Asthma 2024 G.pdf

Therapeutics (1) Abdulrazzaq Y. A. Al Khazzan PhD. Clinical Pharmacy Asthma Assistant professor, Faculty of Pharmacy, UST, Sana'a, Yemen Learning Objectives Upon completion the lecture of Asthma, the student will be able to: 1. Describe the path...

Therapeutics (1) Abdulrazzaq Y. A. Al Khazzan PhD. Clinical Pharmacy Asthma Assistant professor, Faculty of Pharmacy, UST, Sana'a, Yemen Learning Objectives Upon completion the lecture of Asthma, the student will be able to: 1. Describe the pathophysiology and clinical presentation of acute and chronic asthma. 2. List the treatment goals for asthma. 3. Identify environmental factors associated with worsening asthma control. 4. Select inhaled drug delivery devices based upon patient characteristics. 5. List the steps to use metered-dose inhaler correctly. 6. Recommend an asthma medication regimen for an adult patient based on symptoms. 7. Describe the purpose of an individualized asthma action plan. 7/12/2024 DR. ABDULRAZZAQ Y. AL KHAZZAN 2 Definition ❖Asthma is a disorder of the airways characterized by chronic airway inflammation, bronchial hyperresponsiveness, and airflow obstruction. - It is a chronic condition in which inflammation of small bronchi results in recurrent, reversible episodes of airway obstruction, causing wheezing, shortness of breath, chest tightness, and cough. 7/12/2024 DR. ABDULRAZZAQ Y. AL KHAZZAN 3 Definition ▪It is managed using stepwise approach. ▪Management is mainly through the use of inhaled therapies. ▪Patients can have a significant role in self-management. ▪Ensuring patients know how to use their inhaler devices appropriately is a key factor in management. ▪Acute episodes are potentially life-threatening events. 7/12/2024 DR. ABDULRAZZAQ Y. AL KHAZZAN 4 Pathophysiology The major characteristics of asthma include: ▪Airway inflammation ▪Airflow obstruction (Smooth muscle contraction , edema and mucus hypersecretion). ▪Broncheal hyperrespponsivness (BHR) The airway inflammation in asthma is persistent although symptoms are episodic. 7/12/2024 DR. ABDULRAZZAQ Y. AL KHAZZAN 5 Pathophysiology ❖Inhaled allergens, cause an early-phase allergic reaction characterized by activation of immunoglobulin E (IgE) antibodies, mast cells, and macrophages. ❖Mast cells, macrophages, eosinophils, T lymphocytes activation which releases histamine, cytokines, interleukins, and PG that induce airway smooth muscle contraction, mucus secretion, vasodilation and exudation of plasma in the airways. 7/12/2024 DR. ABDULRAZZAQ Y. AL KHAZZAN 6 Pathophysiology Bronchial gland and goblet cell hypertrophy results in excessive mucus production, often more viscous than usual. This can plug the airways in conjunction with epithelial and inflammatory cell debris. 7/12/2024 DR. ABDULRAZZAQ Y. AL KHAZZAN 7 Common triggers in asthmatic patients Examples Allergens Pollen, house dust mites, moulds Chemicals Paints, cleaning products, aerosols Foods Nuts, Dairy products, food dyes, seafood's Industrial Wood dust, cotton, smoke Medications NSAIDs, beta-blockers Others Stress, exercise, viral infection 7/12/2024 DR. ABDULRAZZAQ Y. AL KHAZZAN 8 Signs and symptoms The most common symptoms indicative of asthma are: 1. Wheeze 2. Breathlessness 3. Chest tightness 4. Chronic cough 7/12/2024 DR. ABDULRAZZAQ Y. AL KHAZZAN 9 Investigations Lung Function Tests -A spirometer is used to determine the (FEV1) and (FVC). -A FEV1/FVC ratio is used to determine the severity of airway obstruction. -Peak expiratory flow rate can be used by the patient using a peak flow meter. 