Corticosteroids in Respiratory Care
I.
Primary Use in Respiratory Care
a. To reduce inflammation in the airways
Physiology of Corticosteroids
I.
Identification and Source
a. Corticosteroids are a group of chemicals secreted by the adrenal
gland
b. Adrenal gland
i. located on top of both kidneys
ii. medulla (inner zone)
1. produces epinephrine and norepinephrine
iii. cortex (outer zone)
1. produces corticosteroids
a. glucocorticoids (e.g. Cortisol)
i. allow the body to respond to stress
b. mineralocorticoids (e.g. ALDOSTERONE)
i. control fluid and electrolyte balance
c. sex hormones (e.g. ANDROGENS & ESTROGENS)
i. cause 2° sex characteristics
c. Steroids (glucocorticoids) used in respiratory care are similar to
Cortisol
i. usage has been increasing since the 1970’s and especially
since the inhalation form was developed
ii. a new understanding of asthma as an inflammatory disease
has increased their usage
II.
The Hypothalamic-Pituitary-Adrenal Axis
a. Sequence of glucocorticoid secretion
i. Stimulation of the hypothalamus causes impulses to be sent
to the median eminence
1. Injury
2. Disease
3. Exercise
4. Hypoglycemia (hunger)
ii. Corticotropin releasing factor (CRF) is released from the
median eminence
iii. CRF circulates through the portal vessel to the anterior
pituitary gland
iv. Adrenocorticotropic hormone (ACTH) is released from the
anterior pituitary gland into the bloodstream
v. ACTH stimulates the adrenal cortex to secrete glucocorticoids
(Cortisol)
b. Function of Glucocorticoids
i. Regulation of metabolism to increase blood glucose for energy
1. carbohydrates
2. fats
3. proteins
ii. Lipolysis
iii. Redistribution of fat stores
iv. Breakdown of tissue protein stores
III.
Hypothalamic-Pituitary-Adrenal Suppression With Steroid Use
a. When the body produces endogenous glucocorticoids, there is a
normal feedback mechanism within the HPA axis to limit production
i. As glucocorticoid levels rise, release of CRF and ACTH is
inhibited, and further production is stopped
ii. Similar to the way a thermostat regulates room temperature
b. The body can’t distinguish between endogenous and exogenous
corticosteroids.
c. Administration of exogenous steroids can cause a decrease in the
production of endogenous steroids called adrenal suppression
d. Adrenal suppression begins after one day of systemic administration
and is significant after one week
i. This is a problem because if exogenous steroids are stopped
suddenly, it takes a few days for the natural HPA cycle to
start up again
ii. The body is unable to deal with stresses
1. this is called adrenal shutdown
a. nausea
b. dizziness
c. fatigue
d. weakness
e. salt craving
e. If systemic exogenous steroids have been administered long
enough to cause adrenal suppression, they cannot be stopped
abruptly
f. Three strategies have been developed to administer corticosteroids
without causing adrenal shutdown
i. Wean patients off systemic steroids with a tapered dose
ii. Administer oral steroid therapy QOD
1. Adrenal glands are not suppressed
iii. Use inhaled steroids
1. there is little or no systemic absorption, so no adrenal
suppression
2. cannot abruptly switch from oral to inhaled steroids
a. the oral dose must be tapered
IV.
The Diurnal Steroid Cycle
a. The production of the body’s own glucocorticoids follows a
rhythmical cycle, termed a diurnal or circadian rhythm
b. There is a daily rise and fall of levels in the body
i. Cortisol levels are normally highest in the morning at about
8:00 a.m.
ii. During the day plasma levels gradually fall and are lowest at
around midnight
iii. “Jet Lag” and the delay in adjusting to night shift is caused by
the inability of the body to quickly adjust the levels to the
new time zone
Nature of the Inflammatory Response
One of the major therapeutic benefits of exogenous glucocorticoids
(steroids) is for their anti-inflammatory action
I.
Inflammation
a. The response of vascularized tissue to injury
i. Increased vascular permeability
1. exudate in surrounding tissues
ii. Leukocytic infiltration
1. movement of white blood cells to the area
iii. Phagocytosis
1. WBCs and macrophages ingest and process foreign
material such as bacteria
iv. Mediator cascade
1. release of chemical mediators of inflammation
II.
Inflammation in the Airways
a. Inflammation can occur in the lungs due to:
i. direct trauma
1. gun-shot wound
2. stabbing
ii. indirect trauma
1. blunt chest injury
iii. inhalation of noxious or toxic substances
1. chlorine gas
2. smoke
iv. respiratory infections
v. systemic infections causing septic shock
1. ARDS
vi. chronic bronchitis
vii. asthma
1. allergic
2. non-allergic
b. Inflammation in Asthma
i. See text, page 214, figure 11-4
ii. Asthma is a disease in which there is chronic inflammation
of the airway wall, causing airflow limitation and
hyperresponsiveness to a variety of stimuli
iii. The airway inflammation is mediated by inflammatory cells
1. mast cells
2. eosinophils
3. T lymphocytes
4. macrophages
Inflammation in the lungs results in
5. bronchospasm
6. increased mucus secretion
7. mucosal edema (swelling of the airways)
iv. Symptoms of asthma
1. wheezing
2. dyspnea
3. coughing
4. chest tightness
Corticosteroids Agents
I.
Systemic (oral and IV)
a. Prednisone
b. Methylprednisolone (Solu-medrol)
c. Cortisone
d. Hydrocortisone
II.
