Inhaled Corticosteroids: Clinical Indications

• Adrenal cortical hormones are chemicals secreted by the adrenal cortex, known as steroids.
• Endogenous substances are produced inside the body.
• Exogenous substances are manufactured to be placed inside the body (e.g., medication).
• Immunoglobulin E (IgE) is a gamma globulin produced by cells in the respiratory tract.
• Prostaglandins are hormone-type substances circulating throughout the body.
• Steroid diabetes is hyperglycemia resulting from glucocorticoid therapy; glucocorticoids break down proteins and fats for gluconeogenesis.
• Steroids, also known as glucocorticoids or corticosteroids, produce an antiinflammatory response in the body.

Clinical Indications for Use of Inhaled Corticosteroids

• Inhaled corticosteroids are available for oral inhalation (lung delivery) and intranasal delivery.
• Orally inhaled agents are for maintenance and control therapy of chronic persistent asthma, identified as requiring step 2 care or greater.
• Step 2 asthma is defined as asthma with symptoms occurring more than 2 days/week but not daily, night awakenings occurring 3 to 4 nights/month, with FEV1 or PEF 80% of predicted or greater.
• Inhaled agents can be used with systemic corticosteroids in severe asthma and may allow for reduction or elimination of systemic corticosteroids for asthma control.
• Inhaled corticosteroids with other agents are recommended by the American Thoracic Society (ATS).

Identification of Aerosolized Corticosteroids

• Beclomethasone dipropionate HFA (QVAR)
• Flunisolide hemihydrate HFA (AeroSpan)
• Fluticasone propionate (Flovent HFA, Flovent Diskus)
• Fluticasone furoate (Arnuity Ellipta)

Identification of Aerosolized Corticosteroids (Combinations)

• Fluticasone propionate/salmeterol (Advair Diskus, Advair HFA)
• Budesonide/formoterol fumarate HFA (Symbicort)
• Mometasone furoate/formoterol fumarate HFA (Dulera)
• Fluticasone furoate/vilanterol (Breo Ellipta)

Hypothalamic–Pituitary–Adrenal Axis (HPA Axis)

• This is the pathway for release and control of endogenous corticosteroids.
• Stimulation of the hypothalamus causes impulses to be sent to the median eminence, where corticotropin-releasing factor (CRF) is released.
• CRF goes to the anterior pituitary gland where corticotropin is released into the bloodstream.
• Corticotropin, or adrenocorticotropic hormone (ACTH), stimulates the adrenal cortex to secrete glucocorticoids, such as cortisol.

HPA Suppression with Steroid Use

• The body cannot distinguish between endogenous and exogenous steroids.
• Administration of glucocorticoid drugs raises the body’s steroid level.
• This inhibits the hypothalamus and pituitary glands.
• This is referred to as HPA suppression or adrenal suppression.

Physiology of Aerosolized Corticosteroids

• The production of the body’s own glucocorticoids follows a rhythmic cycle, termed diurnal or circadian rhythm.
• Cortisol levels are highest in the morning at 8 a.m.
• Factors such as jet lag and night shift work can interfere with this cycle.

Alternate-Day Steroid Therapy

• This mimics the natural diurnal rhythm by giving a steroid drug early in the morning when normal tissue levels are high.
• On the alternate day, regular diurnal secretion in the HPA system can resume.

Corticosteroids role

• Corticosteroids treat inflammation.
• Corticosteroids are used with asthmatics and COPD patients to achieve an anti-inflammatory effect.

Nature of Inflammatory Response

• Inflammation produces redness, swelling, heat, and pain.
• The triple response includes redness (local dilation of blood vessels, occurring in seconds), flare (reddish color several centimeters from the site, occurring 15 to 30 seconds after injury), and wheal (local swelling, occurring in minutes).

Nature of Inflammatory Response: Four Categories

• Increased vascular permeability results in the formation of an exudate in surrounding tissues.
• Leukocytic infiltration involves white blood cells (WBC) emigrating through capillary walls (diapedesis) in response to attractant chemicals (chemotaxis).
• Phagocytosis is when white cells and macrophages (in lungs) ingest and process foreign material such as bacteria.
• A mediator cascade occurs when histamine and chemoattractant factors are released at the injury site and various inflammatory mediators, such as complement and arachidonic acid products, are generated.

Inflammation of Airway

• Chronic bronchitis (usually caused by tobacco smoking) and asthma (range of triggers) are most common causes.
• Treatment with antiinflammatory agents such as glucocorticoids is important to reduce the basal level of airway inflammation, reducing airway hyperresponsiveness and predisposition to acute episodes of obstruction.
• Asthmatic reactions are biphasic, with early and late phases.
• The early asthmatic response is caused by immunoglobulin E (IgE).
• The early response peaks at approximately 15 minutes.
• Mast cells and eosinophils are the major cells responsible for the inflammatory response in asthma.
• Mast cell mediators and the release of cytokines recruit other inflammatory cells to cause the late-phase reaction.
• The late-phase response occurs after approximately 6–8 hours and can last up to 24 hours.

This lesson covers adrenal cortical hormones, steroids, and the clinical indications for using inhaled corticosteroids. It also discusses endogenous and Exogenous substances. Orally inhaled agents are for maintenance and control therapy of chronic persistent asthma.