Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ANTIHISTAMINICS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7Linked to original sources

Antihistamine- and decongestant-induced performance decrements.

Among the most common of health problems, allergies afflict more than one of every six Americans. In the allergic reaction, mast cells degranulate, releasing inflammatory mediators such as histamine. These mediators in turn cause smooth muscle contraction, itch, mucus secretion, and vascular leakage. A number of pharmacologic agents, including the H1 receptor antihistamines and the sympathomimetic decongestants, have been developed in an attempt to minimize such effects. Antihistamines were first used clinically 50 years ago. Currently taken by approximately 30 million Americans each year, they are grouped by structure into six classes. Until recently, all of the classes, or first-generation antihistamines, were thought to be relatively equal in efficacy and, because of their ability to cross the blood-brain barrier, they all caused varying degrees of sedation. The effects of antihistamines on psychomotor reflexes and driving skills, antihistamine-induced drowsiness, and the interaction of antihistamines with alcohol and tranquilizers are reviewed. The centrally acting first-generation agents, and the performance decrements these agents commonly induce, are compared with the newer, nonsedating, second-generation antihistamines (eg, terfenadine, astemizole, cetirizine, and loratadine). Although decongestants do not appear to cause impaired performance, this needs to be evaluated further, particularly with regard to decongestant-induced insomnia.

Histamine H1 Antagonists↗

Effects of antihistamines on the cardiopulmonary changes due to canine anaphylaxis.

Histamine has long been considered to be an important chemical mediator in the pathogenesis of immediate hypersensitivity reactions. We evaluated the efficacy of antihistamines to determine the physiological role of histamine in canine anaphylaxis. Either a saline vehicle (control group), an H1 antihistamine (chlorpheniramine, 10 mg/kg), or this H1 antihistamine and an H2 antihistamine (cimetidine, 30 mg/kg) was administered to three separate groups of anesthetized dogs (n = 8). Cardiopulmonary responses and plasma histamine levels were measured after the separate intravenous injection of Ascaris suum antigen and histamine. Results were analyzed only from the animals demonstrating physiological responses or histamine release after antigen injection. In the control group, antigen produced a 43 +/- 15% (mean +/- SE) decrease in mean arterial blood pressure, a 34 +/- 13% fall in cardiac output, and a 19 +/- 9% decrease in lung compliance, whereas pulmonary vascular resistance increased 161 +/- 87% and airway resistance rose 114 +/- 66%. Similar physiological abnormalities were observed with histamine shock. However, peak plasma histamine levels were, in most cases, greater after histamine injection than after antigen injection. An H1 antihistamine alone or in combination with an H2 antihistamine did not alter the physiological changes associated with systemic anaphylaxis. In contrast, the combined use of H1 and H2 antihistamines prevented the cardiopulmonary responses associated with the intravenous administration of histamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Anaphylaxis↗

Antitussive action of antihistamines is independent of sedative and ventilation activity in the guinea pig.

We studied the oral actions of antihistamines from six chemical classes, namely: the ethanolamines (ENA, diphenhydramine and clemastine); ethylenediamines (EDA, pyrilamine and tripelennamine); piperidines (PPD, terfenadine and astemizole); piperazines (PPZ, hydroxyzine and cetirizine); phenothiazines (PTZ, promethazine), and the alkylamines (ALA, chlorpheniramine and bromopheniramine) on cough reflexes, pentobarbital-induced sedation and minute ventilation in the conscious guinea pig. Antihistamines of the ENA class had minimal effects on capsaicin-induced cough although both diphenhydramine (30 and 100 mg/kg p.o.) and clemastine (30 and 100 mg/kg p.o.) increased sedation time (ST). The PPZ class demonstrated both antitussive and sedating activity. The minimum effective oral antitussive dose (MED) of cetirizine and hydroxyzine was 30 and 10 mg/kg, respectively. The EDA did not exhibit antitussive activity. Tripelennamine (10, 30 and 100 mg/kg p.o.) but not pyrilamine enhanced ST. The MED for the PTZ, promethazine, was 10 mg/kg, and at 100 mg/kg promethazine increased ST. The ALA group displayed antitussive activity but only chlorpheniramine (10 mg/kg p. o.) had any effects on ST. The MED for chlorpheniramine and bromopheniramine was 3 and 10 mg/kg p.o., respectively. The PPD antihistamines, namely terfenadine and astemizole, inhibited cough (MED 30 and 10 mg/kg p.o.) without sedative effects. Of the antihistamines tested only promethazine (100 mg/kg p.o.) depressed ventilation responses; however, this dose of promethazine was associated with adverse behavioral effects. The present findings indicate that the antitussive actions of antihistamines are not directly related to histamine H1-receptor blockade because several antihistamines did not antagonize capsaicin-induced cough. In addition, the antitussive actions of antihistamines are independent of their sedative or ventilation effects.

