Corticosteroids

Corticosteroids are for maintenance, and control therapy

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 in combination with other agents are recommended by the ATS and the GOLD for COPD

Intranasal aerosol agents: Management of seasonal and perennial allergic and non allergic rhinitis

Step 2 asthma:

  • > 2 days/week, not daily

  • Night awakenings 3-4 times per month


Aerosolized corticosteroids:

  • Beclomethasone dipropiomate HFA

    • QVAR

  • Flunisolide

    • AeroSpan

  • Fluticasone propionate/salmeteror

    • Advair diskus, advair HFA

      • Used to treat asthma and COPD, 1 puff BID

  • Fluticasone furoate

    • Arnuity ellipta

  • Budesonide

    • Pulmicort flexhaler

    • Pulmicort respules

  • Mometasone furoate

    • Asmanex twist halter

    • Asmanex HFA

  • Ciclesonide

    • Alvesco


Aerosolized corticosteroids (Combinations):

  • Budesonide/formoterol, fumarate HFA

    • Symbicort

  • Mometasone furoate/formoterol, fumarate HFA

    • Duelera

  • Fluticasone furoate/umeclidinium/vilanterol

    • Trelegy elipta

  • Budesonide/glycopyrrolate/formoterol

    • Brezti aerosphere

    • Brezti


Corticosteroids come from two primary sources:

  1. Naturally occurring hormones produced within the body

  2. Synthetic medications developed in labs

The body naturally produces corticosteroids in the adrenal cortex, the outer part of the adrenal glands located on the top of each kidney

3 types produced by the adrenal cortex:

  1. Glucocorticoids/glucocrticosteroids

  • Cortisol (Stress, regulates metabolism, controls inflammation, helps blood pressure)

  1. Mineralocorticoids/aldosterone

  • Regulate body water

  1. Sex hormones

  • Androgens and estrogens:

    • Androgen: Male sex hormone (Testosterone) (Can be seen in both males and females)

    • Estrogen: Female sex hormones (Can be seen in both males and females)

The production and release of these hormones are regulated by the hypothalamic-pituitary-adrenal (HPA) axis, a feedback system involving the hypothalamus, pituitary gland, and adrenal glands.

  • One of the most significant side effects of treatment with glucocorticoid drugs (exogenous corticosteroids) is adrenal suppression or HPA suppression


HPA suppression with steroid use:

  • Body cannot distinguish between endogenous and exogenous

  • Administration of glucocorticoid drugs raises body’s level

  • Inhibits hypothalamus and pituitary glands

  • Referred to as HPA suppression or adrenal suppression

It is seen with systemic administration of corticosteroids, it begins after 1 day of treatment, and is significant after 1 week of oral therapy at usual doses

A primary reason for using aerosolized glucocorticoids is to minimize adrenal or HPA suppression by minimizing the dosage and localizing the site of treatment


Diurnal steroid cycle:

Production of body’s own glucocorticoids follows rhythmic cycle: Circadian rhythm or diurnal

  • Cortisol levels are highest in the morning at 8 am

Jet lag and working night shifts would interfere with the diurnal steroid cycle


Inflammation of airway:

Asthma and Chronic Bronchitis are the most common

Treatment: Anti inflammatory agents such as glucocorticoids is important to reduce basal level of airway inflammation

Reduces airway hyper responsiveness and predisposition of acute episodes of obstruction

  • Asthmatic reactions are biphasic

    • Early phase and late phase

  • Early phase is caused by immunoglobulin E (IgE)

    • Response peaks at 15 minutes

  • Mast cells mediate and release of cytokines recruit other inflammatory cells to cause late phase reaction

    • Response occurs after 6-8 hours, can last up to 24 hours


Corticosteroids effects:

  • Steroids cause leukocytosis through several mechanisms that affect how white blood cells circulate in the body

  • Steroids cause neutrophils that are typically stuck to the walls of blood vessels to detach and enter the main circulation

  • They inhibit the movement of white bloods cells from the bloodstream into the tissues where they would normally fight infection or inflammation

  • Steroids prolong the lifespan of neutrophils, meaning fewer are removed from circulation

  • They stimulate the bone marrow to release more white blood cells into the blood stream

Effects on B receptors:

  • Restore responsiveness to B adrenergic stimulation

  • Enhance B receptor stimulation


Hazards and side effects of systemic administration:

  • Suppression of the HPA axis

  • Immunosuppression

  • Psychiatric reactions

  • Cataract formation

  • Myopathy of striated skeletal muscle

  • Peptic ulcer

  • Fluid retention

  • Hypertension

  • Increased WBCs

  • Dermatological changes

  • Slowing of growth (Children)

  • Hyperglycemia


Hazards and side effects of aerosol administration:

Major:

  • HPA suppression

  • Loss of bone density

  • Growth restriction (Children)

Potential:

  • Adrenal insufficiency

  • Allergic inflammation after cessation

  • HPA suppression

  • Growth reduction (Children)


Topical (Local) side effects with aerosol administration:

Most common:

  • Oropharyngeal candidiasis (Thrush)

  • Dysphonia (Voice alteration)

What to do?:

  • Use minimal dose

  • Use reservoir

  • Rinse mouth


Aerosol steroids in:

Asthma:

  • Early use in asthma

  • Acute and sever

COPD:

  • Relieve symptoms

  • Little to no effect on FEV1


Nonsteroidal Antiasthma Agents:

  • Cromolyn-like-drugs (Mast cell stabilizers)

  • Anti-leukotrienes

  • Monoclonal antibodies

Management of mild persistent asthma

General indications:

  • Cromolyn and Anti-LT as alternatives to ICS in asthma requiring step 2 care

  • Cromolyn is often used with infants and young children as alternatives to ICS in asthma requiring step 2 care because of safety profiles of ICS

  • Anti-leukotrienes can be useful in combinations with ICS to reduce the steroid dose


Cromolyn-like-drugs:

  • Cromolyn (Generic only)

Anti-leukotrienes:

  • Zafirlukast (Accolate)

  • Montelukast (Singulair)

  • 5-LO inhibitor: Zileuton (Zyflo; Zyflo CR)

Monoclonal antibodies:

  • Omalizumab (Xolair)

  • Benrailzumab (Faserna)

  • Mepolizumab (Nucala)

  • Reslizumab (Cinqair)

  • Dupilumab (Dupixent)