少年红矾杏平喘糖浆镇咳、祛痰和平喘作用的实验研究

目的:观察少年红矾杏平喘糖浆(简称平喘糖浆)的止咳、祛痰和平喘作用。方法:采用氨水引起小鼠咳嗽实验观察平喘糖浆止咳作用;通过小鼠酚红祛痰实验观察平喘糖浆排痰作用,通过磷酸组胺所致豚鼠哮喘及离体豚鼠气管平滑肌实验观察平喘糖浆平喘作用。结果:平喘糖浆能明显延长引起半数小鼠咳嗽的氨水喷雾时间(EDT50),增加小鼠气管酚红的排出,显著延长豚鼠由磷酸组胺引起哮喘的潜伏期,明显抑制离体气管平滑肌的收缩。结论:平喘糖浆有祛痰、止咳和平喘作用。     

黄心胶囊镇咳、祛痰及镇痛作用的研究

目的：观察黄心胶囊镇咳、祛痰及镇痛作用。方法：黄心胶囊对浓氨水所致小鼠及豚鼠咳嗽的影响、对小鼠气管排泌酚红及对大鼠排痰量的影响、对化学、物理刺激所致小鼠疼痛反应的影响。结果：灌服黄心胶囊500、250、125mg／kg能明显减少浓氨水引起小鼠的咳嗽次数，250mg／kg能明显减少浓氨水刺激引起豚鼠的咳嗽次数。灌服250mg／kg具有显著增加气管排泌酚红的作用，而灌服625、500和375mg／kg能显著增加大鼠的排痰量。给小鼠灌服黄心胶囊250、500、625mg／kg能显著地减少醋酸所致的扭体反应次数和提高对热刺激的痛反应阈值。结论：黄心胶囊具有镇咳、祛痰及镇痛的作用。     

久咳颗粒镇咳、抗炎和祛痰作用实验研究

目的:研究久咳颗粒的镇咳、抗炎和祛痰药理作用。方法:180只ICR小鼠(雌雄各半)根据体重随机分为正常组、模型组、阳性组以及久咳颗粒高(28 g生药·kg~(-1))、中(14 g生药·kg~(-1))、低(7 g生药·kg~(-1))三个剂量组(n=10),预防性给药7d后,分别考察氨水致小鼠咳嗽模型、二甲苯致小鼠耳廓肿胀模型和气管酚红法中各模型动物的咳嗽潜伏期、咳嗽次数、耳肿胀度和酚红排泌量。结果:与正常组比较,模型组小鼠的咳嗽的潜伏期明显缩短(P0.01)、咳嗽次数明显增加(P0.01),耳肿胀度明显增加(P0.01)而酚红排泌量减少(P0.01);与模型组比较,久咳颗粒高中剂量组小鼠的咳嗽的潜伏期明显延长(P0.05)、咳嗽次数明显减少(P0.05)和耳肿胀度降低(P0.05),且久咳颗粒各剂量组酚红排泌量明显增加(P0.05)。结论:久咳颗粒具有显著的镇咳、抗炎和祛痰作用。     

菖蒲雾化合剂的祛痰、平喘作用

目的验证菖蒲雾化合剂祛痰、平喘的药理作用。方法采用组胺诱导整体动物气管痉挛及豚鼠离体气管法观察菖蒲雾化合剂的平喘作用,用小鼠酚红实验法观察菖蒲雾化合剂的祛痰作用。结果菖蒲雾化合剂可以明显延长组胺致喘的潜伏期,能明显降低组胺及乙酰胆碱引起的豚鼠离体气管的收缩幅度,收缩幅度分别降低62%,69.72%。结论菖蒲雾化合剂具有良好的平喘、祛痰作用。     

双青咽喉片抗炎、镇咳、祛痰及镇痛作用的实验研究

目的：观察双青咽喉片抗炎、镇咳、祛痰及镇痛作用.方法：通过蛋清所致大鼠足趾肿胀实验、腹腔注射醋酸所致小鼠腹腔毛细血管通透性增高实验、二甲苯诱发小鼠耳廓肿实验观察双青咽喉片的抗炎作用;通过浓氨水所致小鼠咳嗽实验和小鼠气管排泌酚红实验观察双青咽喉片的镇咳和祛痰作用;通过醋酸和热板刺激所致小鼠疼痛反应实验观察双青咽喉片的镇痛作用.结果：双青咽喉片能明显减轻蛋清引起的炎症反应,降低腹腔毛细血管通透性,显著降低二甲苯致小鼠耳廓的肿胀度,并能明显减少浓氨水引起小鼠的咳嗽次数,增加气管排泌酚红的作用,减少醋酸致小鼠的扭体次数,提高小鼠对热刺激的痛阈值.结论：双青咽喉片具有抗炎、镇咳、祛痰及镇痛作用.     