Administration, Oral↗

Antihistamines in dermatology.

Along with antibiotics, antihistamines are the most widely used systemic drugs in dermatology. This is attributable to the major role played by histamine in common diseases such as urticaria and atopic eczema. Of the currently recognised four subtypes of G protein-coupled histamine receptors, only the H1 and H2 subtypes have been positively identified in human skin. Traditionally believed to be competitive antagonists of histamine, H1 and H2 antihistamines are now considered to behave as inverse agonists. By consensus, H1 antihistamines are classified as 'first generation' (associated with troublesome side-effects including somnolence, anti-adrenergic and atropine-like actions) and 'second-generation' compounds (in which these side-effects are reduced or absent). The main indications for H1 antihistamines in skin are suppression of pruritus in urticaria and atopic eczema, both of which are associated with increased mast cell numbers and tissue histamine levels. However the evidence basis for use in atopic eczema is ambiguous and controversial, even though these drugs are widely used in practice. Currently, significant side-effects are mainly confined to the first-generation compounds and are especially troublesome in the elderly. Psychomotor impairment may persist throughout the day following administration. Anti-cholinergic and anti-alpha-adrenergic blockade and cardiotoxicity (torsade de pointes) may also occur with first-generation antihistamines. Two early low-sedation second-generation antihistamines caused arrhythmias in a small number of patients but these compounds have now been withdrawn. Generally, the second-generation H1 antihistamines are well tolerated.

Dermatology↗

Antihistamines. Guidelines and implications.

Antihistamines may be used to maximum benefit for the allergic patient if the physician adheres to four guidelines. These guidelines are based upon 1) an appreciation of certain structural and pharmacologic differences among antihistamines, and 2) an understanding of their mechanism of action. Around the clock administration is advisable, the dosage should be titrated for the individual patient, substitutions to another antihistamine should be to a different class of antihistamine, and the efficacy of any single antihistamine usually will diminish with prolonged use, either on the basis of true tolerance or because of psychic factors. There is good theoretical evidence when alpha-adrenergic sympathomimetics, employed as decongestants in combination with antihistamines, should not be given to allergic patients. Two newer drugs, disodium cromoglycate and beclomethasone, may provide symptomatic relief for allergic rhinitis patients. They may benefit the patient who does not obtain full symptomatic relief from antihistamines.

Adrenergic alpha-Agonists↗

Steroid and antihistamines modulate RANTES release in cultured peripheral blood mononuclear cells of atopic patients.

