Lecture 18 Flashcards by Valentina Jones

What causes Asthma

No exact causes but factors
1) Smoking during pregnancy (increases asthma risk in fetus)
2) Obesity
3) Air pollution (environmental)
4) Genetics (family history)
5) Food allergies
6) Antibiotic use and microbiome

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Types of Asthma

Extrinsic (allergic) and Intrinsic (nonallergic) asthma

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What is Extrinsic (allergic) asthma

Caused by allergic reaction
Higher levels of IgE present in blood stream
Airway hyperresponsiveness (AHR) (sign of chronic inflammation and immune dysfunction)

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What is Intrinsic (nonallergic) asthma

Caused by non-allergic factors like:
Stress, anxiety, cold air, dry air, smoke, viruses, infection, etc

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Traits of asthma

Excess mucous secretion and narrowing of the airway lumen

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Symptoms of Asthma

Shortness of breath, chest tightness or pain, wheezing when exhaling (children)

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Asthma triggers

1) Exercised induced (may be worse when air is dry or cold),
2) Occupational asthma (workplace irritants)
3) Allergy-triggered

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Pathway of Extrinsic asthma (allergy)

Allergen enters airway epithelium–>allergen presented to TH2 cells–>trigger IgE antibody production–>Mast cells bind to IgE and undergo degranulation–>Degranulation produces proinflammatory cytokines, chemokines, histamines, prostaglandins, (cycle of constant immune infiltration

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Characteristics of Asthmatic airways

Increased number of blood vessels, subepithelial fibrosis (collogen deposition), goblet cell hyperplasia, smooth muscle hyperplasia, hypertrophy, and an increased volume of submucosal glands

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What is characterized by airway inflammation, obstruction, and breathlessness

Asthma and COPD

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Diagnosis for Asthma and COPD

Decreased FEV 1 relative to their FVC
Decreased Forced expiratory volume (FEV 1) in comparison to their forced vital capacity (FVC)

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Treatment for Asthma

Inhalers, Glucocorticoids, Antileukotrienes, Beta-2 agonists, Methylxanthines, Muscarinic receptor antagonists, monoclonal antibody treatment

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Types of Inhalers

Metered dose inhalers (MDI) and Dry powder inhalers (DPIs)

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Mechanism of inhaled form of glucocorticoid

ex. Budesonide
Budesonide binds to glucocorticoid receptors (GRs)–> activate histone deacetylase 2 (HDAC2)–>inhibit histone acetyltransferase (HAT)–>inhibit synthesis of inflammatory response mediators and phagocytosis

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Overall action of inhaled corticosteroids

ex. Budesonide
Maximize local response and avoid system inflammation

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Anti-inflammatory action of inhaled glucocorticoids

1) Decreased production of prostaglandins, cytokines, and interleukins
2) Decreased proliferation and migration of lymphocytes and macrophages

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What are Antileukotrienes

ex. Montelukast and Zafirlukast
Competitive antagonists of CysLTR 1
Leukotrienes are bronchoconstrictors and vasoactive lipid mediators so Anti that

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What produces Leukotrienes

Neutrophils and dendritic cells
Express 5-LO and 5-LO activating protein (FLAP) required for leukotriene biosynthesis

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When to use Antileukotrienes

Prophylactic treatment to prevent bronchoconstriction, not useful in acute episode

Function of Beta-2 agonist

Relaxation of smooth muscle in lung and dilation of airways (opening)
May result in fight or flight response in children

Mechanism of Beta 2 agonist

Open calcium activated potassium channels leading to hyperpolarization of smooth muscle cells

What is the current medicine of choice for all types of asthma

Beta 2 agonists for their rapid bronchial relaxation with minimal side effects

Types of Beta 2 agonists

1) Short-acting beta 2 adrenergic receptor agonist (SABA)
2) Long-acting beta 2 adrenergic receptor agonist (LABA)

