Pharmacotherapy of pulmonary disease Pneumonia is acute inflammation of the lungs caused by infection An estimated 2 to 3 million people in the US develop pneumonia each year, of whom about 45,000 die. Pneumonia is the most common fatal hospital-acquired infection and the most common overall cause of death in developing countries.

Classification of pneumonia

Hospital-acquired pneumonia (HAP) develops at least 48 h after hospital admission. HAP includes ventilator-associated pneumonia (VAP) postoperative pneumonia pneumonia that develops in unventilated but otherwise moderately or critically ill hospitalized inpatientsIt new category healthcare-associated pneumonia (HCAP), which refers to pneumonia acquired by patients in healthcare facilities such as chronic care facilities, dialysis centers, and infusion centers

Etiology The most common cause is microaspiration of bacteria that colonize the oropharynx and upper airways in seriously ill patients. The most important pathogen is Pseudomonas aeruginosa, which is especially common in pneumonias acquired in intensive care settings and in patients with cystic fibrosis, neutropenia, advanced AIDS, and bronchiectasis. Other important pathogens are gram-negative bacteria (Enterobacter sp, Klebsiella pneumoniae, Escherichia coli, Serratia marcescens, Proteus sp, Acinetobacter) and both methicillin- sensitive and methicillin-resistant Staphylococcus aureus. S. aureus, Streptococcus pneumoniae, and Haemophilus influenzae are most commonly implicated when pneumonia develops within 4 to 7 days of hospitalization High-dose corticosteroids increase the risk of Legionella and Pseudomonas infections.

Risk factors of HAP Endotracheal intubation with mechanical ventilation poses the greatest overall risk. Endotracheal intubation breaches airway defenses, impairs cough and mucociliary clearance, and facilitates microaspiration of bacteria-laden secretions that pool above the inflated endotracheal tube cuff. In nonintubated patients, risk factors include previous antibiotic treatment, high gastric pH (due to stress ulcer prophylaxis or therapy), and coexisting cardiac, pulmonary, hepatic, or renal insufficiency. Major risk factors for postoperative pneumonia are age > 70, abdominal or thoracic surgery, and dependent functional status.

Symptoms and Signs in nonintubated patients are generally the same as those for community-acquired pneumonia: Malaise Cough typically is productive in adults and dry in the elderly Dyspnea usually is mild and exertional and is rarely present at rest Chest pain is pleuritic and is adjacent to the infected area Pneumonia may manifest as upper abdominal pain when lower lobe infection irritates the diaphragm.

Symptoms and Signs also include fever ( may be frequently absent in the elderly ), tachypnea, tachycardia, bronchial breath sounds, egophony, and dullness to percussion. Signs of pleural effusion may also be present Pneumonia in critically ill, mechanically ventilated patients more typically causes fever and increased respiratory rate or heart rate or changes in respiratory parameters, such as an increase in purulent secretions or worsening hypoxemia.

Pharmacotherapy Treatment may begin with initial use of broad-spectrum drugs, which are replaced by the most specific drug available for the pathogens identified by culture. Multiple regimens exist, but all should include antibiotics that are effective against both resistant gram-negative and gram-positive organisms Antibiotics Carbapenem Imipenem/cilastatin 500 mg IV q 6 h or 1 g q 8 h Meropenem 1 g IV q 8 h Monobactam Aztreonam 1 to 2 g IV q 8 h Piperacillin/tazobactam 4.5 g q 6 h

Antibiotics Cephalosporines Ceftazidime 2 g IV q 8 h Cefepime 1 to 2 g q 8 to 12 h These drugs are given alone or combined with vancomycin 15 mg/kg q 12 h Linezolid 600 mg IV q 12 h may be used for some pulmonary infections involving methicillin-resistant S. aureus.

Bronchitis is characterized by inflammation of the bronchial tubes (or bronchi), the air passages that extend from the trachea into the small airways and alveoli Acute bronchitis is inflammation of the upper airways, commonly following a URI Chronic bronchitis is defined clinically as cough with sputum expectoration for at least 3 months a year during a period of 2 consecutive years.

