Bronchodilators Flashcards
Bronchodilators
Bronchodilators act to reduce bronchomotor tone to bring about bronchodilation.
These are symptom relieving treatments that are regularly used in chronic conditions such as asthma and COPD.
Beta-2 agonists
Used in both asthma and COPD this is an important class of bronchodilator. It is utilised in both chronic and acute management of these conditions.
Beta-2 adrenoceptors
Beta-2 adrenoceptors are G-protein coupled receptors found primarily in the lungs. These are key receptors of the sympathetic nervous system that are stimulated by catecholamines such as adrenaline.
Beta-2 adrenoceptors are found throughout the lungs with a particularly high density in the bronchial smooth muscle. Activation of these receptors by the sympathetic nervous system cause bronchodilation through smooth muscle relaxation.
Beta-2 adrenergic agonists are sympathomimetics that activate beta-receptors. These drugs act to relax the airways smooth muscle.
Additional actions include:
Reduced release of inflammatory mediators from mast cells.
Increased mucociliary clearance.
Can be short-acting (e.g Salbutamol) or long-acting (e.g Salmeterol):
Short-acting beta-2 agonists (SABA): The short-acting forms are hydrophilic and as such are quickly metabolised. They have a rapid onset (< 5 minutes) and effects last around 6 hours. They are used as required (PRN). High use indicates inadequately controlled disease.
Long-acting beta-2 agonists (LABA): The long-acting forms are more lipophilic and effects last for around 12 hours. Used in a regular manner, concordance is often poorer than with SABAs.
Many of beta-2 agonists unwanted effects result from its systemic actions: (3)
Tachycardia: Results from activation of beta-1 (dominant receptor in the heart) and beta-2 adrenoreceptors in the heart. May also cause arrhythmias.
Tremor: Results from activation of beta-2 adrenoreceptors in skeletal muscle.
Hypokalaemia: Results from activation of beta-2 adrenoreceptors linked Na/K-ATPase channels leading to increased cellular uptake of potassium. Salbutamol may be used to help treat hyperkalaemia.
Muscarinic antagonists
Used primarily in chronic management of COPD, muscarinic antagonists also play a role in treatment of an acute asthma attack and acute exacerbation of COPD.
Inhaled antagonists
Inhaled muscarinic antagonists block the action of muscarinic acetylcholine receptors, they are non-selective. When administered these agents act to relax the airways smooth muscle.
They are primarily of use in the chronic management of COPD but may be used in the treatment of an acute asthma attack.
Can be short-acting (e.g Ipratropium) or long-acting (e.g Tiotropium).
Typical ‘anti-cholinergic’ effects:
Dry mouth (xerostomia)
Urinary retention
Headache
Exacerbation of glaucoma (pilocarpine - an agonist of M3 - is used in the treatment of angle-closure glaucoma).
Inhaled muscarinic antagonists block the action of muscarinic acetylcholine receptors, they are non-selective. When administered these agents act to relax the airways smooth muscle.
They are primarily of use in the chronic management of COPD but may be used in the treatment of an acute asthma attack.
Can be short-acting (e.g …) or long-acting (e.g …).
Can be short-acting (e.g Ipratropium) or long-acting (e.g Tiotropium).
.. are a nonselective phosphodiesterase (PDE) inhibitor that may be used in the management of COPD and asthma.
Methylxanthines are a nonselective phosphodiesterase (PDE) inhibitor that may be used in the management of COPD and asthma.
Methylxanthines
They occur naturally and are found in coffee, tea and chocolate. Bronchodilation is one of a number of effects of methylxanthines that contribute to its therapeutic effect. However with the advent of newer bronchodilators, methylxanthines have somewhat fallen from favour.
Theophylline may also be used to treat apnea and bradycardia of prematurity.
… may also be used to treat apnea and bradycardia of prematurity.
Theophylline may also be used to treat apnea and bradycardia of prematurity.
Mechanism of action
Two forms are used in clinical practice:
Theophylline is a naturally occurring methylxanthine.
Aminophylline is a 2:1 combination of theophylline and ethylenediamine that is more water-soluble. It can also be administered intravenously.
Their action is a result of adenosine receptor antagonism and indirect adrenergic activity.
Methylxanthines have a similar structure to caffeine, they have a wide range of effects including: (4)
Immunomodulation
Anti-inflammatory
Vasodilation
Bronchodilation