SBI242 Week 7 - Pharmacology of the Respiratory System

What is the function of the immune response and inflammation?

To eliminate pathogens “non-self” and repair tissue

Give some examples of what the immune response and inflammation protect from:

All of the above

Give some examples of physical and chemical barriers.

Skin, epithelial cells, tears, mucus

What is an example of a biochemical and cellular response?

Release of histamine and activation of immune cells

What are some effects of vasodilation?

Increased blood flow, warmth, and redness

What is the effect of vascular permeability?

Fluid leakage into tissues

What are the benefits of inflammation?

Elimination of pathogens, removal of debris, and tissue repair

What are the steps in acute inflammation?

Recognition of pathogen, release of mediators (histamines, eicosanoids), activation of phagocytic cells

What occurs during the immune response if inflammation is inadequate?

Activation of lymphocytes, antibodies production to neutralize antigens

What happens during chronic inflammation?

Release of other classes of mediators - cytokines, cellular damage, e.g., rheumatoid arthritis

What vascular effects result from histamine release?

Vasodilation and increased permeability

What chemotactic factor attracts neutrophils?

Neutrophil chemotactic factor

What chemotactic factor attracts eosinophils?

Eosinophil chemotactic factor

What is synthesized by cyclo-oxygenase during mast cell degranulation?

Prostaglandins

What is the result of neutrophils on the inflammatory process?

Phagocytosis and destruction of pathogens

Mediators of Vasodilation and Increased Vascular Permeability:

All of the above

What is the adhesion of WBCs to the endothelial cells and migration out of blood vessels to site of infection called?

Diapedesis

Name activations of cells involved in the removal of pathogens:

All of the above

What is the role of coagulation in the proteolytic enzyme system?

Thrombin (IIa) to activate complement cascade; Fibrin to limit the spread of infection

What is the role of fibrinolysis?

To dissolve blood clots

What is the role of bradykinin in the kinin system?

Vasodilation, Exudation, Stimulates pain response, Increases prostaglandin synthesis

What are the effects of C3a?

Releases histamine, spasmogen

What is the effect of C3b?

Opsonization of pathogens

What are the effects of C5a?

Chemotaxis and inflammation

What is the effect of C5-9 (MAC)?

Cell lysis and destruction

What activates mast cells in tissues?

C3a, C5a, IgE to release pro-inflammatory mediators including histamine, prostaglandins, leukotrienes and PAF

What do neutrophils do?

Neutrophils phagocytose bacteria, lyse and digest pathogens with reactive oxygen species (ROS) and proteases

Give an example of what natural killer cells do.

Attack and destroy pathogens by identifying that they do not express Major Histocompatibility Complex (MHC) as normal cells do

What is the adaptive humoral immune response?

Production of immunoglobulins (IgEs) by B lymphocytes from bone marrow, stimulated by T Helper cells

What is the adaptive cellular immune response?

Activation of T lymphocytes from Thymus. Further develop into subsets, e.g., cytotoxic, helper cells, natural killer cells

How antibodies assist in opsonization?

By binding to pathogens, marking them for destruction by phagocytic cells

What is hypersensitivity?

An overactive immune response to a harmless antigen

What happens during Type 1 (Anaphylaxis) Hypersensitivity?

Allergens (pollen, dust mites etc) stimulate IgE production, IgE binds to mast cells causing them to degranulate and release pro-inflammatory mediators. Leads to asthma, hay fever, bronchospasm

What happens during Type 2 (Antibody-dependent) Hypersensitivity?

Antibodies bind to cell surface antigens, marking cells for destruction

What happens during Type 3 (Antibody-antigen complex) Hypersensitivity?

Formation of antigen-antibody complexes, deposition in tissues, and complement activation

What happens during Type 4 (Delayed, cell mediated) Hypersensitivity?

Activation of T cells, macrophages, and cytokines, leading to inflammation and tissue damage

What is Autoimmunity?

Response against self-antigens by T and B cells (immune system fails to recognize ‘self’)

What is Immunodeficiency?

Decreased CD4 T-helper cells. Increases susceptibility to infections and increases malignancies

What are the consequences of inflammation?

D) Both B and C

What structures are part of the conducting zone of the respiratory system?

Trachea, bronchi, bronchioles

What structures are part of the respiratory zone of the respiratory system?

Respiratory bronchioles, alveolar ducts, alveoli

What is the primary role of the conducting zone?

Warming, humidifying, and filtering the air

What occurs in the respiratory zone?

Gas exchange between alveoli and blood

What are the two major types of epithelial cells in the alveoli and what are their functions?

Type I pneumocytes (gas exchange) and Type II pneumocytes (surfactant production)

What three types of work are required for breathing during inspiration?

Elastic forces, tissue viscosity, resistance, gravitational

What does FEV1 stand for?

Forced expiratory volume in 1 second

What does FVC stand for?

Forced vital capacity

What are the principal characteristics of Asthma?

Airway inflammation, airway hyperresponsiveness, and mucus hypersecretion

Name some of the most important mediators released during an acute allergic asthmatic episode.

