Week 5 - Asthma Flashcards by Annabel Cookson

What are the main first line drugs of asthma?

Glucocorticoids (steroids)

B2 adrenergic agonists

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Where is the site of bronchodilator action?

Smooth muscle in the bronchiole walls

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Name the types of bronchodilator

B2 adrenergic receptor agonists

Theophylline

Muscarinic receptor antagonists

Leukotriene receptor antagonists

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What is the mechanism of action of B2 adrenergic receptor agonists?

Direct action on B2 adrenoreceptors on bronchiole smooth muscle to relax muscle

Also:
Inhibit mediator release from mast cells and monocytes

May act on cilia to increase mucus clearance

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Name the shorter acting B2 adrenergic receptor agonists and what their duration of action is

Salbutamol
Terbutaline

max effect within 30 mins
lasts 4-6 hours
used “as needed” to control symptoms

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Name the longer acting B2 adrenergic receptor agonists and what their duration of action is

Salmeterol

duration of action = 12 hours
2X daily in patients not controlled with glucocorticoids

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How are B2 agonists administered and why?

Inhalation

to target action in lung
minimise systemic effects

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What are the unwanted effects of B2 agonists?

most common = tremor (activate B2 receptors in skeletal muscle)
result from absorption in to systemic circulation

-some tolerance to them may be developed (receptors get desensitised) - prevent by use of a glucocorticoid

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What is the mechanism of action of theophylline?

Phosphodiesterase (PDE) inhibitor

-mechanism still unclear

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How is theophylline administered?

Orally (sustained release tablet)

IV in acute severe asthma (can’t inhale anything far enough)

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When is theophylline used?

Second line drug

-used with steroid when asthma response to B2 agonist is inadequate

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What are the side effects of theophylline?

CNS - stimulant (tremor, sleep disturbance)
CV (stimulates heart, vasodilation)
GI tract (anorexia, N+V)

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What are the actions of muscarinic antagonists?

Block action of endogenous acetylcholine at muscarinic receptors

relax bronchial smooth muscle - bronchodilatoion
inhibit elevated mucus secretion in asthma
may increase clearance of bronchial secretions

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What is the main muscarinic receptor antagonist used?

Ipratropium

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When are muscarinic receptor antagonists used?

-adjunct to B2 agonists and steroid when these are insufficient

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How are muscarinic receptor antagonists administered and what is their duration of action?

aerosol inhalation
max effect 30 mins, lasts 3-5 hours
poorly absorbed in to systemic circulation

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What are the side effects of muscarinic receptor antagonists?

Few unwanted effects - safe, well tolerated

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What is the mechanism of action of leukotriene antagonists?

act at cysteinyl-leukotriene receptors on bronchiole smooth muscle cells
prevent actions of LTC4 and LTD4 which are bronchial spasmogens and stimulate mucus secretion

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Name some leukotriene receptor antagonists

Montelukast (1X daily)

Zafirlukast (2X daily)

How are leukotriene receptor antagonists administered?

Orally

What are leukotriene receptor antagonists used for?

prevent exercise induced and aspirin sensitive asthma
action additive with B2 agonists
main use as add on for uncontrolled, mild-moderate asthma

What does aspirin block in asthma?

The cyclooxygenase pathway

Therefore more leukotrienes are produced instead of prostaglandins because the pathway is sent to the right

What are the side effects of leukotriene antagonists?

Headache

GI disturbances

What is the mechanism of action of glucocorticoids?

enter cells
bind to intracellular receptors in cytoplasm - GRa and GRb
receptor complex moves to nucleus
binds to DNA in nucleus
alters gene transcription (repression of IL-3)

What are the actions of glucocorticoids?

Reduce production of - cytokines - spasmogens (LTC4, LTD4) - leukocyte chemotaxins (LTB4, PAF) Therefore reduce: - bronchospasm - recruitment and activation of inflammatory cells

Name some glucocorticoids

Beclometasone diproprionate Budesonide Fluticasone propionate Occasionally prednisolone or hydrocortisone

How are glucocorticoids administered and how long does it take for an effect to take place?

Usually given by inhalation (metered dose inhaler, localises effect in lung) Full effect takes several days to develop

Which glucocorticoids are often given for acute exacerbations?

Hydrocortisone Oral prednisolone

What are the side effects of glucocorticoids?

-uncommon with inhaled steroids -oropharyngeal thrush and dysphonia (Minimised using spacer) - oral/regular large doses -serious effects - e.g. Adrenal suppression - pts carry steroid card

What is the mechanism of action of cromoligate?

Not fully understood -mast cell stabiliser (but not main action)

How is cromoligate administered?

Inhalation - aerosol, nebuliser solution or powder Prophylactic use - prevent both phases of attack - most effective in children - effects may take weeks to develop

What are the side effects of cromoligate?

- irritation of upper respiratory tract | - hypersensitivity reactions reported - rare

What is the drug related to cromoligate?

Nedocromil sodium

Who responds to chromoligate?

Not all asthmatics respond - unpredictable - children respond better than adults

What does cromoligate do?

- can reduce both early and late phase responses - reduce bronchial hyper-reactivity - effective in asthma caused by - antigen, exercise, irritants

What does lipocortin do?

Inhibitor of phospholipase A2 - lose production of leukotrienes - reduced inflammation in tissue

What are biologic agents?

- new development - recombinant DNA-derived humanised IgG1 monoclonal antibody - binds to human IgE, inhibits binding of IgE to IgE receptor on the surface of mast cells and basophils - inhibits IgE mediated cascade of asthma

Name a biologic agent

Omalizumab

How are biologic agents administered?

Sub cut injection every 2-3 weeks - absorbed slowly - peak plasma conc. in 7-8 days

What does the IgE antibody cause?

Inflammatory cell recruitment --> bronchoconstriction

What are the side effects of Omalizumab? (Biologic agent)

Few but can be severe - anaphylaxis - allergic reaction to protein - malignancies (slightly higher rate than normal)

What would be used to treat a mild asthmatic with rare attacks?

Inhaled B2 agonist when required

What would be used to treat a mild asthmatic with frequent attacks?

- glucocorticoid for prophylaxis | - B2 agonist when needed for acute attack

What would be used to treat moderate to severe asthma?

-drug combination preferred - usually B2 agonist with glucocorticoid - a combined inhaler

What are the aims of drug treatment in asthma?

- to reduce inflammation - to prevent bronchoconstriction - to restore airways calibre to normal