamine therapy. At the end of treatment (Visit 2), CIU symptom severity and other disease criteria were re-assessed. Adverse events reported during or < or = 30 days after treatment were collected.
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The influence of serotonergic system on the changes in locomotor activity of mice and rats brought about by morphine, fentanyl, codeine and pentazocine and on morphine induced catalepsy in rats was studied. p-Chlorophenylalanine (pCPA) did not affect the behavioral changes produced in mice by morphine, fentanyl, codeine and pentazocine but reduced the behavioral depression produced by these drugs in rats. 5-Hydroxytryptophan (5-HTP) but not tryptophan (TP) reversed the action of pCPA on the effect of morphine and fentanyl. After reserpine the depression produced in rats by morphine and fentanyl was more pronounced. TP did not change the depression produced by combination of reserpine and morphine but counteracted the depression observed after combination of reserpine and fentanyl. In mice reserpine protected against hypermotility produced by morphine or fentanyl and TP potentiated the depression produced by the combination of reserpine and morphine or reserpine and fentanyl. Serotonin precursors, 5-HTP and TP evidently potentiated the morphine induced catalepsy. pCPA counteracted only the enhancement of the catalepsy observed after TP administration. Naloxone abolished the catalepsy after combined treatment with morphine and TP. Similarly but weaker acted cyproheptadine. The results suggest that the serotonin system plays a role in the effects of morphine and fentanyl on rat locomotor activity. An increase in the cerebral serotonin level increases the morphine catalepsy in rats.
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There is a rapidly growing trend in the consumption of herbal remedies in industrialised and developing countries. Users of herbal remedies are at risk of toxicity and adverse interactions of herbal preparations due to their frequent contamination with metals and adulteration with synthetic drugs. The purpose of this study was to assess the quality of herbal remedies present on the market in Saudi Arabia in recent years.
Subjects with ragweed-induced allergic rhinitis (aged 18-60 years) who demonstrated a predetermined severity of symptoms after priming with ragweed pollen in the Environmental Exposure Unit were randomized to receive a single dose of desloratadine, 5 mg; diphenhydramine, 50 mg; or placebo. A comprehensive battery of repeatable, automated neuropsychological tests was administered to subjects before treatment (symptomatic baseline) and 90 minutes after taking study medication.
Seasonal allergic rhinitis causes considerable impairment of health-related quality of life (HQRL). Generic quality-of-life questionnaires enable a comparison to be made between patients with different illnesses, but they often have insufficient depth to measure specific problems that are important to an individual with a particular condition. In order to overcome these shortcomings, the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) was developed. Eighty-nine patients, with a wide range of rhinoconjunctivitis severity, scored a list of 91 problems for importance. The highest-scoring problems were the practical problems: continually having to blow the nose, rub the nose and eyes, and carry tissues. Patients were also bothered by sleep impairments and systemic problems such as tiredness, poor concentration and thirst. Questionnaires have also been developed for adolescents (12-17 years of age)--finding similar results to those for adults--and children (6-12 years of age), who were troubled by their symptoms but did not have the emotional dysfunction experienced by adults and adolescents. All three questionnaires have strong measurement properties and have high reliability and good responsiveness, validity and interpretability. Quality-of-life questionnaires can be used in clinical studies to help elucidate which treatments are preferred by patients and the efficacy of treatment regimens. Disease-specific quality-of-life questionnaires can also be used during routine assessments and may reveal problems not spontaneously volunteered by patients, particularly children. Results can also be compared at each clinic visit to determine whether each intervention has been beneficial.
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In vitro drug metabolism study is an integral part of drug discovery process. In this report, we have described the application of LTQ-Orbitrap hybrid mass spectrometer in conjunction with online hydrogen (H)/deuterium (D) exchange high resolution (HR)-LC/MS for structural characterization of in vitro rat liver microsomal metabolites of antihistamine desloratadine. Five metabolites M1--M5 have been identified, including three hydroxylated metabolites M1--M3, one N-oxide M4 and one uncommon aromatized N-oxide M5. Accurate mass data have been obtained in both full scan and MSn mode support assignments of metabolite structures with reported mass errors less than 3 ppm. Online H/D exchange HR-LC/MS experiments provide additional evidence in differentiating hydroxylated metabolites from N-oxides. This study demonstrates the effectiveness of this approach in structural characterization of drug metabolites.
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People frequently experience wealing and delayed papules from mosquito bites. Wealing is mediated by antisaliva IgE antibodies and histamine. Rupatadine is a new antihistamine effective in allergic rhinitis and urticaria, but the effect on mosquito-bite allergy is not known.
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Our results showed that for a 10(-4) M-histamine stimulation, L and DCL have a similar inhibitory effect on P-selectin expression (IC50 = 13 x 10[-9] M and 23 x 10[-9] M, respectively). L and DCL inhibited significantly IL-6 and IL-8 secretion induced by histamine with a more powerful efficiency of the active metabolite. For the dose of 10(-4) M histamine, a 50% inhibition of IL-6 secretion was obtained for a dose of DCL equal to 2.6 x 10(-12) M whereas the same magnitude of effects were only reached for a higher concentration of L (0.3 x 10[-6] M). Similar results were obtained for IL-8 (IC50 = 0.2 x 10[-6] M for L and 10[-9] M for DCL). Analysis of IL-8 mRNA expression by RT-PCR was in accordance with these data.
