Drugs used in pulmonary diseases LING ZHU

wheezing sputum (phlegm) inflammation Coughing wheezing sputum (phlegm) inflammation

Drugs used in pulmonary diseases Antitussives 镇咳药 Expectorants 祛痰药 Antiasthmatic drugs 平喘药

Anti-asthmatic drugs 平喘药 PÍng chuǎn yào

Asthma is a chronic inflammatory disorder of the airways General characteristics: increased tracheobronchial responsiveness to many stimuli ↓ physiological air passage narrowing this is called airway inflammation, or bronchoconstriction paroxysmal dyspnea, coughing, wheezing, chest tightness Asthma is a chronic inflammatory disorder of the airways within the lungs that affects over 17 million people in the United States. Description of Asthma The lung is the main organ of the respiratory system and its main function is respiration (exchange of gases between the environment and the body). Air enters the nose where it is filtered, warmed and humidified. After passing through the trachea (windpipe), the air travels into the lungs through the bronchi (a system of branching airway tubes that become smaller as they reach deeper into the lung). The smallest of the bronchi, the bronchioles, open into balloon-like sacs called alveoli. An asthma attack occurs when these airways narrow and the muscles around them tightly contract (this is called bronchospasm). The membranes lining the inner walls of the airways become swollen and inflamed, and the glands within these walls produce excess mucus. An asthma attack can be brief or it can last for several days. asthma attack

Allergic asthma

Stimulation-induced asthma

stabilized membrane--cromolyn Basic pharmacology stabilized membrane--cromolyn Antigenen muscle contraction vascular leakage Hyper-secretion edema Histamine SRS-A 5-HT muscle vascular mucus gland mast cells Trachea Bronchi Ach airway narrowing inflammation M-R antagonist exercises irritants dyspnea, coughing wheezing, chest tightness Theophylline Sympathomimetic agents Corticosteroids Leukotriene inhibitors

Treatment of Asthma The first step in asthma management is environmental control. Asthmatics cannot escape the environment, but through some changes, they can control its impact on their health. The second step is to monitor lung function. Asthmatics use a peak flow meter to gauge their lung function. Lung function decreases before the symptoms of an asthma attack - usually about two to three days prior. If the meter indicates the peak flow is down by 20 percent or more from your usual best effort, an asthma attack is on the way. The third step in managing asthma involves the use of medications. There are two major groups of medications used in controlling asthma - anti-inflammatories (corticosteroids) and bronchodilators.

Agents for asthma Relievers are medications used on an as-needed basis that act quickly to reverse broncho-constriction and relieve its symptoms. Controllers are medications taken daily on a long-term basis to keep asthma under clinical control chiefly through their antiinflammatory effects. Medications to treat asthma can be classified as controllers or relievers. Controllers are medications taken daily on a long-term basis to keep asthma under clinical control chiefly through their antiinflammatory effects. Relievers are medications used on an as-needed basis that act quickly to reverse bronchoconstriction and relieve its symptoms.

Agents for asthma Controller Reliever Long-acting β2-agonists Glucocorticosteroids Sablized membrane—cromolyn Leukotriene modifiers Lower dose of theophylline Anti-IgE Reliever Rapid-acting β2-agonists. Systemic glucocorticosteroids Theophylline M-R antagonist Medications to treat asthma can be classified as controllers or relievers. Controllers are medications taken daily on a long-term basis to keep asthma under clinical control chiefly through their antiinflammatory effects. Relievers are medications used on an as-needed basis that act quickly to reverse bronchoconstriction and relieve its symptoms.

Theophylline 茶 碱 Theophylline was first extracted from tea leaves

Theophylline 茶碱 Commonly used Theophylline---茶碱 Aminophylline----氨茶碱 Cholinophylline---胆茶碱 Diprophylline-----二羟丙茶碱 优喘平（优特舒、舒弗美）茶碱缓释片 迄今为止已知茶碱类药物及其衍生物有300多种。临床上较为常用的有氨茶碱、二羟丙茶碱、胆茶碱、茶碱乙醇胺和思普菲林等。 氨茶碱比茶碱水溶性高，易于溶解和吸收。但氨茶碱碱性较高，局部刺激性大，口服易致恶心、呕吐、食欲下降等胃肠道反应。肌注局部可有红肿疼痛等。 喘定（甘油茶碱，二羟丙茶碱）：是茶碱的中性制剂，pH值近中性，对胃肠道刺激小，主要用于口服给药。 胆茶碱：茶碱与胆碱的等分子化合物 。水溶性强，溶解度为氨茶碱的5倍。因此，胃肠吸收较快, 该药的胃肠刺激小，适宜口服 茶碱乙醇胺：为氨茶碱直肠栓剂，用于夜间哮喘，于睡前塞入肛门0．5克，可有效地预防夜间哮喘的发作。 思普菲林：是近年来发现的新一代衍生物。支气管扩张效应是氨茶碱的5倍以上，并无中枢系统、心血管系统兴奋的副作用。与茶碱相比，恩普菲林不增加胃的分泌，也无利尿作用，仅有轻微的恶心、头痛等副作用。 茶碱缓释剂：剂型有持续释放12小时和24小时两种。持续释放12小时的制剂，代表药是茶喘平，口服后在胃肠道中能逐渐、恒速地释放，对胃粘膜的刺激性较普通条碱制剂明显减低。由于茶喘平的疗效可靠、作用时间长和给药方便等优点，使之成为最常用的口服止喘药物。持续释放24／小时的制剂有Theo24、Ccniphlliue和DilatranceAP等。