愈麻沙芬的药理研究

愈麻沙芬在36.26mg/kg时,对小白鼠气管的酚红排泌有明显促进作用,对蛙纤毛运动有一定的促进作用。对小鼠有明显镇咳作用,使咳嗽潜伏期明显延长。在72.5mg/kg即可抑制醋酸诱发的毛细血管通透性增加,也能显著抑制角又菜胶所引起的大鼠足肿胀,对兔耳血管有收缩作用。实验还表明该药能使组胺对豚鼠鼻粘膜致敏的反应减轻、抓鼻次数和喷嚏次数减少。表明该药是一个具有镇咳、祛痰,减轻鼻塞作用的抗感冒药。     

鲜竹沥胶囊药效学研究

鲜竹沥胶囊主要药效学试验,结果表明鲜竹沥胶囊在体外对常见的呼吸道及肠道感染的细菌有一定的抑制作用;能显抑制氨水引起的小鼠咳嗽;能显抑制磷酸组胺引起的豚鼠哮喘;能显增加小鼠呼吸道粘膜排泌酚红的量,具有一定的润肺祛痰作用。     

退热宁的止咳祛痰作用

研究了退热宁的止咳、祛痰作用。结果表明退热宁对氨水引咳的小鼠有明显的镇咳作用,显著增加小鼠气道腔内酚红的排出量,说明该药具有较好的止咳、祛痰作用。     

天龙喘咳灵镇咳祛痰平喘实验研究

对中药复方天龙喘咳灵进行了镇咳祛痰平喘等主要药效学实验研究，结果表明，天龙喘咳灵对小白鼠化学刺激引起的咳嗽有明显抑制作用，对枸檬酸致豚鼠咳嗽能明显延长潜伏期和减少其咳嗽次数，能增强呼吸道分泌功能，有排痰祛痰作用，可明显延长豚鼠实验性哮喘发作潜伏期，有平嘴作用，本研究为天龙喘咳灵临床治疗慢性支气管炎，支气管哮喘等呼吸疾病提供了一定药理学依据。     

慈竹沥的药理初探

本文首次报告用禾本科植物sinocalamus aftiais(Rendle)McClure的鲜杆制得慈竹沥的药理研究结果。采用氨水引咳序贯法,小鼠ig 5ml/kg及30ml/kg慈竹沥的R值分别为186％,226％,认为药该有明显的镇咳作用;气管段酚红法证实,小鼠ig 5、15、30ml/kg慈     

Skin reactivity to histamine and codeine in unselected 9-year-old children from Italy, Poland and Libya

BACKGROUND: Previous studies have shown that histamine skin reactivity (the dimensions of a skin wheal elicited by a prick with histamine 10 mg/ml) in unselected school children has increased in Italy during the past two decades and is higher in Italy than in Poland. Hence this variable can probably be influenced by a changing or different lifestyle. The aim of this study was to compare skin reactivity to histamine and codeine (a marker of histamine releasability from mast cells) in schoolchildren from countries with different lifestyles. METHODS: Six previously unstudied unselected populations of 9-year-old schoolchildren (two each from Poland, Italy, and Libya; n = 863 subjects; 49.0% males) were pricked with two concentrations of histamine (10 and 1 mg/ml) and codeine (90 and 9 mg/ml). RESULTS: The higher concentrations of both pharmacologic agents tested yielded significantly different wheal areas in the three countries: Poland < Italy < Libya (histamine, 11.8, 16.1 and 20.7 mm2; codeine, 9.2, 13.2 and 16.2 mm2; p < 0.001 for all comparisons). The lower concentrations elicited almost matching results. Histamine wheal areas correlated closely with areas elicited by codeine in the same individual: angular coefficients of the histamine to codeine regression lines were 0.535, Italy; 0.551, Libya; 0.612, Poland; and 0.581 for the whole population. More histamine was needed to produce a wheal in Poland than in Libya: a 20-mm2 wheal required an injected histamine concentration of about 8.8 mg/ml in Libya, 29.5 mg/ml in Italy and 102.1 mg/ml in Poland. CONCLUSION: More studies are necessary to explain the observed international differences in skin histamine reactivity and their effect on the prevalence of positive allergen skin tests.     

