BRONCHIAL ASTHMA Flashcards
◦ Episodic shortness of breath ◦ Wheezing ◦ Cough ◦ Chest tightness ◦ Mucus production
ASTHMA
- Most common chronic disease associated with significant morbidity and mortality
- children (8.4%) - greatest among boys (2:1 male-to-female ratio)
Asthma
Triggers of Airway Narrowing
- Allergens
- Irritants
- Viral INfection
- Exercise and cold, dry air
- Air pollution
- Drugs
- Occupational exposures
- Hormona changes
- Pregnancy
Type of Airway Inflammation that leads to contration, hyperresponsive, smooth-muscle proliferation
Type 2 Inflammation
Type of Airway Inflammation that smooth muscle constrict and airway hyperresponsiveness.
Non-type 2 Inflammation
Is the genetic tendency toward specific IgE production in response to allergen exposure.
Atopy
Druga that cause asthma
Beta blockers
ACE inhibitors
PE of asthma
- Tachypnea
- Tachycardia
- use of accessory muscle
- Wheezing, prolonged expiratory phase
- chest become silent with loss of breath sounds in severe
cholinergic agonist, inhaled in increasing concentrations is most commonly used
Methacholine
positive response in perfomance when Challenge with exercise and/or cold, dry air
≥10% drop in FEV1 from baseline
should prompt consideration of ABPA
IIgE Levels >1000 IU/mL
Detect IgE directed at specific antigens (radioallergosorbent test [RAST]), can be useful in confirming atopy.
Skin tests, or their in vitro counterparts
◦ approximate indicator of eosinophilic inflammation in the airways
◦ used to assess adherence to ICSs
◦ Elevated levels (>35–40 ppb) in untreated patients - eosinophilic inflammation.
Exhaled Nitric Oxide Fraction of exhaled nitric oxide (FeNO)
Levels ____ in patients with severe asthma on moderate- to high-dose ICS – poor adherence or persistent type 2 inflammation despite therapy
> 20–25 ppb
Chest roentgenography of asthma
normal but in more severe patients may show hyperinflated lungs
High-resolution CT in asthma px
show areas of bronchiectasis in patients with severe asthma, and there may be thickening of the bronchial walls, but these changes are not diagnostic of asthma.
◦ Relax airway smooth-muscle cells of all airways
◦ inhibition of mast cell mediator release, reduction in plasma exudation, and inhibition of sensory nerve activation
B2-Agonists
B2 Agonist
◦ begins within 3-5 minutes
◦ duration of 4-6 h
SABA (albuterol)
B2 Agonist
◦ duration of 12 h, given BID
◦ Formoterol - quick onset comparable to the short-acting β2-agonists
◦ Their use in asthma is generally restricted to use in combination with an ICS.
LABA (salmeterol and formoterol)
Side Effects of B2 Agonist
muscle tremor and palpitation
Prevent cholinergic nerve-induced bronchoconstriction and mucus secretion
◦ Long-acting muscarinic antagonists (LAMA)
◦ tiotropium bromide or glycopyrronium bromide
◦ may be used as an additional bronchodilator in patients with asthma that is not controlled by maximal doses of ICS-LABA combinations
◦ Side effects: dry mouth, urinary retention and glaucoma
Anticholinergics (Ipratropium bromide)
An oral compound that increases cyclic AMP levels by inhibiting phosphodiesterase, is now rarely used for asthma due to its narrow therapeutic window, drug-drug interactions, and reduced bronchodilation as compared to other agents.
Theophylline
◦ cornerstone of asthma therapy
◦ MOA:
◦ reducing inflammatory cell numbers and their activation in the airways.
◦ ICS reduce eosinophils in the airways and sputum, and numbers of activated T lymphocytes and surface mast cells in the airway mucosa.
◦ major effect is to switch off the transcription of multiple activated genes that encode inflammatory proteins such as cytokines, chemokines, adhesion molecules, and
inflammatory enzymes.
Inhaled Corticosteroids
They are generally used regularly twice a day as first-line therapy for all forms of persistent asthma. Doses are increased, and they are combined with LABAs to control asthma of increasing severity
Inhaled Corticosteroids
◦ lowest doses possible (due to side effects) are used in patients who cannot achieve acceptable asthma control.
◦ are also used to treat asthma exacerbations, frequently at a dose of 40–60 mg/d of prednisone or equivalent for 1–2 weeks.
◦ Intravenous preparations are frequently used in hospitalized patients. Patients are rapidly transitioned to it once their condition has stabilized
◦ Intramuscular triamcinolone acetonide has been used to achieve asthma control and reduce exacerbations
Chronic oral corticosteroids (OCSs)
an inhibitor of 5-lipoxygenase - inhibit production of leukotrienes
Zileuton
inhibit the action of leukotrienes at the CysLT1
receptor
Montelukast and Zafirlukast
are particularly effective in aspirin-exacerbated respiratory disease, which is characterized by significant leukotriene overproduction.
Leukotriene modifiers
inhibit mast cell and sensory nerve activation and are, therefore, effective in blocking trigger-induced asthma such as Exercise-Induced Asthma.
Cromolyn sodium and nedocromil sodium
is a blocking antibody that neutralizes circulating IgE without binding to cell-bound IgE and, thus, inhibits IgE-mediated reactions.
Omalizumab
◦ markedly reduce blood and tissue eosinophils and reduce
exacerbations
◦ patients symptomatic on moderate- to high-dose ICS/LABA, with two or more exacerbations that require OCS per year and with an eosinophil count of ≥300/µL, IL-5–active drugs reduce exacerbations by about half or more.
Anti-IL-5
Anti-IL-5 that blocks IL-5
- mepolizumab
- reslizumab)
Anti-IL-5 that blocks IL-5 receptor
benralizumab
binds to this subunit and, thus, blocks signaling through both receptor IL-4 AND IL-13.
Dupilumab
ASTHMA ATTACKS
◦ increasing chest tightness, wheezing, and dyspnea that are often not or poorly relieved by their usual reliever inhaler.
◦ unable to complete sentences and may become cyanotic
◦ Arterial blood gases : hypoxemia, PCO2 is usually low
Tx of asthma attacks
β2-agonist administered up to every 1 h