7/12/2024 DR. ABDULRAZZAQ Y. AL KHAZZAN 10 Classification of asthma severity in patients by age 7/12/2024 DR. ABDULRAZZAQ Y. AL KHAZZAN 11 Classification of asthma severity in patients by age 7/12/2024 DR. ABDULRAZZAQ Y. AL KHAZZAN 12  Treatment of asthma Chronic asthma : - Goal of Treatment a. Prevent chronic and troublesome problems (cough, breathlessness) b. Reduce use of SABA (2 or less days/week) c. Normal or near normal pulmonary function d. Improve activity level e. Prevent exacerbations & need for emergency 7/12/2024 DR. ABDULRAZZAQ Y. AL KHAZZAN 13 Treatment of asthma Nonpharmacologic therapy 1. Identify and eliminate occupational sensitizers and remove sensitized patients from further exposure. 2. Strongly encourage smokers to quit tobacco use. 3. Before physical activity; use a SABA or ICS–formoterol 5–20 minutes, and warm-up exercises. 4. Ask and advise patients to stop Medications that may worsen asthma symptoms (NSAIDs, β-blockers) 5. Avoid indoor allergens (Mold, rodents and cockroaches, dust mites) 7/12/2024 DR. ABDULRAZZAQ Y. AL KHAZZAN 14 Nonpharmacologic therapy 6.Avoid foods for which there is a confirmed allergy, encourage weight reduction, administer yearly influenza vaccine to patients with moderate-to-severe asthma, administering the pneumococcal and COVID-19 vaccines. 7.Relaxation and breathing exercises to deal with emotional stress. 8.Cover the nose and mouth with a scarf on cold or windy days 9.In areas of high pollution avoid being outdoors and keep windows and doors closed 7/12/2024 DR. ABDULRAZZAQ Y. AL KHAZZAN 15 Treatment of asthma General approach to treatment : Stages : - intermittent asthma - persistent( mild, moderate, sever …) Based on : severity & frequency of symptoms, use of SABA, pulmonary function, quality of life 7/12/2024 DR. ABDULRAZZAQ Y. AL KHAZZAN 16  Treatment options Maintenance Medications used in asthma ❖ Corticosteroid: ICS (Fluticasone, Budesonide, Triamcinolone, Beclomethasone) & Systemic Corticosteroids ❖ SABA (albuterol) ❖LABA (salmeterol, formoterol) ❖Long-Acting Muscarinic Antagonists (LAMAs): Tiotropium & tiotropium bromide) ❖LTRA (Zafirlukast, Montelukast and Zileuton) ❖Anti-IgE Monoclonal Antibody: Omalizomab for patients with moderate-to-severe persistent asthma 7/12/2024 DR. ABDULRAZZAQ Y. AL KHAZZAN 17 Treatment arms : SABA 1. Quick relieve medication: ICS–formoterol Short bursts of systemic corticosteroids 2. Long term control : LABA Anti-IgE Monoclonal Antibody ICS Oral LTRAs LAMA 7/12/2024 DR. ABDULRAZZAQ Y. AL KHAZZAN 18 Intermittent asthma ❖Usually patients use SABA less than (or equal) twice a week Exercise induced asthma (EIA) Seasonal asthma ❖No long term treatment is required, only SABA (albuterol ) for acute symptoms relieve. ❖For prevention two puffs of albuterol or cromolyn or nedocromil prior exposure. 7/12/2024 DR. ABDULRAZZAQ Y. AL KHAZZAN 19 Persistent asthma Usually patients use SABA more than twice a week but not daily. Long term therapy on different levels is needed for all patients. Inhaled corticosteroid (ICS): All adults and adolescents with persistent asthma should receive an ICS-containing treatment to control symptoms and reduce future risk of severe exacerbations. 7/12/2024 DR. ABDULRAZZAQ Y. AL KHAZZAN 20  Adults & adolescents 12+ Confirmation of diagnosis if necessary Symptom control & years modifiable risk factors (see Box 2-2B) Personalized asthma ASS Comorbidities Inhaler technique & ES management W REVIE adherence Patient S Assess, Adjust, Review Symptoms preferences and goals for individual patient needs Exacerbation s Side-effects Treatment of modifiable risk Lung function T factors and comorbidities Patient AD JU S Non-pharmacological strategies satisfaction Asthma medications (adjust down/up/between tracks) Education & skills training STEP 5 STEP 4 Add-on LAMA Refer for assessment STEP 3 Medium dose of phenotype. CONTROLLER and STEPS 1 – 2 Low dose maintenance Consider high dose PREFERRED RELIEVER As-needed low dose