Histamine, interleukins, prostaglandins, leukotrienes, and nitric oxide

What are some examples of reliever medications for asthma?

Salbutamol or terbutaline (short-acting β2-agonist) and ipratropium bromide (anti-muscarinic antagonist)

What are some examples of symptom controller medications for asthma?

Salmeterol and eformoterol (long-acting β2-agonist drugs)

What are some examples of preventer medications for asthma?

Inhaled corticosteroids (e.g., fluticasone propionate), leukotriene-receptor antagonists (montelukast), and cromones (cromoglycate and nedocromil).

What is the mechanism of action of short-acting beta 2 adrenoceptor agonists (Salbutamol)?

Activation of β2-adrenoceptors in bronchial smooth muscle leads to increased cAMP formation, enhancement of calcium extrusion, and binding of intracellular calcium

What is the mechanism of action of anticholinergics for asthma?

Blocking muscarinic receptors, reducing bronchoconstriction

What are some adverse effects of anticholinergics?

Dry mouth, urinary retention, constipation

Corticosteroids (e.g., inhaled corticosteroids) work by:

Decrease activation of lymphoid cells and eosinophils; decrease production and action of cytokines; inhibit COX enzymes; decrease histamine release; decrease mast cell production

What are some adverse effects of inhaled corticosteroids?

Hoarse voice and oral or oesophageal candida infections

What is the mechanism of action of cromones?

Stabilise mast cells, block chloride channels, suppress activation of sensory nerves, desensitise neuronal reflexes, inhibit cytokine release

What is the mechanism of action of leukotriene-receptor antagonists?

Block receptors for the cysteinyl leukotrienes, inhibit pro-inflammatory cytokines

What is the mechanism of action of monoclonal antibodies in asthma management?

Blocking IgE receptors (e.g., omalizumab) or targeting specific cytokines (e.g., IL-4, IL-5, IL-13)

Name some cells that play a major role in inflammation and lung damage:

Neutrophils, macrophages, and CD8+ T-lymphocytes

What is the major mechanism of airflow limitation in emphysema?

Loss of elastic recoil

Name some COPD management strategies

Cessation of smoking, short-acting bronchodilators, influenza vaccinations

What are the main indications for oxygen therapy?

All of the above

What are the symptoms of oxygen toxicity?

Substernal distress, respiratory distress, nausea, vomiting, restlessness, tremors, twitching, paraesthesias, convulsions, dry cough

What are signs of carbon dioxide over-dosage?

Dyspnoea, breath-holding, markedly increased chest and abdominal movements, nausea and raised systolic blood pressure

The conducting zone of the respiratory system includes which of the following:

The pharynx and larynx

What does FEV1 represent?

The volume of air forcefully exhaled in 1 second

In patients with an obstructive lung disease (asthma, COPD, emphysema), the ratio of
FEV1 to FVC is:

Less than 75%

What are the main pathologies of Asthma?

Hyperinflammatory response, mucus hypersecretion, and smooth muscle
constriction (bronchiospasm)

Which of the following inflammatory mediators are released during an acute asthmatic
attack?

All of the above

An example of an asthma reliever medication is:

Salbutamol

The mechanism of action of salbutamol is to:

Activate β2-adrenoceptors on smooth muscle causing increased extrusion of calcium from the cell resulting in lowered concentration of intra-cellular calcium and relaxation of bronchiole smooth muscle

Parasympathetic stimulation on muscarinic receptors on bronchiole smooth muscle cause an increase in intra-cellular calcium, thus resulting in broncho-constriction. Therefore, anti-cholinergic medications such ipratropium bromide:

Block muscarinic receptors on bronchiole smooth muscle resulting in broncho-dilation

Which of the following is NOT an adverse effect associated with inhaled corticosteroid
use?

Gingivitis hyperplasia

A 50-year-old female is diagnosed with moderate persistent asthma. Her medication
regime should include:

Inhaled short acting beta 2 agonist as required; plus a low dose inhaled corticosteroid; plus a long acting beta 2 agonist

The pathophysiology of emphysema is described as:

Abnormal permanent enlargement of gas-exchange airways accompanied by
destruction of alveolar walls

Which of the following is a sign/symptom of chronic bronchitis?

Peripheral oedema

The management of COPD includes:

Short acting B2 agonists, inhaled glucocorticosteriods and oxygen therapy

Oxygen therapy is indicated in cases of hypoxia or hypoxaemia, coronary conditions,
shock and severe haemorrhage. Normal oxygen saturations are considered to be:

94-98%

The respiratory zone of the respiratory system includes which of the following?

Alveoli

What is the recommended pharmacological management of COPD?

Short acting B2 agonists, inhaled glucocorticosteroids, and oxygen therapy

In the treatment of asthma, ipratropium bromide ________ muscarinic receptors in the bronchioles leading to ________.

inhibits; bronchodilation

Why is carvedilol contraindicated for patients with severe asthma?

Because beta blockers inhibit beta 2 receptors in the bronchiole causing bronchi-constriction

Low levels of circulating TSH in the blood indicate:

Overproduction of thyroid hormone

What is FVC?

The maximum volume of air that can be forcefully exhaled after a maximal inhalation