呼吸照护药理学简介课件

1、呼吸照護藥理學簡介Introduction to RespiratoryCare Pharmacology 鍾飲文教授高雄醫學大學呼吸治療學系、胸腔內科07-3121101-5651.tw呼吸照護藥理學簡介 鍾飲文教授先行了解藥理學相關名稱和定義，以及美國和台灣藥物管理之發展其次了解藥物之命名、藥物資訊以及藥物的來源爾後了解到美國和台灣的藥物核准程序再了解如何開立處方最後了解呼吸治療藥理學之總結學習目標先行了解藥理學相關名稱和定義，以及美國和台灣藥物管理之發展學參考資料 Grade Nhire: Raus Respiratory Care Pharmacology. 7

2、th edition, 2008, Mosby 參考資料 Outline ()Pharmacology and the study of Drugs 藥理學和藥物之研究Naming Drugs 藥物之命名Sources of Drug Information 藥物資訊的來源Sources of Drugs 藥物的來源Process of Drug Approval in the United State 美國的藥物核准程序 Chemical identification 化學式確認 Animal studies 動物實驗 Investigational new drug approval 試驗

3、中新藥申請 New drug application 新藥申請 Food and Drug Administration new drug classification system FDA新藥分類系統 Orphan drugs 孤兒藥 Outline ()Pharmacology and thOutline ()The Prescription 處方 Over-the-counter drugs 店頭藥 (不需處方即可購買之藥) Generic substitution in prescriptions 學名藥取代Respiratory Care pharmacology : An Over

4、view 呼吸治療藥理學之總結 Aerosolized agents given by inhalation Related drug group in respiratory careOutline ()The Prescription 處方呼吸照护药理学简介课件Pharmacology and the Study of Drugs() 藥理學和藥物之研究Drugs(藥物) Chemicals(化學製品) 1.與有機體(organisms)作用，改變其功能 (functions)和過程(processes) 2.提供診斷、治療以及預防疾病的方法 ex：oxygen, alcohol, lys

5、ergic acid diethylamide(LSD), heparin, epinephrine,vitamins.Pharmacology and the Study of Pharmacology and the Study of Drugs() 藥理學和藥物之研究Pharmacology(藥理學)：藥物(化學製品)之研究 包括它們的來源(origin)，特性(properties) 及與生命體(living organisms)之交互作用(interaction)Respiratory care pharmacology：治療心肺及重症疾病之藥理學之應用Pharmacology an

6、d the Study of Pharmacology and the Study of Drugs()藥理學和藥物之研究 Pharmacology 1.Pharmacy(藥劑學)： 藥物的製備(preparation)和調劑(dispensing) 2.Pharmacognosy(生藥學)：天然物(包括：植物、動物等)之鑑別(identification)、萃取、活性成分確認、療效評估 3.Pharmacogenetics(藥物基因學)： 藥物療效與基因差異之關聯性研究 4.Therapeutics(治療學)： 為藥物治療疾病之藝術 5.Toxicology(毒物學)： 毒物及其藥理作用，含

7、解毒劑和毒性控制(poison control) 之研究Pharmacology and the Study of 美國藥物管理之發展The first Food and Drugs Act is passed by Congress;the United States Pharmacopeia (USP) and the National Formulary (NF) were given official status.The Harrison Narcotic Act is passed to control the importation, sale, and distribution

8、 of opium and its derivatives, as well as other narcotic analgesics.The Food, Drug, and Cosmetic Actbecomes law. This is the Federal Food, Drug, and Cosmetic Act to protect the pnblic health and protect physicians from irresponsible drug manufacturers.This act is enforced by the Food and Drug Admini

9、stration(FDA).The Durham-Humphrey Amendment defines the drugs that may sold by the pharmacist only on prescripition.The Kefauver-Harris Law is passed as an amendment to the Food, Drug, and Cosmetic Act of 1938.This act requires proof of safety and efficacy of all drugs introduced since 1938.Drugs in

