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Sophie - Applied Physiology & Pharmacology Year 2 > 54.1 Asthma and its Pharmacology > Flashcards

54.1 Asthma and its Pharmacology Flashcards

1
Q

What is asthma?

A

Heterogenous, non-progressive chronic inflammatory respiratory disease
*Various pathobiological mechanisms → different subtypes.
Different onsets, inflammation types, + responses to treatments.

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2
Q

What are asthma attacks?

A

Asthma attacks → recurrent acute exacerbations of episodic bronchoconstriction + mucus hypersecretion causing reversible airflow obstruction.
*Breathlessness, wheezing, + coughing.

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3
Q

What is type 2 asthma?

A

Type 2 asthma → type 2 inflammation.
CD4+ Th2 lymphocytes (+ innate lymphocytes) drive IgE production + secrete CKs IL-4/5/10 –recruit→ eosinophils/ basophils/ mast cells into airways.
E.g. early-onset allergic asthma/ late-onset eosinophilic asthma.

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4
Q

What is non-type 2 asthma?

A

Non-type 2 asthma → inflammation w/out T2 inflammatory markers.
Th1 + Th17, neutrophils, + proinflammatory CKs (e.g. IL-1beta/ IL-6/ TNF-alpha) involved.
E.g. neutrophil asthma

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5
Q

What is the same between non-type 2 and type 2 asthma?

A

All subtypes: ex/intrinsic factors drive exacerbation + production of bronchoconstrictors by mast cells.
E.g. histamine/ PD2/ LTC/ LTD4/ PAF

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6
Q

How can asthma be assessed?

A

NICE 2018 guidelines:
*Clinical setting → spirometry results assessing FEV1/FVC used in diagnosis + assessment of bronchodilator reversibility.
*Asthma –obstructive pulmonary disease→ ↑ airflow obstruction.
*↓ FEV1:FVC ratio (<0.7 usually - due to decrease in FEV1)
*Reversibility of airflow obstruction (assessment of bronchodilator response) = ↑ FEV1 >12% + > 200 ml.

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7
Q

What can be used to grade the severity of asthma exacerbations?

A

*PEFR (peak expiratory flow rate) → maximum flow rate generated during forced exhalation, starting from full inspiration.
*Used to grade severity of exacerbation (along w/ O2 saturation/ HR/ BP/ ABG)

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8
Q

What is the PERF grading for asthma?

A
  1. Moderate: PEFR> 50-75% of best (results <2 years ago)or predicted PEFR + no features of severe asthma
  2. Acute severe: PEFR 33-50% of best or predicted Or any of following: RR > 25/min, HR >11/ min or inability to complete sentences in one breath
  3. Life-threatening: PEFR <33% of best/predicted OR O2 saturation <92% OR altered consciousness, confusion, exhaustion, cyanosis, poor respiratory effort, cardiac arrhythmia
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9
Q

What is the acute management of someone hospitalised with asthma?

A

Acute management of someone hospitalised :
*hypoxic: give controlled supplementary O2.
*Treat with SABA
*poor initial response, consider adding other bronchodilators – ipratropium bromide or xanthines
*For all attacks: give corticosteroid prednisolone.
*Adjuvant, acutely in severe asthma attacks: magnesium sulphate: IV, some bronchodilator effect and membrane stabiliser

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10
Q

Why is FEV1 a truer indication of airway obstruction than PERF?

A

FEV1 is a dynamic measure of flow used that represents a truer indication of airway obstruction than PEFR (since reduced PEFR may be due to muscle weakness that improves maximal effort for exhalation)

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11
Q

How is therapeutic response to antiasthmatic drugs measured?

A
  • FEV1 test
  • Review symptoms
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12
Q

What is the diagnostic feature for asthma on a spirometer?

A

Decreased FEV1

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13
Q

What is the function of relivers?

A

to treat acute symptoms (shortness of breath/ wheezing/ coughing/ chest tightness) - also for COPD exacerbations

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14
Q

What are the different relievers available?

A

*SAMAs (Short-acting muscarinic receptor antagonists) → (e.g. ipratropium bromide)
*SABA (Short-acting beta-2 agonists) → (e.g. salbutamol/ terbutaline/ adrenaline)
*Xanthines → (e.g. IV-administered aminophylline or oral theophylline)

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15
Q

What is the mechanism by which beta-2 agonists cause bronchodilation?

A

Activate beta-2 receptors (GsPCRs)
Increases cAMP, activates PKA, activates MLCP (myosin light chain phosphatase) which dephosphorylates the myosin light chain so it cannot form actin-myosin cross bridges

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16
Q

What is the mechanism by which xanthines cause bronchodilation?

A
  • Competitively inhibit PDE (which usually breaks down cAMP)
  • Increased cAMP levels and/or cGMP –> relaxation (via PKA/PKG)
  • ALSO block adenosine receptors which usually permit Ca2+ entry for contraction
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17
Q

What is the mechanism by which cholinergic receptor antagonists cause bronchodilation?

