70R. Pharmacology in COPD Flashcards
what is COPD
Chronic obstructive pulmonary disorder
what is COPD in tad more detail
Progressive airflow obstruction and lung hyperinflation that is, in some patients, partially reversible
what are symptoms of COPD
dyspnoea, chesty cough, mucus, wheezy, chest
how is COPD diagnosed and what is the FEV1/FVC ratio
through spirometry - Post bronchodilator FEV1/FVC ratio 0.7
what are some of the Systemic manifestations in COPD
deconditioning and muscle weakness
who does copd mainly effect
middle aged/older adults who are smokers and around air pollution
what are the 2 types of COPD
Chronic Bronchitis and Emphysema
what is chronic bronchitis
inflammation of bronchi and bronchioles
what are some symptoms of chronic bronchitis
Cough
Clear mucoid sputum
Infections with purulent sputum
Increasing breathlessness
**Purulent means containing pus, a thick, yellowish liquid that comes from an infection in the body.
what happens in emphysema
distension and damage to the alveoli
destruction of acinial pouching in alveolar sacs
loss of elastic recoil
When someone smokes or is exposed to air pollution, what is stimulated?
Alveolar Macrophages in the lungs
alveolar macrophages that have been stimulated by smoke/air pollution produce what?
Cytokines
activated alveolar macrophages release cytokines which activate what?
neutrophils , CD8 T cells, and more macrophages
after smoking you end up with all these cells: neutrophils , CD8 T cells, and more macrophages. what do they release
matrix metalloproteinases and free radicals
can you give me an examples of a matrix metalloproteinase
elastase
There is an increased resistance to Air Flow During …………….in COPD
expiration
**exhalation phase fails - breathing out is hard work with copd
describe the inhalation of a severe copd patient
near normal
what are the 3 Muscarinic Acetylcholine Receptors in the Airways
M1, M2 and M3
where are M1 receptors found
ganglia (nerve clusters in the airways)
what is M1’s function
helps speed up nerve signals (fast neurotransmission) By making a slow signal that makes the nerve cells fire more often. In summary, nAChRs initiate the fast response, and M1 receptors sustain and amplify this response, ensuring efficient communication in the ganglia
where can you find M2’s
Found on postganglionic neuron terminals.
what are M2’s function
Act as inhibitory autoreceptors.
M2 receptors reduce the release of ACh.
When M2 receptors are blocked, the inhibition is lifted, leading to an increase in ACh release
aka
They act like brakes to reduce the release of ACh.
How: When these receptors are blocked, the brakes are off, and more ACh is released.
when M2’s are blocked what happens to ACh
there is an increase in release
where can you find M3’s
On airway smooth muscles and mucus-secreting cells.
what are M3’s function
Cause muscles to contract and increase mucus production.
When ACh binds to M3 receptors, the muscles contract.
Mucus cells: When ACh binds to M3 receptors, more mucus is produced.
so out of M1-M3 which one is the most important in treatment with patients with copd and why
M3
well if you are reducing M3 which when bound to by ACh causes smooth muscle of the airway to contract and have lots of mucus production then you are not constricting the airway as much which helps people with copd
explained further -
ACh Release: ACh is released from postganglionic parasympathetic fibers and epithelial cells in the airways.
M3 Receptor Activation: ACh binds to M3 receptors on airway smooth muscle (ASM), causing the muscles to contract, leading to bronchoconstriction.
Antagonist Action: Muscarinic receptor antagonists bind to M3 receptors, preventing ACh from binding.
