2- pharmacology COPD Flashcards
what is COPD?
chronic pulmonary obstructive disease
- it’s airflow reduction that can be partially reversible sometimes but progressively worsens (assessed by FEV1 & exacerbations of symptoms)
- can be bronchitis & emphysema
how does smoking lead to chronic bronchitis & emphysema?
smoking →stimulation of resident alveolar macrophages →cytokine production →activation of neutrophils, CD8+ T cells, increasing macrophage numbers →release of matrix metalloproteinases (e.g.elastase), free radicals →chronic bronchitis and/or emphysema
what is chronic bronchitis?
- inflammation of bronchi & bronchioles which has cough & clear mucoid sputum
- may or may not have infections with purulent sputum
- has increasing breathlessness
what is emphysema?
- distension & damage to alveoli
- destruction of alveolar sacs
- loss of elastic recoil
what is resistance in inhalation & exhalation?
normal person = during inhalation, there is some resistance to gas flow but it’s minimal and relatively even between exhalation & inhalation
moderate COPD = resistant pressure increases, turbulent line
severe COPD = inspiration phase is almost as steep as normal person but breathing out is extended with much greater resistance, turbulent and requires a lot of effort
what happens when muscarinic acetylcholine receptors activated?
M3 muscarinic receptor - g coupled protein with Gq protein →activated PLC which converts PIP2 →Ip3 →mediates Ca2+ release from ER and makes contraction
what are M1 receptors?
in ganglion, facilitate fast neurotransmission mediated by ACh acting on nicotinic receptors
what are M2 receptors?
on post ganglionic neuron terminals that act as negative feedback receptors = inhibitory autoreceptors reducing release of Ach
*blocking M2 receptors would increase release of ACh
what are M3 receptors?
expressed on airway smooth muscle cells, mediate contraction in response to Ach
(also present on mucus secreting cells evoking increased secretion)
why is it better to try give more selective for M3 muscarinic antagonists rather than non selective muscarinic antagonists?
Ipratropium = non selective blocker of M1,2,3 - there are prefered agents with selectivity for M3
*we don’t want to block M2 (exerts negative feedback on M1 signalling in preganglionic neuron)
so ideally: inhibit M3 and stimulate M2 (very difficult)
how do you make more specific drug (selective instead of non selective) for muscarinic receptors?
Modifying different groups on back bone can make much more specific drug, who’s half life can be controlled
what effect does blocking M3 receptor antagonist have on airways?
the drug reduced bronchospasm by reducing feel of a need to cough by reducing innervation of muscular around airways so less sensitive to irritant stimuli & also blocks Ach mediated basal tone
the drug will also decrease mucus secretion
- muscarinic receptor antagonists have little effect on progression of COPD, have few adverse effects
how is best way to take muscarinic receptor? (hint - alone or with…)
muscarinic antagonist & beta 2 adrenoceptor because:
- muscarinic antagonist = prevent contraction
- activate Beta 2 agonist = promote relaxation
*muscarinic antagonist alone just prevents contraction so not that good
what are short acting beta agonists?
salbutamol
what are long acting beta agonists?
salmeterol & formoterol = provide bronchodilation but no underlying inflammation
- given in combination with steroid