A Case of Codeine Induced Anaphylaxis via Oral Route

Codeine is widely prescribed in clinical settings for the relief of pain and non-productive coughs. Common adverse drug reactions to codeine include constipation, euphoria, nausea, and drowsiness. However, there have been few reports of serious adverse reactions after codeine ingestion in adults. Here, we present a case of severe anaphylaxis after oral ingestion of a therapeutic dose of codeine. A 30-year-old Korean woman complained of the sudden onset of dyspnea, urticaria, chest tightness, and dizziness 10 minutes after taking a 10-mg dose of codeine to treat a chronic cough following a viral infection. She had previously experienced episodes of asthma exacerbation following upper respiratory infections, and had non-atopic rhinitis and a food allergy to seafood. A skin prick test showed a positive response to 1-10 mg/mL of codeine extract, with a mean wheal size of 3.5 mm, while negative results were obtained in 3 healthy adult controls. A basophil histamine release test showed a notable dose-dependent increase in histamine following serial incubations with codeine phosphate, while there were minimal changes in the healthy controls. Following a CYP2D6 genotype analysis, the patient was found to have the CYP2D6*1/*10 allele, indicating she was an intermediate metabolizer. An open label oral challenge test was positive. To the best of our knowledge, this is the first report of a patient presenting with severe anaphylaxis after the ingestion of a therapeutic dose of codeine, which may be mediated by the direct release of histamine by basophils following exposure to codeine.     

Codeine and cough: an ineffective gold standard

PURPOSE OF REVIEW: Cough is one of the most common reasons why patients visit physicians. The opioid codeine has been a mainstay in the treatment of cough for decades and this drug is widely regarded as the 'gold standard' cough suppressant. RECENT FINDINGS: Recent placebo-controlled studies have shown that codeine is no more effective than placebo in suppressing cough caused by either upper respiratory disorders or chronic obstructive pulmonary disease. These recent reports are not consistent with several older placebo-controlled studies that demonstrated the efficacy of codeine. The reasons for this difference are not fully understood. SUMMARY: We propose that these differences, as well as results from animal models, can be explained by the existence of a complex hierarchical control system that regulates the expression of coughing. This system, known as a holarchy, is composed of regulatory elements known as 'holons' that interact with one another to regulate cough. Based on work in animal models, codeine is proposed to act on an intermediate order holon that may not be critical for coughing under some situations in humans. Testing of this hypothesis and further elucidation of the control system for cough will represent an important direction for future research in this area.     

Effects of Ketotifen on in vitro bronchoconstriction

We have studied the effects of Ketotifen [Ke](10^?4M and 10^?6M) on two in vitro models of bronchoconstriction: actively sensitized guinea-pig trachea (GPT), and passively sensitized human bronchial muscle (HBM). Experiments were performed on matched pairs of tissues. Cumulative dose response curves [CDRC] for histamine and acetyl choline were constructed, and repeated after pre-incubation with Ke or saline control. The effect of Ke on maximal antigen induced contractions was also studied. Contraction of GPT by histamine and acetyl choline was inhibited by Ke 10^?4M, though this effect was not apparent at high doses of acetyl choline. Ke 10^?6M had a weaker inhibitory effect on histamine and acetyl choline induced responses. Contraction of GPT by antigen was unaffected by Ketotifen. In the HBM model. Ke 10^?4M inhibited acetyl choline and antigen induced responses. Ketotifen, 10^?6M had an inhibitory effect on acetyl choline induced contractions, though this was small, and not seen at higher agonist doses. Contraction of HBM by antigen was unaffected by Ke 10^?6M. We were unable to obtain reproducible CD RC's to histamine with HBM. The weaker or absent effects of Ke 10^?6M, a level close to that obtained in clinical practice, may explain some of the poor results of clinical trials, and suggest that efficacy may be improved by the use of higher doses.     

Skin prick test responses to codeine, histamine, and ragweed utilizing the Multitest device

Epicutaneous skin testing is a useful diagnostic tool in evaluating allergic disorders. Utilizing the Multitest device, skin prick test responses to codeine phosphate, histamine phosphate, and ragweed were examined in 56 human subjects. Relationships between the two positive controls, codeine and histamine, and their use as a reference denominator for ragweed reactions were assessed. Ragweed elicited detectable wheals in 15/56. Histamine phosphate (2.75 mg/mL) elicited a positive wheal response in 52/56 subjects, while codeine phosphate elicited a positive wheal in 39/56 and 30/56 subjects at 30 and 3 mg/mL, respectively. Wheal sizes for codeine phosphate at both 30 and 3 mg/mL showed significantly concordant relationships with histamine phosphate-induced wheal sizes (Spearman rho, P = .0084 and .0155, respectively); however the intersubject coefficient of variation was lower for histamine-induced wheal sizes (44%) than for codeine-induced wheal sizes (64% and 65%, respectively for 30 and 3 mg/mL). When a ratio of allergen to positive control reaction size was used to grade ragweed reactions, different patterns were observed using codeine compared with histamine. These results have implications in utilizing codeine phosphate as a positive skin prick test control for allergy testing.     

