1、Drugs for Respiratory System,GAO Fen-Fei,Introduction,Symptom of respiratory system:no sputum-antitussives Coughsputum - expectorantsAsthma - antiasthmatic drugs,支气管痉挛、 粘膜水肿,管腔狭窄,排痰困难,喘 息,阻塞细支气管,呼吸道积痰,刺激气管粘膜,继发感染、加重症状,咳 嗽,排 痰,呼气阻力增加,祛痰药,平喘药,镇咳药,ANTITUSSIVES,Classification: Central antitussives Depen
2、dent central antitussives Independent central antitussives Peripheral antitussives,Dependent Central Antitussives,Opioid alkaloids. Morphine is the most effective drug for the suppression of cough, but have addiction. Mechanism: suppressing of cough center,Codeine,Selectively suppress cough center i
3、n medulla oblongata(延髓). Potency: Suppression of cough: 1/10 of morphine Analgesia: 1/7 of morphine Respiratory depression, constipation, tolerance, dependence that of morphine,Pharmacokinetics: Well absorbed from oral and injection. 10% converted to morphine through demethyl. Clinical Uses: Dry cou
4、gh Adverse Reactions: Respiratory suppression in high dose; Tolerance and physical dependence with frequently repeated administration; Suppress secretion of bronchial gland and movement of cilia.,Independent Central Antitussives,Stereoisomers of opioid molecules that are devoid of analgesic effects
5、and addiction liability. Classification: -orphan(吗啡南类)-antitussives : dextromethorphan(右美沙芬) Amido(胺基)-antitussives: pentoxyverine(喷托维林;咳必清), clofedanol(氯苯达诺;敌退咳) piperidine(哌啶基)-antitussives: cloperastine(氯哌斯汀) morpholine(吗啉基)-antitussives: promolate(普罗吗酯), fominoben(福米诺苯); Others: eprazinone(依普拉酮)
6、, zipeprol(齐培丙醇).,Dextromethorphan,Dextrorotatory stereoisomers of a methylated derivative of levorphanol(羟甲左吗南).Clinical Use: Dry cough. Often + Antihistamine drug,Pentoxyverine,Suppression of cough: 1/3 of codeine. Direct suppression of cough center Atropine-like action and local anesthesia action
7、.,Cloperastine,Derivative of diphenhydramine(苯海拉明). Suppression of cough center Blocking H1-receptor,Peripheral Antitussives,Inhibiting receptor, afferent nerve, efferent nerve of cough reflex arc cough suppression. local anesthesia action: narcotine(那可丁), benzonatate(苯佐那酯); Alleviative action: extr
8、actum glycyrrhizae liquidum(甘草流浸膏), Syrup(糖浆),Expectorants,Mucokinetic drugs Classification: By the mechanism of action: Mucus secretagogue drugs: stimulating gastric mucosa reflex secretion of bronchial gland dilution of sputum. ammonium chloride. Mucolytic drugs: break acid mucin: bromhexine(溴己新;
9、必嗽平) drug-SH S-S of mucin Fragmentation: acetylcysteine(乙酰半胱氨酸) Enzymolysis: -chymotrypsin(糜蛋白酶) Surfactant: tyloxapol(泰洛沙泊)-Fog inhalation,By route of administration： Oral drugs: Fog inhalation drugs: 1.8%NaCl, 2%7.5%NaHCO3.,Asthma,Pathophysiology: Asthma is a disease characterized by airway inflam
10、mation and episodic(发作性的), reversible bronchospasm(支气管痉挛). Two characteristic features: Inflammatory changes in the airway; Bronchial hyperreactivity to stimuli. Important mediators: histamine, LTC4, LTD4, etc.,Antiasthmatic Drugs,Bronchodilators receptor agonists Theophylline Muscarinic antagonists
11、 Anti-inflammatory agents Steroids Anti-leukotriene agents Anti-allergic agents Stabilizer of inflammatory cell membrane H1 receptor blocker,Bronchodilators,Beta Adrenoceptor Agonists,Adrenaline: , agonist Ephedrine: , agonist Isoprenaline：1 ,2 agonist 2-selective agonists Salbutamol(沙丁胺醇，舒喘灵): Terb
12、utaline(特布他林，博利康尼) : Clenbuterol(克仑特罗): Formoterol(福莫特罗): Salmeterol(沙美特罗): Bambuterol(班布特罗):,Adverse Reactions of 2 agonists: Skeletal muscle tremor Cardiac effect: tachycardia(心悸亢进), arrhymias Metabolism disturbance: ketone bodies, acidosis, K+o,Theophylline,Methylxanthine derivatives. Mechanism o
13、f Action: Inhibit phosphdiesterase (PDE); Block adenosine receptors; Increase endogenous catecholamine (CA) releasing; Interfere with receptor-operated Ca2+ channels Ca2+i; Anti-inflammatory action,Clinical Use: Asthma: maintenance treatment Chronic obstructive pulmonary disease (COPD) Central sleep
14、 apnea (CSA) Adverse Reactions: Narrow margin of safety. Toxic effects are related to its plasma concentrations. Gastrointestinal distress, tremor, and insomnia. Cardiac arrhythmias, convulsions(惊厥) lethal.,Muscarinic Antagonists,There are M1, M2, M3 receptor subtype in the airway. Selectively block
15、ing M1, M3 receptor is resulted in bronchodilating effect. Ipratropium bromide binds to all M-R subtypes (M1, M2 and M3 ), and inhibits acetylcholine-mediated bronchospasm.,Anti-inflammatory Agents,Glucocorticoids (GCs),Mechanism of Action: Broad anti-inflammatory efficacy Block the synthesis of ara
16、chidonic acid(花生四烯酸) by phospholipase A2. Reduce bronchial reactivity. Increase the responsiveness of -adrenoceptors in the airway.,Routes of administration: Systemic administration: including oral and injection. More severe toxicity. Inhalation: Common inhalant GCs: FP, BDP, BUD, TAA, FNS,Anti-leuk
17、otriene agents,Cysteinyl leukotrienes is a important inflammatory mediator: Bronchoconstriction, increased bronchial reactivity, mucosal edema, mucus hypersecretion, etc. Leukotrienes resulte from the action of 5-lipoxygenase on arachidonic acid.,Common agents: zafirlukast and montelukast: LTD4-rece
18、ptor antagonists zileuton: 5-lipoxygenase inhibitor,Anti-allergic Agents,Madiators release inhibitors.No bronchodialator action but can prevent bronchoconstriction caused by a challenge with antigen to which the patient is allergic.,Disodium Cromoglycate (SCG),Mechanism of Action: Stabilizer of mass cell membrane: decrease the release of mediators from mast cells. Inhibit the function of sensory nerve ending and neurogenic inflammation in airway. Decrease bronchial hyperreactivity.,Ketotifen,H1 receptor blocker.Prevent and inverse down-regulation of 2-receptor.,
