Showing papers on "Astemizole published in 1986"
TL;DR: The increased prevalence of the restless leg syndrome observed in the group with rheumatoid arthritis may relate to this secondary complication, and in the authors' experience few doctors are aware of this condition.
Abstract: from that among normal controls and patients with osteoarthritis. Immobility per se does not seem to be a primary factor as the patients with osteoarthritis did not show an increased prevalence compared with the control group. Certain medical conditions, including pure iron deficiency, uraemia, pregnancy, gastrectomy, and carcinoma, are associated with the syndrome, providing potential clues about its mechanism.3 Interestingly, these conditions lead to either pure iron deficiency or anaemia of chronic disease, and anaemic patients experience more severe symptoms.4 As patients with rheumatoid arthritis characteristically develop the anaeniia of chronic disease the increased prevalence of the syndrome observed in the group with rheumatoid arthritis may relate to this secondary complication.5 The combination of the restless leg syndrome and rheumatoid arthritis contributes considerably to discomfort and anxiety, and in our experience few doctors are aware of this condition.
162 citations
TL;DR: The antiallergic effectiveness of twelve compounds was studied in ascaris hypersensitive dogs by measuring allergen‐induced skin reactions before and 1, 4, 20, and 72 hr after oral treatment, finding levocabastine and R 57 959 are potentially very effectiveAntiallergic drugs.
Abstract: The antiallergic effectiveness of twelve compounds was studied in ascaris hypersensitive dogs by measuring allergen-induced skin reactions before and 1, 4, 20, and 72 hr after oral treatment. The specific serotonin S2-antagonist ritanserin at 2.5 mg/kg and the selective histamine H2-antagonist cimetidine at 10 mg/kg did not reduce the allergic wheals. Chlorpheniramine and clemastine were inactive at 2.5 mg/kg. The remaining eight compounds studied over a wide dose range produced peak activity at markedly different doses and time intervals (hr). The lowest oral ED50-values in mg/kg were: levocabastine: 0.0035 (4); R 57 959: 0.048 (20); astemizole: 0.13 (20); ketotifen: 0.20 (4); cyproheptadine: 0.21 (4); azatadine: 0.32 (4); oxatomide: 1.26 (20); terfenadine: 1.26 (1). The lowest oral ED50-values in dogs and in rats (compound 48/80 lethality test) were similar, the largest difference being a fourfold potency gain of oxatomide in dogs. The short-acting compounds in rats (azatadine, cyproheptadine, ketotifen, and terfenadine) had also a duration of action of less than 12 hr in dogs. Levocabastine, R 57 959, astemizole, and oxatomide acted more than 16 hr. Maximal inhibition of the allergic wheal volumes was highest with levocabastine (90%); it reached 80% with R 57 959 and ranged from 67 to 78% with the remaining compounds. On the basis of their activity characteristics in dogs, levocabastine and R 57 959 are potentially very effective antiallergic drugs.
85 citations
TL;DR: It is concluded from these and other studies that the lack of significant sedative effects shown with loratadine is due to its poor penetration into the CNS and selectivity for peripheral histamine receptors.
69 citations
TL;DR: Astemizole (load) and hydroxyzine were significantly more effective than terfenadine and astemizoles (no load) in reducing wheal size and the incidence of adverse effects was low overall and lowest in the astemIZole ( no load) and terfenADine groups, although this difference was not statistically significant.
Abstract: Thirty-two healthy volunteers completed a 14-day, double-blind, noncrossover study comparing the efficacy and adverse effects of astemizole, terfenadine, and hydroxyzine. The subjects received either astemizole (load), 30 mg once daily for 1 week and then 10 mg once daily for 1 week, or astemizole (no load), 10 mg once daily for 2 weeks, or terfenadine, 60 mg twice daily for 2 weeks, or hydroxyzine, 50 mg once daily for 2 weeks. Before and on days 7 and 14 of treatment, five intradermal tests with various amounts of histamine phosphate (range 0.3 to 40 μg) were performed. Wheal-and-flare responses were traced, and the areas were computed by use of a graphics tablet. All four H i -receptor antagonist treatment regimens were equally effective in reducing the flare response to histamine. Astemizole (load) and hydroxyzine were significantly more effective than terfenadine and astemizole (no load) in reducing wheal size. The incidence of adverse effects, including sedation, was low overall and lowest in the astemizole (no load) and terfenadine groups, although this difference was not statistically significant.
