COPD1 Medications 2023 (1).pptx

COPD – Chronic Obstructive Pulmonary DiseasePharmacotherapy Jennifer Hofmann Pharmacology Objectives      Identify the pathogenesis, etiology and classification of chronic obstructive lung disease (COLD) or COPD. Describe the beta-adrenergic agents, ipratropium bromide, inhaled long-acti...

COPD – Chronic Obstructive Pulmonary DiseasePharmacotherapy Jennifer Hofmann Pharmacology Objectives      Identify the pathogenesis, etiology and classification of chronic obstructive lung disease (COLD) or COPD. Describe the beta-adrenergic agents, ipratropium bromide, inhaled long-acting antimuscarinic (LAMAs)/ anticholinergics and corticosteroids, roflumilast and relate them to treatment of COPD. Discuss the role of long-term oxygen therapy in the treatment of COPD. Describe the appropriate antimicrobials utilized to treat infectious exacerbations of COPD. Review current treatment guidelines at http://www.goldcopd.org/. COPD – Background Information  Airflow obstruction from chronic bronchitis and/or emphysema  Due to chronic inflammation of terminal airways and distal airspaces ◦ Usually caused by cigarette smoking Pathophysiology of COPD  Chronic bronchitis ◦ Excessive mucous production and cough ◦ Hyperplasia of mucus glands, smooth muscle hypertrophy, inflammation ◦ Repeated infections  Emphysema ◦ Destruction of the acinar walls diminished gas exchange ◦ Dyspnea at rest is predominant symptom Key Indicators for COPD Case of COPD   A 52 y/o male 45 pack year tobacco smoker with HTN c/o increasing SOB that began over 3 yrs ago. His breathing has gotten progressively worse and he is now unable to walk 100 yards without having to stop and catch his breath. He also has a “smokers cough” which he produces 1 tsp of whitish yellow thick sputum esp after coughing. He drinks 1-2 beers per night. Denies h/o asthma, allergies, TB, occupational exposure to dusts, fumes, chemicals etc. (drives a truck that delivers food products). No fever, chills, night sweats, edema, chest pain, palpitations, dizziness, weight loss or gain, anorexia Diagnosis of COPD Chronic cough  Dyspnea, chronic and progressive, all day and worse with exertion  Sputum production often after coughing  Risk factors esp. tobacco smoking  Airflow limitation:  ◦ Spirometry ◦ FEV1/FVC <70% post bronchodilation Tools to Assess COPD Severity  https://www.catestonline.org/patient-site-tes t-page-english.html Severity of Breathlessness Assessment Tool (Grades 04)strenuous  Grade 0- breathless with exercise  Grade 1: short of breath when hurrying on level or walking up slight hill  Gr 2:walk slower or must stop for breath when walking at my own pace on level  Gr 3: stop for breath after walking 100m or a few minutes on level  Gr 4: breathless while dressing, undressing, cannot leave house COPD Classification  Group A: Less symptomatic, low risk of future exacerbations: ◦ •mMRC grade 0 to 1 or CAT score <10 Zero to one exacerbation per year without hospitalization  ●Group B: More symptomatic, low risk of future exacerbations: ◦ mMRC grade ≥2 or CAT score ≥10 ◦ Zero to one exacerbation per year without hospitalization  ●Group E: High risk of future exacerbations: ◦ •≥2 exacerbations per year or ≥1 hospitalization for exacerbation Overview: GOLD Tx Recommendations Single-agent long-acting bronchodilator(LAMA or LABA) therapy for less severe symptoms and low exacerbation risk (Group A).  •Dual long-acting bronchodilator therapy for more severe symptoms and low exacerbation risk (Group B).  •Dual long-acting bronchodilator therapy for high exacerbation risk, regardless of symptoms (Group E, replacing previous Groups C and D categories).  Topic: COPD Med Overview by Group Goals of Therapy for COPD  Smoking cessation is #1 ◦ Pharmacotherapy  Nicotine replacement products  Bupropion  Varenicline (Chantix) Improvement in obstructive status  Tx and prevent acute exacerbations  Improve quality of life  ◦ Risk for exacerbations?  ≥2 acute COPD exacerbations in the past 12 months  Any hospitalization for COPD in the past 12 months  Reduce mortality, hospitalizations Topic: Summary Slide of COPD Medications Topic: Smoking and COPD Nicotine Replacement  Nicotine Replacement Therapy (NRT) ◦ Long acting Transdermal Patch Short-acting forms of NRT (lozenge, gum, inhaler, or nasal spray)  Nicotine Gum or Lozenge  Nicotine Nasal Spray  Nicotine Inhaler  Varenicline (Chantix) ◦ partial agonist at the alpha-4 beta-2 nicotinic receptor  Bupropion SR Background: Monitoring Tools  Efficacy ◦ Clinical – decrease in dyspnea, improved exercise tolerance, less tachypnea ◦ Pulmonary function tests esp. FEV1 and FEV1/FVC ratio ◦ ABG in acute exacerbations and periodically in moderate and severe COPD Bronchodilators (LABAs/ LAMAs)are central to pharmacotherapy for COPD  LAMAs ◦ LAMAs include tiotropium, aclidinium, umeclidinium (DPIs) ◦ Glycopyrrolate and Revefenacin are available as a solutions for nebulization. ◦ OR.. LABAs ◦ LABAs include salmeterol, formoterol, arformoterol (solution), indacaterol*, vilanterol**(used in combo inhalers), and olodaterol(SMI) ; all are beta-2 selective Medications: COPD Therapy Class: Antimuscarinics (Inhaled) aka AMAs Mechanism of action  Blocks effect of ach at M (muscarinic) receptors on smooth muscle bronchodilation  Improves PFTs (measure of lung function) ◦ Role: First line bronchodilator for stable COPD ◦ Types: ◦ Short acting (SAMAs)  Name: Ipratropium bromide (inhaled MDI, or nebulized  2 puffs or more QID (short acting)  Peak and duration of action Long acting (LAMAs) (daily use)  Tiotropium (Spiriva)(dry powder inhalation) once daily or  Aclidinium (Tudorza Pressair [U.S.] Twice daily and Combination as Anoro Ellipta –  Umeclidinium 62.5 mcg/vilanterol 25 mcg: 1 inhalation once daily  Revefenacin – Revefenacin is available as a solution for nebulization. ◦ AE: few such as dry mouth and metallic taste Medications for COPD Class: (B2 agonists) - Inhaled ◦ B-2 agonists bronchodilator class: ◦ MOA:  B2 agonists (inhaled) increase cAMP and cause relaxation of smooth muscle  bronchodilation  May improve symptoms with small improvement of FEV1 ◦ AE:  Tremor  Sinus tachycardia (monitor esp. in cardiac patients) ◦ Short acting (SABAs)  NAMES (albuterol, levalbuterol,)  Duration of action lasts 4-6 hours (refer to asthma lecture and clin med) ◦ Long-acting B-2 agonists (LABAs)  Names: salmeterol, formoterol (rapid onset long duration), arformoterol, indacaterol, vilanterol (in combo inhalers), and olodaterol  Route and duration  Inhaled is preferred route of administration  DPI, SMI or solution for nebulization  Duration 12-24 hours Class – Combination LABA+LAMA Inhalers  Tiotropium-olodaterol – Combination tiotropiumolodaterol ◦ (2.5 mcg/2.5 mcg per actuation, two inhalations once daily) is delivered via soft mist inhaler (SMI).  ●Umeclidinium-vilanterol – ◦ Umeclidinium-vilanterol (62.5 mcg/25 mcg per actuation) is a dry powder inhaler used at a dose of one inhalation daily for COPD Role:  Useful when two bronchodilators are needed  Additive effects on the lung function and health status Class: Corticosteroids (inhaled, ICS)  Class: INHALED corticosteroids (ICS)  Names: (see asthma lecture) ◦ Note: there are combo inhalers including 3 in 1 LABA/LAMA/ICS  MOA: Anti-inflammatory actions but less effects than with asthma  Indications for COPD: DIFFERENT THAN ASTHMA !!  GOLD indications for advisability of ICS therapy in patients with exacerbations despite dual therapy with LAMA-LABA, :  ●Patients with exacerbations and ≥300 eosinophils/microL are likely to have a favorable response to ICS and may have exacerbations following cessation of ICS therapy.  ●Patients with exacerbations and ≥100 but <300 eosinophils/microL may have a favorable response to ICS therapy.  ●Patients with exacerbations and <100 eosinophils/microL are unlikely to respond to ICS treatment and are at increased risk of infectious complications. ICS are not favored unless there is an alternative indication (eg, concomitant asthma). Class: Corticosteroids (inhaled, ICS) Adverse Effects Class: Corticosteroids (inhaled, ICS)  AE:  ◦ dysphonia, skin bruising, and oral candidiasis ◦ increased risk of lung infection in patients ◦ Possibly fractures ◦ Possibly cataracts ◦ See asthma and Glucocorticosteroids lectures CLASS: Oral Corticosteroids: ◦ Names: prednisone, methylprednisolone ◦ Indications  Po/IV steroids for acute exacerbations short term 5-14 days ◦ AE/ concerns  Long term oral glucocorticosteroids are not recommended  AE of Corticosteroids are significant so weigh risks and benefits Class: Combination Inhaled corticosteroid (ICS), LAMAS, LABAS Triple combination glucocorticoid/longacting muscarinic antagonist/long-acting beta agonist inhaler Fluticasone furoate 100 Trelegy Ellipta mcg/umeclidin 1 inhalation (United ium 62.5 once daily; DPI States) mcg/vilanterol 25 mcg Budesonide 160 mcg/glycopyrr olate 9 mcg/4.8 mcg formoterol Breztri Aerosphere (United States and Canada) 2 inhalations twice daily; MDI Class: Methylxanthines  Names: ◦ theophylline and aminophylline  Indications ◦ ◦ ◦ ◦ ◦ Second line for COPD due to AE Benefits Valuable in exacerbations of COPD May improve respiratory muscle function Add to TX in patients who have not received optimal response to both anticholinergics and beta agonists MOA: bronchodilation via inhibition of enzyme, PD, that breaks down cAMP REVIEW ASTHMA LECTURE Class: Methylxanthines Name: Theophylline  Risks ◦ Low TI (serum levels must be measured) ◦ Requires loading dose to achieve steady state ◦ Levels above 35-40 mcg/ml are associated with arrhythmias and seizures ◦ Drug interactions, ◦ Smoking and EtOH increases clearance of theophylline  Adverse effects (many) ◦ GI (N/heartburn, ◦ HA, insomnia ◦ CNS stimulation  seizures  Dosing issues ◦ Sustained release 400-900m/day ◦ Serum levels (peak) Medication: RoflumilastDaliresp   Name: Roflumilast-Daliresp (DA-li-resp), Indications: ◦ severe COPD in patients with chronic bronchitis.  