A

Block parasympathetic nerve reflexes that usually cause airways to tighten –> bronchospasm
Via M3 receptors

18
Q

What are some adverse effects of beta-2 agonists?

A
  • Result from systemic absorption
  • Tremor
  • Tachycardia
  • Cardiac dysrhythmia
  • Also - desensitisation when used too much; may lose effect when most needed
19
Q

What are some adverse effects of cholinergic receptor antagonists?

A
  • Wider inhibition of parasympathetic NS
  • Inhibition of secretions - e.g. mouth dryness, reduced gastric acid secretion
  • Skin flushing
  • Dizziness, nausea
  • Tachycardia
20
Q

What are some adverse effects of xanthines?

A
  • Due to PDE inhibition: nausea, vomiting, headaches, gastric discomfort
  • Due to adenosine receptor antagonism: diuresis, epileptic seizures
  • Due to both: cardiac arrhythmias
21
Q

When are relievers sufficient?

A

For mild asthma, relievers usually sufficient to keep asthma under control + achieve reversibility of airflow obstruction

22
Q

What are controllers?

A

Controllers → to slow progression of disease. For individuals w/ poorly control of asthma.
*Regular use of controllers + maintenance therapy targeting underlying inflammation in airways that contributes to pathogenesis
*Over time → prevents asthma attacks + symptoms w/ aim of achieving more adequate long-term control.

23
Q

What are some controllers?

A

*Immunomodulatory corticosteroids → (e.g. beclomethasone/ prednisolone)
*LABAs (Long-acting beta-2 agonists) → (e.g. salmeterol)
*Leukotriene receptor antagonists → (e.g. zafirlukast/ montelukast)

24
Q

Combination of LABAs + immunomodulatory corticosteroids shown to best improve asthma control - why is this?

A

ICS ↑ gene transcription of beta-2 Rs → helps protect against ↓-reg of Rs in association w/ long-term beta-agonist use.

25
Q

What is the mechanism of corticosteroids to treat asthma?

A
  • Corticosteroids inhibit the synthesis and action of the enzyme phospholipase A2 which is required for the synthesis of both prostaglandins and leukotrienes.
  • They also suppress transcription of many cytokines.
  • Thus, the corticosteroids inhibit acute inflammation.
26
Q

What are some adverse effects of corticosteroids?

A
  • Higher risk of infection
  • Mood changes
  • Fluid retention, weight gain
  • Easy bruising
  • Muscle wasting, weakness
  • Fat redistribution
  • Osteoporosis
  • Think CUSHING’S disease; excess corticosteroids
27
Q

Do bronchodilators affect the underlying disease?

A

No, they just reduce symptoms

28
Q

What is COPD?

A

Progressive, irreversible disease caused by chronic alveolar damage leading to a remodelling of the airways and sustained decreases in gas exchange

29
Q

What are some triggers for asthma?

A

Allergens - like pollen
Antigens
Exercise
Cold air
Anxiety

30
Q

What are the two types of bronchodilators in terms of duration of effect?

A

Short-acting: stop asthma attack
Long-acting: constant bronchodilation so symptoms of an acute attack are less severe

31
Q

What happens to mucus in an asthma attack?

A

Becomes progressively more viscous (due to increasing sympathetic nervous activity)
Overall production increases

32
Q

What is a cellular change caused by asthma over time?

A

Airway epithelial desquamation

33
Q

What is airway epithelial desquamation?

A

The shedding of airway epithelial cells

34
Q

What is given as a beta-2 agonist in extreme acute cases?

A

Adrenaline

35
Q

What is the difference in duration of asthma vs COPD symptoms?

A

Asthma: short, acute attacks
COPD: more constant, chronic symptoms

36
Q

Which drugs are able to treat eosinophilic but not non-eosinophilic asthma?

A
  • Corticosteroids
  • Inhibitors of type 2 inflammation
37
Q

Which other symptom makes bronchoconstriction and the accompanying symptoms worse? How?

A

Inflammatory oedema
Makes lungs even more stiff and tight –> harder to breathe (worsened dyspnoea)

38
Q

Which symptoms do asthma and COPD share?

A
  • Cough
  • Chest tightness
  • Wheezing
  • Dyspnea
39
Q

Why is obstruction worse on exhalatation in asthma?

A
  • Lung scaffolding collapses to become smaller on exhalation than inhalation
  • Air is trapped in alveoli - so becomes more difficult to empty them (rather than inhale)
40
Q

What is COPD caused by?

A

Often due to exposure to noxious chemicals (e.g. cigarette smoke) → Triggers abnormal inflammation
*More destructive, irreversible pathology compared to asthma.
CD8+ Tcells induce neutrophils + macrophages to produce abundance of proteases → emphysema
Elastase → degrades lung elastin
Inflammatory leukocytes → ↑ destructive oxidants
*COPD affects both airways + lung parenchyma
Asthma → only airways.

41
Q

What can be used to treat COPD?

A

Relievers
*Corticosteroid resistance in COPD large problem

Sophie - Applied Physiology & Pharmacology Year 2 (32 decks)

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