53 citations
TL;DR: Increased plasma levels of prostaglandin D2 and blood histamine after heat challenge indicate a role for mast cell degranulation in the pathophysiology of the syndrome, and no evidence was found for the activation of the alternative complement pathway.
Abstract: A case of localized heat urticaria in a 70-year-old woman is reported. Increased plasma levels of prostaglandin D2 and blood histamine after heat challenge indicate a role for mast cell degranulation in the pathophysiology of the syndrome. Treatment with astemizole increased the temperature threshold to wealing, but not to itch or erythema. The patient was partially desensitized by repeated exposure to heat and this was further improved by indomethacin. After treatment there was no increase in plasma prostaglandin D2 on challenge. No evidence was found for the activation of the alternative complement pathway.
51 citations
TL;DR: The study suggests that oral astemizole is at least as good as nasal beclomethasone in the maintenance treatment of hay fever and that it offers the additional advantage of improved control of eye symptoms.
Abstract: Seventy-four patients with a well documented history of seasonal allergic rhinitis were randomly allocated to receive either astemizole 10 mg orally per day or beclomethasone 100 micrograms in each nostril twice daily on a double-blind double-dummy basis. The patients were studied in a general practice setting and were seen at entry, during the study and at the end of the study by a single observer, the author. Assessment was by diary card incorporating five 10 cm visual analogue scales related to the four symptoms of sneezing, rhinorrhoea, blocked nose and itchy eyes and an overall assessment of hay fever symptoms. Patients were asked if the medication had upset them in any way at each observer assessment. Symptom severity, as recorded by the visual analogue scales, was not significantly different for sneezing, rhinorrhoea, blocked nose or overall between the two groups but the symptom scores for itchy eyes were significantly better for the astemizole group. Adverse effects were minimal and of a minor nature only. There was no real difference between the two groups regarding adverse effects. The study suggests that oral astemizole is at least as good as nasal beclomethasone in the maintenance treatment of hay fever and that it offers the additional advantage of improved control of eye symptoms.
43 citations
TL;DR: Steady‐state plasma levels were in close agreement with predicted levels, indicative of linear pharmacokinetics of AST in man, and an equal bioavailability of the drug from the three formulations were demonstrated.
Abstract: The pharmacokinetics and dose-proportionality of astemizole (AST) (10, 20, and 30 mg given orally) were studied in 12 healthy male subjects by radioimmunoassay after selective extraction, enabling the determination of the plasma levels of AST and its major metabolite desmethylastemizole (DES-AST). Peak levels of AST were reached within 1 hr. Plasma levels decayed biphasically with terminal half-lives of about 1 day for AST and about 10 days for DES-AST. Areas under the curve of parent drug accounted for 5% of those of DES-AST. The bioavailability/bioequivalence of AST was studied in 21 healthy subjects according to a three-way cross-over design. Subjects received orally 30-mg doses as a tablet, suspension, or solution. The study demonstrated an equal bioavailability of the drug from the three formulations since rate and extent of absorption were not significantly different. In patients with perennial allergic rhinitis, treated for 20 weeks with AST 10 mg/day, steady-state was reached within 1 week for AST and within 4 weeks for DES-AST. Elimination half-lives after chronic treatment were similar to those after single dosing. Steady-state plasma levels were in close agreement with predicted levels, indicative of linear pharmacokinetics of AST in man.
