门诊皮肤病患者抗组胺药物处方习惯演变研究

目的了解2006年至2010年门诊皮肤病患者抗组胺药物处方习惯及其演变。方法采用7日法对2006年至2010年中每年7月1日至7日所有门诊过敏性皮肤病、瘙痒性皮肤病患者抗组胺药物处方情况进行调查分析,并进一步从抗组胺药物处方中最常使用的抗组胺药物、平均处方剂量、联合用药和合并用药等方面作分析比较。结果第一代H1受体拮抗剂处方频率逐年下降,第二代H1受体拮抗剂率呈现逐年增加;同时使用2种抗组胺药频率逐年增加,少部分同时使用3种抗组胺药的情况。抗组胺药物主要合并免疫调节剂、糖皮质激素,合并免疫调节剂处方频率逐年增加。结论本站2006年至2010年在门诊皮肤疾病患者抗组胺药物处方习惯和方式方面是比较合理和安全的,同时存在一些不合理用药现象,临床应提高认识、规范管理、合理用药。     

我院门诊抗组胺药的应用状况分析

目的了解基层医疗单位门诊抗组胺药的应用情况,为临床合理使用抗组胺药和药物供应管理提供科学依据。方法通过随机抽样查阅江苏省沛县疾病预防控制中心皮肤科2008年1至12月的过敏性皮肤病、瘙痒性皮肤病门诊处方3662份,根据《门诊病人基本情况调查表》内容逐项填写,汇总并进行统计分析。结果抗组胺药使用率偏高（79.93%）,主要应用的是第1代和第2代H1受体拮抗剂、部分H2受体拮抗剂和少数具有抗组胺作用的药物;存在同时使用1～3种抗组胺药,未能充分利用第2代抗组胺药的特点,抗组胺药选择缺乏针对性及部分药物使用剂量偏大、疗程较长,增强了治疗效果却忽略了药物毒副作用等问题。结论基层医疗单位皮肤科抗组胺药使用率偏高,存在一些不合理用药现象,临床应提高认识、规范管理、合理用药。     

皮肤病医院2010-2012年门诊药房抗组胺药物使用情况分析

目的 分析和了解2010至2012年间我院门诊药房抗组胺药物的使用情况及存在问题.方法 利用医院信息系统（HIS）,提取我院在2010至2012年门诊药房抗组胺药物的使用情况数据,包括药物名称、药品规格、使用量、销售量等.同时,结合皮肤科对门诊过敏性皮肤病、瘙痒性皮肤病所开具的处方3000份,并进行回顾性分析,评价抗组胺药物的使用情况.结果 门诊药房抗组胺药物的使用情况基本合理,部分处方中用法用量有不足之处,主要表现为剂量较大而且疗程较长,其中联合用药也有不合理之处,过分注重疗效而忽视了抗组胺药物的毒副作用.结论 门诊部门应加强对抗组胺药物的合理使用,降低药物的毒副作用,保证病人身体健康.     

我院皮肤科抗组胺药物的处方分析研究

<正> 抗组胺药物指能与内源性组胺竞争性的与组胺受体结合,从而拮抗组胺过分释放而产生各种病理效应(毛细血管扩张以及通透性增加、平滑肌痉挛、分泌粘液以及产生瘙痒感)的药物。虽然已发现存在四种组胺受体亚型,但目前应用于临床的药物只有受体1抑制剂和受体2抑制剂。对于皮肤科而言又以受体1抑制剂的为主,常用来治疗变态反应性皮肤病(如荨麻疹、湿疹等)和某些具有瘙痒症状的非变态性皮肤病(如瘙痒症等)。按照对中枢系统抑制作用的强弱,组胺受体1抑制剂又分为第一代和第二代。第一代药物,包括氯苯那敏、异丙嗪、多塞平,因为脂溶性强容易进入血脑屏障,且为非P-gp底     

2003～2007年我院组胺H1受体拮抗剂应用分析

目的：研究我院2003-2007年组胺H1受体拮抗剂的用药情况,了解组胺H1受体拮抗剂在我院临床治疗中的应用现状和发展趋势。方法：对我院2003-2007年组胺H1受体拮抗剂的用药品种、消耗金额、DDDs、DDDc等进行统计分析。结果：5年中,我院组胺H1受体拮抗剂的用药金额逐年上升,且第2代远远大于第1代。DDDs平均值排名前3位的是西替利嗪、氯雷他定、左西替利嗪,每年的平均DDDc值比较稳定。结论：安全、高效且与其他药物相互作用少的第2代组胺H1受体拮抗剂是抗过敏治疗的主导药物,传统组胺H1受体拮抗剂的改良剂型以及安全性更可靠的组胺H1受体拮抗剂是研究方向。     