ICS- maintenance ICS- maintenance ICS- (Track 1). Using ICS- ICS- formoterol formoterol formoterol, formoterol as reliever reduces formoterol ± anti-IgE, anti- the risk of exacerbations IL5/5R, anti-IL4R, See GINA RELIEVER: As-needed low-dose ICS- severe compared with using a SABA formoterol anti-TSLP asthma reliever STEP 5 guide STEP 4 Add-on LAMA STEP 3 Medium/high Refer for assessment of phenotype. CONTROLLER and STEP 2 Low dose dose Consider high dose ALTERNATIVE RELIEVER STEP 1 Low dose maintenanc maintenance ICS- maintenance ICS- (Track 2). Before considering a e ICS-LABA LABA Take ICS maintenance LABA, ± anti-IgE, regimen with SABA reliever, whenever SABA ICS anti-IL5/5R, anti- check if the patient is likely to taken IL4R, anti-TSLP RELIEVER: As-needed short-acting beta2- be adherent with daily agonist controller Other controller options for Add LAMA or LTRA or Add azithromycin (adults) or Low dose ICS whenever Medium dose ICS, HDM SLIT, or switch LTRA. As last resort either track (limited indications, SABA taken, or daily or add LTRA, or add to high dose ICS consider adding low dose or less evidence for efficacy or LTRA, or add HDM SLIT HDM SLIT OCS but consider side- safety) effects GINA 2022, Box 3-5A © Global Initiative for Asthma, www.ginasthma.org  Confirmation of diagnosis if necessary Adults & adolescents Symptom control & modifiable 12+ years risk factors (see Box 2-2B) Confirmation Comorbidities of diagnosis if necessary Personalized asthma management ASS InhalerSymptom control & modifiable technique & adherence Patientrisk factorsand(see preferences goalsBox 2-2B) ES Assess, Adjust, Review W REVIE S for individual patient needs Comorbidities Symptoms Exacerbations ASS Inhaler technique & adherence Side-effects W Patient preferences and goals ES Lung function Treatment of modifiable risk factors REVIE ST and comorbidities S Patient satisfaction ADJU Non-pharmacological strategies Symptoms Asthma medications (adjust down/up/between tracks) Education & skills training Exacerbations STEP 5 Side-effects Add-on LAMA TreatmentSTEP 4 of modifiable risk factors Lung function Refer for assessment Patient satisfaction STEP T 3 and comorbidities Medium dose of phenotype. Consider U S Non-pharmacological maintenance strategies CONTROLLER and STEPS 1 – 2 A D J Low dose high dose maintenance PREFERRED RELIEVER ICS-formoterol maintenance Asthma medications As-needed low dose ICS-formoterol (adjust down/up/between ICS-formoterol, tracks) (Track 1). Using ICS-formoterol ICS-formoterol ± anti-IgE, anti-IL5/5R, Education & skills training anti-IL4R, anti-TSLP as reliever reduces the risk of exacerbations compared with See GINA RELIEVER: As-needed low-dose ICS-formoterol severe using a SABA reliever asthma guide STEP 5 STEP 4 Add-on LAMA Refer for assessment STEP 3 Medium/high dose maintenance of phenotype. Consider CONTROLLER and STEP 2 Low dose high dose maintenance ICS-LABA ALTERNATIVE RELIEVER STEP 1 Low dose maintenance ICS-LABA, ± anti-IgE, (Track 2). Before considering a Take ICS whenever maintenance ICS ICS-LABA anti-IL5/5R, anti-IL4R, regimen with SABA reliever, SABA taken anti-TSLP check if the patient is likely to be adherent with daily controller RELIEVER: As-needed short-acting beta2-agonist Other controller options for either Add LAMA or LTRA or Add azithromycin (adults) or Low dose ICS whenever Medium dose ICS, or HDM SLIT, or switch to LTRA. As last resort consider track (limited indications, or less SABA taken, or daily LTRA, add LTRA, or add high dose ICS adding low dose OCS but evidence for efficacy or safety) or add HDM SLIT HDM SLIT consider side-effects GINA 2022, Box 3-5A, 1/4 © Global Initiative for Asthma, www.ginasthma.org 7/12/2024 DR. ABDULRAZZAQ Y. AL KHAZZAN 23 Acute asthma ❑In severe acute asthma, patients may be unable to communicate in complete sentences. ▪Mental status changes may indicate impending respiratory failure. ❖Mild: PEF>70% of personal best value ❖Moderate: PEF> 40% to 69% of personal best value ❖Severe: PEF< 40% of personal best value 7/12/2024 DR. ABDULRAZZAQ Y. AL KHAZZAN 24 Acute asthma treatment 1. Oxygen therapy 2. SABA: up to two treatment 20 minutes apart, each treatment is 2-4 MDI puffs (SABA to be continued up to 24-48 hours after response). 