40 citations
01 Jan 1986
TL;DR: Astemizole was globally considered to be the most effective drug by both investigator and patients, with excellent/good results in 77% of the patients compared with 55% to 60% in the terfenadine group.
Abstract: Two new non-sedating antihistamines, astemizole (10 mg per day) and terfenadine (120 mg per day), were compared in a double-blind randomized study in 42 adult patients suffering from chronic urticaria. The trial lasted 4 weeks. Patients were evaluated at 2 and 4 weeks and kept a daily diary of their symptoms. There was a statistically significant decrease in pruritus, erythema and urticaria papules in both groups throughout the study. Changes in papule size, number and frequency were greater in the astemizole group though not significantly different to the terfenadine group. The effect of astemizole increased with time whereas that of terfenadine decreased after about 3 weeks of treatment. Astemizole was globally considered to be the most effective drug by both investigator and patients, with excellent/good results in 77% of the patients compared with 55% to 60% in the terfenadine group. Both drugs were reported to be more effective and faster acting than other antihistamines taken previously. Side-effects were infrequent and minor in both groups.
25 citations
TL;DR: It was concluded that AST is a potent and safe drug for symptomatic control of chronic idiopathic urticaria and major sedative effects were observed in only two of 27 patients receiving AST.
Abstract: The efficacy and safety of astemizole (AST), a new long-acting H1 antagonist with minimal sedative or anticholinergic side effects, were studied in an 8-week double-blind trial of 51 patients with chronic idiopathic urticaria. Patients with chronic idiopathic urticaria were randomized to AST-treated (10 mg every day) or placebo-treated groups. Patients were followed at weekly intervals and evaluated for pruritus, erythema, extent of wheals, frequency of urticarial episodes, and total control of urticaria. Only three of 27 AST-treated patients stopped the double-blind phase before 8 weeks because of inadequate response as compared to 11 of 24 placebo-treated subjects (p = 0.027). On the last evaluable visit of the double-blind phase of the study, 85% of the AST-treated patients reported an excellent or good response compared to 30% of the placebo-treated group (p = 0.0001). AST-treated patients also reported significant improvement compared to placebo-treated patients in pruritus (p = 0.0001), erythema (p = 0.0001), and extent of wheals (p = 0.003). Mild sedative effects were observed in only two of 27 patients receiving AST. It was concluded that AST is a potent and safe drug for symptomatic control of chronic idiopathic urticaria.
24 citations
TL;DR: Treatment with astemizole resulted in significant improvement of pruritus, erythema, number of wheals, frequency of urticarial attacks, and control of urtics in patients with chronic idiopathic urticaria.
Abstract: Astemizole is a new H 1 histamine-receptor antagonist that has a long elimination half-life and high H 1 -receptor affinity This double-blind study evaluated the safety and efficacy of astemizole in the treatment of chronic idiopathic urticaria (more than or equal to 3 months) Seventeen male and 34 female adult patients with chronic idiopathic urticaria entered the 2-month study After a 48- to 72-hour washout, half the subjects were prerandomized to receive astemizole (10 mg), and the other half received placebo Placebo-treated patients who were unable to complete the full 8 weeks because of uncontrolled chronic urticaria symptoms were entered into a 2-month open astemizole trial Treatment with astemizole, as measured at the end point of each patient's treatment and compared to placebo, resulted in significant improvement of pruritus, erythema, number of wheals, frequency of urticarial attacks, and control of urticaria ( p ⩽ 003) The overall response to astemizole was significantly better than for placebo, according to both the investigator's and the patient's global evaluations ( p p = 0005) Six of 26 (24%) of the placebo-treated patients in the double-blind study had good to excellent results on the basis of global assessments Thirteen of 16 patients with placebo-treatment failures who received astemizole in the open trial improved significantly from baseline symptoms of pruritus, erythema, and number of wheals ( p ⩽ 005) No significant side effects were reported except mild sedation in three astemizole-treated subjects Astemizole, a new, potent, long-acting H 1 antihistamine, is a safe, effective, and convenient treatment for chronic idiopathic urticaria
24 citations
TL;DR: A sensitive radioimmunoassay is described for the determination of astemizole in human plasma and the cross‐reactivity of the antibodies with structurally related metabolites resulted in the production of antiserum capable of detecting less than 0.05 ng/ml of a stemizole.