Effect of codeine on objective measurement of cough in chronic obstructive pulmonary disease

BACKGROUND: Codeine is the standard antitussive treatment to which novel agents are compared. Little is known about the objective effect of any treatments on cough in chronic obstructive pulmonary disease (COPD). OBJECTIVE: To quantify the effect of codeine on objective cough frequency (quantified as time spent coughing: cough seconds, cs/h), citric acid cough threshold, and subjective measures in a double-blind, placebo-controlled crossover study in COPD. METHODS: We studied 21 patients with physician-diagnosed, stable disease who complained of cough (76.9% male; mean age, 67.7 years; mean predicted FEV(1), 53.4%; median smoking history, 43.5 pack-years). Each subject performed a cough challenge (single breath, citric acid), 10-hour daytime ambulatory and overnight cough recordings, subjective cough scores, and visual analog scales at baseline and on 2 study days, 1 week apart. Codeine phosphate 60 mg or matched placebo were given, in random order, at the start of each cough recording (0 and 12 hours). RESULTS: Median time spent coughing at baseline was 8.27 cs/h (interquartile range [IQR], 5.94-11.67); after placebo treatment, 7.22 cs/h (IQR 4.42-10.40); and after codeine treatment, 6.41 cs/h (IQR 3.86-9.10). Codeine treatment had a significant effect on time spent coughing compared with baseline (P = .02) but not compared with placebo (P = .52). There were no significant differences in cough challenge thresholds (log concentration of tussive agent causing 2 coughs or log concentration of tussive agent causing 5 coughs) or subjective cough measures for codeine compared with placebo. CONCLUSION: In this study, codeine was no more effective than placebo in patients with COPD complaining of cough. CLINICAL IMPLICATIONS: Codeine is the antitussive agent to which we compare new treatments; however, in a group of stable patients with COPD, it had no effect on cough frequency over placebo.     

The effect of salmeterol and salbutamol on mediator release and skin responses in immediate and late phase allergic cutaneous reactions

BACKGROUND: Salmeterol is a long-acting beta2-agonist which in animal studies has been shown to possess anti-inflammatory effects on early (EAR) and late (LPR) phase allergic responses. PURPOSE: To evaluate the anti-inflammatory effects of intradermally injected salmeterol and salbutamol on clinical and biochemical EAR and LPR in human skin. METHODS: Measurement of wheal and flare reactions to allergen, codeine, and histamine, and LPR (induration) to allergen. Assessment of histamine and prostaglandin D2 (PGD2) release by microdialysis technique in EAR, and measurement of mediators in LPR by suction blister technique. RESULTS: Both beta2-agonists inhibited allergen-induced histamine release and wheal and flare reactions with maximum inhibition of 40-50% at 10(-6) M, a concentration which reduced PGD2 synthesis by approximately 55%. Histamine release by codeine and skin reactions to codeine and histamine were not or only marginally reduced. Salmeterol and salbutamol (10(-6) M) inhibited clinical LPR at 6 h by 71% and 48%, Except for the clinical LPR, no statistical differences were found between the two drugs on any parameters. None of the drugs inhibited levels of histamine, tryptase, myeloperoxidase, or eosinophil cationic protein in LPR. CONCLUSIONS: Salmeterol and salbutamol inhibited allergen-induced skin responses, and reduced mediator release in EAR but not LPR. In general, the anti-inflammatory effects of salmeterol did not differ from those induced by salbutamol.     

Reaction pattern to histamine and codeine in a human intradermal skin test model

BACKGROUND: Skin prick and intradermal skin tests (IDT) are useful tools in evaluating IgE-mediated allergic disorders. In the literature, many variations of the techniques used are described. No general agreement exists on test procedures and reading of test results. OBJECTIVE: To analyse test conditions for IDT to facilitate comparability between different study protocols. METHODS: We tested 24 healthy volunteers with three concentrations of histamine and codeine each on the upper back, lateral upper arm and volar forearm, with/without addition of ethylene diamine tetra-acetic acid. Reading of the resulting weal was performed by taking a digital image of the weal, later outlining the weal perimeter in triplicate and calculating the weal area using the NIH Image J software version 1.3. RESULTS: Weal size was dose dependent for both substances, generally larger on the upper back than on the forearm and upper arm, and larger after codeine than after histamine. Addition of the Ca2+ -chelator ethylene diamine tetra-acetic acid did not significantly affect weal size. Weal size induced by histamine showed better consistency than that induced by codeine. CONCLUSIONS: The results and our technique provide valuable tools for the daily routine as well as for the ability to compare information of intradermal tests from different studies or clinical reports. When assessing skin reactivity, we recommend the use of 1 mg/mL codeine as well as 0.1 mg/mL histamine to reflect aspects of mast-cell releasability and of vascular reactivity. The involvement of local factors influencing the vascular reactivity or differences in opiate receptor density on mast cells surfaces needs to be addressed in future studies.