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Respiriatory: Airway Disease > Pharmacotherapy of airflow obstruction > Flashcards

Pharmacotherapy of airflow obstruction Flashcards

1
Q

What 2 categories can drugs for airflow obstruction be divided into?

A
  • Preventers (anti-inflammatory)

* Relievers (bronchodilators)

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2
Q

Describe an asthmatic inflammatory response to an allergen

A
  • Allergen digested into TSLP
  • TSLP digested and presented by dendritic cells
  • Dendritic cell travels to lymph node and presents antigen to CD4+ T cell via MHC II complex
  • Proliferate to form TH0 cells
  • TH0 cell proliferates to form TH2 cell
  • TH2 cell releases IL-4, which stimulates expansion of B cell population
  • TH2 also releases IL-5 which recruits eosinophils
  • B cells proliferate to form plasma cells, which secrete IgE
  • IgE binds to IgE receptors on mast cells, activating them
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3
Q

What do eosinophils do?

A

Release

  • Basic and cationic proteins
  • Leukotrienes
  • Cytokines
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4
Q

What causes hyper-secretion of mucous in asthma?

A

Leukotriene D4 acting on goblet cells

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5
Q

What cell releases Leukotriene D4?

A

Mast cells

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6
Q

When are monoclonal antibodies used to treat asthma?

A

When inhaled corticosteroids are ineffective in treating inflammation

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7
Q

What is a reliever drug for asthma?

A

Short-acting B2 agonist

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8
Q

What is the 1st line preventer for asthma?

A

Inhaled corticosteroids (e.g. cromoglycate)

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9
Q

What are examples of controllers?

2nd line additives to ICS

A
  • Theophyline
  • Leukotriene receptor agonist (LTRA)
  • Long-acting B2 agonist (LABA)
  • Long-acting muscarinic antagonists (LAMA)
  • Anti-IgE
  • Anti-IL5
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10
Q

What treatment is used for the most severe cases of asthma?

A

Oral corticosteroids

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11
Q

What combinations of treatment are used for severe asthma?

A
  • SABA
  • Inhaled corticosteroids
  • LABA/LAMA
  • LTRA/Theo/Anti-IgE/Anti-IL5
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12
Q

When is the only time LAMA and LABA can be used?

A

In addition inhaled corticosteroids

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13
Q

What is the disadvantage of using corticosteroids?

A

May predispose COPD sufferers to pneumonia

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14
Q

How do corticosteroids predispose COPD sufferers to pneumonia?

A
  • Local immune suppression

* Impaired mucocilliary clearance

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15
Q

Are oral steroids (e.g. prednisolone) used for maintenance of asthma?

A

No, only used for acute exacerbations

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16
Q

Why is prednisolone (oral steroid) only used for acute exacerbations and not maintenance therapy?

A

It has a very low therapeutic ratio

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17
Q

What is an example of an oral steroid used in asthma?

A

Prednisolone

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18
Q

What is an example of an inhaled corticosteroid?

A

Beclomethasone

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19
Q

Why are inhaled steroids used for maintenance monotherapy in asthma?

A

They have a high therapeutic ratio

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20
Q

When is the only time inhaled corticosteroids are effective in treating asthma?

A

In combination with LABA

not as monotherapy

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21
Q

What effect does an ICS/LABA combo have on COPD in ACOS?

A

If COPD sufferer has eosinophilia (>4%), reduces exacerbations in eosinophilic COPD (aka ACOS)

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22
Q

What is used to optimise lung delivery of inhaled corticosteroids?

A

Extra fine solution HFA/spacer

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23
Q

Why are doses of inhaled corticosteroids kept low in patients with ACOS?

A

Want to remove eosinophils but do not want to cause pneumonia

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24
Q

What is the safest inhaled corticosteroid to use in COPD?