Abstract: A sensitive radioimmunoassay is described for the determination of astemizole in human plasma. Immunization of rabbits with an astemizole hapten, conjugated with bovine serum albumin, resulted in the production of antiserum, capable of detecting less than 0.05 ng/ml of astemizole. Because of the cross-reactivity of the antibodies with structurally related metabolites, plasma samples had to be submitted to two distinct extraction procedures prior to radioimmunoassay. The most selective procedure enabled the measurement of unchanged astemizole as confirmed by high-performance liquid chromatography. The other extraction procedure allowed the determination of the fraction astemizole plus hydroxylated metabolites, which consisted mainly of astemizole and its major metabolite desmethylastemizole.
TL;DR: In numerous tests no evidence of central activity was found and toxicity studies have shown astemizole to be a very safe drug despite of its long duration of action.
Abstract: In the compound 48/80 lethality test in rats, which is based on the specific activation of mast cells, astemizole was selected as a potent, long-acting and orally very effective inhibitor of anaphylactoid shock. In comparison to other histamine-H1 antagonists astemizole was also a very effective inhibitor of allergic reactions in rats and dogs and remarkably free of non-specific interactions with other biological amines and normal body functions. In numerous tests no evidence of central activity was found and toxicity studies have shown astemizole to be a very safe drug despite of its long duration of action. A daily dose of 10 mg of astemizole was found clinically free of side-effects and more effective than conventional antihistamine treatment.
Journal Article•
TL;DR: None of the treatments produced any significant or consistent effects when assessed on objective and subjective measures of performance, critical flicker fusion threshold, sedation and sleep and there were no treatment differences in the nature and number of adverse effects reported.
Abstract: This study was a single and repeated dose comparison of mequitazine 5 mg, astemizole 10 mg and placebo and their effects on CNS activity, psychomotor performance and subjective appraisals of alertness. Nine Caucasian female volunteers aged between 29 and 40 years, declared healthy following a medical examination and who showed sensitivity to antihistamine sedation, were admitted to the study. Subjects were allocated to treatment in a randomized block design by which each subject received single and repeat doses of mequitazine 5 mg, astemizole 10 mg and placebo under double-blind conditions. Objective assessments (choice reaction time, critical flicker fusion threshold, simulated car tracking task, Stroop test) and subjective assessments (sedation and sleep rating scales, adverse effects and event recording) were made. Assessments were performed on day 1 and day 8 at pre-dosing (0 h) and at 1.5, 3.5 and 5.5 h following drug administration. Choice reaction times were dissimilar 5.5 h post-drug administration, the mequitazine group having a reaction time comparable to baseline and faster than the astemizole and placebo treatment groups. However, none of the treatments produced any significant or consistent effects when assessed on objective and subjective measures of performance, critical flicker fusion threshold, sedation and sleep and there were no treatment differences in the nature and number of adverse effects reported.
TL;DR: Beclomethasone dipropionate and astemizole are equally effective in the symptomatic treatment of atopic perennial rhinitis, but beclomethistamines may offer superior symptom relief in non‐atopic perennial Rhinitis.