10、 use before that time have not been reviewed but are under study.1971 The Controlled Subsances Act becomes effective;this act lists requirements for the control , sale, and dispensation of narcotics and dangerous drugs.Five schedules of controlled substances have been defined, Schedule I to Schedule

11、 V generally define drugs of decreasing potential for abuse, increasing medical use, and decreasing physical dependence.Examples of each schedule are as follows:Schedule : All nonresearch use isillegal ; examples: heroin, marijuana, LSD, peyote, and mescalineSchedule : No telephone prescriptions, no

12、 refills; examples: opium, morphine, certain barbiturates Schedule : Prescription must be rewritten after 6 months, or five refills; examples: certain opioid doses, glutethimide (Doriden), and some other barbituratesSchedule : Prescription must be rewritten after 6 months or five refills; penalties

13、for illegal possession differ from those for Schedule drugs; examples: phenobarbital, barbital, chloral hydrate, meprobamate (Equanil, Miltown), and zolpidem (Ambin)Schedule : As for any nonopioid prescription drug; examples: narcotics contanining nonnarcotics in mixture form, such as cough preparat

14、ions or Lomotil (diphenoxylate, narcotic with 2.5 mg and atropine sulfate,nonnarcotic).Raus Respiratory Care Pharmacology. 7th edition, 2008, Mosby美國藥物管理之發展The first Food and Dr1906 國會通過第一個藥物食品法;美國藥典及國家處方集取 得官方認可1914 通過Harrison麻醉藥品管理條例，對鴉片及其衍生物及 其他麻醉藥品之輸入、販售及配送進行管理1938 制定食品、藥品及化妝品法，也就是現行用以保障公共 衛生及醫師

15、免於不負責任的藥廠影響的聯邦法律，由藥 物食品局(FDA)執行1952 Durham-Humphrey修正案，規定藥物需有處方才得由 藥師販售 Kefauver-Harris法案修正1938年之食物、藥品及化妝 品法，本法案要求1938年後上市之藥品需有安全性及有 效性之證明，1938年之前之藥物雖然沒有重新檢討，但 仍需重新研究1971 管制藥品法生效，本法列出有關麻醉及危險藥品之管制、 販售及配送等措施。分為五等級，級數越高，其濫用之 可能性越低，醫療用途越高及成癮性越低美國藥物管理之發展1906 國會通過第一個藥物食品法;美國藥典及國家處方集取 第一級(schedule): 非研究用途皆

16、為非法，如heroin, marijuana, LSD, peyote&mescaline第二級(schedule): 不得以電話處方，非經診察不得單純領藥(refill)，如:opium, morphine, certain barbituates, amphetamines第三級(schedule): 處方在6個月後需重新開立，或只可單純領藥五次，如某些opioid doses，glutethimide(Doriden)，和某些barbituates第四級(schedule): 處方在6個月後需重新開立，或只可單純領藥五次，但非法擁有之處罰與第三級不同，如phenobarbital, ba

17、rbital, choral hydrate, meprobamate (Equanil, Miltown) 和zolpidem(Ambien)第五級(schedule): 非鴉片類藥物，如含有麻醉與非麻醉之混合藥物，例如:咳嗽藥或Lomotil (diphenoxylate, narcotic with 2.5mg and atropine sulfate, nonnarcotic)美國藥物管理之發展第一級(schedule):美國藥物管理之發展台灣藥政紀要1983優良藥品製造標準(GMP) 1985優良藥品調劑作業規範(GDP) 1988完成實施藥品GMP制度1990實施藥品再分類1993

18、藥事法公布施行1993新藥監視制度-要求執行國內臨床試驗1994藥事法施行細則公佈施行1995無菌製劑確效作業實施1996藥品優良臨床試驗規範(GCP)1998成立財團法人醫藥品查驗中心(CDE)1998藥品非臨床試驗優良操作規範(GLP)1998藥品非臨床試驗安全性規範1999管制藥品管理條例公佈施行1999建立全國藥物不良反應(ADR)通報系統1999推動醫療器材GMP1999修訂藥品優良製造規範(cGMP)2000罕見疾病防治及藥物法公布施行2000藥害救濟法公布施行2000醫療器材重新分類分級管理2001成立財團法人藥害救濟基金會(TDRF)2002啟動海外藥廠查核制度2003推動優良

