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Clinical Pharmacology > 12) Pharmacology of Asthma > Flashcards

12) Pharmacology of Asthma Flashcards

1
Q

What are the features of asthma?

A

Mucosal oedema
Bronchoconstriction
Mucus plugging
Eventually, airway remodelling and bronchial hyperresponsiveness

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2
Q

What is the early/immediate phase of asthma?

A

Allergen binds to IgE on mast cells causing release of histamine = bronchospasm

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3
Q

What is the late phase of asthma?

A

Leucocytes migrate to area in an immune system response

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4
Q

How can asthma vary from person to person?

A

Eosinophilic v neutrophilic inflammation
Symptoms
Triggers
Treatment response

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5
Q

Describe the autonomic modulation of the airway:

A

Sympathetic: bronchodilation via beta 2
Parasympathetic: bronchoconstriction via M3

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6
Q

Describe the stepwise approach to treating asthma:

A

Step up and down with treatment based on symptoms and response to treatment

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7
Q

What are the goals in controlling asthma?

A

Minimal symptoms
Minimal need for reliever
No exacerbations
No limitation on physical activity

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8
Q

Describe step 1 of the treatment for asthma, including what drugs are used:

A

Mild intermittent asthma

Uses short acting B2 agonists (salbutamol) for symptom relief as required

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9
Q

What is the mechanism of action of beta 2 agonist?

A

Bind to B2 receptor (Gs) -> increased cAMP -> inhibition of MLCK -> relaxation of SM

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10
Q

Describe the PK and PD of beta 2 agonists:

A

Majoirty of drug deposited in upper airway and/or swallowed to be removed by liver
Variation in half life for different onsets and durations

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11
Q

What are some side effects of beta 2 agonists?

A

Tremor, palpitations, tachycardia

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12
Q

What is drug is given in step 2 and when is it started?

A

Inhaled corticosteroids

If using Beta agonist: 3 or more times a week, or waking once or more a week

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13
Q

What is the mechanism of action of corticosteroids?

A

Suppress pro-inflammatory transcription

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14
Q

How are corticosteroids modified for treatment of asthma?

A

Given lipophilic side chain - increase uptake and rapid inactivation following systemic absoprtion

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15
Q

Which patients have a better treatment response to inhaled steroids?

A

Eosinophilic asthma

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16
Q

What drugs is given in step 3 of the treatment approach?

A

Long acting beta 2 agonist (salmeterol or formoterol)

17
Q

What alternative drugs can be given in step 3/4?

A

High dose ICS
Leukotriene receptor antagonists
Theophylline
Tiotropium

18
Q

What is the effect of leukotriene receptor antagonists?

A

Block the effects of LTC4 - prevent bronchoconstriction, mucus secretion and mucosal oedema

19
Q

What are the side effects of leukotriene receptor antagonists?

A

Rare but: angioedema, dry mouth, fever

20
Q

What effect do methylxanthines (e.g. theophylline) have on the body?

A

Antagonise adenosine receptors and inhibit phosphodiesterase

21
Q

What are the side effects of methylxanthines?

A

Nausea, headache, reflux, psychomotor agitation, tachycardia

22
Q

What are potential drug interactions with methylxanthines?

A

Erythromycin, ciprofloxacin

23
Q

Name some long acting anticholinergics:

A

Ipratropium, tiotropium

24
Q

What is the mechanism of action of long acting anticholinergics?

A

Inhibit bronchoconstriction and mucus secretion at M3 receptor

25
Q

What are some side effects of long acting anticholinergics?

A

Dry mouth, urinary retention, glaucoma

26
Q

What drugs can be used in step 5?

A

Oral steroids, biological therapies

27
Q

What is the effect of anti-IgEs (omalizumab)?

A

Reduces exacerbation rates, prevents IgE binding to receptors so no cross linking of mast cells

28
Q

What is the effect of anti-IL5 (mepolizumab)?

A

Reduces peripheral blood and airway eosinophil numbers, reducing exacerbation

29
Q

If a drug has 10 micron particles where will it be deposited?

A

Mouth and oropharynx

30
Q

If a drug has 1-5 micron particles where will it be deposited?

A

Small airways

31
Q

If a drug has 0.5 micron particles where will it be deposited?

A

Alveoli

32
Q

How is severe acute asthma defined?

A

Unable to complete sentences
RR >= 25
Pulse >110
Peak flow 33-50% predicted

33
Q

How is life threatening acute asthma defined?

A

As in severe plus:
O2<92%, pO2<8kPa, pCO2>4.5kPa
Silent chest, cyanosis, hypotension, bradycardia

34
Q

What is the treatment for an asthma attack?

A

High flow O2
Nebulised salbutamol
Oral prednisolone (40mg)
If no improvement: nebulised ipratropium, IV aminophylline

Clinical Pharmacology (24 decks)

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