Corticosteroids Available for Inhalation
Drug
Beclomethasone dipropionate
Triamcinolone acetonide
Flunisolide
Fluticasone propionate
Budesonide
Fluticasone propionate /
Salmeterol
Brand Name
Beclovent
Vanceril
Azmacort
AeroBid
AeroBid-M
Flovent
Flovent Rotadisk
Pulmicort
Turbuhaler
Pulmicort Respules
Advair Diskus
Formulation
MDI
MDI
MDI
MDI
DPI
DPI
SVN
DPI
Pharmacology of Corticosteroids
I.
Mode of Action
a. Inhibit many of the cells involved in airway inflammation
b. Reduce the number of mast cells in the airways
c. Inhibit plasma exudation
d. Inhibit mucus secretion
II.
Effect on White Blood Cell Count
a. Reduces the accumulation of neutrophils at inflammatory sites
and increases the number in circulation
i. Causes an overall increase in the white blood cell count
b. Reduces the number of monocytes, basophils and eosinophils
i. Asthmatics who would otherwise have a higher than
normal eosinophil count will have a low count after
initiation of steroids
c. Constrict the microvasculature to reduce leakage of cells and
fluids into inflammatory sites
III.
Effect on ß Receptors
a. Restore responsiveness to ß-adrenergic stimulation
i. Increase the number of ß2 receptors
ii. Increase the affinity of the receptors for ß-agonists
b. Effect is seen 1-4 hours after IV administration
c. IV bolus is given in status asthmaticus for this effect
Hazards and Side Effects of Steroids
I.
Side effects seen with systemic administration
a. These effects are caused by the high levels of circulating
glucocorticoids caused by exogenous administration as compared
to normal endogenous levels
i. H-P-A suppression
ii. Immunosuppression
1. Increased risk of infection
iii. Psychiatric reactions
1. Insomnia
2. Mood changes
3. Manic-depression
4. Schizophrenia
iv. Cataract formation
v. Myopathy of skeletal muscle
vi. Osteoporosis
vii. Peptic ulcer
viii. Fluid retention
ix. Hypertension
x. Increased WBC count
xi. Dermatologic changes
1. Thinning of the skin
xii. Redistribution of subcutaneous fat
1. Cushingoid appearance
a. central obesity
b. hump back
c. moon face
xiii. Growth restriction
xiv. Increased glucose levels
II.
Side effects seen with inhaled aerosol
a. Oropharyngeal fungal infection
i. Caused by the immunosuppressive properties of steroids
ii. Common organisms
1. Candida albicans (thrush)
2. Aspergillus
iii. Treat with topical antifungal agents
iv. Prevention
1. use reservoir device
2. rinse mouth after use
b. Dysphonia
i. Hoarseness
ii. Change in voice quality
c. Cough
d. Bronchoconstriction
III.
Precautions
a. Cannot switch from oral or IV to inhaled without tapering
i. not enough systemic absorption
b. Not indicated for acute asthma attack
i. Steroids don’t treat bronchospasm
c. Inhaled steroids may be inadequate during times of increased
stress (infections)
i. may need systemic steroids
d. Incorrect use of metered dose inhaler can prevent adequate
amount of drug delivery
Clinical Application of Aerosol Steroids
I.
Use in Asthma
a. Acute episodes
i. inhaled steroids are not of use in acute episodes
ii. IV large bolus for status asthmaticus with follow up drip or
oral
1. fairly slow action, but given ASAP so antiinflammatory effects start sooner
2. may help in ER by enhancing ß2 effects of
sympathomimetic drugs like albuterol
iii. Chronic Asthma
1. inhaled steroids are first line drugs for maintenance
of mild, moderate and severe asthma
2. these patients may need a dose pack of oral steroids
periodically for infections or other stresses
a. dose pack
i. a packet of oral steroids with specific
instructions for tapering off (e.g. take
4/day for two weeks, then 3 per day for
two weeks, etc)
3. for chronic asthma, use in the following order
a. inhaled
b. qod oral
c. daily oral
4. Oral steroids are usually the last drug to try and first
to discontinue in treating asthma due to side effects
II.
Use in Chronic Obstructive Pulmonary Disease (COPD)
a. regular treatment with inhaled glucocorticosteroids is
appropriate for symptomatic COPD patients with an FEV1 < 50%
predicted (Stage III: Severe COPD and Stage IV: Very Severe
COPD) and repeated exacerbations
i. This treatment has been shown to reduce the frequency of
exacerbations and improve health status
ii. Inhaled glucocorticosteroid combined with a long-acting
ß2-agonist is more effective than the individual
components
b. Long-term treatment with oral steroids is not recommended in
COPD
i. Steroid myopathy contributes to muscle weakness,
decreased functionality and respiratory failure in patients
with advanced COPD
ii. Oral steroids may be used intermittently for times of stress
Androgenic (Anabolic) Corticosteroids
I.
Testosterone
a. endogenous sex hormone secreted by adrenal cortex in both
men and women (less in women)
b. produces secondary male sexual characteristics, including
increase in muscle mass (anabolic effects).
c. Derivatives have been developed which minimize masculinizing
effects and maximize anabolic effects
II.
Medical Uses
a. Treatment of anemia
i. increases RBC production
b. hypogonadism
i. stimulates sexual development
III.
Use by Athletes
a. controversial due to many side effects
b. increase body weight and mass
i. increase performance, endurance and strength