RANTES plays a crucial role in cell recruitment in allergic inflammation. We investigated the pharmacological modulation of RANTES release in cultured peripheral blood mononuclear cells obtained from allergic patients with active asthma. Chemokine production was assessed before and after 15 day treatment with histamine-1 receptor antagonists (antihistamines) (Loratadine or Cetirizine) and a steroid (Deflazacort), both in unstimulated and PHA-stimulated cell cultures. Results were compared with those obtained from placebo-treated patients. During the treatment period, patients recorded morning and evening peak expiratory flow (PEF) by the mini-Wright procedure. PEF absolute values and diurnal variability significantly improved respect to the pre-treatment in steroid-treated patients, in comparison to the placebo and antihistamine-treated groups (p<0.001 and 0.01, respectively). PEF diurnal variability in the antihistamine-treated group were lower than placebo-treated group without statistical significance (p=0.06). No differences could be found in RANTES levels in supernatants of all cultures between the two antihistamines. RANTES release significantly decreased in supernatants of all cell cultures from steroid (p<0.01) and antihistamine (p=0.03 and 0.04) groups after treatments, compared to the basal values; whereas it increased slightly in controls. Co-variance analysis on RANTES levels, adjusting for pre-treatment values, showed a significant reduction of RANTES release by PHA-stimulated PBMCs from steroid (p=0.003) and anti-histamine (p=0.03) groups, with respect to the placebo group. The same statistical tool applied between the steroid and the antihistamine groups showed, after therapy, the lowest levels of RANTES to be associated with steroid treatment (p=0.005). The study shows that the steroid is the most effective drug in modulating RANTES release from PBMCs. However, antihistamines, which are able to reduce cell recruitment due to chemokine release, avoiding important side effects, may be useful in long term therapy in controlling and preventing allergic inflammation.

Journal Article↗

[Functional neuropharmacology in the human brain using positron emission tomography: PET imaging of impaired cognitive performance induced by sedative antihistamines].

Antihistamines are the efficacious drugs to be used for the symptomatic relief of allergic diseases. The safety issue of antihistamines is of central importance because of their widespread use in current medical practice. Positron emission tomography (PET) was used to better understand the pharmacological effects of antihistamines on the central nervous system. The H1 receptor occupancy was examined in young male volunteers with [11C]-doxepin after the oral or intravenous administration of antihistamines. In other studies, the cognitive performance was also measured tachistoscopically before and after taking antihistamines. The H1 receptor occupancy in the human cortex caused by antihistamines is significantly correlated with the reported values of incidence of sleepiness in clinical trials, and the occupancy is well proportional to the impaired cognitive performance. To understand the brain mechanism of antihistamine-induced "sleepiness and impaired cognition", the regional cerebral blood flow (rCBF) during the task was measured using 3D-PET and H2(15)O before and after administration of d-chlorpheniramine. After its administration, the rCBF was significantly decreased on the bilateral middle temporal gyrus, midbrain and anterior cingulate. These findings suggest that H1 receptor blockade would be affected on the activity of the attention and cognitive system in the brain.

Animals↗

Do antihistamines have a role in asthma therapy?

The coexistence of allergic rhinitis with asthma is widely recognized by clinicians. Histamine, a common mediator for both diseases, has a substantial role in the pathophysiology of asthma through its ability to produce smooth muscle contraction and promote vascular permeability. Because antihistamines often are administered to manage allergic rhinitis symptoms, the effects of antihistamines in asthma should be evaluated. The usefulness of first-generation antihistamines is limited by their side-effect profile, namely sedation and cognitive impairment. Second-generation antihistamines have only a modest effect in attenuating bronchospasm induced by histamine, cold air, exercise, and allergen bronchoprovocation, suggesting that second-generation antihistamines do not have a direct role as a single agent for treating asthma. Studies have shown that controlling allergic rhinitis with antihistamines has a small, indirect effect in improving asthma symptoms. Future work should be directed at improving the potency of antihistamines and defining their antiinflammatory activity.

Anti-Asthmatic Agents↗

Antihistamines and epithelial cells.

Antihistamines have long been utilized in the symptomatic management (antihistaminic effects) of allergic rhinitis and conjunctivitis. Investigation into the nonsedating second-generation antihistamines suggests that they also possess antiinflammatory activity, and may be useful in the management of inflammation associated with allergic airway disease. In vitro studies have shown that these antihistamines decrease the migration and activation of eosinophils and diminish the release of pro-inflammatory mediators from mast cells and basophils after induction by immunological and nonimmunological stimuli. In vivo studies have also demonstrated that these antihistamines decrease inflammatory cell infiltration in allergic airway disease, and mediator release from mast cells and basophils. Epithelial cells, due to their spatial arrangement and predominance in the airways, play a pivotal role in the etiology of airway disease. There is evidence that antihistamines may modulate airway inflammation by influencing the activity of these airway epithelial cells. Studies have shown that expression of adhesion molecules on epithelial cells is decreased by second-generation antihistamines. Collectively, these studies suggest that second-generation H1-histamine receptor antagonists have potential use either as safe antiinflammatory alternatives to corticosteroids or as rescue medication in combination with corticosteroids for the management of severe airway disease.