Actions of theophylline smooth muscle relaxation high concentrations : phosphodiesterase inhibition ↓ intracellular cAMP↑ cardiac stimulation positive chronotropic theophylline is both a 1.competitive nonselective phosphodiesterase inhibitor, [11] which raises intracellular cAMP, activates PKA, inhibits TNF-alpha [12] [13] and inhibits leukotriene [14] synthesis, and reduces inflammation and innate immunity [14] 2.nonselective adenosine receptor antagonist [15], antagonizing A1, A2, and A3 receptors almost equally, which explains many of its cardiac effects

mechanisms of theophylline inhibition of adenosine cell surface receptors modulators of adenylyl cyclase activity isolated airway smooth muscle Adenosine contraction histamine release from lung cells Promote releaseing of Adr theophylline is both a competitive nonselective phosphodiesterase inhibitor, [11] which raises intracellular cAMP, activates PKA, inhibits TNF-alpha [12] [13] and inhibits leukotriene [14] synthesis, and reduces inflammation and innate immunity [14] nonselective adenosine receptor antagonist [15], antagonizing A1, A2, and A3 receptors almost equally, which explains many of its cardiac effects

Actions of theophylline 2. Anti-inflammatory action: low-dose theophylline: inhibit late response to antigenic challenge 3. Increase contraction of muscle

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Cardiovascular Effects Direct positive chronotropic Direct enhanced myocardial contractility Low doses: increased catecholamine release High doses: enhanced calcium influx

Renal Effects: Weak diuretics-- not therapeuticly important Increased glomerular filtration Reduced tubular sodium reabsorption

Multiple effects CNS stimulatory effect mainly on the medullary respiratory center. kidney weak diuretics cardiovascular positive chronotropic smooth muscle Dilation esp. bronchodilation Gastrointestinal Tract gastric acid & digestive enzymes↑ skeletal muscle enhanced contraction

theophylline: Clinical Use Effective bronchodilator Relieves airway obstruction in acute asthma Decreases frequency and severity of symptoms in chronic asthma Used in therapy for COPD

Theophylline Therapeutic/toxic effects: related to plasma concentration 5-20 mg/L ---improvement pulmonary function > 20 mg/L—nausea, vomiting, headache, anxiety, anorexia > 40 mg/L—seizures, arrhythmias

Sympathomimetic drugs 拟肾上腺素药

sympathomimetic drugs action ad use Side action Epineph-rine αβ Rapid potent Sc, inhale urgent Arrhyth-mias ephedrine Long duration Less potent Sc, po, im Pre treat-ment CNS excitation Isoprote-renol β inhale salbutamol terbutaline β2 Inhale, po, sc regular Muscle tremor Nervous

potency / long duration inhale / p.o regular treatment tremor 沙丁胺醇salbutamol 舒喘灵(宁) 喘乐宁 克仑特罗clenbuterol 克喘素 氨哮素 特布他林terbutaline 博利康尼 喘康速 福莫特罗formoterol 沙美特罗 salmeterol stimulate β2-R potency / long duration inhale / p.o regular treatment tremor 瘦肉精是一类药物，而不是一种特定的物质，是指能够促进瘦肉生长的饲料添加剂。任何能够促进瘦肉生长、抑制肥肉生长的物质都可以叫做“瘦肉精”。 有数种药物被称为瘦肉精，例如莱克多巴胺（Ractopamine）及克伦特罗（Clenbuterol）等

Muscarinic Antagonists

Muscarinic Antagonists Mechanism of Action: M- R: Contraction of airway smooth muscle Increased mucous secretion

Clinical Use— Antimuscarinic Drugs Effective bronchodilators Antimuscarinic drugs are only capable of preventing the cholinergic-mediated bronchospasm Preferred route of administration (enhanced organ selectivity): inhalation Antimuscarinic with limited systemic adverse effects: ipratropium bromide

Muscarinic Antagonists Ipratropium bromide 异丙托溴胺、异丙托品 Oxitropium 氧托溴胺、氧托品 Isopropylscopolamine 异丙东莨菪碱 Tiotropium 噻托溴胺、泰乌托品 可必特气雾剂： 异丙托品 + 沙丁胺醇

Sodium Cromoglycate 色甘酸钠 sè gān suān nà

Cromoglycate 色甘酸 ----action Inhibit: antigen- induced asthma exercise- induced asthma Reduce bronchial hyper-activity No direct effect on airway smooth muscle tone Will not reverse asthmatic bronchospasm 色甘酸钠（sodium cromoglicate， intal 咽泰）

