Untitled Quiz

Course Information

• Course title: Pharmacotherapeutic II
• Course code: PHAR520
• Course coordinator: Fouad Sakr, PharmD, MPH, PhD
• Faculty members: Jihan Safwan, PharmD, MPH; Dalal Mourad, PharmD; Rebecca Lteif, PharmD; Alaa Shamseddine, PharmD
• University: Lebanese International University
• School: School of Pharmacy

Chapter 1: Asthma - Part 1: Chronic Asthma

• Learning Objectives:
  • Learn epidemiology, pathophysiology, and risk factors of asthma.
  • Describe common signs and symptoms of an asthma attack.
  • Assess patient knowledge of asthma and medication.
  • Differentiate the stages of asthma.
  • Develop a treatment plan for a patient with asthma.
  • List common asthma triggers.
  • Educate patients on avoidance techniques and non-pharmacological treatment.
  • Educate patients on managing asthma using an asthma action plan.
  • Learn the treatment of an acute asthma attack.
• Introduction:
  • Asthma is a common and potentially serious chronic inflammatory disease of the airways.
  • Respiratory symptoms include wheezing, breathlessness, chest tightness, and coughing.
  • Limitation of activity is a common symptom.
  • Flare-ups (attacks) are more frequent and severe in high-risk patients and when uncontrolled, requiring urgent healthcare and may be fatal.
  • Asthma can be effectively treated allowing most patients to achieve good control.

Epidemiology

• Approximately 7% of the US population has asthma.
• Asthma is the most common chronic disease among children in the US.
• Prevalence is highest in children aged 5-17 years.
• Boys are more commonly affected than girls, and women are more commonly affected than men.
• It is a third leading cause of preventable death due to inadequate assessment of severity and therapy.

Etiology

• Heterogeneous: Asthma has varied causes.
• Host factors: Genetic predisposition to atopy and airway hyperresponsiveness, and obesity.
• Environmental risk factors: Outdoor and indoor allergens, respiratory (viral) infections, occupational sensitizers, tobacco, smoke and outdoor/indoor air pollution.
• Hygiene Hypothesis: Lack of early childhood exposure to microbes may lead to immune system dysregulation, increasing susceptibility to allergies and asthma.

Protective and Risk Factors

• Protective factors: Being a younger sibling, natural birth, breastfeeding, farm living, diverse and healthy microbiota, high socioeconomic status, a healthy diet, low pollution rates, and exercise.
• Risk factors: Asthma history in the family, urban living, cesarean section, formula feeding, sheep farming, pressed or loose hay, altered dietary practices, community-associated infections, dysbiotic microbiota, respiratory viral infections, lower socioeconomic status, increased smoking rates, higher stress, and use of antibiotics.

Pathophysiology

• Trigger factor leads to airway inflammation.
• Inflammation causes hypersecretion of mucus, airway muscle constriction and swelling, bronchial membrane swelling.
• Morphological changes include:
  • Inflammatory cells infiltrating the airway lumen with edema and debris,
  • Epithelial desquamation, - Airway remodeling (altered structure/function), - Basement membrane hypertrophy,
  • Mucus production and plugging of the airways, and
  • Smooth muscle hypertrophy and hyperplasia.
  • Production of nitric oxide, which amplifies the inflammatory process.
• This results in narrow breathing passages and symptoms such as wheezing, coughing, shortness of breath, and tightness in the chest.

Diagnosis

• Signs and Symptoms: More than one symptom (e.g., wheezing, shortness of breath, cough, chest tightness) often worse at night or in the early morning. Symptoms vary over time. Symptoms occur or worsen in the presence of triggers (e.g., allergens, exercise).
• Physical examination: Often wheezing on auscultation.
• Spirometry: Reduced FEV1/FVC ratio (compared to normal values for age, sex, and height). Reversible obstruction with bronchodilator use (increase in FEV1 of ≥12% and ≥200 ml after inhalation of a bronchodilator).
• Peak expiratory flow (PEF): Reduction in PEF compared to expected (based on charts or normative data) or improvement of FEV1 or PEF after inhalation of bronchodilator.
• Positive methacoline challenge: Inducing bronchoconstriction.
• Exercise-induced bronchoconstriction (EIB): Drop in FEV1/FVC ≥15-20% compared to baseline.
• Skin tests with allergens: Measuring specific IgE in serum

Review of Pharmacotherapy

• Controller medications: Used to reduce airway inflammation, control symptoms, and reduce the risk of exacerbations and decline in lung function. Inhalable corticosteroids (ICS), LABA, leukotriene modifiers, Anticholinergic, and Monoclonal antibodies.
• Reliever medications: Used for rapid relief of breakthrough symptoms and prevention of exercise-induced bronchospasm (EIB). Short-acting beta2-agonists (SABAs) and Anti-inflammatory reliever (AIR).

