Corticosteroids

Dr. Phoebe Bacalso

CLINICAL INDICATIONS FOR USE OF INHALED
CORTICOSTEROIDS
• Orally inhaled agents: Maintenance, control therapy of chronic
asthma, identified as requiring step 2 care or greater by the National
Asthma Education and Prevention Program Expert Panel
• Intranasal aerosol agents: Management of seasonal and perennial
allergic and nonallergic rhinitis.
Hypothalamic-
Pituitary-
Adrenal-Axis
Hypothalamic-Pituitary-
Adrenal Suppression
with Steroid Use

• Exogenous corticosteroid
agents can suppress the
HPA axis and the adrenal
gland.
• Levels of endogenous
corticosteroids follow a
daily, or diurnal, rhythm.
Overview of Immune Mechanisms
in Allergy and Inflammation
Cell-mediated
• T-lymphocytes mediate the immune response
• Helper/T4(CD4) CELLS:
• TYPE 1 (TH1) delayed-type hypersensitivity reactions and
other related to macrophage activation and T cell-
mediated immunity by production of interferon-gama
and interleukin2 (IL-2)
 Inflammation produces general symptoms of
INFLAMMATORY redness, swelling, heat, and pain

Redness: Local dilation of blood vessels,

occurring in seconds
NATURE OF

Flare: Reddish color several centimeters from

RESPONSE

the site, occurring 15 to 30 seconds after injury

Wheal: Local swelling, occurring in minutes

NATURE OF INFLAMMATORY
RESPONSE
• Increased vascular permeability: An exudate is formed in the
surrounding tissues.
• Leukocytic infiltration: White blood cells emigrate through
capillary walls (diapedesis) in response to attractant chemicals
(chemotaxis).
• Phagocytosis: White blood cells and macrophages (in the lungs)
ingest and process foreign material such as bacteria.
• Mediator cascade: Histamine and chemoattractant factors are
released at the site of injury, and various inflammatory mediators
such as complement and arachidonic acid products are generated.
Inflammation in the Airway
• The two most common inflammatory diseases of the airway:
• Chronic Bronchitis
• Asthma
• Glucocorticoids are mainstay for treating asthma
 Caused by a range of
triggers and involves a
complex pathology

Asthma
Chronic inflammation of
the airway wall: airflow
limitation and
hyperresponsiveness to
various stimuli
 Extrinsic Asthma

• Dependent on atopy or allergy

• Childhood onset
• Immunoglobulin mediated

Asthma Intrinsic Asthma

• Shows no evidence of
sensitization to common
inhaled allergens
• Nonallergic form
• Adult onset
 Beclomethasone Dipropionate (Qvar)

Flunisolide (AeroBid, AeroSpan)

Aerosolized Budesonide

Corticosteroids Mometasone

Fluticasone

Budesonide/Formoterol
 All of the steroids available as orally
inhaled agents are also available in an
intranasal formulation

Intranasal
Corticosteroids Exact indications for the intranasal
preparations vary by specific agent, but
intranasal steroids generally are used to
treat allergic or inflammatory nasal
conditions and seasonal or perennial
allergic or nonallergic rhinitis and to
prevent recurrence of nasal polyps
 GC are are lipid-soluble and act
on intracellular receptors to
produce anti-inflammatory
effects

Mode of Action Upregulation of anti-

inflammatory proteins (B
receptors and lipocortin) and
the downregulation of
proinflammatory proteins
(cytokines and substance P)
 • Suppression of factors such as
activator protein-1 (AP1), and
nuclear factor-Kb (NFkb)à
downregulation of gene expression
Mode of for proinflammatory mediators
Action such as cytokines
• NFkb regulates genes that have
increased expression in asthma
 • Effects on WBC Count
• GC cause depeletion of neutrophil
stores and their accumulation at
inflammatory sites and in exudates
• Demargination: increase the
number of neutrophils in
Mode of Action circulation as cells leave stores
 • Effects on B receptors
• Ability to restore responsiveness to
B-adrenergic stimulation
• GC enhance B-receptor stiumalation
Mode of by increasing the number and
Action availability of B-receptors on the cell
surfaces and by increasing affinity of
the receptor for B-agonists
• Glucocorticoids: inhibit the release
of arachidonic acid through
phospholipase A2 inhibition,
thereby producing direct anti-
inflammatory properties in the Mode of
airways Action
CytokinesInvolved in Airway Inflammation That Are Suppressed by Glucocorticoids
Hazards/Side Effects
• Immunosuppression: susceptibility to infection by bacterial, viral, fungal
• Cataract formation
• Myopathy of striated skeletal muscle can occur
• Steroid-induced osteoporosis
• Peptic Ulcer Disease
• Steroid-induced diabetes
• Retard bone growth and epiphyseal maturation
Hazards/Side Effects

Dermatologic Puffy
Fluid retention
changes appearance

Oropharyngeal
Increased WBC Fungal Dysphonia
infections
Source
• Rau’s Respiratory Care Pharmacology, 8the edition