Asthma

Question 0

Asthma epidemiology

Answer 0

5-10% of population Increasing Can be fatal

Question 1

Asthma definitions

Answer 1

Defined as reversible increases in airway resistance, involving bronchi construction and inflammation.

Question 2

Asthma spirometry characterisations

Answer 2

Reversible decreases in the FEV1:FVC (less than 70-80% suggests increased airway resistance ). Variations in PEF, which improve with a beta-2 agonist (+morning dipping).

Question 3

Control of bronchial calibre - PARASYMPATHETIC (3)

Answer 3

ACh acts on M3 (muscarinic) receptors Bronchoconstriction Increase mucus

Question 4

Control of bronchial calibre - SYMPATHETIC (3)

Answer 4

Circulating adrenaline acting on beta-2 adrenoceptors on bronchial smooth muscle to cause relaxation. Plus sympathetic fibres releasing NA acting on beta-2 adrenoceptors on parasympathetic ganglia to inhibit transmission. Beta-2 adrenoceptors also on mucus glands to inhibit secretion.

Question 5

Asthmatic attack, provoking factors (5)

Answer 5

Allergens Cold air Viral infections Smoking Exercise

Question 6

Asthmatic attacks, phases

Answer 6

May be characterised by early (immediate) phase followed by late phase. Sometimes just one or the other.

Question 7

Asthma - Clinical features

Answer 7

Wheezing Breathlessness Tight chest Cough (worse at night/ exercise) Decreases in FEV1 (reversed by beta-2 agonist)

Question 8

Asthmatic attack, method of action

Answer 8

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Question 9

Asthmatic attack, graph

Answer 9

Pic

Question 10

Asthma, Spasmogens

Answer 10

Histamine Prostaglandin, D2 Leukotrienes (C4 & D4) Platelet activating factor (PAF) See pic

Question 11

Asthma, Chemotaxins & role

Answer 11

Leukotriene B4, PAF Lead to late phase Attract leukocytes, esp eosinophils and mononuclear cells Leading to inflammation and airway hyper-reactivity

Question 12

Pharmacological management of Asthma - Principles (2)

Answer 12

BRONCHODILATORS Reverse bronchospasm (early phase) Rapid relief (“relievers”) PREVENTION Used to prevent an attack May be anti-inflammatory “Preventers”

Question 13

Beta-2 adrenoceptor agonists - examples & action

Answer 13

E.g. Salbutamol (ventolin) First choice agents Increased FEV1 Act on beta-2 adrenoceptors on smooth muscle to increase cAMP

Question 14

Salbutamol Action

Answer 14

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Question 15

Beta-2 agonist, use

Answer 15

Given by inhalation Prolonged use may lead to receptor down-regulation

Question 16

LABA - Long acting beta agonists, example & use

Answer 16

E.g. salmeterol Given for long term prevention and long term control (overnight) Do not relieve an attack Used in addition to other agents

Question 17

Xanthines, example, action & use (5)

Answer 17

E.g. Theophylline Bronchodilators 2nd line, not as good as beta-2 agonists Phosphodiesterase inhibitors Oral (or IV aminophylline in an emergency) Narrow T.I. - plasma conc is often monitored Theophylline has range of interactions Largely removed by hepatic metabolism May cause hypokalaemia esp when used with beta-2 agonists

Question 18

Theophylline action

Answer 18

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Question 19

Muscarinic receptor antagonists - example (2) & action (3)

Answer 19

E.g. Ipratropium - short acting (tds) Tiotropium - long acting (od) Block parasympathetic bronchoconstriction Inhalation - prevents anti muscarinic side effects Limited/ little value in asthma, but widely used in COPD

Question 20

Muscarinic receptor antagonists action

Answer 20

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Question 21

Anti Inflammatory agents. Use and action

Answer 21

PREVENTATIVE- do not reverse an attack Corticosteroids E.g. Beclometasone (becotide, inhalation) or prednisolone (oral ) Anti- inflammatory by activation of intracellular receptors, leading to altered gene transcription (decrease cytokine production) and production of lipocortin

Question 22

Anti inflammatory agents in asthma. MOA

Answer 22

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Question 23

Lipocortin action in asthma

Answer 23

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Question 24

Steroid in asthma. Use

Answer 24

Given with beta-2 agonists, reduce receptor down regulation

Question 25

Asthma steroids, side effects

Answer 25

Inhalation - throat infections (Immunosuppression –> superficial fungal infections) - hoarseness (Laryngeal myopathy) - counsel rinsing mouth out after inhalation, use a spacer device to help Oral administration leads to widespread side effects - adrenal suppression - diabetes - osteoporosis - immunosuppression

Question 26

Asthma, Cromones use

Answer 26

Sodium cromoglicate Preventative (early and late) Poorly effective Inhalation Uncertain action - may reduce reflexes of sensory nerves - reduce release of PAF (platelet activating factor) and cytokines

Question 27

Asthma. LTRAs example and use

Answer 27

Leukotriene receptor antagonists E.g. Monteleukast Recent introduction and now have an increased role as add-on therapy Preventative AND bronchodilator Antagonise actions of LTs

Question 28

BTS Stepped Care Guidelines for adults

Answer 28

Regular review Step up/ down as appropriate Pic

Question 29

Managing acute asthma

Answer 29

Consult BNF/BTS Depending on severity, may involve: Oxygen (40-60%) Nebulised (via spacer) beta-2-adrenoceptor agonist (e.g. Salbutamol or terbutaline) Oral prednisolone or IV hydrocortisone In a life threatening attack, following must be added Nebuliser ipratropium (relives bronchospasm, anticholinergic) Subcutaneous beta-2-adrenoceptor agonist IV aminophylline, provided the patient is not already receiving a xanthine Magnesium sulphate IV also used unlicensed

Question 30

Asthma and NSAIDs

Answer 30

Non-steroidal anti-inflammatory drugs (NSAIDs) e.g. aspirin, ibuprofen may provoke asthma by increasing Leukotriene production.

Membran lipid –> AA –> — prostaglanins / ++ leukotrienes

Question 31

Asthma and beta blockers

Answer 31

• These are contraindicated in asthma (and used with caution in COPD) as they block bronchial b2 adrenoceptors and may cause bronchospasm
• This even applies to ‘selective’ b1-antagonists