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The new H1-receptor antagonists terfenadine and cetirizine provided significantly better protection than the older antihistamines against the action of histamine in the skin and airways. None of the antihistamines showed evidence of anticholinergic activity in the asthmatic airways at the doses studied.
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Antihistamines are known to belong to the chemical class that may induce long QT syndrome. Among them, cyproheptadine has been shown to exert multifaceted actions on the ventricular repolarization phase; namely, shortening of the action potential duration at supra-therapeutic concentrations of 2 - 8 μM and prolongation of the QT interval at ≥ 10 μM. Since information is limited regarding the in vivo electrophysiological effects of cyproheptadine, we assessed it using the halothane-anesthetized guinea-pig model, which was compared with effects of another antihistamine drug, hydroxyzine. Sub-therapeutic to therapeutic doses of hydroxyzine at 1 and 10 mg/kg, i.v. prolonged the QT interval and duration of monophasic action potential, whereas therapeutic to supra-therapeutic doses of cyproheptadine at 0.1 and 1 mg/kg, i.v. hardly affected the indices of ventricular repolarization. These results suggest that cyproheptadine may be categorized into antihistamines with little effect on the ventricular repolarization.
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The effect of sublingual immunotherapy on quality of life (QoL) was examined in patients with grass pollen-induced rhinoconjunctivitis. Patients (n = 855) were randomised to once-daily grass allergen tablets (2,500; 25,000; or 75,000 SQ-T Phleum pratense extract; GRAZAX or placebo. Treatment was initiated 8 weeks before the start of the grass pollen season and continued throughout. If symptoms were present, patients received loratadine or placebo rescue medication. There were three major findings: in patients using loratadine, grass allergen tablets provided QOL benefits over placebo; Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score was 17% (p = 0.006) and 20% (p = 0.020) greater with 75,000 SQ-T tablet than with placebo at first and second seasonal visit, respectively; in patients not using loratadine, grass allergen tablets improved QoL more than placebo; RQLQ score was 21% greater (p = 0.021) with 75,000 SQ-T tablet at second seasonal visit; grass tablets (without loratadine) had a greater effect on QoL than loratadine alone. RQLQ score was 26% (p = 0.014) greater with 75,000 SQ-T tablets than loratadine at second seasonal visit. These data show that sublingual immunotherapy with grass allergen tablets improves QOL in allergic rhinoconjunctivitis, reduces symptoms, and that this effect is greater than rescue antihistamine alone.
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The inhibition of histamine effects in the skin may be useful in predicting the clinical utility of newly introduced antihistamines in treating allergic disorders.
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1. Intrahypothalamic injection of either 5-hydroxytryptamine (5-HT) (20 mug) or tryptamine (1 mug) caused hypothermia and hyperthermia respectively in lightly restrained rats maintained at an ambient temperature of 20 +/- 1 degrees C.2. Both the 5-HT- and the tryptamine-sensitive sites were located within the same region of the preoptic area.3. When rats were tested at different ambient temperatures (4, 20 and 29 degrees C), intrahypothalamic injection of 5-HT caused a marked fall in core temperature (-1.3 degrees C) in rats maintained at 4 degrees C, but smaller responses were obtained at 20 and 29 degrees C (-0.9 and -0.5 degrees C respectively). Tryptamine caused a significant hyperthermia in rats kept at 20 degrees C, but had no significant effect in rats maintained at either 4 or 29 degrees C.4. The hypothermic effect of 5-HT was selectively antagonized by systemic pre-treatment with cyproheptadine (2.5 mg/kg), but not by methergoline (0.625 mg/kg) and methysergide (0.2 mg/kg). In contrast, the hyperthermic effect of tryptamine was blocked by methergoline and methysergide, but not by cyproheptadine.5. Cyproheptadine (2.5 mg/kg) reduced the ability of rats to cope with a heat load but had no effect on the response to cold. In contrast, methergoline (0.625 mg/kg) and methysergide (0.2 mg/kg) reduced the ability to cope with cold but the rats' ability to cope with a heat load remained intact.6. These results suggest the existence of two indoleamine pathways within the preoptic anterior hypothalamus involved in the control of body temperature: a serotonergic pathway mediating heat loss and a non-serotonergic pathway mediating heat gain. The non-serotonergic system may exert its effects by modulating the activity of a central serotonergic system.
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To investigate whether cortisol secretory patterns are associated with a response to cyproheptadine treatment in Cushing's disease, we studied two patients with a hyperpulsatile pattern and one patient with a hypopulsatile pattern before and during chronic cyproheptadine therapy (24 mg daily). In the two patients with a hyperpulsatile cortisol secretory pattern, pituitary magnetic resonance imaging with gadolinium did not reveal a pituitary adenoma, whereas in the patient with a hypopulsatile cortisol secretory pattern, a microadenoma was identified. Plasma cortisol levels were measured every 30 min for 24 h. In the two patients with a hyperpulsatile cortisol secretory pattern, chronic treatment with cyproheptadine resulted in sustained clinical and biochemical improvement and normalization of the median of absolute and relative increments in cortisol spikes. In the patient with a hypopulsatile cortisol secretory pattern, only a reduction of cortisol spikes was noticed during treatment. These results suggest that patients with Cushing's disease who are characterized by a hyperpulsatile cortisol secretory pattern and in whom no pituitary lesion can be identified by magnetic resonance imaging, cyproheptadine treatment may be useful.