19、調劑及給藥安全作業規範(GDDP)2004實施銜接性試驗評估2004藥事法修法台灣藥政紀要1983優良藥品製造標準(GMP) 1999推動管制藥品的分類在台灣管制藥品依行政院衛生署公告之管制藥品管理條例第三條之說明如下：管制藥品係指下列藥品： 一、成癮性麻醉藥品。 二、影響精神藥品。 三、其他認為有加強管理必要之藥品前項管制藥品限供醫藥及科學上之需用，依其習慣性、依賴性、濫用性及社會危害之程度，分四級管理。其分級及品項，由中央衛生主管機關設置管制藥品審議委員會審議後，報請行政院核定後公告之。案例：第一級管制藥品：Morphine、Heroin、Opium、Cocaine等。第二級管制藥品：Co

20、deine、Hydromorphine、Fentanyl、Pethidine、Methsdone 等。第三級管制藥品：Tramadol、Ketamine等第四級管制藥品：Diazepam、Estazolam等管制藥品的分類在台灣管制藥品依行政院衛生署公告之管制藥品管呼吸照护药理学简介课件Naming Drugs(藥物之命名)Chemical name(化學名)：藥物的化學結構Code name(編號名)：藥廠給予，可能成為藥物的試驗性化學品一個名稱Official name：正式名Generic name：學名Brand (trade)name：商標名Naming Drugs(藥物之命名)Ch

21、emical nGeneric Name(學名) 當化學產物有治療的效果，而藥廠想將之上市，美國命名協會(United States Adopted Name, USAN)給予這個化學物的名稱。與編號(採用數字)不同的是，學名是基於藥物的化學結構，如isoproterenol有isopropyl group連在胺基酸鏈的末端氮上(terminal nitrogen)與商標名(brand name)不同的是generic name是非專利名(nonproprietary)Generic Name(學名) 當化學Official Name(正式名) 當試驗藥品完全通過可做一般用途，且被收錄於美國藥

22、典-國家處方集(United States pharmacopeia-National Formulary)，學名就成為正式名，因為正式核可的藥品可能由很多藥廠以不同的名字在市場銷售，建議臨床醫師使用無專利性的正式名，而非商標名。Official Name(正式名) 當試驗藥品完全通過台灣藥典台灣並沒有如美國藥典之國家處方集收錄通過臨床驗的藥品。在台灣藥品一旦通過新藥上市申請衛生署會給予藥品許可證號，我們可以利用衛生署網頁上的【藥品醫材化妝品許可證號查詢】來確認。想要了解藥品相關的資訊可以查詢【MIMS台灣藥品手冊、MIMS簡明處方藥典、常用藥品手冊】等，這些收錄台灣上市藥品的藥品資料，不過內

23、容較為簡略。但若想要更清楚藥品完整的資料，就必須使用【各國的藥典】來查詢，或利用藥品資料整合軟體，如：Micromedex。台灣藥典台灣並沒有如美國藥典之國家處方集收錄通過臨床驗的藥品衛生署藥品醫材化妝品許可證號查詢衛生署藥品醫材化妝品許可證號查詢MIMS台灣藥品手冊、MIMS簡明處方藥典MIMS台灣藥品手冊、MIMS簡明處方藥典Trade Name, Brand name & proprietary name(商標名、專利名)特定藥廠給的名稱，如：Generic Name : albuterolTrade Name : Proventil(Schering-Plough) Ventolin(

24、Glaxo-Wellcome)Trade Name, Brand name & propExampleCode name : ICI 204, 219Chemical name : 4-(5-cyclopentyloxy-carbony- lamino-1-methy1-indal-3-ylmethyl)-3-methoxy- N-O-tolylsulfonylbenzamideOfficial name : ZafirlukastGeneric name : Zafirlukast Trade name : Accolate(Zeneca Pharmaceuticals)ExampleCod