Abstract: An open cross-over trial comparing astemizole with intra-nasal aqueous beclomethasone dipropionate was carried out in forty-five perennial rhinitis patients attending a S.W. London general practice. Each drug was given for 12 weeks, separated by 4-8 weeks without medication. The principal outcome measure was a 7-day symptom diary completed by patients during weeks 4, 8 and 12. Patients were skin tested to seven common inhalant allergens. Half the patients beginning either regime failed to respond adequately within 2 weeks. Doubling the dose in these patients achieved satisfactory symptom control in an additional 67% on beclomethasone dipropionate and 45% on astemizole. Symptom diary scores showed beclomethasone dipropionate to be significantly more effective than astemizole in the treatment of skin test negative patients; but the two drugs were of equal benefit in the treatment of skin test positive patients. Sneezing and rhinorrhoea were the same on both drugs, but nasal blockage tended to be less severe on beclomethasone dipropionate. There was no significant difference between drugs in the frequency or duration of side effects. Beclomethasone dipropionate and astemizole are equally effective in the symptomatic treatment of atopic perennial rhinitis, but beclomethasone dipropionate may offer superior symptom relief in non-atopic perennial rhinitis.
TL;DR: It might thus be concluded that astemizole is free of CNS‐depressant effects in Thai volunteers.
Abstract: The absence of CNS-related side effects of astemizole, a new long-acting specific histamine, H1-antagonist, has been reported by many authors. To investigate the influence of this new antihistamine on psychomotor performance in Thais, oral therapeutic doses of 10 mg once daily were administered for 7 days to 21 healthy Thai volunteers (13 males and eight females). Ages ranged from 22 to 37 years and body weights from 40 to 65 kg. The study used a double-blind crossover design. Subjective assessments were carried out by means of a visual analogue rating scale and a four-point alertness rating scale and objective assessments by means of card sorting, glass bead picking, and recording of reaction times for visual stimuli in a choice situation. Compared to placebo, astemizole caused no change in any of the ratings or performances at either 1 or 2 h subsequent to the first and last (i.e., seventh) dose. It might thus be concluded that astemizole is free of CNS-depressant effects in Thai volunteers.
TL;DR: In this article, astemizole was synthesized by varying in particular the alkyl and aralkyl groups implanted on the piperidine, benzimidazole, and bridging amine nitrogen.
Abstract: Newly synthesized diphenylbutylpiperidine derivatives were devoid of neuroleptic activity but were moderately active histamine antagonists in vitro. Their structural relation to classical antihistamines was not evident, but the requirement of a piperidino-2-aminobenzimidazole core was confirmed by the synthesis of R 39848, which was more potent. About 500 new compounds related to R 39848 were synthesized by varying in particular the alkyl and aralkyl groups implanted on the piperidine, benzimidazole, and bridging amine nitrogen. Potency, oral activity, and long duration of action in the compound 48/80 lethality test in rats prompted the selection of R 43512 (astemizole) for detailed pharmacological studies. Antiallergic specificity and lack of central effects were the conclusions of all studies, and the higher clinical effectiveness of astemizole was in agreement with a dosage that is not limited by central or other side effects. More extensive chemical modifications of the astemizole molecule were explored, and it is possible that some recent compounds may either have an increased antiallergic effectiveness (R 57959) or be useful in other indications because of a different profile of peripheral actions.
TL;DR: There were no serious adverse clinical or laboratory sequelae, with only mild sedation and no anticholinergic adverse effects, in a 14-year-old girl who took an overdose of 200 mg of astemizole.
Abstract: A case is reported of a 14-year-old girl who took an overdose of 200 mg of astemizole. There were no serious adverse clinical or laboratory sequelae, with only mild sedation and no anticholinergic adverse effects. The apparent half-life of this dose over the next 37 h was 31 h.
01 Jan 1986
TL;DR: The global assessments made by the investigator at 4 weeks and the patient at 8 weeks indicated significantly better overall symptom control in the astemizole group, with side-effects being few and minor.