抗高血压药物的临床应用调查与分析

目的调查分析我院门诊抗高血压药物的使用情况,为抗高血压药物在临床的合理使用提供依据。方法抽取我院2011年至2012年门诊抗高血处方3612张,应用Excel统计抗高血压药的处方数、药物种类、联合用药情况,并进行排序。结果门诊最常用的抗高血压药物是钙离子拮抗剂、血管紧张素Ⅱ受体拮抗剂和血管紧张素转换酶抑制剂,联用方式以二联用药为主,三联次之。结论我院抗血压药物的应用基本合理,符合目前高血压的治疗原则。     

2006年我院门诊第3季度皮肤病用药调查分析

目的:了解我院门诊皮肤病的常见病种及其用药情况。方法:运用医院药房计算机网络管理系统对部分皮肤病药物(口服抗组胺药、局部用药物)进行统计分析,抽取皮肤科处方对临床诊断及皮肤病用药进行分析。结果:处方平均金额74.46元,其中41.5%的处方金额在10元~50元之间,新型口服抗组胺药使用较多(销售金额占97.72%),局部用药物以品牌药居多且占据较大的金额比例(超过75%),近半数(48.8%)的患者因皮炎与湿疹及荨麻疹类皮肤病就诊。结论:我院门诊皮肤病用药基本合理。     

门诊患者组胺H1受体拮抗剂利用调查

目的:了解组胺H1受体拮抗剂的药物利用情况.方法:随机抽取我院2003年8月份10 475张门诊处方,采用限定日剂量(DDD)法,分析药物利用指数(DUI)和用药频度(DDDs).结果:使用组胺H1受体拮抗剂的处方有532张(4.90%),共有9种药物,大部分药物的DUI≤1,其中西替利嗪的用药频率最高,酮替芬次之.结论:我院H1受体拮抗剂的使用基本合理.     

H1受体拮抗剂门诊用药情况分析

目的探讨门诊H1受体拮抗剂的临床用药。方法调查并分析2005年8月～2007年7月每月1周门诊处方的H1受体桔抗剂使用情况。结果第2代H1受体桔抗剂中高效低毒药物应用最多，第3代H1受体桔抗剂应用呈上升趋势。结论高效、低毒、价廉的药物是医生、患者的首选。     

某院门诊口服抗糖尿病药物的使用分析

目的调查门诊糖尿病患者口服抗糖尿病药物的应用情况,分析其联合用药情况和处方习惯。方法随机抽取我院2013年4月至6月口服抗糖尿病药物的门诊处方,对口服抗糖尿病药物的品种、数量及其合理性进行分析,为临床合理应用提供参考。结果399张糖尿病患者门诊处方中,其中单用占78．9％,两联用药占18.3％,三联用药占2．5％;常用的口服抗糖尿病药物与促胰岛素分泌剂、双胍类、α-葡萄糖苷酶抑制剂和胰岛素增敏剂。结论依据各类口服抗糖尿病药物的作用机制和不同特点,我院口服抗糖尿病药物的应用是较合理的。     

Histamine and leukotriene receptor antagonism in the treatment of allergic rhinitis: an update

Allergic rhinitis represents a global health burden. The disease can seriously affect quality of life and is associated with multiple co-morbidities. Histamine and leukotrienes are important pro-inflammatory mediators in nasal allergic inflammation. Their actions on target cells are mediated through specific receptors and, consequently, molecules that block the binding of histamine and leukotrienes to their receptors have been important areas of pharmacological research. The published literature of the pathophysiology of histamine and leukotrienes, and the effects of histamine H(1)-receptor antagonists (H(1) antihistamines) and leukotriene antagonists in monotherapy or in combination therapy in the treatment of allergic rhinitis was reviewed. The presented results are based on the best available evidence. The efficacy of H(1) antihistamines and leukotriene antagonists (montelukast in particular) in allergic rhinitis has been established in numerous randomised placebo-controlled trials. Results from meta-analyses indicate that H(1) antihistamines and leukotriene antagonists are equally effective in improving symptoms of allergic rhinitis and quality of life, but that both drugs are less effective than intranasal corticosteroids. Data on the combination of H(1) antihistamines and leukotriene antagonists in allergic rhinitis are limited. The available evidence shows that a combined mediator inhibition has additional benefits over the use of each agent alone, but is still inferior to intranasal corticosteroids. More well designed studies are needed to fully understand the benefits of a concomitant use of these agents.     