25、e name : ICI 204, 21呼吸照护药理学简介课件Sources of Drugs(I)藥物的來源Cromolyn Sodium:khellin (prototype) Ammi Visnaga (muscle relaxant) (Eastern Mediterranean)Raus Respiratory Care Pharmacology. 7th edition, 2008, MosbySources of Drugs(I)藥物的來源CromoCurare 劍毒: vine (South American Indians)Curare 劍毒: vine (South Ame

26、ricaDigitalis 毛地黃: foxglove (Digitalis purpurea) - MayansRaus Respiratory Care Pharmacology. 7th edition, 2008, MosbyDigitalis 毛地黃: foxglove (DigitOpium alkaloids 鴉片鹼: poppy seedOpium alkaloids 鴉片鹼: poppy seeSources of Drugs ()藥物的來源Animal:Thyroid hormone,insulin,pancreatic dornasePlant : khellin (Am

27、mi visnaga), atropine(belladonna alkaloid), digitalis(foxglove), reserpine(Rauwolfia serpentine), volatile oil of eucalyptus, pine, aniseMineral : Copper sulfate, magnesium sulfate(epsom salts), mineral oil (liquid bydrocarbons)Sources of Drugs ()藥物的來源Ani呼吸照护药理学简介课件Process of Drug Approval in The Un

28、ited States(美國的藥物核准程序)()1.Length : 13-15 y/o (chemical synthesis marketing approval by FDA, in 1980s)2.Cost : $350 million $500million (含失敗的例子，成功率1/1000)Process of Drug Approval in TMajor Steps in the Process of Marketing a drug in the United StatesIsolation and Identification of the Chemical Animal

29、 studies General effects Special effects on organ systems Toxicology studiesInvestigational New Drug (IND) Phase 1 studies: Small number, healthy subjects Phase 2 studies: Small number, subjects with disease Phase 3 studies: Large, multicenter studiesNew Drug Application(NDA) Reporting system for fi

30、rst 6 monthsProcess of Drug Approral in The United States(美國的藥物核准程序)()Major Steps in the Process of Chemical IdentificationIdentify a chemical with the potential for useful physiological effectsEx: Paclitaxel (Taxol): needles and bark of the western yew treeRaus Respiratory Care Pharmacology. 7th ed

31、ition, 2008, MosbyChemical IdentificationIdentifAnimal Studies動物實驗1.General effect on -Organisms -Specific organs: liver, kidneys2.Toxicology study -mutagenicity -teratogenicity -effect on reproductive fertility -carcinogenicityAnimal Studies動物實驗1.General eInvestigational New Drug Approval1.化學物經動物實驗

32、後，向FDA申請為Investigational New Drug(IND)試驗性新藥2.進行人體試驗分三步驟，三年內完成 Phase 1 : small group of healthy volunteers, establish its activity (pharmacokinetic description:rates of absorption,distribution, metabolism, elimination) Phase 2 : treatment for a small number of individuals with disease Phase 3 : large

33、, multicenter studies, establish safety & efficacyInvestigational New Drug ApproNew Drug Application 新藥申請1.IND完成後，向FDA申請為新藥new drug application(NDA)，核可後即可在一般臨床使用2.追踪6個月，注意是否有問題發生3.如無，則醫生可列為處方，用以治療病人New Drug Application 新藥申請1.INThe Thalidomide Story沙利竇邁的故事1.1950年thalidomide以安眠藥(hypnotic agent, sleepi

34、ng aid)在美上市2.懷孕婦女服用後，生下小孩產生畸形，海豹肢症(phocomelia, limb truncation)3.現在用來治Leprosy(痲瘋)，也可用來改善TB及AIDS體重減輕的症狀，同時也可減緩HIV病毒複製的速度4.Thalidomide是免疫調節劑(immunomodulatory agent)，可減少腫瘤坯死因子(tumor necrosis factor- ,TNF- )的產生，而TNF-可引起組織消蝕(tissue wasting)，發燒(fever)及夜間盜汗(night sweats)The Thalidomide Story沙利竇邁的故事1Food an

