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CHRONIC OBSTRUCTIVE PULMONARY DISEASE • • • • • • • • • • • • • • • • • • • • • Chronic obstructive pulmonary disease (COPD) is defined as a disease state characterized by airflow limitation that is not fully reversible COPD includes emphysema- an anatomically defined condition characterized by destruction and enlargement of lung alveoli and chronic bronchitis- a clinically defined condition with chronic cough and phlegm CLINICAL SIGNS CRITERIA FOR SEVERITY OF AIRFLOW OBSTRUCTION IN COPD: Patient Group A, Low Risk, Less Symptoms: GOLD 1 or GOLD 2 and/or 0-1 exacerbation per year and No hospitalization for exacerbation; and CAT score < 10 or mMRC grade 0-1 Patient Group B, Low Risk, More Symptoms: GOLD 1 or GOLD 2 and/or 0-1 exacerbation per year and No hospitalization for exacerbation and CAT score ≥ 10 or mMRC grade ≥ 2 Patient Group C , High Risk, Less Symptoms: GOLD 3 or GOLD 4 and/or ≥ 2 exacerbations per year or ≥ 1 with hospitalization for exacerbation and CAT score < 10 or mMRC grade 0-1 Patient Group D, High Risk, More Symptoms: GOLD 3 or GOLD 4 and/or ≥ 2 exacerbations per year or ≥ 1 with hospitalization for exacerbation and CAT score ≥ 10 or mMRC grade ≥ 2 PHARMACOLOGIC TREATMENT (STABLE COPD): BRONCHODILATORS: Increase the FEV1 or change other spirometric variables, usually by altering airway smooth muscle tone Improve emptying of the lungs, tend to reduce dynamic hyperinflation at rest and during exercise and improve exercise performance Long-acting Inhaled Bronchodilators are convenient and more effective at producing maintained symptom relief than Short-Acting Bronchodilators • • • • • • • • • • • • • • • • • • • • • • • • Treatment with a Long-Acting Inhaled Anticholinergic drug reduces the rate of COPD exacerbations and improves the effectiveness of pulmonary rehabilitation Combining bronchodilators may improve efficacy and decrease the risk of side effects compared to increasing the dose of a single bronchodilator BETA2-AGONISTS The principal action of Beta2-Agonists is to relax airway smooth muscle by stimulating Beta2-Adrenergic receptors, which increases cyclic AMP and produces functional antagonism to bronchoconstriction Regular and an as-needed use of Short-Acting Beta2-Agonists improve FEV1 and symptoms Long-Acting Inhaled Beta2-Agonists, such as Salmeterol and Formoterol, show a duration of effect of 12 hours or more Indacaterol is a once daily Beta2-Agonist with a duration of action of 24 hours Indacaterol has significant effects on breathlessness, health status and exacerbation rate Short- Acting: SALBUTAMOL, FENOTEROL Duration of Action (hours) 6-8 h Long-Acting: FORMOTEROL, SALMETEROL, INDACATEROL ( ultra LONG) BETA2-AGONISTS adverse effects: Resting sinus tachycardia Cardiac rhythm disturbances in very susceptible patients Hypokalemia (when treatment is combined with Thiazide Diuretics) ANTICHOLINERGICS: The most important effect of anticholinergic medications is blockage of acetylcholine’s effect on muscarinic receptors Short-Acting drugs block M2 and M3 receptors and modify transmission at the preganglionic junction The Long-Acting Anticholinergic Tiotropium has a pharmacokinetic selectivity for the M3 and M1 receptors The bronchodilating effect of Short-Acting Inhaled Anticholinergics lasts 8 hours Acclidinium has a duration of at least 12 hours Tiotropium and Glycopyrronium have a duration of action of more than 24 hours ANTICHOLINERGICS adverse effects: The main side effect is dryness of the mouth A bitter, metallic taste ( after using Ipratropium) Acute urinary retention (in patients with prostatic hypertrophy) Acute glaucoma has been precipitated when nebulized doses are given via a face mask (probably by a direct effect of the solution on the eye) Paradoxical bronchoconstriction due to sensitivity to Benzalkonium chloride, which is the preservative in the nebulizer solution Short-Acting: IPRATROPIUM BROMIDE • • • • • • • • • • Long-Acting: TIOTROPIUM , GLYCOPYRRONIUM BROMIDE , ACLIDINIUM METHYLXANTHINES: Theophylline is effective in COPD but, due to its potential toxicity, inhaled bronchodilators are preferred when available METHYLXANTHINES, mechanism of action: Relaxation of airway smooth muscle and inhibition of mediator release Theophylline raises intracellular cAMP by inhibiting Phosphodiesterase Antagonism of Adenosine Anti-inflammatory activity on T-lymphocytes METHYLXANTHINES, adverse effects: Toxicity is dose related Gastro-intestinal: nausea, vomiting Cardiovascular: dilatation of vascular smooth muscle –headache, flushing and hypotension; tachycardia and cardiac dysrhythmias (atrial and ventricular) Central nervous system: insomnia, anxiety, agitation, hyperventilation, headache COMBINATION BRONCHODILATOR THERAPY: Fenoterol+Ipratropium • • • • • INHALED GLUCOCORTICOSTEROIDS Long-term monotherapy with inhaled and systemic glucocorticosteroids is not recommended in COPD Long-term, regular use of inhaled glucocorticosteroids brings benefits for patients in heavy and very heavy stage