Chronic Obstructive Pulmonary disease 2006/05/25

Transcription

1 Chronic Obstructive Pulmonary disease : 2006/05/25

2 Definition of COPD COPD is a disease state characterized by airflow limitation that is not fully reversible. The airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases GOLD

3 Asthma & COPD

4 Risk Factor for COPD Host factor Exposures Genes (eg( : alpha-1 antitrypsin deficiency) Airway hyperresponsiveness Lung growth Tobacco smoke Occupational Dusts And Chemicals Indoor and Outdoor Air pollution Infections Socioeconomic states

5 Diagnosis of COPD SYMPTOMS cough sputum dyspnea EXPOSURE TO RISK FACTORS tobacco occupation indoor/outdoor pollution SPIROMETRY

6 Spirometry Forced Vital Capacity (FVC) and Forced Expiratory Volume in one second (FEV1) Calculate the FEV1/FVC ratio. Appropriate normal values for the person's sex, age,and height. Normal adults: FEV1/FVC is between 70%-80% ; less than 70% indicates airflow limitation and the possibility of COPD

7 Stages of COPD

8 Goal of therapy Prevent disease progression Relieve symptoms Improve exercise tolerance Improve health status Prevent and treat complications Prevent and treat exacerbations Reduce mortality Prevent or minimize side effects from treatment

9 Management of COPD Assess and Monitor Disease Reduce Risk Factors Manage Stable COPD Manage Exacerbations

10 Management of COPD Mild to Moderate COPD (Stages I and II) Involves the avoidance of risk factors to prevent disease progression and pharmacotherapy as needed to control symptoms. Severe (Stage III) and very Severe ( (Stage IV) ) : Often require the integration of several different disciplines, a variety of treatment approaches, and a commitment of the clinician to the continued support of the patient as the illness progresses.

11 Assess and Monitor Disease-1 Initial Diagnosis : Chronic cough Chronic sputum Dyspnea history of exposure to risk factors Medical history : Asthma Allergy ;sinusitis or nasal polypus Respiratory infections in childhood Other respiratory diseases Physical Examination : Considerations in Performing Spirometry

12 Differential diagnosis of COPD Diagnosis COPD Asthma Suggestive Features Onset in mid-life Symptoms slowly progressive Long smoking history Dyspnea during exercise Largely irreversible airflow limitation Onset early in life (often childhood) Symptoms vary from day to day Symptoms at night/early morning Allergy,rhinitis,and/or eczema also present Family history of asthma largely reversible airflow limitation

13 Differential diagnosis of COPD Tuberculosis Bronchiectasis Congestive Heart Failure Onset all ages Chest X-rayX shows ling infiltrate or nodular lesions Microbiological confirmation.high local prevalence of tuberculosis Large volumes of purulent sputum Commonly associated with bacterial infection Coarse crackles/clubbing on auscultation Chest X-ray/CTX shows bronchial dilation,bronchial wall thickening Fine basilar crackies on auscultation Chest X-rayX shows dilated heart,pulmonary edema pulmonary function tests indicate volume restriction, not airflow limitation

14 Reduce risk factor-2 Smoking cessation is the single most effective and cost effective way in most people to reduce the risk of developing COPD and stop its progression.

15 Reduce risk factor-2

16 Manage Stable COPD-3 Patient education Pharmacologic therapy Bronchodilator Corticosteroids : FEV1<50% predicated and repeated exacerbations Vaccines : Influenza vaccines reduce serious illness and death in COPD patients by 50% Antibiotics : not recommended Mucolytic agents,water : not recommended Antitussives : contraindicated to regularly in stable COPD Respiratory stimulants agents : not recommended for regular use

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18 Bronchodilator

19 Bronchodilator Bronchodilator medications are central to symptom management in COPD Inhaled therapy is preferred The choice between ß2-agonist anticholinergic anticholinergic theophyllin combination therapy depends on availability and individual response in terms of symptom relief and side effects Bronchodilators are prescribed on an as-needed or on a regular basis to prevent or reduce symptoms Long-acting inhaled bronchodilators are more effective and convenient, but more expensive

20 Bronchodilator Combining bronchodilators may improve efficacy and decrease the risk of side effects compared to increasing the dose of a single bronchodilator The bronchodilating effect of short-acting inhaled anticholinergics lasts longer than that of short- acting β2-agonists, with some bronchodilator effect generally apparent up to 8 hours after administration Efficacy of theophylline in COPD were done with slow-release preparations. Theophylline is effective in COPD but, due to its potential toxicity, inhaled bronchodilators are preferred when available

21 2-agonists The principal action of agonists is to relax airway smooth muscle by stimulating 2-- adrenergic receptors, which increases cyclic AMP and produces functional antagonism to bronchoconstriction. Oral therapy is slower in onset and has more side effects than inhaled treatment.

