SGD4 - Isaac

LO7 – Describe the medications used in asthma treatment including

their pharmacological properties and side effects.
SABA and LABA
Short acting ß-2 agonists (SABA)
First-line treatment for acute asthma; bronchodilators of choice.
Administered rapidly after a quick history, physical examination, and
vital examination are done.
MDI SABA delivered via spacer (loaded one puff at a time and given
separately) has the same efficacy as nebulized SABA.
Parenteral/subcutaneous route SABA should be given in children with
moderate to severe/life-threatening acute exacerbations.
Long-acting ß-2 agonists (LABA)
E.g. salmeterol, formoterol
Treatment option for nocturnal asthma (instability/suboptimal
treatment) which are often controlled by appropriate doses of ICS.
When symptoms remain troublesome, adding LABA can relieve
symptoms and lessen the morning dip in lung function.
Mode of action
Mode of action Both SABA and LABA fall under the class of bronchodilators.
They mimic the actions of naturally occurring catecholamines to activate
adrenergic receptors to produce parasympathetic and sympathetic
physiological responses.
They mimic the actions of naturally occurring catecholamines to activate
adrenergic receptors to produce parasympathetic and sympathetic
physiological responses.
Beta-2 agonists act as ligands to adrenergic receptors with increased
selectivity towards beta-2 adrenergic receptors.
Activation of the beta-2 adrenergic receptor initiates a transmembrane signal
cascade, which involves G protein and adenylyl cyclase.
Mode of action
Adenylyl cyclase increases intracellular cAMP via the hydrolysis of
ATP, which serves to activate cAMP-dependent protein kinase A (PKA).
PKA acts to phosphorylate Gq-coupled receptors leading to a cascade
of intracellular signals, which reduces intracellular Ca2+ or decrease
the sensitivity of Ca2+.
The change in Ca2+ results in the inhibition of myosin light chain
phosphorylation, subsequently preventing airway smooth muscle
contraction (underlying mechanism behind beta-2 agonist; promotes
bronchodilatory effects)
Side effects
Potential side effects include:
Tremors
Tachycardia
Palpitations
Nervous tension
Headache
Muscle cramp
These side effects are seen more often during initial exposure
(improve and disappear completely after a few days/few weeks of
use)
Corticosteroids
Systemic corticosteroids
Essential in treatment of acute exacerbation to hasten recovery and
should be given early.
Administered via oral or IV route (parenteral route is indicated in
children who are vomiting/unable to tolerate orally or children with
moderate to severe/life-threatening acute exacerbations).
Inhaled corticosteroids
Treatment of choice in preventing asthma exacerbation in patients
with persistent asthma.
Regular use of ICS reduces the frequency of asthma symptoms,
bronchial hyper-responsiveness, risk of serious exacerbation, and
improves the quality of life.
Mode of action
Corticosteroids diffuse across the cell membrane and bind to
glucocorticoid receptors (GR) in the cytoplasm.
Activated GRs rapidly translocate to the nucleus where they produce
their molecular effects.
A pair of GRs (GR homodimer) bind to glucocorticoid response
elements (GRE) in the promoter region of steroid-responsive genes
and switches on the gene transcription for genes encoding β2-
adrenergic receptors and the anti-inflammatory proteins secretory
leukoprotease inhibitor and mitogen-activated protein kinase
phosphatase-1 (MKP-1) which inhibits MAP kinase pathways.
Side effects of inhaled corticosteroids
Local adverse effects include:
Dysphonia
Oral candidiasis
Reflex cough
Bronchospasm
These adverse effects are less common with low-dose compared to
high-dose inhaled corticosteroids, and are also mitigated by spacer
use when taking the medication via metered-dose inhalers
Leukotriene Receptor Antagonist (LTRA)
Leukotriene Receptor Antagonist (LTRA)
LTRAs are of definite role in management of wheezy infants and
toddler and moderate to severe chronic asthma.
Most commonly used in pediatrics is cysteinyl leukotriene
antagonists: Montelukast, Zafirlukast.
Mode of action
Leukotrienes are synthesized from arachidonic acid by the action of 5-
lipoxygenase in many inflammatory cells in the airways.
Cysteinyl leukotrienes (LTC4, LTD4, and LTE4) have amino acid moiety
and bind to cysteinyl leukotriene receptors (CysLT1 and CysLT2).
Bronchoconstriction, vascular permeability, eosinophil recruitment,
and chronic inflammation are mediated through the G protein-
coupled activation of cysteinyl leukotriene receptors.
Montelukast and zafirlukast are antagonists to cysteinyl leukotriene
CysLT1 receptors but not CysLT2 receptors.
Side effects
Side effects of leukotriene receptor antagonists may include the
following:
Headache
Gastrointestinal disorders
Pharyngitis
Fatigue
Upper respiratory tract infection
Cutaneous rash
Reversible alterations in levels of serum transaminase