Abstract: A study was carried out in general practice during the summer months of 1985 to compare the efficacy and tolerance of astemizole suspension with terfenadine suspension in the treatment of paediatric hay fever. The 65 patients who entered the study were all aged between 6 and 12 years and had suffered from hay fever in at least one previous season. Each child was randomly allocated to receive either 5 ml astemizole suspension (1 mg/ml) once daily or 5 ml terfenadine suspension (6 mg/ml) twice daily for a period of 8 weeks on a single-blind basis. Symptom scores assessed by the patient (or parent/guardian) on two visual analogue scales for ocular and nasal symptoms showed no significant difference between the treatment groups, neither did an analysis of visual analogue scores for runny nose, blocked nose, wheeze, sneezing or eye symptoms assessed by the investigator on entry or after 4 and 8 weeks. The global assessments made by the investigator at 4 weeks and the patient at 8 weeks, however, indicated significantly better overall symptom control in the astemizole group. Both treatments were well tolerated, side-effects being few and minor.
TL;DR: In this paper, a double-blind randomized study comparing astemizole 10 mg o.i.d. with terfenadine 60 mg b.v.d was conducted.
Abstract: Ninety-seven university students presenting with hay fever symptoms were evaluated in a double-blind randomized study comparing astemizole 10 mg o.d. with terfenadine 60 mg b.i.d. Patients were seen at bi-weekly intervals by their treating physician and scored their symptoms daily for a period of 4 weeks. Breaking the code revealed that 45 patients had received astemizole and 52 terfenadine. Both groups were comparable with regard to age, sex, weight, duration of disease, and symptom severity at start. At the end of treatment, symptom ratings showed a significant improvement of all typical hay fever symptoms in both treatment groups except for blocked nose. Global evaluation of treatment, however, was significantly in favour of the astemizole group of which 71% of the patients were considered as excellent or good responders, as compared to 55% in the terfenadine group. Neither of the two compounds was associated with sedative effects; other side effects were virtually absent in both groups.
Journal Article•
TL;DR: It can be concluded that astemizole cannot be eliminated by dialysis because of its high protein binding capacity.
Abstract: Four patients undergoing hemodialysis because of terminal renal insufficiency have taken 10 mg of astemizole on two consecutive days. The elimination was followed for 7 days and was found not to be delayed. During dialysis no decrease of the plasma levels of astemizole and its hydroxylated metabolites were observed. On the contrary, a small nonsignificant increase was found which can be explained by the thickening of the blood after ultrafiltration. It can be concluded that astemizole cannot be eliminated by dialysis because of its high protein binding capacity.
Journal Article•
TL;DR: SIR Dr MB Emanuel (November 1985;40:799) has misinterpreted his work' in an attempt to explain the surprising inability of Drs PH Howarth and ST Holgate to find an effect of terfenadine, and it is made quite clear that tachyphylaxis is not demonstrated, despite the evidence indicating that their maximal therapeutic effect is comparable to and no greater than that of the old Hi antihistamines.
Abstract: SIR Dr MB Emanuel (November 1985;40:799) has misinterpreted our work' in an attempt to explain the surprising inability of Drs PH Howarth and ST Holgate to find an effect of terfenadine (September 1984;39:668-72). The quotation selected by Dr Emanuel in fact came from a report of a study comparing chlorpheniramine with astemizole, and the phrase "suggests tolerance" referred to tachyphylaxis with chlorpheniramine. I now appreciate the unfortunate ambiguity introduced by its context and wish therefore to make it quite clear that we have not demonstrated tachyphylaxis with terfenadine. In fact, we found that with the recommended dose of 60 mg twice daily terfenadine "was still clinically effective [in chronic dermographic urticarial after 47-84 days' treatment"; there was a slight, insignificant change in the linear part of the weal forceresponse curve with continued treatment but no change in the clinically more relevant weal threshold force. We have since found no pharmacological evidence of tachyphylaxis using full histamine weal dose-response curves before and after administration of 60mg twice daily terfenadine for six weeks3; nor was there any greater effect from doubling the dose, which would have been expected had there been tachyphylaxis. The apparent ineffectiveness of terfenadine in the study of Drs Howarth and Holgate cannot therefore be explained by tachyphylaxis or use of too low a dose (see letter by Dr B Freedman, May 1985;40:399); but it can be explained, at least in part, by reduced