22 2-agonists Adverse effects : resting sinus tachycardia (rare event with inhaled therapy) exaggerated somatic tremor hypokalemia ( especially when combined with thiazide diuretics and oxygen consumption )

23 2-agonists Short-acting Drug Fenoterol Trade name Berotec* Inhaler (μg) 200 (MDI) Solution for Nebulizer Oral Duration of action (hr) 4-6 Frandyl* 2.5 mg Salbutamol Buventol* Easyhaler Ventolin* 200 (DPI)( 5mg/2.5 ml 2mg 4-6 MDI = metered dose inhaler DPI = dry power inhaler

24 Fenoterol Fenoterol HBr 2.5mg Tab (Frandyl( Frandyl*) [B] Dosage: Adult : PO, mg tid Pediatric : PO, mg/kg/day 0.15mg/kg/day div. 3 dose or <1yr : PO, 1.25mg bid-tid 1-6yrs : PO, mg 2.5mg tid 6-14yrs : PO, 2.5mg tid P : Tab: 2.5mg(22062), Berotec MDI: 300puff/set(29073) ADR : tachycardia, nervousness, palpitations, muscle tremor

25 Salbutamol Ventolin* sulphate 2mg Tab [C] Dosage: Adult : PO, mg tid-qid qid,, Max. 32 mg/day Pediatric : 2-6yrs: 2 PO, 0.1 to 0.2 mg/kg/dose 3 times/day, Max. 12mg/day yrs: PO, 2 mg times/day, Max. 24 mg/day P : Tab: 2mg(22064), Combivent MDI: 200puff/B(29100), Nebuliser sol'n: 5mg/2.5mL(29086) ADR: Common : hypokalemia,, nausea, nervousness, palpitations, tachycardia, tremor Serious : erythema multiforme (in children), Stevens-Johnson syndrome

26 Salbutamol Ventolin* nebules 5mg/2.5mL Amp [C] Dosage: Adult : Asthma: nebulization,, 2.5 mg times daily Pediatric : Asthma: nebulization,, 0.63or1.25 mg 3-43 times daily P : Tab: 2mg(22064), Combivent MDI: 200puff/B(29100), Nebuliser soln: 5mg/2.5mL(29086) ADR: Common : hypokalemia, nausea, nervousness, palpitations, tachycardia, tremor Serious : erythema multiforme (in children), Stevens-Johnson syndrome NOTE : Nebulizer sol'n dilute with NS deliver over min

27 2-- --agonists Long-acting Drug Trade name Inhaler (μg) Solution for Nebulizer Oral Duration of action (hr) Formoterol Oxis* 9 (DPI)( 12+ Salmeterol Servent* 25 (MDI)( 12+ Bambuterol Baburol* 10mg 24 Procaterol Meptin* 25μg 8-12 Meptin* syrup 5μg/ml

28 Hexoprenaline Ipradol*: 5mcg/2ml Amp [B] Dosage: Acute asthma :1amp Severe Dyspnoea : 1.5amp-2amp(max.2mp) Status asthmaticus:1amp tid-qid /day Onset: 3 to 15 minutes Duration : 34 to 37 minutes (IV) Adverse Reactions: Arrhythmias, muscle tremor

29 Formoterol Oxis* Turbuhaler 9 mcg/dose, 60dose/B[C] Dosage: Adult : Inhalation, 9mcg qd-bid, Max. 36mcg/day Pediatric : Inhalation > 5 yrs: same as adult P : Oxis Turbuhaler: : 60dose/B(29093) ADR : Common : dizziness, headache, palpitations, restlessness, tremor NOTE : 1.Each metered dose of Oxis Turbuhaler (12mcg) correspond to 9mcg formoterol fumarate dihydrate from the mouthpiece of the inhaler. 2.Contraindications: significantly worsening or acutely deteriorating asthma

30 Salmeterol Serevent*Inhaler25mcg/puff 60puff/Bot [C] Dosage: Adult Inhalation, puffs bid Pediatric 4 4 yrs: Inhalation, 2 puffs bid P : Seretide Evohalar: : 120puff/B(29097), Serevent Inhaler: 60puff/B(29056) ADR: Common : dizziness, headache, tachycardia,tremor, throat irritation tion Serious : asthma-related death, worsening of asthma-related events in African Americans NOTE 1. Not be used to relieve symptoms of acute asthma 2. Not a substitute for oral or inhaled corticosteroids 3. Exercise-induced induced bronchospasm (EIB) - do not used salmeterol for 12 hr after initial dose; patients using salmeterol twice daily should not use salmeterol for EIB