Mechanism of Action Alters function of calcium → inhibits cell activation Airway nerves------cough Mast cells -------degranulation Eosinophils---------inflammatory

Cromoglycate ------------ Pharmacokinetics Poorly absorbed administered by microfine powder inhalation or aerosol -------- may cause throat irritation

Clinical Use 1. Pre-treatment for asthma: Reduces blocks bronchoconstriction antigen inhalation aspirin-induced blocks environmental agents Reduces bronchodilators medication requirements symptomatic severity

Clinical Use 2. Reducing symptoms allergic rhinitis

Cromoglycate ◆Adverse/Side effects: --------minor and localized throat irritation cough mouth dryness wheezing chest tightness

Corticosteroids Corticosteroid effects: Anti-inflammatory action Diminish bronchial reactivity Increase airway diameter Reduced frequency of asthma attacks Corticosteroids are given in two ways - inhaled via a metered dose inhaler (MDI) or orally via pill/tablet or liquid form. The inhaled corticosteroids include fluticasone (Flovent), budesonide (Pulmicort), flunisolide (AeroBid), triamcinolone (Azmacort) and beclomethasone (Beclovent and Vaceril). The oral corticosteroids (pill/tablet form) are prednisone (Deltasone, Meticorten or Paracort), methylprednisolone (Medrol) and prednisolone (Delta Cortef and Sterane). The oral corticosteroids (liquid form) are Pedipred and Prelone. These liquid forms are used for asthmatic children.

Mechanisms of action: corticosteroids Primary: anti-inflammatory action------ Inhibition of cytokine production Secondary: enhancement of beta-receptor agonist effects

Clinical Use: Corticosteroids Inhaled glucocorticosteroids are the most effective controller medications currently available Systemic glucocorticosteroids are important in the treatment of severe acute exacerbations

Leukotriene modifiers

Leukotriene Pathway Inhibitors Zeleuton arachidonic acid eosinophils, 5-lipoxygenase macrophages, mast cells basophils Leukotriene LTB4--chemattractant LTD4--bronchoconstriction LTC4 mucosal edema mucus hypersecretion bronchial reactivity↑ Anti-inflammatories reduce the number of inflammatory cells in the airways and prevent blood vessels from leaking fluid into the airway tissues. By reducing inflammation, they reduce the spontaneous spasm of the airway muscle. Anti-inflammatories are used as a preventive measure to lessen the risk of acute asthma attacks. Zafirlukast (Accolate) and zileuton (Zyflo), are a class of anti-inflammatories called leukotriene inhibitors. Taken orally, these drugs work by inhibiting leukotrienes (fatty acids that mediate inflammation) from binding to smooth muscle cells lining the airways. These drugs prevent rather than reduce symptoms and are intended for long-term use. Zafirlukast Montelukast

Other drug groups Calcium channel blockers Nitric oxide donors Potassium channel activators Anti-IgE monoclonal antibodies

Antitussives 镇咳药

Antitussives Central antitussives Peripheral antitussives Codeine 可待因 Dextromethorphan 右美沙酚 Benzonatate 苯佐那酯 Benproperin 苯丙哌林 Pentoxyverine 喷托维林（咳必清，维静宁） Noscapine 那可丁 Inhibit CNS Local anesthetics Clinical uses: cough without sputum

Expectorants 祛痰药

Expectorants Dilute sputum drugs Resolve sputum drugs Amine chloride 氯化铵 Glyceryl guaiacolate 愈创木酚甘油醚 （愈创甘油醚） Carbocisteine 溴己新（必嗽平、必消痰） Acety-cysteine 乙酰半胱氨酸 （痰易净、易咳净） Dilute ropy sputum Decompose glutinous protein in sputum Clinical uses: Cough with ropy sputum 祛痰是治疗咳嗽中最重要的对症措施之一，它不仅能间接起到镇咳、平喘的作用，有利于控制感染，而且能与病因的治疗相辅相成。祛痰药有两种： 　　一是恶心性祛痰药，常用的有氯化铵、桔梗、远志、愈创甘油醚。此类药能将黏稠的痰稀释，使之容易咳出，所以又可以减轻咳嗽。空腹服用效果明显，由于它剂量过大就可能会引起呕吐，因此临床较少单独应用此类祛痰药，一般多用其合剂。适用于急性呼吸道炎症时痰液黏稠不易咳出的病人。对于患有消化系统疾病，特别是患有胃溃疡病患者应慎用。 　　二是黏液溶解药：能使稠厚的痰液溶解，黏度降低而易于咯出。常用的有：（1）必嗽平（溴已新），临床适用于慢性支气管炎、肺气肿、矽肺等积有白色黏痰不易咳出者。（2）化痰片即强利痰灵片，适用于慢性支气管炎、支气管哮喘、支气管扩张、肺部感染、肺癌等呼吸道疾病引起的痰液黏稠。（3）沐舒坦，适用于急性及慢性支气管炎、支气管哮喘、肺气肿、成人呼吸窘迫症等。另外常用的还有甘草合剂，具有镇咳祛痰作用。适用于一般性咳嗽及上呼吸道感染、急性支气管炎初期的咳嗽。