Asthma Flashcards

1
Q

What type of hypersensitivity reaction is Asthma?

A

Type 1 hypersensitivity reaction
(IgE hypersensitivity)
Asthma is an inflammatory disease

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2
Q

What nerve system is dominant in the airways?

A

Parasympathetic division
It is carried by Nerve X (Vagus nerve) - The ganglia of the nerves are inside the bronchi and bronchioles
Parasympathetic division causes contraction of smooth muscle

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3
Q

What is the effect of parasympathetic innervation of the bronchioles/airways?

A

Bronchial smooth muscle contraction mediated by ACh acting upon the M3 muscarinic receptors
Increased mucus secretion mediated by ACh acting upon M3

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4
Q

What types of transmitters can be used to dilate the airways?

A

Vasoactive Intestinal peptide

Nitric oxide

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5
Q

What effect does the sympathetic system have on the bronchial smooth muscle?

A

Dilation of smooth muscle - Activated by Beta 2 receptors.
Decreased mucus secretion by Beta 2 adrenoceptors
Increased mucociliary clearance - mediated by Beta 2 adrenoceptors

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6
Q

What are the pathological changes associated with chronic asthma?

A
Increased mass of smooth muscle (Hyperplasia and hypertrophy) - narrowing the airways
Basement membrane thickening 
Hyperresponsiveness 
Colagen disposition 
Accumulation of interstitial fluid 
Increased secretion of mucus
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7
Q

How does hyper-responsiveness and hyper-reactivity of the airways occur in asthma?

A

Exposure of C fibres (Irritant receptors)

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8
Q

How can the hyper-responsiveness of the airways be tested?

A

Provocation tests with inhaled bronchoconstrictors (Spasmogens)
e.g. histamine or methacholine

The less drug needed to induce hyper-reactivity the more severe the asthma

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9
Q

Explain the phases of an asthma attack?

A

Early phase - caused by the bronchospasm in relation to a stimulation
Late phase - Inflammatory response

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10
Q

Explain the development of allergic asthma?

A

Presentation of antigen
Phagocytosis of antigen by dendritic cells
T -helper 2 cells produce IL 4 to activate B cells
B cells become plasma cells and secrete IgE
T helper 2 cells produce IL 5 and activate Eosinophils
Mast cells activated by IL4 and IL 13 from TH2
Dendritic cell presents antigen to Mast cell - causes degranulation and release of Histamines and Leukotrienes (LTC4 and LTD4)

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11
Q

Release of what factors promote inflammation in the airways?

A

LTC4

Platelet activating factor (PAF)

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12
Q

What are the two different types of drugs in Asthma?

A

Relievers:
SABA - salbutamol
LABA - salmeterol
CysLT1 antagonists - Montelukast

Controllers:

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13
Q

Describe how Beta 2 agonists work? (e.g. salbutamol/salmeterol)

A

Antagonists to all spasmogens
Acton the Beta 2 receptor
Causes phosporylation of Protein Kinase A - inhibits enzyme
Prevents MLCK causing contraction

Increase mucus clearance and decrease release from Mast cells and Neutrophils
Increase cGMP - promotes broncho dilation
Help with nocturnal symptoms

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14
Q

What are LABA’s useful for (salmeterol) ?

A

Nocturnal asthma

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15
Q

What type of medications are contraindicated in asthma?

A

Beta blockers

ACE inhibitors

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16
Q

How do cysteinyl leukotrienes receptor antagonists cause bronchodilation?

A

Antagonise competitvely on the CystLT1 receptor on Mast cells.
e.g. Montelukast/Zafirlukast
This is used as an add on therapy for mild/persistent asthma and Exercise induced asthma

17
Q

What are the effects of Xanthines?

A

e.g. Theophylline and Aminophylline

Combine bronchodilator and anti-inflammatory actions
Inhibits release from mast cells
Increases mucus clearance

18
Q

What are the side effects of Beta 2 agonists?

A

Tachycardia
Tremor
Anxiety

19
Q

What are the two types of asthma ?

A

Extrinsic asthma - trigger factor known

Intrinsic asthma - no known trigger

20
Q

What is the histopathology of inflammation in asthma?

A

Epithelial detached

Disordered cells

21
Q

What is the clinical syndrome of asthma?

A

Episodic symptoms
Diurnal variability
Associated atopy
Wheeze

22
Q

How is asthma diagnosed?

A
Reduced forced expiratory ratio (<75%) 
Provocation testings (with exercise/histamine)
23
Q

What are two types of steroids the adrenal gland prodces?

A

Mineralocorticoids - e.g. aldosterone. Regulates salt and water
Glucocorticoids - e.g. cortisol. Reduce inflammation

24
Q

What are the effects of inhaled steroids and how do they work?

A

e.g. Beclomethosone

Steroids are lipophilic molecules and they enter the cells by diffusion of the plasma membrane
Steroid combines with GR-alpha
Transports to the nucleus
Combines with the Glucocorticoid response elements in the promoter regions (GRE)
Switch on or switch off specific genes

Reduce Inflammation
Decrease the formation of TH 2 cells
Reduces Interleukin cytokines
Reduce the recruitment of inflammatory cells

25
What are the side effects of steroids in the oropharynx?
Dysphonia - hoarse and weak voice | Oropharyngeal candidiasis
26
What effects do cromolins have and who are they usefull for?
They are Mast cell stabilisers e.g. sodium cromoglicate Weak anti-inflammatory effect Decrease the sensitivity with irritant receptors with sensory C fibres Most effective in young children
27
What are the effects of monoclonal antibodies in asthma and how do they work?
Monoclonal antibodies direct against IgE (e.g. Omalizumab) Binds the IgE via the FC region to prevent attached of FC epsilon receptors on Inflammatory cells
28
What is fexofenadine and what is it used for?
Useful for seasonal asthma | Anti-histamine
29
What are features of a severe asthma attack?
Peak flow < 50 Tachycardia > 110 Tachyponea Cannot finish sentences
30
What type of spirometry does asthma show?
Obstructive spirometry
31
What is the treatment for acute asthma?
1. Oxygen - high flow 2. Bronchodilators (Nebulise with Oxygen) 3. Nebulised Ipratropium 4. IV bronchodilators 5. Steroids - IV Prednisolone/ IV hydrocortisone 6. Magnesium 7. Aminophylline 8. CXR
32
What are precipitate an asthma attack?
Exercise Beta blockers Ibuprofen
33
What treatment can be given if an allergenic trigger is found for the asthma?
H1 receptors antagonists
34
What is the function of the M1, M2, M3 receptor?
M1 - enhance the cholinergic response M2 - inhibit ACh release M3 - Mediate bronchoconstriciton and Muscus secretion Part of Parasympathetic system
35
What anticholinergics are used in asthma?
SAMA (short acting Muscarnic antagonist) - Ipratropium | LAMA (long acting) - Tiotropium
36
What are the features of a fatal asthma attack?
Peak flow < 33% Cyanosis Silent chest PaCO2 >6