Pharmacology of Respiratory system Flashcards
describe the end of terminal bronchioles
do not take part in airway respiration, they don’t have air sacs at there terminal points
describe what the parasympathetic system does to the airways
- Bronchoconstriction
- Acetylcholine causes this by binding to M3 (muscarinic 3) receptor
- It innervates smooth muscle in bronchi
what does the parasympathetic system innervate in the airways
- It innervates smooth muscle in bronchi
describe what the sympathetic system innervate
- There is not good evidence that sympathetic nerves innervate the airways
- It can innervate the adrenal medulla that leads to the release of adrenaline, and this can lead to release of mediators that have an effect on the airway smooth muscle cells therefore it innervates them indirectly
- Targets for the sympathetic system – submucosal gland
- Can cause hypersecretion of the submucosal glands
what does the sympathetic system do in the airways
- THEY REGULATE BRONCHILA BLOOD FLOW AND MUCUS SECRETION
what is the receptor for the sympathetic system in the airways
beta 2 (Major drug target for drugs used to treat elements of the respiratory tract)
where are the cell bodies of the preganglionic fibres of the parasympathetic system located
located in the brainstem
where are the cell bodies of the postganglionic fibres of the parasympathetic system located
- Cell bodies of the postganglionic fibres are embedded in the walls of the bronchi and bronchioles
how does the parasympathetic system cause bronchodilation
bronchial smooth muscle contraction caused by M3 muscarinic ACh receptors on ASM cells, and increased mucus secretion mediated by M3 muscarinic ACh receptors on gland cells
how does bronchoconstriction happen
- Acetylcholine binds to G protein via G coupled muscarinic M3 receptors
- this increases phospholipase C and therefore IP3 (as it splits into IP3 and DAG)
- IP3 binds to ligand gated IP3 receptors on the endoplasmic reticulum
- This causes calcium to be released from the endoplasmic reticulum into the cytoplasm
- The calcium then binds to calmodulin and causes myosin light chain kinase MLCK to become active forming the calcium MLCK complex
- This phosphorylated the light chain of myosin
- This causes actin myosin cross linking and smooth muscle contraction
How does bronchodilator happen
- Bronchodilator nerves in human airways are non-adrenergic non cholinergic NANC
- Neurotransmitter is NO(nitric oxide)
- NOS expressed in epithelial and nerve cells
what are Two major respiratory conditions
Asthma and COPD
what is asthma and COPD caused by
- This is driven by inflammatory cells and mediators
- In the airways if there is chronic inflammation it leads to airway remodelling such as bronchoconstriction and mucus hypersecretion
what are the types of bronchodilators
SAMA and LAMA
SABA and LABA
What do SAMA and LAMA do
- Short or long acting muscarinic antagonists (SAMA and LAMA) block the binding of acetylcholine to M3 muscarinic receptors= inhibits smooth muscle contraction
what do SABA and LABA do
- Short or long acting beta 2 adrenergic receptor agonists (SABA/LABA) bind to beta 2 adrenergic receptor and induce a cascade of signal transduction events and activation of PKA – can lead to phosphorylation of complex = leads to smooth muscle relaxation
describe the steps of asthma management
- Preventer removes inflammation and prevents asthma from taking place
- If person doesn’t respond to low dose ICS up the dose – but this can increase adverse effects – this may predispose the individual to pneumonia
- Increase dose of ICS and they still don’t have well controlled asthma then you use a LABA – add on therapy not firstline therapy – studies that are shown that individuals with asthma on LABA therapy have increased risk of morbidity
- Then combination of ICS and LABA.- can increase dose of combination to improve asthma management
- Step up scale of severity if asthma is not managed well
what drugs are used in a asthma management
- Reliver SABA as required –take when asthma is worsened,
- LABA – used as add on therapy to ICS
what does ICS stand for
inhaled corticosteroids
describe how inhaled corticosteroids ICS works
- Goal to reduce underlying inflammation
- Steroid – can go through the lipid
1. CS can cross the membrane
2. It binds to the glucocorticoid receptor in the cytoplasm this allows it to go through the nucleus through the nuclear membrane
3. Where it binds to GRE glucocorticoid response elements
4. This leads to upregulation of genes that increase anti-inflammatory mediators – reduce inflammation
5. Or recruits parts of the transcription machinery that reduces the production of proinflammatory mediators therefore reducing inflammation
how does IgE mediated allergy cause asthma
- APC processes antigen
- Exposes it on the MHC II
- Presents it to naïve T cells
- Causes development of TH2 type of cells
- TH2 produces IL4 and IL13
- B cells produce IgE
- IgE binds to mast cells
- Sensitised mast cells
- Exposure to allergen
- IgE crosslinking and mast cell degranulation and release mast cell mediators – these lead to inflammation in allergic asthma and allergic conditions
- Leads to the release of IL5 activates eosinophils – these drive inflammation which is an aspect of asthma
asthma statistics
- Allergy a major trigger
- 150 million Europeans have allergy
- Asthma – usually linked to food allergies which leads to worsening of the asthma this can increase the risk of fatality
- 90% of people with asthma have allergies to air allergens – duct, pollen and fungi
- 142 billion euros can be saved with proper diagnosis and treatment
what’s different between COPD management and asthma management
in COPD management LABA/LAMA can be used as a first line therpay whereas in asthma it is not
how many groups of treatment are there in COPD
4
ABCD
how do you divide the groups up in COPD
- If you have 0 or 1 moderate exacerbations that did not lead to hsoptial administrations then you fall into group A or B
- If you have had greater or equal to 2 moderate exacerbrations that did not lead to hospital admission or greater or equal to 1 exacerbations that lead to a hospital admission then you are group C and group D
- COPD assessment (CAT score) and mMRC (questionnaire of breathlessness)
the lowest risk group in COPD is
group A
the highest risk group in COPD is
group D
ICS is not as effective in …
COPD as they are in asthma in dampening the underlying inflammation
what drugs are prescribed in
- group A
- group B
- group C
- group D
- Group A – bronchodilator
- Group B – LAMA/LABA
- Group C – LAMA
- Group D - LAMA or LAMA and LABA or ICS and LABA