Antimuscarinic effects of antihistamines: quantitative evaluation by receptor-binding assay

Quantitative evaluation of antimuscarinic effects of antihistamines (H1- and H2-receptor antagonists) was carried out using a receptor-binding assay. The -inhibition constants (Ki values) of twenty seven H1-receptor antagonists, one related antidepressant and three H2-receptor antagonists at H1-receptors and muscarinic receptors in the bovine cerebral cortex were determined. All the H2-receptor antagonists examined showed very low affinity for the muscarinic receptors. On the other hand, some H1-receptor antagonists (mequitazine, cyproheptazine, clemastine, diphenylpyraline, promethazine, homochlorcyclizine and alimemazine) had high affinity for the muscarinic receptors (Ki = 5.0-38 nM). Another group of H1-receptor antagonists (mepyramine, terfenadine, metapyrilen, azelastine, hydroxyzine and meclizine) had low affinity for the muscarinic receptors (Ki = 3,600-30,000 nM). Thus, a broad range of antimuscarinic potencies among the antihistamines was demonstrated. These results should provide helpful information with regard to the clinical and experimental use of antihistamines.     

Antipruritic activity of the kappa-opioid receptor agonist, TRK-820

The effects of the kappa-opioid receptor agonist, TRK-820, (-)-17-(cyclopropylmethyl)-3, 14beta-dihydroxy-4, 5alpha-epoxy-6beta-[N-methyl-trans-3-(3-furyl) acrylamido] morphinan hydrochloride, on the itch sensation were compared with those of histamine H1 receptor antagonists, using the mouse pruritogen-induced scratching model. Peroral administration of TRK-820 reduced the numbers of substance P- or histamine-induced scratches dose dependently. No obvious suppression of the spontaneous locomotor activity was observed at the doses used for the experiments, indicating that the inhibition of scratches was not due to the effect on general behavior. Furthermore, the scratching inhibitory activity of TRK-820 was dose dependently antagonized by the specific kappa-opioid receptor antagonist, nor-binaltorphimine, suggesting that the inhibitory activity was mediated via kappa-opioid receptors. Histamine H1 receptor antagonists, chlorpheniramine and ketotifen, did not inhibit substance P-induced scratches, or did so only partially. Both antihistamines inhibited the histamine-induced scratches completely. These results suggest that TRK-820 has antipruritic activity which is mediated by kappa-opioid receptors, and is effective in both antihistamine-sensitive and -resistant pruritus.     

Usefulness of HeLa cells to evaluate inverse agonistic activity of antihistamines

Antihistamines are thought to antagonize histamine and prevent it from binding to the histamine H₁ receptor (H1R). However, recent studies indicate that antihistamines are classified into two groups, i.e., inverse agonists and neutral antagonists on the basis of their ability to down-regulate the constitutive activity of H1R. As H1R is an allergy-sensitive gene whose expression influences the severity of allergic symptoms, inverse agonists should more potently alleviate allergic symptoms than neutral antagonists by inhibiting H1R constitutive activity. Therefore, it is important to assess inverse agonistic activity of antihistamines. Here we report a novel assay method using HeLa cells expressing H1R endogenously for evaluation of inverse agonistic activity of antihistamines. Pretreatment with inverse agonists down-regulated H1R gene expression below to its basal level. On the other hand, basal H1R mRNA expression was unchanged by neutral antagonist pretreatment. Both inverse agonists and neutral antagonists suppressed histamine-induced H1R mRNA elevation. Classification of antihistamines on the basis of their suppressive activity of basal H1R gene expression was consistent with that of inositol phosphate accumulation in H1R-overexpressed cells. Our data suggest that the assay method using HeLa cells is more convenient and useful than the existing methods and may contribute to develop new antihistamines with inverse agonistic activity.     

Rational use of antihistamines in allergic dermatological conditions

For many years, the use of antihistamines in dermatological conditions has been closely linked to the treatment of urticarias and to the symptomatic relief of pruritus. H1-receptor antagonists are the first-line drugs for urticarias. Those urticarias of type I immunological origin respond better than physical urticarias. H2-receptor antagonists may be added for refractory patients but are rarely effective alone. Conventional H1-blockers are frequently associated with somnolence and anticholinergic effects. Therefore, new antihistamines without depressive effects on the central nervous system have recently been introduced. In other pruritic conditions such as atopic dermatitis the limited effects of these drugs suggest that histamine is not the only mediator involved in pruritus. In these cases, their beneficial effects seem to be due mainly to their sedative properties; recently available nonsedative H1-blockers are less effective.     