35、d Drug Administration New Drug Classification System (FDA新藥分類系統)Chemical/pharmaceutical standing1=New chemical entity2=New salt form 3=New dosage form4=New combination5=Generic drug6=New indicationTherapeutic potential A=Important (significant) therapeutic gain over other drugsAA=Important therapeut

36、ic gain, indicated for a patient with acquired immunodeficiency syndrome (AIDS);fast-trackB=Modest therapeutic gain C=Important options; little or no therapeutic gainFood and Drug Administration NOrphan Drugs (孤兒藥)治療罕見疾病之藥罕見：(U.S.A.) a. 少於二十萬人或發生率萬分之五，但不預 期可回收藥物開發之成本Orphan Drugs (孤兒藥)治療罕見疾病之藥Example

37、s of orphan drugs of interest to respiratory care clinicians showing either a proposed use or an approved use*by the food and Drug AdministrationDRUGAcetylcysteine 1 Proteinase inhibitor (Prolastin)*Beractant (Survanta)*Colfosceril palmitate(Exosurf Neonatal)*Cystic fibrosis transmembrane conductanc

38、e regulatorDornase alfa(Pulmozyme)*Nitric oxide (INOmax)Tobramycin by inhalation (TOBI)*PROPOSED USEIV for moderate to severe acetaminophen overdoseReplacement therapy in the 1- proteinase inhibitor congenital defectPrevention or treatment of RDS in the newbornPrevention or treatment of RDS in the n

39、ewbornTreatment of cystic fibrosisReduce mucus viscosity and increase airway secretion clearance in cystic fibrosisTreatment of persistent pulmonary hypertension of the newborn, or acute respiratory distress in adultsTreatment of Pseudomonas aeruginosa in cystic in cystic fibrosis or bronchiectasisE

40、xamples of orphan drugs of in台灣新藥研究發展與核准上市過程(與美國差不多)1.經由實驗室之研究，汰選找出具有發展潛力之新化學物質(NEC;New Chemical Entity)，進行化學、物理性質之分析研究，主成分安定性試驗，分析方法之確認。2.進行動物之藥理試驗，包括動物體內及動物體外試驗。3.進行動物毒性及安全性試驗。4.進行處方研究和劑型設計。5.申請進入人體臨床試驗階段(IND;Investigational New Drug)。6.人體臨床試驗階段。7.申請新藥上市許可(NDA;New Drug Application)。8.列入新藥監視(PMS;Po

41、st Marketing Surveillance)。台灣新藥研究發展與核准上市過程(與美國差不多)1.經由實驗呼吸照护药理学简介课件The prescription(處方)處方係指藥物之開立，及關於調劑和服用方式之特別指示醫師(physician)，整骨師(osteopath)，牙醫師(dentist)，獸醫(veterinarian)可開處方，脊椎指壓治療師(chiropractors)及驗光師(opticians)則不可開。醫方可以英文或拉丁文開立，單位用公制(metric)或藥局衡量法(apothecary measures)美國1971年管制藥品法(controlled Substa

42、nces Act)通過後，開立麻醉藥(narcotics)或管制藥品，則需附緝毒局(Drug Enforcement Administration, DEA)提供之註冊號碼(registration number)The prescription(處方)處方係指藥物之開立，Raus Respiratory Care Pharmacology. 7th edition, 2008, MosbyRaus Respiratory Care Pharmac1.病人姓名、住址、開立日期2.R:表示處方(recipe)，即指示藥師去調劑或準備以下的藥品，這是所謂的標題(Superscription)3.處