bioavailability. Thus, although the recommended dose of terfenadine was used, it was incorporated into a capsule to make it indistinguishable in appearance from astemizole. Desirable though that may have been for the execution of a double blind trial, it appears to have had an adverse effect on bioavailability because histamine wealing was impaired much less by terfenadine 60mg twice daily in the particular preparations they used than by the astemizole 10mg daily; whereas it is clear from full histamine weal dose-response curves with regular terfenadine and astemizole that these doses are approximately equiactive.3 In terfenadine and astemizole we have two interesting, still comparatively new, HI receptor antagonists, and with few exceptions the evidence indicates that their maximal therapeutical effect is comparable to and no greater than that of the old Hi antihistamines despite much greater inhibition of histamine wealing, presumably because only part of the various disease processes is due to histamine.34 Their main advantage lies in a greater therapeutic ratio because of the absence of unwanted effects such as drowsiness, although this does preclude their use for itch other than that due to peripheral histamine release.6 Nevertheless, our own studies show that their different biokinetic effects on histamine wealing corresponds to their different therapeutic properties. Thus astemizole has a slow onset of effect (days), which can be overcome only in part by use of a loading dose, and a very slow offset, weal inhibition still being apparent as much as a month after the drug has been stopped; whereas the onset of effect of terfenadine was apparent by 2-4 hours and its offset by 24 hours. The disadvantage of a slow onset is obvious for initial treatment, but is less well recognised for long term administration. Thus when prolonged symptomatic treatment is required until there is spontaneous remission it is desirable to ask patients to stop the drug from time to time to see whether they still need it, and this is more easily done when recurrence can rapidly be brought under control by a drug with a quick onset of effect. The advantage of a once daily, weekly, or fortnightly dosage is considerable for some patients but has to be balanced against the unknown risk of drug persistence if toxicity occurs; and in the case of these new drugs it is far too soon to be sure that it won't. For these reasons I believe that clinicians and clinical pharmacologists should themselves consider the desirability or otherwise of possible manipulation of speed of binding and dissociation of drugs such as histamine receptor antagonists before they are presented with new hybrids and "act-alikes." Meanwhile it is the clearcut biokinetic differences between terfenadine and astemizole which should dictate their clinical use. SAM SHUSTER Department of Dermatology Royal Victoria Infirmary Newcastle upon Tyne NE] 4LP
TL;DR: It is suggested that astemizole has the advantage of greater patient convenience and cost effectiveness in hay fever sufferers.
Abstract: SummaryAn open, parallel group study was carried out in 95 hay fever patients during the 1984 season to compare the efficacy of oral astemizole with that of topical sodium cromoglycate. Patients were allocated at random to receive astemizole once daily (30 mg during the first week, then 10 mg for the rest of the study period) or sodium cromoglycate (2%), administered 6-times daily intranasally and 4-times daily in the eyes, for a maximum of 8 weeks. The severity of patients' nasal and ocular symptoms was assessed daily on two separate 100 mm visual analogue scales throughout the study period. No statistically significant difference could be detected between the two treatment groups in the control of either nasal or ocular symptoms. Side-effects in both groups were minor and transient. It is suggested that astemizole, however, has the advantage of greater patient convenience and cost effectiveness in hay fever sufferers.
Journal Article•
TL;DR: Astemizole is a potent H1-antagonist devoid of sedative effects, which was found at single oral daily doses to be very effective in the treatment of allergic rhinitis, allergic conjunctivitis, and urticaria.
Abstract: Astemizole is a potent H1-antagonist devoid of sedative effects, which was found at single oral daily doses to be very effective in the treatment of allergic rhinitis, allergic conjunctivitis, and urticaria. Its interaction potential on other drugs was studied in various ways. Studies on salivary antipyrine clearance, the 6-beta-hydrocortisol excretion, the elimination rate of ethanol and the indocyanine-green clearance are presented. No changes were observed. Astemizole also was given in combination with diazepam or alcohol. Psychomotor performance failed to show any effects. In none of these studies was there any evidence of interaction of astemizole on other drugs. This review summarizes the data available thus far.
