70R. Pharmacology in COPD

Question 1

what is COPD

Answer 1

Chronic obstructive pulmonary disorder

Question 2

what is COPD in tad more detail

Answer 2

Progressive airflow obstruction and lung hyperinflation that is, in some patients, partially reversible

Question 3

what are symptoms of COPD

Answer 3

dyspnoea, chesty cough, mucus, wheezy, chest

Question 4

how is COPD diagnosed and what is the FEV1/FVC ratio

Answer 4

through spirometry - Post bronchodilator FEV1/FVC ratio 0.7

Question 5

what are some of the Systemic manifestations in COPD

Answer 5

deconditioning and muscle weakness

Question 6

who does copd mainly effect

Answer 6

middle aged/older adults who are smokers and around air pollution

Question 7

what are the 2 types of COPD

Answer 7

Chronic Bronchitis and Emphysema

Question 8

what is chronic bronchitis

Answer 8

inflammation of bronchi and bronchioles

Question 9

what are some symptoms of chronic bronchitis

Answer 9

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.

Question 10

what happens in emphysema

Answer 10

distension and damage to the alveoli

destruction of acinial pouching in alveolar sacs

loss of elastic recoil

Question 11

When someone smokes or is exposed to air pollution, what is stimulated?

Answer 11

Alveolar Macrophages in the lungs

Question 12

alveolar macrophages that have been stimulated by smoke/air pollution produce what?

Answer 12

Cytokines

Question 13

activated alveolar macrophages release cytokines which activate what?

Answer 13

neutrophils , CD8 T cells, and more macrophages

Question 14

after smoking you end up with all these cells: neutrophils , CD8 T cells, and more macrophages. what do they release

Answer 14

matrix metalloproteinases and free radicals

Question 15

can you give me an examples of a matrix metalloproteinase

Answer 15

elastase

Question 16

There is an increased resistance to Air Flow During …………….in COPD

Answer 16

expiration

**exhalation phase fails - breathing out is hard work with copd

Question 17

describe the inhalation of a severe copd patient

Answer 17

near normal

Question 18

what are the 3 Muscarinic Acetylcholine Receptors in the Airways

Answer 18

M1, M2 and M3

Question 19

where are M1 receptors found

Answer 19

ganglia (nerve clusters in the airways)

Question 20

what is M1’s function

Answer 20

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

Question 21

where can you find M2’s

Answer 21

Found on postganglionic neuron terminals.

Question 22

what are M2’s function

Answer 22

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.

Question 23

when M2’s are blocked what happens to ACh

Answer 23

there is an increase in release

Question 24

where can you find M3’s

Answer 24

On airway smooth muscles and mucus-secreting cells.

Question 25

what are M3's function

Answer 25

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.

Question 26

so out of M1-M3 which one is the most important in treatment with patients with copd and why

Answer 26

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

Question 27

so these muscarinic receptor antagonists do what? (in summary)

Answer 27

- reduces bronchospasm - blocks ACh from increasing basal tone - decreases mucus secretion

Question 28

are muscarinic receptor antagonists curing the copd

Answer 28

No, they have a palliative effect: These medications mainly provide symptomatic relief and have little effect on the progression of COPD.

Question 29

what are the 2 types of muscarinic antagonists

Answer 29

SAMA and LAMAs short acting muscarinic antagonist long acting muscarinic antagonists

Question 30

name a SAMA

Answer 30

Ipratropium

Question 31

name 4 LAMAs

Answer 31

§ Tiotropium § Glycopyrronium § Aclidinium § Umeclidinium

Question 32

how are SAMA/LAMAs administered

Answer 32

inhalation

Question 33

which out of theses LAMAs § Tiotropium § Glycopyrronium § Aclidinium § Umeclidinium are black triangle drugs and need MHRA surveillance

Answer 33

Glyc, aclid and umec

Question 34

what does atropine and ipratropium and tiotropium have on there chemical structure to avoid adverse effects

Answer 34

quaternary ammonium group

Question 35

is ipratropium selective or non selective

Answer 35

non selective blocker of M1,2 and 3

Question 36

why are M3 Selective Blockers Superior to Ipratropium?

Answer 36

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.

Question 37

what are the 3 types of beta-adrenoreceptor agonists administered by inhalation

Answer 37

SABA- salbutamol LABA - salmeterol and formoterol UltraLABA - indacaterol and olodaterol

Question 38

so which should you use for copd patients? Muscarinic antagonists or beta adrenoreceptor agonists?

Answer 38

both combined

Question 39

what do A combination of a β2 agonist and a muscarinic antagonist do/increase

Answer 39

increase FEV1 (forced expiratory volume)

Question 40

what are the benefits of having combination inhalers

Answer 40

easy to use dont allow adjustment of the dosage

Question 41

why is it a good idea to take a LABA and a LAMA

Answer 41

LAMA - blocks activation of ACh so prevents bronchoconstriction LABA - agonist on B2 causes relaxation

Question 42

what are MABAs

Answer 42

muscarinic antagonist and Beta2 agonist. Basically a single drug that is both of these combined

Question 43

what other drugs are used to treat copd

Answer 43

glucocorticoids

Question 44

B-adrenoceptor agonists and/or muscarinic receptor antagonists can be co-administered with ...................... in combination inhalers.

Answer 44

glucocorticoids

Question 45

what do glucocorticoids increase risk of in COPD patients

Answer 45

Pneumonia

Question 46

what do triple inhalers contain

Answer 46

LABA, LAMA and glucocorticoid

Question 47

what is a benefit of glucocorticoid steroids

Answer 47

when given with a LABA they are helpful to patients with severe exacerbations

Question 48

what are some downsides to glucocorticoids

Answer 48

- increased pneumonia risk - do not alone suppress inflammation -might not work if patient smokes

Question 49

apart from LAMAs, LABAs and glucocorticoids, what other drugs are used in COPD (name 2)

Answer 49

Phosphodiesterase-4 (PDE4) Rofumilast

Question 50

Explain Phosphodiesterase-4 (PDE4) mode of action

Answer 50

PDE4 is an enzyme expressed in inflammatory cells like neutrophils, T cells, and macrophages. Blocking PDE4 can reduce inflammation and immune cells

Question 51

Explain rofumilast mode of action

Answer 51

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

Question 52

what are some side effects of rofumilast

Answer 52

gastrointestinal effects

Question 53

what are some comorbidities associated with COPD

Answer 53

Osteoperosis GI diseases Metabolic Syndromes Resp disease CardioVas Diseases Depression and anxiety

Question 54

what approach should you take when treating COPD

Answer 54

personalized patient centered approach - precision medicine

Question 55

personalized patient centered approach - precision medicine in COPD should include....

Answer 55

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.