Anti-Inflammatory Agents, Non-Steroidal↗

Affinity for the P-glycoprotein efflux pump at the blood-brain barrier may explain the lack of CNS side-effects of modern antihistamines.

First generation H1 receptor antagonists are often associated with adverse CNS effects such as sedation, whereas modern, second generation antihistamines are generally non-sedating. The difference in therapeutic profile is mainly due to the poor CNS penetration of the modern derivatives. Current explanations for the differential ability of classical and modern antihistamines to cross the blood-brain barrier (BBB), based on differences in lipophilicity or protein binding, are inadequate. We have tested the hypothesis that non-sedating antihistamines fail to enter the CNS due to recognition by the P-glycoprotein (Pgp) drug efflux pump expressed on the luminal surface of cerebral endothelial cells forming the BBB in vivo. The ability of several sedating and non-sedating antihistamines to affect the uptake of the Pgp model substrate [3H]-colchicine was examined using the immortalised rat brain endothelial cell line, RBE4, an established in vitro model of the BBB expressing Pgp. All second generation antihistamines tested, significantly increased net accumulation of [3H]-colchicine to a level similar to that caused by the Pgp inhibitor verapamil. By contrast, the first generation antihistamines showed no affinity for Pgp. The results indicate that differences in the ability of classical and modern antihistamines to interact with Pgp at the BBB may determine their CNS penetration and as a consequence the presence or absence of central side-effects.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

New findings in pharmacological effects induced by antihistamines: from PET studies to knock-out mice.

Antihistamines are efficacious drugs to be used for the symptomatic relief of allergic diseases. The safety issue of antihistamines is of central importance because of their widespread use in current medical practice. To better understand the pharmacological effects of antihistamines on the central nervous system (CNS), we used two kinds of new methods, positron emission tomography (PET) and gene targeting regarding on histamine H1 receptors. The histamine H1 receptor occupancy was examined in young male volunteers with[11C]-doxepin (a potent H1 antagonist) after the oral or intravenous administration of antihistamines. In other studies, the cognitive performance was also measured tachistoscopically before and after taking antihistamines. The mutant mice lacking H1 receptors were used in the behavioural and neurochemical experiments to re-evaluate the role of H1 receptors. The H1-receptor occupancy in the human frontal cortex caused by antihistamines is significantly correlated with the reported values of incidence of sleepiness in clinical trials, and the occupancy is well proportional to the impaired cognitive performance. The behavioural studies of the H1-receptor knock-out mice confirmed the role of H1 receptors in arousal, the sleep-wake cycle, locomotion, nociception and aggressive behaviour. The pharmacological effects induced by H1 antagonism were re-evaluated by the PET and gene-targetting. Although any serious effects could not be observed in mice by the destruction of the H1-receptor gene, the cognitive performance was impaired in humans after taking first generation antihistamines in recommended doses.

Animals↗

[Projection of new antihistamines].

The metabolic fate of most antihistamines is not clearly established. The drugs usually appear to be extensively metabolized,mainly in the liver. Some second generation antihistamines are metabolized principally by the cytochrome P-450 microsomal enzyme system, mainly by the isoenzyme 3A4 (CYP3A4), although other isoenzyme,including CYP1A2 and CYP2D6, also may be involved. However,other second generation antihistamines appear to be only minimally metabolized in the liver. Serious cardiac effects (prolongation of the QT interval, arrhythmias, torsades de pointes, ventricular fibrillation, arrest, hypotension, palpitations, syncope, dizziness, and/or death) have been reported rarely in patients receiving terfenadine or astemizole. Cardiotoxic effects ussually were associated with higher than recommended dosages and/or increased plasma concentrations of the drugs and their active metabolites. No clinically important adverse effects or changes in the QT intervals were reported after concomitant administration of ketoconazole with fexofenadine. Patients receiving an azole, antifungal, a macrolide, quinine or grapefruit juice also appear to be at substantial risk of such toxicity, probably secondary to interference with metabolism of the antihistamine. Second-generation H1 receptor antagonist have been studied extensively in the treatment of asthma. Many of these drugs have been reported to inhibit eosinophil and basophil chemotaxis and therefore might have an effect on the inflammatory reactions that characterise this disease. Safe use of antihistamines during pregnancy has not been established; therefore, the drugs should not be used in women who are or may become pregnant unless the potential benefits justify the possible risks to the fetus. Antihistamines should not be administered to premature or full-term neonates. Young children may be more susceptible than adults to the toxic effects of antihistamines.

