2.3) Chronic Obstructive Pulmonary Disease (COPD).pptx

Bronchial Asthma.pptx Pharmacotherapeutics

1. C hronic O bstructive P ulmonary Disease Dr. SARITA SHARMA Associate Professor Department of Pharmacology MMCP (MMDU)

2. CONTENTS BACKGROUND Colds & Flu COPD 1) E tiology 2) Clinical presentations 3) Pathophysiology 4) Diagnosis 5) Management

3. The respiratory tract is divided into upper and lower parts: the upper respiratory tract consists of sinuses, middle ear, pharynx, epiglottis and larynx. The lower respiratory tract consists of below the larynx i.e., bronchi, bronchioles and alveoli. Respiratory tract infections are the most common group of infections seen in world wide.

4. Most of the infections are viral, for which only symptomatic treatment is available. Viral respiratory tract infections are usually mild and self-limiting, but influenza and severe acute respiratory syndrome (SARS) have resulted in serious consequences. Patients suffering from bacterial infections are treated with antibiotics. Oral Cephalosporins have better clinical efficacy than P enicillins in the treatment of streptococcal pharyngitis.

5. There is a controversy about otitis media, whether it should be treated with antibiotics. A meta analysis clinical trail have concluded that antibiotics reduces pain with in 2 – 7 days, but do not reduce the hearing problems and also cause side effects.

6. Colds and flu: Viral URTIs are extremely common. These infections are usually caused by rhinovirus, coronavirus, parainfluenza virus, syncytial virus, influenza virus and adenovirus. It includes the symptoms of rhinitis, pharyngitis and laryngitis. These type of respiratory illnesses are particularly seen in young children, elderly and immunocompromised people. The management of these infections is symptomatic and consists of rest, adequate hydration, analgesics and antipyretics.

7. Chronic obstructive pulmonary disease (COPD) and chronic obstructive airway disease (COAD) are commonly used clinical terms for various pathological conditions of respiratory system. Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation and is not fully reversible. The airflow limitation is usually progressive, associated with abnormal inflammatory response of the lungs to noxious (harmful or toxic) particles. E ntities included in COPD are Chronic bronchitis, Emphysema, Bronchiectasis and Small airways disease (bronchiolitis)

8. But the most common conditions comprising COPD are chronic bronchitis and emphysema. Chronic bronchitis is a disease associated with excess mucus secretion into the bronchial tree with persistent cough . Patient suffer with cough for 3 months in one year and is continued for at least 2 consecutive years. Emphysema is a disease characterised by abnormal and permanent enlargement of the airspaces of the terminal bronchioles, accompanied by destruction of walls without fibrosis.

9. E T I O L O G Y: Smoking:: The most common identified factor implicated to cause COPD is heavy smoking. Heavy cigarette smokers have 4 to 10 times greater tendency to develop COPD. Different actions of prolonged cigarette smoking on the lungs include: i ) Impairs ciliary movement. ii ) Inhibits the function of alveolar macrophages. iii) Hypertrophy and hyperplasia of mucus-secreting glands .

10. iv ) Obstruction of small airways. v ) Stimulation of vagus and causing bronchoconstriction . 2) Atmospheric pollution The incidence of COPD is higher in industrialised urban areas due to air pollution. Certain atmospheric pollutants that increase the risk of developing COPD include sulfur dioxide, nitrogen dioxide, particulate dust and toxic fumes . 3) Occupation::: Workers working in occupations like cotton mills ( byssinosis ), plastic factories etc. get exposed to different organic or inorganic dusts thereby increasing the risk to develop COPD.

11. 4) Infections Bacterial , viral and mycoplasmal infections do not initiate COPD but usually considered as secondary cause for COPD. Cigarette smoke predisposes to infections have a significant role to develop acute COPD exacerbations. C L I N I C A L P R E S E N T A T I O N S Initial symptoms of COPD include chronic cough and sputum production; patients suffer with cough & sputum production for several years. The physical examinations are normal till mild stage of COPD.

12. When airflow limitation becomes severe, patient suffer from cyanosis (Bluish discolouration of skin as seen in CO poisoning ) of mucosal membranes and develop “ barrel chest ” (partial enlargement of rib cage). Symptoms also include::: increased resting respiratory rate , shallow (Deep) breathing and pursing of the lips (contracting the lips in a round shape) during expiration. Patients with COPD exacerbation have fatigue, malaise, chest tightness, worsened dyspnea , decreased exercise tolerance, increase in sputum volume and increase in need of bronchodilators .

13. P A T H O P H Y S I O L O G Y : The most common etiology is exposure to tobacco smoke. O ther chronic inhalational exposures also lead to COPD. Inhalation of noxious particles stimulates the activation of neutrophils, macrophages, and CD8+ lymphocytes thereby releasing a variety of chemical mediators such as tumor necrosis factor α , interleukin 8 and leukotriene B4 . I nflammatory mediators cause widespread destructive changes in the airways , pulmonary vasculature and lung parenchyma.

14. Centrilobular emphysema is seen in heavy cigarette smokers affecting respiratory bronchioles. Panlobular emphysema is seen in AAT deficiency people affecting the alveolar ducts and sacs . In severe COPD , secondary pulmonary hypertension progresses to right sided heart failure ( cor pulmonale ). D I A G N O S I S The diagnosis of COPD depends on: Patient’s symptoms. History of exposure to etiological factors such as tobacco smoke and occupational exposures.

15. 1) PULMONARY FUNCTION TESTS Assessment of airflow limitation through spirometry is accepted world wide for diagnosing and monitoring COPD. The forced expiratory volume after 1 second ( FEV1) is reduced . The forced vital capacity ( FVC) may also be decreased . I f the reduction ratio of FEV1 : FVC is less than 70%, considered as hallmark for COPD.