43、方本文(inscription):開立的藥物名稱(name)及數量(quantity)4.下題辭(subscription):指示藥師如何準備藥物(directions on preparing medication)，例如製成藥膏，則寫成“ft ungt” make an ointment5.sig(signa)表示“write”此transcription或signature表示藥師在藥袋上對指示用藥方法的標示6.開立處方者(name of the prescriber)，此處為開立醫師簽名處，但注意的是上面第5點之signature 表示對患者用藥之指示，而非醫師簽名1.病人姓名、住址、

44、開立日期Abbreviations and Symbols Used in Prescriptions(處方之縮寫及代號) (I)Abbreviations and symbols used in prescriptionsABBREVIATION MEANINGaa of each ac before a mealad lib as much as desiredalt hor every other houraq dest distilled waterbid twice dailyC, cong gallonc with cap capsulecc cubic centimeterdil

45、 dilutedtd give such doseselix elixiremuls emulsionet andex aq in waterext extractfld fluidft makeG gramABBREVIATION MEANINGGelg gramgr graingtt a drophs at bedtimeIM intramuscularIV intravenousL literlin a linimentliq liquid, solutionlot lotionM mixmist, mixt mixtureml milliliternebul a spraynon re

46、p not to be repeatednpo nothing by moutho,o pintOD right eyeol oil Abbreviations and Symbols UsedAbbreviations and Symbols Used in Prescriptions(處方之縮寫及代號) () Abbreviations and symbols used in prescriptionsABBREVIATION MEANINGOS left eyeOU both eyesp afterpart aeq equal partspc after mealspil pillpla

47、cebo I please(inert substitute)po pillprn as neededpr rectallypulv popowderq everyqh every hourqid four times dailyqod every other dayqd every dayq2h every 2 hoursq3h every 3 hoursq4h every 4 hoursABBREVIATION MEANINGqs as much as required(quantity sufficient)qt quantRx, R takes wuthoutsig wirtesol

48、solutionsolv dissolvesos if needed (for one time)spt spiritsp frumenti whiskeyss halfstat immediatelysyr syruptab tablet or tabletstid three times dailytr, tinct tinctureung ointment ut dict as directedvin wineAbbreviations and Symbols UsedOver-The-Counter DrugsOTC:不需處方即可購買之藥Asthmallaler Mist, Medih

49、aler-Epi,Primatent MistRaus Respiratory Care Pharmacology. 7th edition, 2008, MosbyOver-The-Counter DrugsOTC:不需處方Viagra OnlineViagra OnlineGeneric substitation in prescription 允許藥師調劑時，得以相同之學名藥(generic)取代商標名(brand)，因為學名藥沒有負擔原廠開發的成本，較為便宜，可為病人節省金錢Generic substitation in prescr呼吸照护药理学简介课件Respiratory Car

50、e Pharmacology：An Overview(呼吸治療藥理學之總結) 不只牽涉肺部，而且與心臟、血管有關，故牽涉之藥物範圍相當廣泛Respiratory Care Pharmacology：Aerosolized Agents Given by Inhalation(吸入治療之噴霧藥劑)優點： 1.藥量比全身給藥低 2.比口服或靜脈給藥副作用少及輕 3.作用速度(onset of action)較快 4.藥物分布以呼吸道為主，較少全身性生 體活性(systemic bioavailabity) 5.無痛，相對安全且使用方便Aerosolized Agents Given by InAe

51、rosolized Agents(噴霧藥劑) (I)DRUG GROUP THERRAPEUTIC AGENTSAdrenergic agents adrenergic: Relaxation of bronchial smooth muscle and bronchodilation, to reduce Raw and improve ventilatory flow rates in airway obstruction such as COPD, asthma, CF, acute bronchitis. Adrenergic:E.g., epinephrine: topical va

52、soconstriction and decongestion.EpinephrineIsoproterenolIsoetharineTerbutalineMetaproterenolAlbuterolPirbutterolBitolterolLevalbuterolSalmeterolFormoterolAnticholinergic agentsRelaxation of cholinergic-induced bronchoconstriction to improve ventilatory flow rates in COPD and asthma. Ipratropium bromideMucoactive agentsModification of the pro