asthma Flashcards
pathophysiology
what is asthma?
inflammatory condition which there is recurrent reversible airways obstruction in response to stimuli that do not affect non-asthmatic subjects.
signs and symptoms
patients experience intermittent attacks of wheezing, shortness of breath- with difficulty breathing in and out - sometimes cough
acute asthma attacks
= reversible but the underlying pathological disorder can progress in older patients to a chronic state - resembling COPD. - caused by combination of genetic and environmental factors.
risk factors of asthma
- genetics
- allergens
- RSV and HRV
- traffic related air pollution, nitric dioxide, particulate matter,
- tobacco smoke
- obesity
asthma triggers
- dust
- dust mites
- pollen
- mould
- animal hair/ fur
- cold air
- common allergens
- airborne pollutants
what are the 2 main phases of asthma attack ?
- immediate phase
- late (or delayed) phase
asthma pathophysiology
asthma consists of airway hyper-responsiveness
1) airway wall inflammation , involving neutrophils , T cells, alveolar dendritic cells and macrophages.
2) characterised by the recruitment of T cells (cytotoxic) by dendritic cells in the alveolar air spaces and of eosinophils in bronchioles.
3) hyper secretion of bronchial mucous glands, along with infiltration by inflammatory cells.
4) Vasodilation of the bronchial microvasculature with increased vascular permeability and oedema.
hypersensitivity
bronchial hyper- reactivity ( hyper- responsiveness) is abnormal sensitivity to a stimuli which can result in bronchoconstriction.
Th2 Pathway implicated
Bronchodilators - Adrenergic receptors
- all are typical G protein-couples receptors
- alpha - adrenergic receptors ( 2 sub types)
- beta - adrenergic receptors ( 3 sub types)
B1 = found mainly in the heart - responsible for the effects of catecholamines.
B2 = responsible for causing smooth muscle relaxation in many other tissues.
Bronchodilators - (SABA) Salbutamol
B2 receptors = predominant receptors on the bronchial smooth muscle.
- dilate blood vessels and bronchi
- precursor = adrenaline
- relieve symptoms = activation of B2 = relaxation of smooth muscle and widening of the airway
- symptomatic asthma = prescribe inhaled SAB2A - salbutamol, terbutaline
Pharmacokinetics of Salbutamol
Absorption - well absorbed after oral administration
Distribution - doesn’t cross BBB
Metabolism - metabolised to inactivate metabolites in the liver.
Excretion - excreted in urine and small amounts in faeces.
Long acting beta agonists (LABA)
E.g. - salmeterol, formoterol
- bind to 2 sites on the receptor - the active and eco sites of the b2 adrenergic receptor = longer duration of effect
relieve symptoms = activation of B2 = relax smooth muscle and widen airways
- use in conjunction wit ICS - can be prescribed if asthma is uncontrolled by SABA alone .
Methylxanthines
E.g - Theophylline
- can be used as an add- on therapy - treatment of asthma.
- relaxes smooth muscle of bronchial airways and pulmonary blood vessels
- reduces airway responsiveness to histamine, methacholine, adenosine and allergens
- competitively inhibits phosphodiesterase (PDE)
PDE - enzyme responsible for breaking down cyclic AMP in smooth muscle cells, possibly resulting in bronchodilation.
anti- inflammatory (ICS)
Inhaled Corticosteroids (ICS)
- glucocorticoids are the main therapy in achieving anti inflammatory action in asthma.
- ICS restrain clonal proliferation of Th cells and decrease formation of cytokines.
- Th cytokines that recruit and activate eosinophils and are responsible for promoting the production of IgE and the expression of IgE receptors.
- Glucocorticoids inhibit the generation of vasodilators PGE2 and PGI2 by inhibiting induction of COX2
anti - inflammatory (steroids)
Given as ICS - e.g. Beclomethasone Dipropionate
- if inflammation is severe can give oral steroids - Prednisolone