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The effect of cyproheptadine (CPH) on glucose tolerance, serum immunoreactive insulin (IRI) and structure of pancreatic islets in albino rats has been studied. Hyperglycemia with glucose intolerance was observed after 10 days of administration of CPH (40 mg/kg, ip). There was insignificant change of fasting IRI after the treatment. Histological studies indicated degranulation and vacuolation of beta cells with enlargement of capillaries. Improvement in blood glucose, glucose tolerance and structure of islets with proliferation of small pancreatic ducts and cell cords were observed 10 days after the withdrawal of CPH.
A total of 428 patients with an unsatisfactory response to loratadine completed the double-blind treatment period. After 2 weeks of treatment, azelastine nasal spray (P < 0.001), azelastine nasal spray plus loratadine (P < 0.001), and desloratadine (P = 0.039) significantly improved the total nasal symptom score compared with placebo.
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The pharmacological mechanisms of allergic cough in the guinea pig were studied. Actively sensitized guinea pigs were exposed to aerosols of antigen to elicit coughing. In separate experiments, naive guinea pigs were exposed to aerosols of capsaicin to elicit coughing. Both allergic and capsaicin-induced cough were inhibited by loratadine (0.3-10 mg kg-1 p.o.) and chlorpheniramine (0.1-3.0 mg kg-1 p.o.). Neither cimetidine (10 mg kg-1 s.c.), nor thioperamide (3-10 mg kg-1 s.c.), inhibited allergic or capsaicin-induced cough. Codeine (3-30 mg kg-1 p.o.), salbutamol (0.003-3.0 mg kg-1 s.c.) and ipratropium (0.03-1.0 mg kg-1 s.c.) inhibited both allergic and capsaicin-induced cough. Hexamethonium (10 and 30 mg kg-1 s.c.) inhibited allergic, but not capsaicin-induced cough. Allergic and capsaicin-induced cough were unaffected by phenidone (5.0 and 10.0 mg kg-1 s.c.). Indomethacin (5.0 and 10.0 mg kg-1 s.c.) had no effect on allergic cough but slightly inhibited capsaicin-induced cough. We conclude that allergic and capsaicin-induced cough are modulated by histamine H1 receptor and cholinergic mechanisms. Histamine H2 or histamine H3 receptor mechanisms, and lipoxygenase and cyclooxygenase products of arachidonic acid metabolism do not influence allergic and capsaicin-induced cough. Ganglionic mechanisms play a minor role in the production of allergic cough and no role in capsaicin-induced cough.
The authors appraised the clinical efficacy of desloratadine in patients with seasonal allergic rhinitis and rhinoconjunctivitis.
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Loratadine improves the effectiveness of flunisolide in treatment of NARES with no change in safety, and with no sedation.
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The thromboxane A2 (TXA2) plasma level in kappa-carrageenin (KC)-induced acronecrosis in the rat tail has been studied. TXB2 as stable metabolite of TXA2 was determined by a radioimmunoassay (RIA). 30 min after KC i.v. injection, the increase in the plasma TXB2 level was highest in Barby:Wistar rats but not in Halle:Wistar rats. Lambda-carrageenin (LC) increased the TXB2 levels in both strains of Wistar rats, although it did not induce acronecrosis. Drugs inhibiting TXB2 formation, namely dexamethasone, acetylsalicylic acid, Hoe 944, R 68070 or chlorpromazine, had only a small effect on acronecrosis frequency. Heparin inhibited TXB2 formation and acronecrosis frequency while the serotonin antagonist cyproheptadine decreased only the acronecrosis frequency but caused no change in TXB2 plasma level. These data demonstrate that the kappa-carrageenin-induced acronecrosis is followed by an increased formation of TXA2 in rats.
Currents were studied using the whole-cell configuration of the patch-clamp technique in Ltk- cells transfected with the gene encoding hKv1.5 channels.
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Nearly 100 cases of atopic myelitis have been reported in Japan. However, it has only been described in two non-Japanese patients, both from Western Europe. We report a European individual who developed cervical myelitis while resident in Japan. This showed a partial response to corticosteroids. There was no clinical or radiological dissemination for over 5 years, at which time she had a brainstem relapse caused by a new lesion in the medulla oblongata. The patient had high serum total IgE with evidence of allergy to several antigens, including house dust mite and soya. It is possible that the incidence of atopic myelitis may be underestimated where it is not standard practice to measure serum IgE levels in patients with myelopathy. Such cases will instead be subsumed into the diagnostic category of clinically isolated syndrome. However, it remains uncertain whether atopic myelitis is a distinct disease or falls within the spectrum of demyelinating diseases. Further studies are required to fully elucidate the relationship between atopy and the incidence and severity of CNS inflammatory disorders.
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Membranes prepared from rabbit erythrocyte hemolyzed in isosmotic imidazole (151 mmol.L-1, pH 7.4) buffer showed an enhancement of calmodulin (CaM) activated Ca(2+)-ATPase activity compared with the membrane prepared in hypotonic imidazole (10 mmol.L-1, EGTA 1 mmol.L-1, pH 7.4) buffer. The Ca(2+)-ATPase activity of the former (activated-calmodulin) was inhibited by cyproheptadine (Cyp) with IC50 75 mumol.L-1 (95% confidence interval was 18-319 mumol.L-1, r = 0.9118), while the Ca(2+)-ATPase activity of the latter (inactivated) was hardly influenced by Cyp. The results suggest that cyproheptadine antagonizes CaM, and its actions of the calcium antagonism and the anti-myocardial injury may, at least partially, be related to its CaM antagonism.
This systematic review was aimed at identifying in the most important databases, up to January 2013, the double-blind placebo-controlled randomized trials administering rupatadine in allergic rhinitis. No restriction was introduced for treatment duration and dose, study design, population age, allergen exposition and disease classification. The methodological quality of included studies and risk of bias were systematically assessed. Meta-analysis was performed when possible to summarize information.