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Cyproheptadine (Periactin) is a first-generation antihistamine available in over-the-counter cold medications and is used to treat allergic-type symptoms. Although antihistamines in general have long been known to cause serious side effects, especially when taken in overdose, few reports that specifically address cyproheptadine-related fatalities exist. A 42-year-old healthy female was found dead at her home with no anatomic cause of death and a recent history of suicidal ideations. Toxicology revealed cyproheptadine and citalopram in the femoral postmortem blood at concentrations of 0.49 and 2.3 mg/L, respectively. Vitreous, urine, and bile analysis were also performed, yielding concentrations of < 0.04 and 0.80 mg/L in the vitreous for cyproheptadine and citalopram, respectively; 0.23 and 8.2 mg/L in the urine; and 30.7 and 9.0 mg/L in the bile. The cause of death was determined to be cyproheptadine and citalopram intoxication, and the manner was ruled a suicide. Although cyproheptadine is widely available in the United States and Europe, there are only two published fatalities due to this antihistamine and only one that specifically cites blood and tissue concentrations. Therefore, this case study will be beneficial to the forensic toxicology community by providing additional information regarding postmortem interpretation.
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With quality of care and patient safety as major public health concerns, effective policies are needed to avoid PIRx occurrences and improve the quality of prescribing among elderly residents in NHs. Additional studies are needed to determine the impact of PIRx on this NH population.
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Among 296 hemodialyzed patients, 65 suffered from uremic pruritus. Fifty-two patients participated in the study. The patients were treated for 2 weeks with naltrexone (50 mg/day; 26 patients) or loratadine (10 mg/day; 26 patients), after a washout of 48 h. Pruritus intensity was scored by a visual analogue scale (VAS). Adverse events were carefully searched for. The two groups were statistically equivalent.
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Effects of 11 histamine H1 receptor antagonists on IgE-mediated biphasic cutaneous reaction in mice were examined. The immediate phase reaction (IPR) assessed at 1 hour after antigen application was significantly inhibited by all antihistamines examined. The inhibition of IPR by cetirizine and mequitazine were potent, but those by cyproheptadine and diphenhydramine were weak. The later phase reaction (LPR) assessed at 24 hours after antigen application was inhibited by chlorpheniramine, oxatomide, ketotifen, mequitazine, emedastine, terfenadine and azelastine. The inhibition of LPR by emedastine was potent, but those by ketotifen and terfenadine were only partial. Emedastine inhibited both IPR and LPR comparably. Present results indicate that H1 receptor activation is involved in the IPR of the biphasic cutaneous reaction, and that the blockade of H1 receptors at IPR does not contribute to the attenuation of following LPR. Histamine H1 receptor antagonists inhibiting the LPR have a property distinct from H1 receptor antagonism, which may have an additional benefit for the treatment of allergic diseases.
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The inability to successfully feed a young infant or child is as worrisome to parents as it is to the health care provider. Early growth failures are likely to reflect difficulty with infant homeostasis and often respond to medical management of the physical problem that is temporarily interfering with the infant's ability to feed by mouth. In addition to medical management, however, treatment also necessitates investigation and management of behavioral problems that so universally accompany growth failure. This article presents a case study of a child who presented with poor growth and respiratory symptoms associated with nonregurgitant gastroesophageal reflux, a clinical entity that can be difficult to recognize. Although surgical management of this condition was successful, persistent failure-to-thrive continued and was seemingly recalcitrant to treatment. The use of cyproheptadine as an appetite stimulant to promote weight gain in this child is discussed with a review of the current literature regarding this pharmacologic approach to poor weight gain. A behavioral-based treatment plan is described as an alternate management method, avoiding the use of pharmacologic agents in general.
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Seventeen patients with perennial asthma, stable on a moderate dose of inhaled steroid, participated in a crossover study comparing the clinical effect of a non-sedative, potent and highly selective H1 antagonist (loratadine 10 mg) with placebo. Each treatment period began with 2 weeks run-in followed by 8 weeks on either antihistamine or placebo. During the 8-week periods inhaled steroid was gradually tapered according to a fixed scheme. One patient was withdrawn from active treatment and three from placebo periods because of decreasing lung function (P greater than 0.1). Among the remaining 13 patients there was a threefold (1.8-4.8) decrease in the bronchial sensitivity to histamine during treatment with antihistamine compared to placebo (P less than 0.01). There was a trend in favour of active treatment with regard to changes in all symptom scores, lung function and use of escape medication, but these differences were not statistically significant. The increase in FEV1 was less than 5% of predicted normal (P less than 0.05). We concluded that the bronchial response to histamine can be attenuated by loratadine, an oral H1 receptor antagonist, but further studies are necessary to assess the clinical usefulness and place of loratadine in the therapy of asthma.