3. Systemic corticosteroids: oral corticosteroid continued until PEF is at least 70% or for 3-10 days. 4. Antibiotics only when bacterial infection is strongly suspected. PEF and oxygen saturation are the most essential to be monitored. 7/12/2024 DR. ABDULRAZZAQ Y. AL KHAZZAN 25 Drugs in use β2-adrenergic agonists -Bronchodilation -Mostly used as inhalation (SABA & LABA) rapid onset fewer adverse effects -Oral & injectable forms also available but delayed onset of action and more AEs (tachycardia , tremor, hypokalemia) 7/12/2024 DR. ABDULRAZZAQ Y. AL KHAZZAN 26 Drugs in use SABA : For rapid reverse of airway obstruction (intermittent, acute asthma, exercise) Onset: 70% or for (3-10 days ) - Usually, Methylprednisolone, Prednisolone or Prednisone are used. Dose of prednisolone 1-2mg/kg (40-60 mg as single or divided dose ) 7/12/2024 DR. ABDULRAZZAQ Y. AL KHAZZAN 32 Anticholinergics ✓Effective against cholinergic-mediated bronchoconstriction ✓Not as effective as β2 agonists. Ipratropium bromide (immediate action) ✓MDI & solution for nebulization ✓Used as adjunctive therapy ✓ Onset : 15 min duration: 4-8 hours Tiotropium bromide Onset : 30 min (long acting, 24 hour duration) Limited evidence, studies are ongoing 7/12/2024 DR. ABDULRAZZAQ Y. AL KHAZZAN 33 Leukotriene modifiers: –Add on therapy to ICS or LABA for long term control –Less effective than ICS and LABA combination. ▪Montelukast:10 mg Once daily without regard to food. ▪Zafirlukast: 20mg Twice daily one hour before or 2 hours after food. 7/12/2024 DR. ABDULRAZZAQ Y. AL KHAZZAN 34 Omalizumab Anti- IgE antibody Approved for treatment of allergic asthma not well controlled by ICS. Because high cost, its indicated in step 5 or 6 for patient with allergic sever persistent asthma. -Given SC every 2-4 weeks -Initial dose is dependent on weight and serum IgE level. Omlizumab dose :150-375mg Need observation for Anaphylaxis after 2-24 hours from administration. 7/12/2024 DR. ABDULRAZZAQ Y. AL KHAZZAN 35 Outcome evaluation Chronic Asthma -Assess onset, duration, and timing of subjective symptoms -Monitor the use of SABAs. -Determine the frequency of patient exacerbations. -Measure lung function using office spirometry yearly in patients older than 5 years. -Identify environmental factors triggering asthma exacerbations. 7/12/2024 DR. ABDULRAZZAQ Y. AL KHAZZAN 36 Outcome evaluation Chronic Asthma -Perform medication reconciliation to determine drug and disease state interactions. -Assess the patient’s inhaler technique at every visit -Determine adherence to long-term controller medications. -Assess the patient’s understanding. -Review and update the patient’s asthma action plan. -Update the patient’s immunization status. 7/12/2024 DR. ABDULRAZZAQ Y. AL KHAZZAN 37 References 1. Chisholm-Burns MA, Wells BG, Schwinghammer TL. Pharmacotherapy principles and practice: 6th edition. McGraw-Hill; 2022 2. Wells BG ,DiPiro J, Schwinghammer T, DiPiro C. Pharmacotherapy handbook 12th edition. New York: McGraw-Hill Education; 2023. 3. Joseph T. DiPiro, et al, Pharmacotherapy: A Pathophysiologic Approach, McGraw-Hill Education, 12th Edition 2021. 4. Zeind CS, Carvalho, Michael G.,. Applied therapeutics : the clinical use of drugs. 11th Edition: Wolters Kluwer Health,; 2018. 7/12/2024 DR. ABDULRAZZAQ Y. AL KHAZZAN 38