Super-additive interaction of the reinforcing effects of cocaine and H1-antihistamines in rhesus monkeys

Histamine H1 receptor antagonists can be sedating and have behavioral effects, including reinforcing and discriminative stimulus effects in non-humans, that predict abuse liability. Previous research has suggested that antihistamines can enhance the effects of some drugs of abuse. We have reported a synergistic interaction between cocaine and diphenhydramine (DPH) in a self-administration assay with monkeys. The present study was designed to extend those findings to other combinations of cocaine and DPH, and to the mixture of cocaine and another H1-antihistamine, pyrilamine. Rhesus monkeys were prepared with chronic i.v. catheters and allowed to self-administer cocaine, DPH or pyrilamine alone or as mixtures under a progressive-ratio schedule of reinforcement. Cocaine, DPH and pyrilamine alone maintained self-administration and cocaine was the stronger reinforcer. When cocaine was combined with DPH or pyrilamine in a 1:1, 1:2 or 2:1 ratio of the ED₅₀s, the combinations were super-additive as reinforcers. Reinforcing strength of the combinations was greater than that of the antihistamines alone but not greater than cocaine. The data support the prediction that the combination of cocaine and histamine H1 receptor antagonists could have enhanced potential for abuse relative to either drug alone. The interaction may involve dopamine systems in the CNS.     

Anti-inflammatory activity of H1-receptor antagonists: review of recent experimental research

OBJECTIVE: To compare the anti-inflammatory effects of fexofenadine with other H(1)-receptor antagonists in vitro. DATA SOURCES: Published literature. STUDY SELECTION: Recent experimental studies on anti-inflammatory effects of H(1)-receptor antagonists. Databases searched: Medline, Medscape. Period covered: 1990-2003. Search terms: second-, third-generation antihistamines; sedating, nonsedating antihistamines; in vitro anti-inflammatory activity; cetirizine; ebastine; loratadine; fexofenadine; desloratadine. RESULTS: Second- and third-generation H(1)-receptor antagonists may demonstrate significant in vitro anti-inflammatory activity at concentrations considered to be clinically relevant. In some instances, higher (supraclinical) concentrations are required to achieve comparable effects. CONCLUSIONS: Experimental research suggests that second- and third-generation H(1)-receptor antagonists may achieve anti-inflammatory effects in a clinical context. Further studies are required to support this conclusion.     

Nonsedating histamine H1-receptor antagonists

The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosages of the nonsedating histamine H1-receptor antagonists terfenadine, astemizole, loratadine, and acrivastine are reviewed. Terfenadine and astemizole are chemically unrelated to histamine H1-receptor antagonists such as diphenhydramine and chlorpheniramine. Loratadine is structurally related to the antihistamine azatadine, and acrivastine is a side-chain-reduced metabolite of the antihistamine triprolidine. Like other histamine H1-receptor antagonists, they competitively block histamine receptor sites rather than inhibiting histamine release. All four drugs have relatively long half-lives and are rapidly absorbed after oral administration. Terfenadine, astemizole, and loratadine are metabolized extensively in the liver; terfenadine and astemizole are both 97% protein bound. Terfenadine 60 mg twice daily has been shown to be as effective as conventional antihistamines for the treatment of seasonal allergic rhinitis. In clinical trials, astemizole 10 mg daily was comparable to or better than chlorpheniramine for treatment of chronic rhinitis. Both terfenadine and astemizole were effective for treatment of chronic urticaria. For treatment of seasonal allergic rhinitis, loratadine combined with pseudoephedrine may be preferable to triprolidine-pseudoephedrine and acrivastine-pseudoephedrine combinations that require more frequent dosing. Acrivastine must be administered more frequently than the other nonsedating antihistamines. None of these four agents impairs psychomotor activity. Infrequently reported adverse effects include dry mouth, skin reactions, and weight gain. The absence of substantial sedative effects and the less-frequent dosing schedules make these agents good alternatives to the classic antihistamines for treatment of seasonal and chronic rhinitis and chronic urticaria.     

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.     

Emerging safety issues regarding long-term usage of H(1)receptor antagonists

The second generation histamine H(1)-receptor antagonists are important therapeutic tools in the treatment of atopic disease and may also have a place as an adjunct therapy for those patients whose allergic asthma coexists with allergic rhinitis. They are amongst the most widely prescribed and safest drugs in the world. However, as second generation H(1)-receptor antagonists are used to treat non-life threatening conditions, the risk of adverse effects is of vital importance. For many, the potential for sedation by some of the newer antihistamines still remains an issue, while there have recently been widespread concerns regarding the potential for cardiotoxicity and the impact of drug-drug interactions associated with some second generation H(1)-receptor antagonists. Consequently, progress with this class of drugs should involve not only increased efficacy but also improvements in their safety and specificity. Moreover, there is a trend towards using second generation H(1)-receptor antagonists as long-term therapy rather than confining their use to treating the short-term manifestations of allergic disease. To this end, a number of novel, potent and safe antihistamines have been developed which are either metabolites of active drugs or enantiomers. This review will examine some of the safety issues associated with established and newer second generation drugs particularly in relation to their long-term usage in adults and children.