Result: This blockade prevents the contraction of airway smooth muscle, thereby reducing bronchoconstriction and helping to keep the airways open
so these muscarinic receptor antagonists do what? (in summary)
- reduces bronchospasm
- blocks ACh from increasing basal tone
- decreases mucus secretion
are muscarinic receptor antagonists curing the copd
No, they have a palliative effect: These medications mainly provide symptomatic relief and have little effect on the progression of COPD.
what are the 2 types of muscarinic antagonists
SAMA and LAMAs
short acting muscarinic antagonist
long acting muscarinic antagonists
name a SAMA
Ipratropium
name 4 LAMAs
§ Tiotropium
§ Glycopyrronium
§ Aclidinium
§ Umeclidinium
how are SAMA/LAMAs administered
inhalation
which out of theses LAMAs § Tiotropium
§ Glycopyrronium
§ Aclidinium
§ Umeclidinium
are black triangle drugs and need MHRA surveillance
Glyc, aclid and umec
what does atropine and ipratropium and tiotropium have on there chemical structure to avoid adverse effects
quaternary ammonium group
is ipratropium selective or non selective
non selective blocker of M1,2 and 3
why are M3 Selective Blockers Superior to Ipratropium?
Because with ipratropium you block M1,2 and 3. Blocking M3 and M1 is desirable but blocking M2 is not. This is because release of Ach from parasympathetic postganglionic neurons is increased by auto receptor antagonism
and remember you don’t want to block M2 because M2 Receptors: Act as inhibitory autoreceptors that reduce ACh release. Blocking M2 receptors can increase ACh release, potentially worsening bronchoconstriction.
what are the 3 types of beta-adrenoreceptor agonists administered by inhalation
SABA- salbutamol
LABA - salmeterol and formoterol
UltraLABA - indacaterol and olodaterol
so which should you use for copd patients? Muscarinic antagonists or beta adrenoreceptor agonists?
both combined
what do A combination of a β2 agonist and a muscarinic antagonist do/increase
increase FEV1 (forced expiratory volume)
what are the benefits of having combination inhalers
easy to use
dont allow adjustment of the dosage
why is it a good idea to take a LABA and a LAMA
LAMA - blocks activation of ACh so prevents bronchoconstriction
LABA - agonist on B2 causes relaxation
what are MABAs
muscarinic antagonist and Beta2 agonist. Basically a single drug that is both of these combined
what other drugs are used to treat copd
glucocorticoids
B-adrenoceptor agonists and/or muscarinic receptor antagonists can be co-administered with …………………. in combination inhalers.
glucocorticoids
what do glucocorticoids increase risk of in COPD patients
Pneumonia
what do triple inhalers contain
LABA, LAMA and glucocorticoid
what is a benefit of glucocorticoid steroids
when given with a LABA they are helpful to patients with severe exacerbations
what are some downsides to glucocorticoids
- increased pneumonia risk
- do not alone suppress inflammation
-might not work if patient smokes
apart from LAMAs, LABAs and glucocorticoids, what other drugs are used in COPD (name 2)
Phosphodiesterase-4 (PDE4)
Rofumilast
Explain Phosphodiesterase-4 (PDE4) mode of action
PDE4 is an enzyme expressed in inflammatory cells like neutrophils, T cells, and macrophages.
Blocking PDE4 can reduce inflammation and immune cells
Explain rofumilast mode of action
Roflumilast is a selective PDE4 inhibitor that suppresses inflammation and emphysema in animal models of COPD.
It is approved for oral treatment of severe COPD, particularly in patients with chronic bronchitis and a history of exacerbations
what are some side effects of rofumilast
gastrointestinal effects
what are some comorbidities associated with COPD
Osteoperosis
GI diseases
Metabolic Syndromes
Resp disease
CardioVas Diseases
Depression and anxiety
what approach should you take when treating COPD
personalized patient centered approach - precision medicine
personalized patient centered approach - precision medicine in COPD should include….
Frequent Exacerbations: Monitor and manage based on exacerbation frequency.
ICS(inhaled corticosteroids) History: Review exacerbation history before starting or continuing ICS.
Side Effects: Regularly assess the risk of pneumonia and other side effects from ICS.
Patient Preferences: Engage patients in treatment decisions to enhance adherence and outcomes.