31 Bambuterol Baburol* * 10mg Tab [B] Dosage: Adult : Asthma: 10-20mg qhs Dosing adjustments in hepatic impairment : NDA Dosing adjustments in renal impairment : NDA P : Tab: 10mg(22068) ADR: Tremor, headache, uneasiness NOTE : Prodrug of terbutaline

32 Procaterol Procaterol (MEPTIN*)- 25mcg tab [UK] Procaterol (MEPTIN*)- 5mcg/ml 60ml/B [UK] Dosage: Adult : Asthma: PO, mcg bid Pediatric : Asthma: PO, 25-50mcg 50mcg bid 0.5 ml/kg/day bid P : Tab: 25mcg(22065), Syrup: 60mL/Bot(28687) ADR : Tachycardia, arrhythmia (in higher dose), nervousness, headache, tremor

33 Drug Interaction Interaction with ß-22 agonists ß Blocker Propranolol has been associated with the exacerbation of asthmatic symptoms in known asthmatics Patients with asthma or chronic obstructive pulmonary disease may tolerate cardioselective beta blockers better than nonselective agents cardioselective beta blockers Acebutolol, Atenolol, Betaxolol, Bisoprolol

34 Drug Interaction MAO-I Interaction with ß-22 agonists Concurrent use of ß-2 Agonists and MAO-I I may result in an increased risk of tachycardia agitation or hypomania Digoxin Concurrent use of Albuterol and digoxin may result in an decreased digoxin serum level

35 Drug Interaction Interaction with ß-22 agonists Diuretics ECG changes and hypokalemia associated with diuretics may worsen with co administrate of Albuterol and Salmeterol

36 Anticholinergic

37 Anticholinergic bronchodilator effect : B.B.B. Onset Duration Tachyphylaxis Adverse effects : poorly absorbed dryness of the mouth

38 Anticholinergic

39 Anticholinergic Short-acting Drug Trade name Solution for Nebulizer Duration of action (hr) Ipratropium Ipratran* 0.5mg/2ml 6-8

40 Ipratropium Ipratran* nebuliser sol n n 0.5mg/2mLAmp[B] Dosage: Adult : 500mcg tid-qid qid,, Max. 2 mg/day Pediatric : mcg tid P : Combivent MDI: 200puff/B(29100), Nebuliser soln: 0.5mg/2mL(29077) ADR : Common : bitter taste, dry mouth, nasal congestion, nasal dryness Serious : hypersensitivity reactions (angioedema( angioedema, bronchospasm, urticaria,, anaphylaxis, oropharyngeal edema), paralytic ileus

41 Combination bronchodilator therapy Combining bronchodilators with different mechanisms and durations of action may increase the degree of bronchodilation for equivalent or lesser side effects. A combination of a short-acting β2-agonist and an anticholinergic produces greater and more sustained improvements in FEV1 than either drug alone and does not produce evidence of tachyphylaxis over 90 days of treatment.

42 Combination bronchodilator therapy C o m b in a tio n T h e r a p y in C O P D C O P D p a tie n ts fro m c e n te rs in 2 5 c o u n trie s, o f w h o m re c e iv e d tre a tm e n t L a n c e t ; :

43 Drug Salbutamol/ Ipratropium Formoterol/ Budesonide Salmeterol/ Fluticasone Combination therapy Combination short-acting β2-agonist plus anticholinergic in one inhaler Trade name Combivent* Combination long-acting β2-agonist plus glucocorticosteroids in one inhaler Symbicort* Seretide*125 Inhaler(μ g) 120/20(MDI) 4.5/160(DPI) 25/125(MDI) Duration of action (hr) 6-8

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45 Methylxanthines Controversy remains about the exact effects of xanthine derivatives. They may act as nonselective phosphodiesterase inhibitors but have also been reported to have a range of non-bronchodilator actions the significance of which is disputed Xanthine preparations are lacking in COPD. Changes in inspiratory muscle function have been reported in patients treated with theophylline but whether this reflects changes in dynamic lung volumes or a primary effect on the muscle is not clear Efficacy of theophylline in COPD were done with slow- release preparations Theophylline is effective in COPD but due to its potential toxicity inhaled bronchodilators are preferred when available

46 Methylxanthines Drug Trade name Oral (mg) Vial for injection (mg) Duration of action (hr) Aminophyllin Theophylline Aminophylline* Nosma*-SRMC mg/10ml Variable up to 24 Telin*-SR 200 Thoin*-SRMC 250 SR = sustained release SRMC= sustained release microsphere capsule

47 Aminophylline Aminophylline* * 250mg/10 ml [C] Dosage: For Acute bronchospasm Adult : slow IV (rate<20mg/min)ld6mg/kg (given over min) Pediatric : >6M slow IV (rate<20mg/min)ld1mg/kg (given over min) anhydrous theophylline aminophylline 78.9% Aminophylline sol'n n PH > 8 crystal IV adminstration is preferred for treatment of Acute bronchospasm