Why use SABA

ex. Salbutamol (albuterol) and R-albuterol (decreased tachycardia and palpitations, SNS)
Rapid onset (15-30 minutes)
Duration (4-6 hours)
Good for acute attacks
At high doses–>cardiac stimulation

Why use LABA

ex. Salmeterol, Formoterol Long duration due to long, lipophilic side-chain that allows active portion to continuously bind and unbind to receptors of smooth muscle in lung

Where are Methylxanthines found

Alkaloids found in tea, coffee, chocolate

Characteristics of Methylxanthines

ex. Theophylline 1) Broncho-dilating and anti-inflammatory 2) Taken orally (cannot be inhaled) 3) Given alongside glucocorticoids (synergy)

When to use muscarinic receptor antagonist

In chronic inflammatory syndromes (mostly COPD and some asthma) When parasympathetic reflexes become overactive and easily triggered, leading to bronchoconstriction Parasympathetic

Mechanism of Muscarinic receptor antagonists

Cholinergic control of airway in smooth muscle (dominated by muscarinic receptor M3)

Types of Muscarinic receptor antagonists

Long-acting muscarinic antagonists (LAMAs) and Short-acting muscarinic antagonists (SAMAs)

What can monoclonal antibody treatment target in Asthma and COPD

ex. Omalizumab (IgE) in age 6+ (have normal IgE levels), Mepolizumab and reslizumab (IL-5) Antibodies against IgE and IL-5 Only use in sever cases

What are the most powerful Asthma controllers (severe cases)

Oral corticosteroids, but long term use cause serious toxicity or Monoclonal antibody therapy

Why shouldn't adults stop inhaled corticosteroid therapy

Risk of exacerbation

Administration of Asthma treatments

Corticosteroids-->inhaled Antileukotrienes-->Orally and metabolized by P450s Beta 2 agonist-->inhaled (cannot be taken orally) Muscarinic receptor antagonists-->inhaled

Side effects of glucocorticoids

Dysphonia and thrush (fungal infection) In children-->growth deceleration with high doses Inhaled is safe during pregnancy

Side effects of Antileukotrienes

Zileuton-->elevates liver enzymes so inhibits CYP1A2 Oral glucocorticoids + Antileukotrienes-->eosinophilic granulomatosis (Churg-Strauss), potentially fatal

Side effects of Beta 2 agonists

Skeletal muscle tremor, heart palpitations and tachycardia, nausea, and vomiting LABA must be accompanied with inhaled glucocorticoids to address underlying inflammation (or else fatal)

Side effect of monoclonal antibodies

Risk of sensitivity reactions and rarely anaphylaxis

Side effect of Theophylline

Headache, nausea, vomiting, GI distress, and tremulousness Can lead to Arrhythmia, seizures, and tachycardia

What is the Main cause of Chronic obstructive pulmonary disease (COPD)

Smoking, but other causes are environment and Alpha-1 deficiency related emphysema Affects primarily 65+

Marks of COPD

Limited Airflow due to emphysema, bronchitis, and bronchiectasis

Treatment for COPD

LABAs (salmeterol or formoterol), inhaled muscarinic receptor antagonists, ultra long acting beta 2 agonists (indaceterol, olodaterol, and vilanterol)

Classes of COPD for diagnosis

GOLD 1(mild)- Gold 4 (very severe) Group A-->low risk, low symptoms Group B--> low risk, high symptoms Group C-->high risk, low symptoms Group D-->high risk, high symptoms risk = risk of exacerbations (worsening respiratory symptoms)

Medical intervention of COPD

Lung volume reduction surgery and bronchoscopic intervention and as a last resort lung transplantation

Diagnosis of Asthma-COPD overlap syndrome (ACOS)

If young patient has COPD like symptoms but incompletely reversible airway constriction

Ways to improve ACOS symptoms

No treatment 1) Low dose-inhaled corticosteroids 2) LABA (not alone) 3) LAMA

What can treat EVALI

Influenza cannot be distinguished from EVALI Corticosteroids may help with EVALI but can worsen respiratory infections