Adult↗

[Data on the safety of antihistaminics obtained from published clinical trials].

BACKGROUND: We studied H1 antihistaminic safety, with respect to CNS, and clinical trial validity to determine its adverse effects and generalize the results. METHODS AND RESULTS: We employed clinical trials published between 1990-94, selecting them according to several quality criterion to obtain reliable and extrapolable conclusions. Patients that use modern antihistaminics have less adverse effects (32.5%), than those patients that use classics ones (78.6%) and similar to placebo (27.7%). Loratadine (28.4%) and noberastine (22.3%) are the antihistaminics with less adverse effects. Sedation (13.2%) and fatigue (4.9%) are the adverse effects more frequently produced by antihistaminics. Headache (6.7%) that is a frequent adverse effect, has a doubtful causality relationship with the use of antihistaminic. CONCLUSIONS: Second generation antihistaminics have less adverse effects and similar efficacy than classics ones. Noberastine and loratadine are the antihistaminics with less adverse effects in this study.

Age Factors↗

Histamine and the antihistaminic drugs.

The tissues affected by histamine and anaphylactic reactions are identical. Epinephrine antagonizes the action of histamine by acting on effector cells in a direction opposite to that of histamine. The so-called antihistaminic drugs block rather than antagonize the action of histamine. The injection into the human body of epinephrine or certain antihistaminic substances provokes the release of histamine and thereby produces a rise in the histamine blood level. There is a remarkable conformity of potency of antihistaminics as determined by Dale experiments and by histamine intoxication experiments in the intact guinea pig. Neoantergan, Pyribenzamine and Histadyl are usually superior to other compounds when potency is assayed by these methods. All antihistaminics provide similar protection again animal anaphylaxis. Larger doses are necessary to protect against anaphylaxis than against histamine intoxication. The differences in potency as determined by Dale experiments and histamine experiments in animals are not found in clinical use. One compound is not generally superior to all others in the treatment of any one or several allergic disorders. The antihistaminic drugs are beneficial in the symptomatic treatment of allergic rhinitis, acute urticaria and angioneurotic edema, and mild non-infective bronchial asthma. Their effectiveness in the management of moderately severe and severe non-infective bronchial bronchial asthma; infective bronchial asthma; migraine; atopic dermatitis (disseminated neurodermatitis), and pruritus of skin disorders other than acute urticaria and angioneurotic edema, is not worthy of particular commendation. The size of the dose of any antihistaminic substance influences the incidence of but not the type of side-effect that may accompany its usage. The quality of side effects varies according to the drug, although there is an individuality of response for each patient which must be reckoned with. In selecting an antihistaminic compound it is necessary to consider the percentage of cases in which side effects occur, as well as the percentage of good results. Optimal results are obtained by employing combinations of compounds and changing from one to the other as the case demands.

Allergens↗

Comparative safety of H1 antihistamines.