Corticosteroids

• Inhalable corticosteroids (ICS): Most effective anti-inflammatory for asthma. First line treatment for asthma. Usually high topical potency with low systemic side effects. Dosage (low, medium, high) varies by patient, so some patients need medium or high dose.
• Systemic corticosteroids: Used for short courses to control acute exacerbations or long-term control in severe, difficult-to-manage conditions.
  • Risk of side effects like growth suppression, hypertension, and more.

Beta Agonists

• Short-acting beta2-agonists (SABAs): Used as relievers on an as-needed basis. Stimulates beta2-adrenergic receptors for bronchodilation.
• Relatively fast onset of action (~5 mins) with short duration of action (~4 hours).
• Long-acting beta2-agonists (LABAs): Used for long-term prevention. Bronchodilation for more than 12 hours. Usually used in combination with ICS for better control.

Leukotriene Modifiers

• Use: Prevent the release of inflammatory mediators.
• Major advantages: Effective orally, administered once or twice per day, contributes to patient adherence, and patient satisfaction.
• Disadvantages: Less effective than low doses of ICSs, and unpredictable response.

Anticholinergics

• Tiotropium Bromide: Long-acting muscarinic antagonist. Modestly improves lung function and reduces exacerbations. Mostly used in steps 4 and 5 and in patients 6 years or older with a history of exacerbations. Some side effects include dry mouth, dyspepsia, abdominal pain, vomiting, constipation, GERD, stomatitis, tachycardia, angina pectoris, headache, dizziness.

Monoclonal Antibodies

• Anti-IgE: Omalizumab is the anti-IgE antibody, used as an add-on therapy in Step 5. It binds to IgE antibody, preventing binding to mast cells, to reduce inflammatory mediators release.
• IL-5 inhibitors: (e.g., mepolizumab, reslizumab, benralizumab) used for severe eosinophilic asthma when eosinophils are elevated and exacerbations are frequent (Step 4 or 5).
• IL-4 inhibitor: Dupilumab is used as an add-on treatment for severe eosinophilic asthma, or for patients with moderate to severe atopic dermatitis (Step 5).

Others

• Mast cells stabilizers (Nedocromil and cromolyn): Weak anti-inflammatory effect and low efficacy.
• Sustained-release theophylline: Weak efficacy in asthma.
• Add-on azithromycin: This option is for adult patients with persistent asthma despite moderate to high-dose ICS and LABA. May be considered long-term treatment and requires monitoring (Steps 4 or 5). This is considered an adjunctive therapy in specific scenarios.
• Allergen-specific immunotherapy: An option for patients whose asthma is related to allergies, particularly dust mites and grass pollens.

Asthma Management

• Stepwise approach: Managing asthma treatment starts with assessing symptom control, risk factors, and the patient’s preference, then adjusting therapy as needed (Step Up/Step Down).
• Goals of therapy: Achieving good symptoms control to maintain normal activity levels, having normal or near-normal lung function, and avoiding serious flare-ups.

Special Considerations

• Perimenstrual asthma is asthma that worsens premenstrually. More common in older patients, higher BMI, more severe asthma, or aspirin-exacerbated respiratory disease.
• Asthma in pregnancy: There is currently not sufficient evidence of a direct impact on diet to manage or prevent asthma. Obesity in pregnancy may be associated with increasing risk of asthma in children.

Exercise-Induced Bronchospasm

• Pulmonary functions (FEV1 and PEF) changes during and following exercise.
• Characteristics: Often exercise-induced and exacerbated by cold, dry air. Acute management typically involves SABA treatment.
• Prevention: Albuterol or Formoterol before exercise is frequently used to prevent asthma.

Nocturnal Asthma

• Asthma worsening during sleep (nadir at 3–4 am).
• Factors contributing to nocturnal asthma include high levels of epinephrine, low levels of cortisol, allergies, improper environmental control, Gastroesophageal reflux, obstructive sleep apnea, and sinusitis. This is treated similarly to persistently uncontrolled cases.

Primary Prevention of Asthma

• Gene-environment interactions: The development of asthma results from multiple factors combining environmental and genetic susceptibility.
• Interventions: Strategies focused on avoidance of tobacco smoke during pregnancy and early life, encouragement of vaginal delivery, advice on breast-feeding, and limiting paracetamol (acetaminophen) and broad-spectrum antibiotics in the first year of life may yield some success.

Case Studies

• Case Study #1 and #2: Provided as questions to stimulate further thought.
• Includes patient details, current symptoms, history, and diagnostic findings.
• Provide insights for proper management approach
• Specific questions to help the learner formulate potential treatment strategies for the given scenarios, including considerations of severity, appropriate medications, dosage, and appropriate clinical decision-making flowcharts..