The FDA approved indication is for the reduction of exacerbations in patients with chronic bronchitis, severe or very severe airflow limitation, and a history of exacerbations. Route and directions  ORAL (po) Daliresp is 500 mcg taken orally daily at the same time each day for severe COPD with repeated exacerbations ◦ MOA:  phosphodiesterase 4 inhibitor which reduces lung inflammation. ◦ Effects  May improve or stabilize lung function (questionable data)  May reduce exacerbations modestly  May improve QOL (quality of life) AE: nausea, diarrhea and weight loss as well as mood changes and insomnia Medication Overview: Clinical apps  Start with an INHALED long-acting bronchodilator such as LA antimuscarinic (Spiriva, Tudorza) preferred  OR long-acting beta-agonist (salmeterol, etc) for persistent symptoms. ◦ Combine a bronchodilator from each class if one isn't enough. ◦ Add an inhaled steroid for patients with severe COPD...frequent exacerbations...or asthma symptoms and eosinophilia.  Note: steroids increase the risk of pneumonia and possibly fractures. Topic: Exacerbations of COPD  Definition: COPD exacerbation as an event characterized by:  dyspnea and/or cough and sputum that worsens over ≤14 days with possible tachypnea and/or tachycardia caused by  airway infection, pollution, or other insult to the airways  Clinical diagnosis (Refer to Clin Med – Pulm)  Treatment (overview) setting (Clin Med) ◦ Oxygen therapy, controlled and repeat ABG after 30-60 minutes of therapy to check for CO2 retention ◦ Bronchodilators (SABAS and SAMAs) - inhaled ◦ Po or IV steroids  Give ORAL prednisone 40 mg/day for 5 -14days. Higher doses cause more adverse effects...and IV steroids are not more effective ◦ Antibiotics  Outpatient  Inpatient  Pseudomonas risk Topic: COPD Exacerbations BACKGROUND  Background: ◦ Acute bacterial exacerbations are a common cause of hospitalization and mortality  Most common organisms ◦ H. flu, M.cat, S. pneumo and H. parainfluenzae ◦ Enterobacteriaceae  Signs and symptoms of acute bacterial exacerbation ◦ Increased dyspnea and cough ◦ Increased sputum ◦ Purulent sputum Topic: COPD Exacerbation Class: Setting and Antibiotics  Treatment setting: triage (clin med)  Outpatient (many can treat outpatient) or Inpatient? ◦ Uncomplicated cases without comorbidity and FEV1 > 50% of predicted ◦ Antibiotics  Outpatient vs inpatient antibiotics Topic: Inpatient Treatment with Antibiotics  Indications: ◦ Inpatient moderate to severe COPD without risk for Pseudomonas  Indications: ◦ Inpatient with risk factors for Pseudomonas infection ◦ Assess risk factors Class/names: ◦ beta-lactam/b-lactamase inhibitor   Alternative ◦ Fluoroquinolones  Gemifloxacin moxifloxacin, levofloxacin ◦ Class/ names:  High dose fluoroquinolones such as ciprofloxacin or levofloxacin  Piperacillin/tazobactam Topic: Immunotherapy for COPD Influenza vaccine yearly  Vaccination against pertussis (Tdap: tetanus, diphtheria, acellular pertussis) is recommended as a one-time dose as an adult (≥19 years  Pneumococcal vaccine  ◦ > 65 years may need every 5 years Topic: Long term Oxygen  Stable COPD patients with ◦ Resting PaO2 of < 55mmHg or ◦ PaO2 < 60mm Hg with  Evidence of right heart failure or polycythemia impaired neuropsych function ◦ Reduces mortality ◦ Fewer hospitalizations ◦ Improved quality of life ◦ Usually delivered by mask or NC Topic: Non-pharmacologic Measures  Exercise and Pulmonary Rehab ◦ Daily to weekly Nutrition  Oxygen therapy for very severe COPD  Surgical options  Review of Therapy for COPD   Patient ed: Smoking cessation encouraged, attempted ALWAYS Bronchodilators such as inhaled antimuscarinics/ B2 agonists are central to therapy ◦ If FEV1 < 50% and repeated exacerbations esp with asthma and elevated eos add inhaled corticosteroids ◦ Systemic CS for short term use in exacerbations   Influenza, COVID, and pneumococcal vaccines Antibiotics for infectious exacerbations References  http://www.goldcopd.com