16. If FEV1 is less than 80% after bronchodilator therapy, confirms the presence of airflow limitation that is not fully reversible. If FEV1 is less than 12 % after inhalation of rapid acting bronchodilators, become an evidence for irreversible airflow obstruction .

17. ARTERIAL BLOOD GASES : Significant changes in arterial blood gases are not usually present in COPD. Decrease in ABG levels may lead to hypoxemia and hypercapnia ( Increase in CO2 levels). Hypoxemia usually occurs initially during exercise and also develop at rest as the disease progresses . Hypoxemia also occur due to hypoventilation of lung tissue.

18. Patients with severe COPD have low arterial oxygen tension level i.e ., PaO2 45 to 50 mm Hg and elevated arterial carbon dioxide tension level i.e., PaCO2 50 to 60 mm Hg. If acute respiratory distress develops either due to pneumonia or due to COPD exacerbations, the PaCO2 level increases sharply resulting in an uncompensated respiratory acidosis.

19. T R E A T M E N T: The goals of therapy include R elieve symptoms Improve exercise tolerance I mprove overall health status Prevent disease progression P revent and Treat exacerbations P revent and Treat complications R educe morbidity and mortality

20. NON PHARMACOLOGIC THERAPY Smoking cessation is the most effective strategy that reduces the risk of developing COPD and also is the only intervention proved that decline FEV1 values . Pulmonary rehabilitation programs include smoking cessation , breathing exercises , supplemental oxygen, nutritional support and psycho educational care . Intramuscular influenza vaccine is recommended annually . Polyvalent pneumococcal vaccine is indicated for COPD patients at any age and revaccination is recommended for patients older than 65 years for every 5 years.

21. S Y M P A T H O M I M E T I C S β 2 Selective sympathomimetic drugs allow bronchial smooth muscles to get relaxed and dilated by stimulating adenyl cyclase enzyme thereby increasing the formation of cyclic adenosine monophosphate (cAMP). Administration via metered dose inhaler (MDI) or dry powder inhaler is as effective as nebulization therapy . It is usually preferred due to low cost and easily available . These dugs also improve muco ciliary clearance. SAI: Stimulation, Administration, Improve

22. ALBUTEROL AND TERBUTALINE are preferred short acting agents due to greater β 2 selectivity when compared to isoproterenol and isoetharine. The inhalation route is preferred in order to have better efficacy and less adverse effects . These drugs are used for acute relief of symptoms and the duration of action of short acting β 2 agonists is 4 to 6 hours.

23. FORMOTEROL AND SALMETEROL are long acting inhaled β 2 agonists given for every 12 hours on a scheduled basis that dilates bronchial smooth muscles. Formoterol and arformoterol are available in United States as nebulized solutions in 2007 . These drugs are given to those patients who frequently need short acting β 2 agonists . These drugs also decrease nocturnal symptoms, improve quality of life but are not indicated for acute relief of symptoms.

24. A N T I C H O L I N E R G I C S When given by inhalation , anticholinergic drugs dilates the bronchial smooth muscles by competitively inhibiting cholinergic receptors. These drugs also block various actions of acetylcholine.

25. IPRATROPIUM BROMIDE has slower onset of action but have prolonged bronchodilator effect when compared to short acting β 2 agonists. Its optimum effect seen within 1.5 to 2 hours and duration of action lasts for 4 to 6 hours. The recommended dose via MDI is two puffs four times in a day. It is also available as a solution for nebulization . Due to poor absorption : side effects include blurred vision , dry mouth , metallic taste, tachycardia and urinary retention.

26. TIOTROPIUM BROMIDE is a long acting agent act against cholinergic bronchoconstriction for more than 24 hours. Its onset of action is seen within 30 minutes with a optimum effect in 3 hours. The recommended dose is one capsule given once daily using HandiHaler inhalation device. As it acts locally, tiotropium bromide is well tolerated and the most common side effect is dry mouth.

27. N O T E : Combination of β 2 agonist and inhaled anticholinergic drugs are used to treat worsened symptoms of progressed disease. Combining bronchodilators with other drugs of different mechanisms of action have better efficacy at lower doses and also reduces adverse effects. Combination of both short and long acting β 2 agonists with ipratropium provide symptomatic relief and improve in pulmonary function. Combivent is a product containing albuterol and ipratropium, available as MDI to treat chronic COPD.

28. Antimicrobial Therapy Many COPD exacerbations occur due to viral or bacterial infections while 30 % of exacerbations occur with unknown factors. Antibiotics are commonly used and should be initiated if at least two of the following three symptoms are present: ( 1) Increased dyspnea ( 2) Increased sputum volume ( 3) Increased sputum purulence ( f luid component of inflammation….PUS)

29. Selection of antimicrobial drug depends on most likely causable organisms . The most common organisms for acute COPD exacerbation are Haemophilus influenzae , Haemophilus parainfluenzae and Streptococcus pneumonia. Antimicrobial treatment should be initiated within 24 hours of symptoms to prevent unnecessary hospitalization and is continued for at least 7 to 10 days .

30. In uncomplicated exacerbations , recommended therapy include M acrolide ( azithromycin , clarithromycin), S econd or third generation cephalosporin Doxycycline Trimethoprim sulfamethoxazole ( cotrimoxazole ) should not be used due to increasing pneumococcal resistance . Amoxicillin and first generation cephalosporins are not recommended due to β lactamase susceptibility. Erythromycin is not recommended due to insufficient activity against Haemophilus influenzae .

31. In case of complicated exacerbations like drug resistant pneumococci , such as β lactamase producing H. influenza: recommended therapy includes amoxicillin clavulanate or fluoroquinolone drugs such as levofloxacin, gemifloxacin , moxifloxacin .