48 Aminophylline Aminophylline* * 100mg Dosage: For Acute bronchospasm Adult (smoker) :oral LD=7.5mg/kg,followed by 3.75mg/kg q4h*3 MD=3.75mg/kg q6h Adult (nonsmoker) :LD=7.5mg/kg,followed by 3.75mg/kg q6h*2 MD=3.75mg/kg q8h Pediatric(6M-9yrs) : oral LD=7.5mg/kg,followed by 5mg/kg q4h*3 MD=5mg/kg q6h Pediatric(9-16yrs):oral LD=7.5mg/kg,followed by 3.75mg/kg q4h*3 MD=3.75mg/kg q6h

49 Theophylline For Asthma & COPD Dosage: Adult & Pediatric (>6 M, asthma) initial 12mg/kg/day (or 400mg/day) div into 2 dose at 12hr may be increased by 2-3mg/kg/day2 at 3-day3 >16yrs Max : 13mg/kg/day or 900mg/day 12-16yrs 16yrs Max : 18mg/kg/day 9-12yrs Max : 20mg/kg/day 1-9yrs Max : 24mg/kg/day

50 Theophylline Agents that decrease theophylline levels Aminoglutethimide Barbiturates Charcoal Hydantoins 2 Ketoconazole Rifampin Smoking Sulfinpyrazone Sympathomimetics (β- agonist) Thioamines 3 Carbamazepine 1 Isonizide 1 Loop diuretic 1 1.May increase or decrease theophylline leveals 2.Decreased hydantoin leveals may also occur 3.Increase theophylline clearance in hyperthyroid patients

51 Theophylline Agents that increase theophylline levels Allopurinol Disulfiram Quinolones β-blockers(non- selective) Ca channal blockers Cimetidine Contraceptives,oral Corticosteroids Ephedrine Influenza virus vaccine Interferon Macrolides Mexiletine Thiabendazole Thyroid hormones 4 Carbamazepine 1 Isonizid 1 Loop diuretics 1 4. Decrease theophylline clearance in hypothyroid patient

52 Theophyllin level range Year adult <60yr adult 60-80yr adult >80yr pediatric Conc mcg/ml ml 8-15 mcg/ml ml 6-11 mcg/ml ml 6-11 mcg/ml ml

53 Manage Exacerbations-4 The most common causes of an exacerbation are infection of the tracheobronchial tree and air pollution but the cause of about one-third of severe exacerbations cannot be identified Inhaled bronchodilators (particularly inhaled ß2- agonists and/or anticholinergics) theophylline theophylline and systemic preferably oral glucocorticosteroids are effective treatments for exacerbations of COPD

54 Inhaled Glucocorticosteroids Drug Trade name Inhaler(μ g) Solution for Nebulizer Budesonide Dusma* 200(MDI) Pulmicort* terbuhaler 200(DPI) Pulmicort* Respules 1mg/2ml Fluticasone Flixotide* Evohaler 50(MDI)

55 Systemic Glucocorticosteroids Drug Trade name Oral Prednisolone Compesolone* 5mg Methyl-prednisolone Metisone* 4mg

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57 New Version of COPD guideline in Taiwan ( ) / Tiotropium bromide ( ( ) 18 (DPI)( (-) (-) (-) 24 Ipratropium bromide ( ) Oxitropium bromide ( ) Formoterol Salmeterol Fenoterol Salbutamol Terbutaline Fenoterol /Ipratropium/ Salbutamol/Ipratropium (MDI)( 100 (MDI)( (MDI( MDI DPI) 25-50( 50(MDI DPI) ( 200(MDI) 100, 200 (MDI( MDI DPI) 400,500 (DPI)( 200/80 (MDI)( 75/15 (MDI)( (-) 1.25/ (-) (-) 0.05% ( ( ) (-) (-) (-) 5 0.1, % ( ( ) 2.5, , *

58 New Version of COPD guideline in Taiwan Aminophylline Theophylline SR SR Beclomethasone Budesonide Fluticasone Triamcinolone Formoterol/Budesonide Salmeterol/Fluticasone Prednisolone Methyl-prednisolone ( ) (MDI( MDI DPI) 100, 200, 400 (DPI)( (MDI( MDI DPI) 100(MDI) 4.5/ /320(DPI) 50/100,250,500 (DPI)( 25/50,125, 250 (MDI) / , 0.25, ,8, *

59 Reference : 1. Applied Pharmcotherapy 2. CCIS 3. Drug Facts & Comparisons 4. Drug Information Handbook 5. Mary Anne Koda-Kimble,et Kimble,et al. Applied therapeutics : the clinical use of drugs.8 ed. Lippincott Williams & Wilkins,2005