Journal Article•
TL;DR: Evidence that the dextran‐induced edema formation in mouse ear is predominantly mediated by serotonin is provided, but a participating role for a lipoxygenase‐derived arachidonic acid metabolite(s) is suggested.
Abstract: Intravenous injection of dextran T500 and pontamine sky-blue dye into mice results in increased vascular permeability and edema formation, characterized by an intense blueing of the ears. By determining the amount of extravasated dye, we compared a number of S2-serotonin antagonists, H1- and H2-antihistamines, anticholinergics, and inhibitors of arachidonic acid metabolizing enzymes for their effects on ear edema. All S2-antagonists tested (cinanserin, cyproheptadine, ketanserin, and ritanserin) dose-dependently suppressed ear blueing. Some H1-antihistamines (astemizole and azatadine) were also inhibitory, but other H1-antagonists (brompheniramine, chlorpheniramine, levocabastine, and pyrilamine) failed to weaken the reaction. The anti-dextran activity of the H1-blockers seemed to be related to their ability to abolish serotonin-induced vascular permeability of the mouse ear. Of the compounds interfering with arachidonic acid metabolizing enzymes, only BW 755C, a lipoxygenase inhibitor, proved active. The cyclo-oxygenase inhibitors indomethacin and suprofen, the thromboxane synthetase inhibitor dazoxiben, the H2-antagonists cimetidine and ranitidine, and the antichlinergics isopropamide and hexamethonium were inactive. These data provide evidence that the dextran-induced edema formation in mouse ear is predominantly mediated by serotonin, but they also suggest a participating role for a lipoxygenase-derived arachidonic acid metabolite(s).
Journal Article•
TL;DR: Astemizole proved in this study to be a very effective antihistamine being able to achieve good results even in hard to cure cases like cold urticaria.
Abstract: 20 patients, 12 suffering from chronic urticaria, 2 from acute urticaria, 1 from pressure urticaria, 2 from cold urticaria and 3 from urticaria factitia were treated in an open pilot study with the new H1-antihistamine Astemizole. The dosage was in all cases 1 X 10 mg per day. The onset of action as well as the efficacy maximum were registered. Astemizole proved in this study to be a very effective antihistamine being able to achieve good results even in hard to cure cases like cold urticaria. On the 1. day 35% of the patients had noticed an onset of action. 75% of the patients had an onset of action within the first 2 days. The efficacy maximum was achieved within the first 2 days in 60% of the patients.
TL;DR: The case highlights certain principles which I think will concern your readers and is likely to concern the author's readers.
Abstract: listed drug carbocisteine for a patient who had had a course of radiotherapy to the larynx several years previously and who was experiencing severe respiratory stridor and aphonia. This was on the recommendation of the ear, nose, and throat surgeon and carbocisteine was the only treatment of all those that had been tried that had helped the patient appreciably. After reading the leaflet referred to above I had no doubt that my duty was to continue to prescribe the drug in this case and I endorsed the prescriptions accordingly. When the pricing bureau subsequently refused payment I was obliged to pay the pharmacist personally and apply to the DHSS for reimbursement. This was refused on the grounds that a committee ofexperts had pronounced the entire group of mucolytic drugs to be valueless. In correspondence over the past six months the DHSS has remained intransigent. This is in spite of the fact that the committee of experts changed its mind during this period and decided that the mucolytics did after all have an effect on mucus accumulation, but only in the case of infants on respirators and in certain manifestations of cystic fibrosis-a judgment which seemed to me to cast doubt on their scientific humility, and perhaps even on their expertise. My patient, a particularly brave and deserving individual, now breathes safely through a permanent tracheostomy. However, the case highlights certain principles which I think will concern your readers. J A R WILLIS