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Year 2 Applied Pharmacology > Asthma Drugs > Flashcards

Asthma Drugs Flashcards

1
Q

What is the difference between acute and chronic asthma?

A

Chronic is recurrent attack of reversible airway obstruction of air flow - can be controlled. Acute is severe asthma that can be fatal and is not easily reversed with drugs.

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2
Q

What are the features of asthma?

A

Characterised by: inflammation in the airways and hyper-reactivity to bronchioles to: irritant chemicals, cold air and stimulant drugs. Also - bronchoconstriction and mucus secretion.

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3
Q

What is the aim of drug treatment in asthma?

A

To reduce inflammation, prevent bronchoconstriction and restore airways calibre to normal.

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4
Q

What are the different types of stimuli that can trigger an asthma attack?

A

Exercise, respiratory infection, atmospheric pollutants. Allergens such as pollen, dust mite proteins and animal dander.

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5
Q

How does asthma develop?

A

Allergen activates B cells. IgE is made and presents onto mast cell. Presentation of antigen onto mast cells causes inflammatory cell recruitment and bronchoconstriction.

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6
Q

What are the 2 different phases of an asthma attack?

A

Early phase: bronchospasm

Late phase: inflammation

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7
Q

What stages are involved in the early phase of attack?

A

Bronchial muscle contracts. Mast cells release spasmogens: histamine, leukotrienes and prostaglandin D2. Mast cells also release inflammatory mediators: interleukins 4, 5 and 13, macrophage inflammatory protein, tumour necrosis factors and chemokines.

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8
Q

What stages are involved in the late phase of attack?

A

Progressing inflammatory reaction - lymphocytes and eosinophils invade. Agents from inflammatory cells cause: damage and loss of bronchial epithelium, smooth muscle hypertrophy and hyperplasia, hyper-reactivity to irritant stimuli.

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9
Q

What are the actions of bronchodilators?

A

Dilate bronchioles and increase air flow to alveoli. Relax smooth muscle cells around walls of bronchioles.

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10
Q

What are the different types of bronchodilators?

A

B2 adrenergic receptor agonists. Theophylline. Muscarinic receptor antagonists. Leukotriene receptor antagonists.

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11
Q

What is the action of B2 adrenergic receptor agonists?

A

Direct action on B2 adrenoceptors on bronciole smooth muscle to relax muscle. Also: inhibit mediator release from mast cells and monocytes and may act on cilia to increase mucus clearance.

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12
Q

How are the B2 adrenoceptors activated?

A

B2 receptor attaches to cell membrane, ATP causes inactive protein kinase A to be activated which causes protein phosphorylation and then muscle relaxation.

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13
Q

What are the short acting B2 agonists called?

A

Salbutamol and Terbutaline. Max effect within 30 mins, lasts 4-6 hours.

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14
Q

What is the longer acting B2 agonist called?

A

Salmeterol - 12 hours.

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15
Q

How are B2 agonists administered?

A

By inhalation

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16
Q

What are the unwanted effects of B2 agonists?

A

Most common is tremor. Some tolerance may develop.

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17
Q

What is Theophylline?

A

Formed from xanthine (constituent of coffee and tea). Mechanism unclear but it is a Phosphodiesterase inhibitor (PDE).

18
Q

When is Theophylline used?

A

Second line drug - sustained release tablet. Used with steroid when asthma response to B2 agonist inadequate. Given IV in acute severe asthma.

19
Q

What are the side effects of Theophylline?

A

Tremor/Sleep disturbance. Stimulates heart, vasodilation. Anorexia, N&V.

20
Q

What is the name of the main muscarinic receptor antagonist?

A

Ipratropium - lasts 3-5 hours. Given by inhalation.

21
Q

What are the actions of muscarinic antagonists?

A

Relax bronchial smooth muscle - bronchodilation. Inhibit elevated mucus secretion. Block action of acetylchloine at muscarinic receptors.

22
Q

What happens in the muscarinic system in the normal airways?

A

Low levels of Ach released from cholinergic nerves in the airways: few muscarinic receptors activated, smooth muscle relaxed, airways open.

23
Q

What happens in the muscarinic system in ASTHMA?

A

Evidence for increased Ach release: muscarinic receptors activated, smooth muscle contracted, narrowed airways.

24
Q

What are the 2 types of Leukotriene receptor antagonists?

A

Montelucast

Zafirlukast

25
Q

Why are leukotriene antagonists prescribed?

A

Prevent exercise-induced a d aspirin sensitive asthma. Action additive with B2 agonists. Main use as add on for uncontrolled, mild-moderate asthma.

26
Q

What do leukotrienes do?

A

Cause bronchoconstriction and increase vascular permeability.

27
Q

What are the actions of leukotriene antagonists?

A

Act at leukotriene receptors on bronchial smooth muscle cells. Prevent actions of LTC4 and LTD4 (these are bronchial spasmogens and stimulate mucus secretion).

28
Q

What are the side effects of leukotriene antagonists?

A

Headache and GI disturbance.

29
Q

What are the main type of anti-inflammatory drugs used in asthma?

A

Glucocorticoids - beclometasone, budeonside, fluticasone propionate, prednisolone or hydrocortisone.

30
Q

What are the actions of glucocorticoids?

A

Reduce production of cytokines, spasmogens and leucocyte chemotaxins. Therefore reduce bronchospasm and recruitment of inflammatory cells.

31
Q

What is the mechanism of glucocorticoid action?

A

Enter cells, bind to intracellular receptors in cytoplasm, receptor complex moves to nucleus, binds to DNA in nucleus, alters gene transcription.

32
Q

What are the side effects of glucocorticoids?

A

Oral thrush and dysphonia. serious - adrenal suppression.

33
Q

What does cromoglicate do?

A

Can reduce both early and late phase responses. Reduces bronchial hyper-reactivity. Effective in asthma caused bu antigens and irritants.

34
Q

What is the mechanism of cromoglicate?

A

Mast cell stabiliser may reduce neuronal reflexes, inhibit release of T cell cytokines, affect inflammatory cells.

35
Q

What are the side effects of cromoglicate?

A

Irritation of upper resp tract. Hypersensitivity reactions supported.

36
Q

What is the main biologic agent used in asthma?

A

Omalizumab - monoclonal antibody. S/C injection every 2-3 weeks.

37
Q

What is the mechanism of Omalizumab?

A

Binds to human IgE and inhibits binding of IgE to IgE receptor on the surface of mast cells. This stops bronchoconstriction.

38
Q

What are the side effects of omalizumab?

A

Anaphylaxis and rare malignancies.

39
Q

What is prescribed for a person with mild asthma and rare attacks?

A

Inhaled B2 agonist when required.

40
Q

What is prescribed for a person with mild asthma and more frequent attacks?

A

Glucocorticoid and B2 agonist.

41
Q

What is prescribed for a person with moderate to severe asthma?

A

Drug combination preferred: B2 agonist with glucocorticoid in combined inhaler.

Year 2 Applied Pharmacology (12 decks)

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