A

Beclomethasone

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25
Why are inhaled corticosteroids not effective in non-eosinophilic COPD?
Cannot melt away neutrophils
26
What are the most dangerous steroids for COPD?
* Fluticosone proprionate | * Flucticosone furoate
27
Why are fluticosone proprionate and flucticosone furoate the most dangerous steroids for COPD?
Stay in the lungs for a long time causing immuno-suppression (greater risk for pneumonia)
28
Why do inhaled corticosteroids have a large therapeutic ratio?
Directly delivered to site of tissue action (lungs) – do not require large doses
29
What is eosinophilia?
>4% eosinophils in the blood
30
How to corticosteroids work?
Not bronchodilators - they target eosinophilic inflammation
31
What is the effect of inhaled corticosteroid on peak flow in asthma sufferers?
* Increases peak flow | * Variability of peak flow diminishes
32
What size must particles be to get delivered past the carina?
They must be less than 5um (microns)
33
How many times does the bronchial tree divide?
23
34
What is a spacer?
Plastic holding chamber
35
What are the advantages of a spacer?
* Requires less coordination * Decreases particle size and velocity * Reduces oropharyngeal and laryngeal side effects * Reduces systemic absorption from swallowed fraction * Acts as a holding chamber for aerosol * Improves lung deposition
36
What are dry powder inhalers?
Emit dry powder, not pressurised aerosol
37
What is the advantage of dry powder inhalers?
* Easy to use - do not require coordination
38
What are the disadvantages of dry powder inhalers?
* Particle size is large - stuck in airways, poor lung deposition * Can cause oropharyngeal candidiasis if deposited in oropharynx
39
What are cromones used to treat?
Asthma
40
What is the function of cromones?
* Mast cell stabiliser | * Weak anti-inflammatory properties
41
How are cromones administered?
Inhaled route only
42
Why are cromones not used much?
Poor efficacy
43
What do LTRAs do?
Block cysteinyl leukotriene D4
44
What are prostaglandins and thromboxanes blocked by?
Aspirin
45
What do prostaglandins and thromboxanes do?
* Prostaglandins - cause pain | * Thromboxanes - platelet aggregation (clotting)
46
What does LD4 do?
* Promotes mucous secretion (hyper-secretion) * Mucocilliary dysfunction * Increases vascular permeability (oedema) * Amplifies cascade * Promotes smooth muscle contraction
47
What are LTRAs used to treat?
Asthma
48
What is the function of LTRAs in treating asthma?
Anti-inflammatory
49
What is an example of an LTRA?
Monteleukast
50
Are LTRAs the 1st line treatment for inflammation in asthma?
No, the are 2nd line treatment - complementary to inhaled corticosteroid
51
Are LTRAs steroids?
No, but still anti-inflammatory
52
What is an example of an anti-IgE monoclonal antibody?
Omalizumab
53
What does omalizumab do?
* Inhibits the binding to the high-affinity IgE receptor | * Inhibits TH2 response and associated mediator release from basophils/mast cells
54
What is the function of anti-IgE monoclonal antibodies and anti-IL5 drugs?
* Prevent exacerbations - do not improve lung function
55
Are anti-IgE monoclonal antibodies and anti-IL5 drugs effective in COPD?
No, asthma only
56
What are examples of anti-IL5 drugs?
* Mepolizumab | * Resilizumab
57
What do anti-IL5 drugs do?
Block the effects of IL-5 which is responsible for eosinophilic inflammation in asthma
58
What do B2-agonists do?
* Bronchodilators - stimulate bronchial smooth muscle B2-receptors * Increase cAMP levels
59
What is an example of a short-acting B2-agonist?
Salbutamol
60
What are examples of long-acting B2 agonists?
* Salmeterol | * Formoterol
61
What is SMART?
Single maintenance and deliver therapy
62
What drugs are used in SMART for asthma?
Beclometasone and formoterol in combination inhalers
63
Should salmeterol and formoteral (LABAs) be given on their own?
No, only with corticosteroids
64
What do M3 receptors on airway smooth muscle cells mediate?
* Bronchoconstriction | * Mucous secretion
65
What are muscarinic antagonists?
Bronchodilators - block M3 receptors
66
What is an example of a short-acting muscarinic antagonist?
Ipratropium
67
What are examples of long-acting muscarinic antagonists?
* Tiotropium * Glycopyronium * Umeclidinium
68
What are muscarinic antagonists used for?
* To reduce exacerbations in COPD | * Used in combination with ICS to treat asthma
69
What is the problem with administering B2 agonists regularly?
Body adapts - B2 receptors internalise, meaning there are less receptors available to mediate effect of adrenaline
70
What are methylxanthines?
* Bronchodilators | * Anti-imflammatory
71
What is an example of a methylxanthine?
Theophyline (oral)
72
What are the functions of methylxanthines?
* Prevent nocturnal dips (peak flow falls at night) * Inhibits phosphodiesterase enzymes, increasing cAMP * Adenosine antagonist
73
What are methylxanthines used to treat?
Asthma and COPD
74
What are PDE4 inhibitors?
Anti-Inflammatory drugs (minimal effect on FEV1)
75
What is an example of a PDE4 inhibitor?
Roflumilast
76
What are PDE4 inhibitors used for?
COPD only
77
What are the adverse effects of PDE4 inhibitors?
* Nausea * Diarrhoea * Headache * Weight loss
78
What are examples of mucolytics?
* Carbocisteine | * Erdosteine
79
What is the function of mucolytics?
To reduce sputum viscosity and so reduce exacerbations in COPD
80
What is the treatment for chronic asthma?
* Inhaled corticosteroid - suppress inflammatory cascade * Plus non-steroid anti-inflammatory therapy e.g. theophylline, anti-leukotriene, cromoglycate * Plus LABA/LAMA - stabilise smooth muscle
81
What are inhaled steroids not used to treat?
Acute asthma
82
What is the treatment of acute asthma?
* Oral prednisolone or IV hydrocortisone * Nebulised high dose salbutamol * At least 60% O2 * Assisted mechanical intubated ventilation if falling PaO2 and rising PaCO2
83
What should never be used in the treatment of asthma?
Respiratory stimulants
84
What happens to FEV1 over the course of an individual's life?
Will fall continuously and smoothly
85
What is the effect of smoking of rate of FEV1 fall over an individual's lifetime?
Much sharper decline
86
What is the effect of stopping smoking on the rate of FEV1 fat over an individual's lifetime?
Stopping smoking will never restore the lost FEV1, but the subsequent rate of loss may revert to normal
87
What is the treatment of acute COPD?
* Nebulised high dose salbutamol + ipratropium * Oral prednisolone * Antibiotic if infection * 24-28% O2 titrated against PaO2/PaCO2 * Physiotherapy to aid sputum expectoration * Non-invasive ventilation to allow higher FiO2 * Intubated assisted ventilation only if reversible component e.g. pneumonia
88
What is never used to treat acute COPD?
Inhaled corticosteroids

Respiriatory: Airway Disease (10 decks)

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