2. Outline
Part 1
• Asthma as an inflammatory disease
• Role of steroids in the treatment for asthma
exacerbation
• Steroids vs Steroids
• Management of Asthma Exacerbation
Part 2
• COPD as an inflammatory disease
• Management of COPD exacerbation
• Role of Systemic Corticosteroids in the treatment
of COPD Exacerbation
9. Asthma Exacerbations
• EXACERBATION is an acute or sub-acute
worsening of symptoms and lung function compared
with the patient’s usual status
• Terminology considerations:
• ‘Flare-up’ is the preferred term for discussion with
patients as ‘Exacerbation’ is a difficult term for patients
• ‘Attack’ has highly variable meanings for patients and
clinicians
• ‘Episode’ does not convey clinical urgency
Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2015. Available from: www.ginasthma.org
11. Acute Exacerbation
Management Considerations
Early treatment is vital in managing an acute
episode and should be initiated before patient reaches
hospital
The goals of treatment include:
Arterial oxygenation
Relief of airway obstruction
Reduction of inflammation
Prevention of relapse
Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2015. Available from: www.ginasthma.org
12. Acute Asthma Exacerbations
Role of Corticosteroids
Early use of corticosteroids is associated with:
• Reduced risk of relapse
• Reduction in hospitalization rate
• Reduction in β-agonist use
The main corticosteroids used for asthma include:
• Methylprednisolone
• Prednisolone
• Prednisone
Fiel SB, et al. J Asthma. 2006;43:321-331.
15. Pharmacology of SteroidsRELATIVE POTENCY AND EQUIVALENT DOSES
OF DIFFERENT SYSTEMIC STEROIDS
Brunton LL, Lazo JS, Parker KL, eds. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 11th ed. New York, NY: McGraw-Hill; 2006.
18. Potential Benefits of Corticosteroids in
the Treatment of Asthma
• Enhancement of B receptor responsiveness by upregulating B
receptors on airway smooth muscle
• Dec in capillary basement membrane permeability; dec vascular leak
from endothelial cells
• Dec leukocyte attachment; dec number of eosinophils, mast cells,
and dendritic cells
• Modulation of calcium migration intracellularly
• Reduction in airway mucus production
• Suppression of IgE receptor binding
• Interruption of arachidonic acid inflammatory pathways
• Decreased airway smooth muscle contraction, mucosal edema, and
airway inflammation
• Airway remodeling
• Decreased cytokine and mediator production from epithelial cells
•
19. Adverse Reactions to
Glucocorticoids
• Ophthalmic – cataracts, inc IOP,
glaucoma
• CV– HTN, CHF, VTE
• GI – PUD, pancreatitis
• Endocrine/Metabolic
• truncal obesity, moon facies, buffalo
hump, lipomatosis, hepatomegaly
• Acne, hirsutism, ED, menstrual
irregularities
• Growth suppression in children
• Hyperglycemia, DKA
• Negative balance of N, K,Ca
• Na retention, hypoK, met alka
• Secondary adrenal insufficiency
• Musculoskeletal– proximal myopathy,
osteoporosis, vertebral compression
fractures, Avascular necrosis of
femoral and humeral heads
• Neuropsychiatric – convulsion,
benign intracranial hypertension,
affective, behavioral, cognitive
defects
• Dermatologic – facial erythema, thin
fragile skin, petechiae and
ecchymoses, violaceous striae,
impaired wound healing
• Immune, infectious – suppression of
delayed hypersensitivity; neutrophilia,
monocytopenia, lymphocytopenia,
dec inflammatory responses;
susceptibility to infection
Jameson L, et. al. ENDOCRINOLOGY Adult and Pediatric
(Chap 100 Glucocorticolid Therapy. Axelrod, L;) 7th edition, Elsevier 2016
20. Corbridge, Thomas. Et al. Severe Asthma Exacerbation
Textbook of Critical Care, Elsevier, 2011
21.
22.
23.
24.
25.
26. Rajaram, S Life Threatening Asthma
Critical Care Medicine 3rd Ed, Elsevier 2008
27.
28.
29.
30.
31.
32.
33.
34.
35.
36. Summary
ON ASTHMA:
Airway inflammation is a KEY feature of asthma
Patients present with variable symptomatology
and asthma severity
Control is a major challenge in asthma
management
Symptom control and reduction of risk are major
goals of therapy
37. Summary
ON CORTICOSTEROIDS:
Corticosteroids play important role in asthma
management:
acute exacerbations of asthma
maintenance therapy for severe asthma
short courses for worsening asthma
In Acute Exacerbations of Asthma, systemic
corticosteroids reduce:
relapse rate
B agonist use
hospital admissions
Basic pharmacologic properties are important
considerations in choosing appropriate systemic steroid
for asthma management
Notas do Editor
Systemic corticosteroids may be compared based on their glucocorticoid (anti-inflammatory) and mineralocorticoid (sodium retention) properties <REF Brunton, p. 1594A, 1594B,
1594D>. The duration of action for corticosteroids approximates their duration of HPA axis suppression and may be classified as <REF Brunton, p. 1594C; AHFS, p. 3101C>:
• short acting: 8 to 12 hour biological half-life
• intermediate acting: 12 to 36 hour biological half-life
• long acting: 36 to 72 hour biological half-life
Using cortisol (hydrocortisone) as the reference point, the following table lists systemic corticosteroids and their relative potencies, duration of action, and equivalent doses <REF
Brunton, p. 1594C>.
Methylprednisolone is more slowly absorbed and binds primarily to albumin, which has a large binding capacity. The stronger binding capacity allows for greater penetration and longer retention in the lung tissue
Methylprednisolone vs Prednisolone: Lung Penetration
Vichyanond and colleagues conducted a pharmacokinetic study to evaluate the penetration of glucocorticoids into the lung. This study compared the concentration of methylprednisolone and prednisolone in the bronchoalveolar space of 17 rabbits after administration of the drugs. Both drugs were administered in a randomized, crossover, manner using a loading dose followed by a continuous infusion for 180 minutes to achieve steady-state plasma concentrations between 200 to 2000 ng.
This slide shows the correlation between bronchoalveolar lavage fluid (BALF) and plasma concentration. Methylprednisolone had a greater BALF concentration than prednisolone at plasma concentrations >5 ng/µg. BALF concentrations continued to increase with increasing methylprednisolone concentration, while BALF concentrations remained linear with increasing prednisolone concentrations. These data suggest that methylprednisolone has a higher degree of bronchoalveolar penetration than prednisolone and therefore is beneficial for treating pulmonary disorders.
Vichyanond P et al. J Allergy Clin Immunol. 1989;84:867.