Etiology Acute bronchitis is frequently a component of a URI caused by rhinovirus, parainfluenza, influenza A or B, respiratory syncytial virus, coronavirus, or human metapneumovirus. Less common causes may be Mycoplasma pneumoniae, Bordetella pertussis,Chlamydia pneumoniae, Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae Cigarette smoking is indisputably the predominant cause of chronic bronchitis. Common risk factors for acute exacerbations of chronic bronchitis are advanced age and low forced expiratory volume in one second

Symptoms and Signs of acute bronchitis Cough generally lasts from days Sputum production is reported in half the patients, it is may be clear, yellow, green, purulent (50%) or even blood-tinged Fever is a relatively unusual sign and, when accompanied by cough, suggests either influenza or pneumonia Severe cases may cause general malaise and chest pain With severe tracheal involvement, symptoms include burning, substernal chest pain associated with respiration, and coughing. Other symptoms are following: Sore throat, Runny or stuffy nose, Headache, Muscle aches

Symptoms and Signs of chronic bronchitis When a stable patient experiences sudden clinical deterioration with increased sputum volume, sputum purulence, and/or worsening of shortness of breath, this is referred to as an exacerbation of chronic bronchitis, as long as conditions other than acute tracheobronchitis are ruled out

Treatment of acute bronchaitis Symptom relief (acetaminophen, hydration, possibly antitussives) Inhaled β-agonist or anticholinergic for wheezing Sometimes oral antibiotics for patients with COPD Antitussives should be used only if the cough is interfering with sleep Dextromethorphan use as tablet or syrup at a dose of 15 to 30 mg po 1 to 4 times/day Codeine 10 to 20 mg po q 4 to 6 h Benzonatate 100 to 200 mg po tid

Expectorants Guaifenesin 200 to 400 mg po q 4 h in syrup or tablet form Multiple expectorants bromhexine, ipecac, and saturated solution of K iodide (SSKI) Aerosolized expectorants such as N-acetylcysteine are generally reserved for hospital-based treatment of cough in patients with bronchiectasis or cystic fibrosis Topical treatments such as acacia, licorice, glycerin, honey, and wild cherry cough drops or syrups (demulcents), are locally and perhaps emotionally soothing, but their use is not supported by scientific evidence.

beta2-agonist bronchodilators may be useful in patients who have associated wheezing with cough and underlying lung disease (albuterol) or an anticholinergic (ipratropium) for ≤ 7 days Oral antibiotics are typically not used except in patients with pertussis or in patients with COPD who have at least 2 of the following: Increased cough Increased dyspnea Increase in sputum purulence

Oral antibiotocs for pharmaconherapy of acute bronchitis amoxicillin 500 mg po tid for 7 days doxycycline 100 mg po bid for 7 days azithromycin 500 mg po once/day for 4 days, trimethoprim/sulfamethoxazole 160/800 mg po bid for 7 days influenza vaccine may reduce the incidence of upper respiratory tract infections and, subsequently, reduce the incidence of acute bacterial bronchitis.

Pharmaconherapy of chronic bronchitis For patients with an acute exacerbation of chronic bronchitis, therapy with short-acting B-agonists (Albuterol, Metaproterenol sulfate, Salmrterol, Formoterol) or anticholinergic bronchodilators (Ipratropium, Tiotropium) should be administered during the acute exacerbation In addition, a short course of systemic corticosteroid (Fluticasone, Beclomethasone) therapy may be given and has been proven to be effective

Pharmaconherapy of chronic bronchitis Antibiotics, are recommended in patients older than 65 years with acute cough if they have had a hospitalization in the past year, have diabetes mellitus or congestive heart failure, or are on steroids Amoxicillin and clavulanate is a good alternative antibiotic for patients allergic to or intolerant of the macrolide class Eryhtromicin, Azithtromicyn is indicated for staphylococcal, streptococcal, chlamydial, and mycoplasmal infections. Azithromycin treats mild-to- moderate microbial infections. Tetracycline is less effective than erythromycin. Cefditoren (400-mg daily) is indicated for acute exacerbation of chronic bronchitis caused by susceptible strains of S pyogenes