obstruction, who suffer from frequent exacerbations (>= twice a year) INHALED CORTICOSTEROIDS: Beclomethasone , Budesonide , Fluticasone ORAL CORTICOSTEROIDS: An important side effect of long-term treatment is steroid myopathy Systemic corticosteroids for treating acute exacerbations have been shown to improve symptoms, lung function, reduce rate of treatment failure, and shorten length of hospital stay COMBINATION LONG-ACTING BETA2-AGONISTS PLUS CORTICOSTEROIDS IN ONE INHALER: • Salmeterol+Fluticasone • Formoterol+Beclometasone • Formoterol+Budesonide ADVERSE EFFECTS OF INHALED STEROIDS: Candidiasis of the pharynx or larynx ( Using the minimum effective dose, or a ‘spacer device’, or gargling/using mouthwashes after dosing, minimizes this problem) • • • • • • • • • • • • A hoarse voice may develop due to a laryngeal myopathy at high doses Bruising and skin atrophy occur at high doses Inhibition of long bone growth during prolonged highdose treatment in children Posterior subcapsular cataracts may develop following prolonged use PHOSPHODIESTERASE-4 INHIBITORS: Reduce inflammation by inhibiting of the breakdown of intracellular cyclic AMP Roflumilast has no direct bronchodilator activity, Improve FEV1 in patients treated with Salmeterol or Tiotropium PHOSPHODIESTERASE-4 INHIBITORS, adverse effects: Nausea, Reduced appetite, Abdominal pain, Diarrhea, Sleep disturbances, headache Patient group A: • Recommended first choice: SABA as needed or SAMA as needed • You can use a combination of short-acting drugs ( SABA and SAMA) or one of the Long-acting agents ( LAMA or LABA) • Other Possible Treatments: Theophylline Patient group B: • From this group symptomatic treatment should be regular • Recommended first choice: LAMA (long-acting muscarinic antagonis) or LABA ( long-acting Beta2-Agonist) • Alternative Choice: LAMA and LABA • Other Possible Treatments: SABA or/and SAMA, Theophylline Patient group C: • • • Recommended First Choice: LABA + ICS or LAMA Alternative Choice: LABA and LAMA or LAMA and inh-PDE4 or LABA and inhPDE4 Other Possible Treatments: SABA Or/and SAMA, Theophylline Patient group D: • • • Recommended First Choice: LABA + ICS Or/and LAMA Alternative Choice: LABA + ICS and LAMA or LABA + ICS and inh-PDE4 or LABA and LAMA or LAMA and inh-PDE4 Other Possible Treatments: Carbocysteine, SABA Or/and SAMA, Theophylline 1. • • • • • • • • • • • • • 1. 2. 3. • • • EXACERBATION of COPD, pharmacologic treatment: The three classes of medications most commonly used for exacerbations of COPD are: Bronchodilators , Corticosteroids, Antibiotics Treatment of patients with mild exacerbation COPD includes increasing the daily dose Inhaled Short-acting bronchodilators (Muscarinic Antagonist or/and Beta2agonist) Antibiotics and Oral Corticosteroids used for exacerbations of COPD lengthen the next exacerbation of the disease and reduce the risk of death Modification of treatment Long-acting bronchodilators (formoterol, indacaterol) or orally (Theophylline) by using the maximum dose or adding drugs from the other treatment groups, which were not used as maintenance therapy In the case of hospitalization use of glucocorticoids orally and intravenously allows for a significant reduction in the number of failures and shorter hospital stay SHORT-ACTING BRONCHODILATORS: Short-Acting inhaled Beta2-Agonists with or without Short-Acting Anticholinergics are usually the preferred bronchodilators for treatment of an exacerbation Intravenous Methylxanthines (Theophylline) is considered second-line therapy, only to be used in selected cases when there is an insufficient response to Short-Acting Bronchodilators Increase doses and/or frequency of Short-Acting Bronchodilators Combine Short-Acting Beta2-Agonists and Anticholinergics Use spacers or air-driven nebulizers CORTICOSTEROIDS: systemic corticosteroids shorten recovery time, improve lung function (FEV1) reduce the risk of early relapse, treatment failure, and length of hospital stay Prednisone p.o 40 mg/daily, or i.v: Metyloprednisolone 40 mg/daily or Hydrocortisone 100 mg every 6-8 h The latest randomized studies suggest: a dose of 40 mg Prednisone per day for 5 days ANTIBIOTICS: Antibiotics should be given to patients with exacerbations of COPD who have three cardinal symptoms: Increase in dyspnea Increase in sputum volume Increase in sputum purulence Have two of the cardinal symptoms, if increased purulence of sputum is one of the two symptoms or require mechanical ventilation (invasive or noninvasive) ANTIBIOTICS: The recommended length of antibiotic therapy is usually 5-10 days The choice of the antibiotic should be based on the local bacterial resistance pattern • 1. 2. • 1. 2. 3. • First- choice: Amoxicillin or Amoxicillin with Clavulanic Acid Second-choice or in case of failure of initial treatment: Second-generation Cephalosporins or Macrolide (Clarithromycin, Azithromycin) or Moxifloxacin, Levofloxacin In exacerbations caused by Pseudomonas Aeruginosa the first choice antibiotic is Ciprofloxacin • RESPIRATORY SUPPORT: OXYGEN THERAPY, VENTILATORY SUPPORT