In the allergic reaction, mast cells degranulate, releasing inflammatory mediators including histamine. The H1 receptor antihistamines have been developed over the past 50 years to minimize the clinical symptoms caused by this reaction. Currently, H1 antihistamines are taken by approximately 30 million Americans per year. First-generation H1 antihistamines, some of which are available without prescription, can cross the blood-brain barrier and have been reported to produce sedation in 10% to 25% of users. When activities that require mental alertness and concentration are considered--school performance and driving, for example--this effect is troublesome and even potentially hazardous. The newer, second-generation H1 antihistamines (eg, astemizole, cetirizine, loratadine, terfenadine) have difficulty entering the brain because they are typically large, lipophobic molecules that have charged side chains and are extensively bound to protein. Consequently, they appear to induce sedation less commonly than classic antihistamines. Since a primary tenet of medical care has always been primum non nocere--first of all, in the management of clinical illness, do no harm--it is important in these "State-of-the-Art Perspectives" to address the comparative safety of the H1 antihistamines. A number of methodologies have been used to make this assessment, including the multiple sleep latency test, the P300 (P3) wave of the auditory-evoked potential, self-ratings, visual function tests, and tests that measure reaction times, visual-motor coordination, and driving skills. The effect of the interaction of H1 antihistamines with alcohol and tranquilizers also has been examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Central Nervous System↗

Antihistamine therapy in allergic rhinitis.

Allergic rhinitis is a common disorder that is associated with a high incidence of morbidity and considerable costs. The symptoms of allergic rhinitis are primarily dependent upon the tissue effects of histamine. Antihistamines are the mainstay of therapy for allergic rhinitis. Recently, a second generation of antihistamines has become available. These agents lack the adverse effect of sedation, which is commonly associated with older antihistamines. Current practice of antihistamine therapy in allergic rhinitis often involves random selection among the various agents. Based upon the available clinical trials, chlorpheniramine appears to be the most reasonable initial antihistaminic agent. A nonsedating antihistamine should be used initially if a patient is involved in activities where drowsiness is dangerous. In this comprehensive review of allergic rhinitis and its treatment, the current as well as future options in antihistamine pharmacotherapy are emphasized.

Histamine H1 Antagonists↗

Pharmacist advice to asthmatics regarding antihistamine use.

Due to the frequency of asthmatics having concurrent allergic symptoms, patients may seek relief from antihistamines, which are currently labeled with warnings against their use in asthmatics. A survey was conducted in the Chicago area to evaluate the advice rendered by pharmacists regarding the use of antihistamines in asthmatics and their opinions about the current product labeling. Thirty percent of the surveys were returned. Nearly half (48%) of the surveyed pharmacists advise their asthmatic customers to avoid antihistamines and 75% of this group recommend avoidance because they believe antihistamines worsen asthmatic symptoms, despite the lack of sufficient clinical data to support this concern. Only 17% of pharmacists advise that antihistamines pose no problems for asthmatics. The latter group is the most aware that there is controversy surrounding the current labeling. Overall, half the pharmacists surveyed believe the current labeling is not appropriate for patients with asthma. Until the labeling is revised, physicians should be aware that pharmacists may advise their asthmatics against using antihistamines even though antihistamines should be only contraindicated in cases of proven adverse reactions.

Asthma↗

A study of prescribed H1-antihistamine preparations over a period of 12 months in community pharmacy.

A survey on the prescribing pattern of H1-antihistamine preparations was carried out in four socio-economic areas in Liverpool: the City Centre, an Affluent Area, a Poor area and a Council Estate. The purpose of this study was to find out which H1-antihistamines were prescribed from the wide range available; to discover if there was a trend in the use of these agents over a 12-month period and to suggest possible explanations for these findings. The majority of H1-antihistamine preparations were prescribed in the Affluent Area followed by the City Centre, Poor Area and the Council Estate. In all four areas, over 7.0% of all total items dispensed in a year contained H1-antihistamine drugs, and the lowest use (3.7-9.2%) fell in the summer months while the highest use was in January (8.2-14.1% of items containing H1-antihistamine dispensed per month). Thus the general trend in the use of these drugs may not follow the trend of the hay fever season and it is probably true that H1-antihistamines were more frequently prescribed for treatment of other conditions (common cough and cold) than rhinitis alone. The most widely prescribed classes of H1-antihistamines were alkylamines and ethanolamines, followed by the phenothiazines and ethylenediamines while the piperazines were not prescribed. Triprolidine, diphenhydramine, promethazine and brompheniramine were the top four most widely prescribed drugs.

Dosage Forms↗