Drugs used in the Treatment of COPD Flashcards
(46 cards)
What are the causes of COPD?
- Smoking
* Air pollution (not as important)
What are the effects of COPD?
- Airflow reduction that is partially reversible with bronchodilators in some patients (lowered FEV1, FVC) *cough
- mucus production
What is COPD divided into?
Chronic bronchitis and emphysema
Explain the process of how smoking causes COPD
- Smoking (air pollution)
- Stimulation of resident alveolar macrophages
- Cytokine production
- Activation of neutrophils, CD8+T cells
- Increased macrophage numbers
- Release of matrix metalloproteinases (e.g. elastase) and free radicals
What are the signs and symptoms of chronic bronchitis?
- inflammation of bronchi and bronchioles
- cough
- clear mucoid sputum
- infections with purulent sputum
- increasing breathlessness
What is emphysema?
- loss of elastic recoil
* distension and damage to alveoli
What is an important treatment to reduce parasympathetic neuroeffector transmission in COPD?
Muscarinic receptor antagonists
What are muscarinic receptor antagonists?
- Competitive antagonists of bronchoconstriction caused by smooth muscle M3 receptor activation
- M3 receptor activated in response to ACh released from postganglionic parasympathetic fibres
What are the different types of muscarinic ACh receptors expressed in human airways?
M1, M2 and M3
Where are airway M1, M2 and M3 receptors found?
- M1 - cell bodies of post-ganglionic neurones
- M2 - post-ganglionic neurones terminals
- M3 - airway smooth muscle cells
What is the function of M1 receptors in the airway?
- Controls fast neurotransmission by ACh acting on nicotinic receptors (nAChR)
- Controls slow e.p.s.p. that increases action potential frequency from nicotinic receptor stimulation
What is the function of M2 receptors in the airway?
Inhibitory autoreceptors reducing release of ACh (their blockade thus increases the release of ACh)
What is the function of M3 receptors in the airway?
- Control contraction in response to ACh
* Also present on mucus-secreting cells causing increased secretion
Why is Ipratropium (SAMA) no longer used in the treatment of COPD?
It is a non-selective muscarinic antagonist, meaning it blocks M1, M2 and M3 indiscriminately
Why are non-selective muscarinic antagonists not useful in the treatment of COPD?
Blockage of M1 and M3 is beneficial, but blockade of M2 is counter-active
- When block M1 receptor, reduces amount of AcH released onto airway SM cell – blockage is beneficial
- M2 receptors act in a negative feedback to reduce release of AcH – when stimulated, reduce the volume of AcH transmitted to SM
- If block M2 receptor – block inhibition of Ach and results in increase in concentration of AcH in junction between neuron and muscle
Which muscarinic receptor is the most important to target in COPD?
M3 - muscarinic receptor antagonist will cause relaxation of bronchial smooth muscle
What are examples of muscaranic receptor antagonists used in the treatment of COPD?
- Ipratropium (SAMA - not really used anymore)
- Tiotropium (LAMA)
- Glycopyronium (LAMA)
- Aclidinium (LAMA)
- Umeclidinium (LAMA)
How are muscaranic receptor antagonists administered in COPD?
All administered by inhalation
What is the advantage of using Tiotropium (etc) as opposed to Atropine?
- Atropine is a tertiary amine (nitrogen is not always positively charged) so when it is not positively charged, it can pass across biological membranes in airways and enter into systemic circulation
- Tiotropium (etc) is a quaternary ammonium so is always positively charged and cannot enter systemic circulation (restricted to airways)
Why is it important that ‘-iums’ don’t enter systemic circulation?
Would effectively block all activities of parasympathetic NS
What are the effects of muscaranic receptor antagonists?
- Reduce bronchospasm caused by irritant stimuli and also block ACh-mediated basal tone
- Decrease mucous secretion
- Have little effect on the progression of COPD as their effect is mainly palliative
- Have few adverse effects (little systemic absorption due to quaternary ammonium group)
What is Ipratropium?
A non-selective blocker of M1, M2 and M3 receptors - preferred agents with some selectivity for M3 are available
Why is bronchospasm caused by irritant stimuli known as a vago-vagal reflex?
Both sensory and motor components of reflex are in same nerve (CN X – vagus)
How do modern muscaranic receptor antagonists work?
They are selective M3 blockers - block transmission by ACh acting on ASM M3 receptors
