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Respiratory Pharmacology Flashcards

1
Q

Give two respiratory disorders which are related to the conducting zone.

A

Asthma

Allergic bronchitis

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2
Q

What type of respiratory disorders are related to the respiratory zone?

A

Chronic obstructive pulmonary diseases

  • Small airways disease
  • Emphysema
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3
Q

What happens in allergic asthma when the allergen is inhaled?

A

Localised immune cells in airways recognise allergen and become activated and release proinflammatory mediators:

  • Histamine
  • Prostaglandins
  • Leukotrienes
  • Cytokines

Released molecules cause:

  • Oedema
  • Mucus secretion
  • Bronchoconstriction/spasm
  • Inflammation
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4
Q

What are the three stages/changes in lung function after exposure to an allergen?

A

Immediate asthmatic response

Delayed/late asthmatic response

Airway/bronchial hyperresponsiveness

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5
Q

Describe the immediate asthmatic response. (2)

A

Decreased lung function within minutes and recover in 15-30 mins

Entirely due to bronchospasm caused by mediators (platelet-activating factor, leukotrienes) released from allergen-triggered mast cells

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6
Q

Describe the delayed asthmatic response.

A

Few hours after initial response (in 50-60% of asthmatics)

Airway narrowing mainly due to mucosal swelling/oedema as a result of inflammatory cells being recruited in response to the immediate response

Partly bronchospasm

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7
Q

Describe the airway hyperresponsiveness stage.

A

Non-allergen stimuli

Combined effects of bronchospasm on an inflamed oedematous airway which is very sensitive to any inhaled irritant

Body tries to heal and alters architecture of lungs = airways hyperplasia

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8
Q

What types of drugs can be used as bronchodilators?

A

β2-agonists

Muscarinic antagonists

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9
Q

What types of anti-inflammatory drugs are there? (5)

A

Glucocorticosteroids

Xanthines

Cromones

Leukotriene antagonists

Anti-IgE

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10
Q

What drugs are used to treat symptoms of asthma?

A

Short-acting β2-agonists/SABAs

Long-acting β2-agonists/LABAs

Theophylline (xanthine)

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11
Q

Give an example of a short-acting β2-agonist.

A

Salbutamol

Terbutaline

Fenoterol

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12
Q

Give an example of a long-acting β2-agonist.

A

Salmeterol

Formoterol

Indacaterol

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13
Q

What is the structure of a β2-agonist based on?

A

Adrenaline and isoprenaline

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14
Q

How can you increase the bioavailability of a β2-agonist?

A

Increase the length of the tail added to the endogenous structure

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15
Q

Give an example of an ultra LABA.

A

Vilanterol

Olodaterol

Carmoterol

Milveterol

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16
Q

Describe the mechanism of a β2-agonist on smooth muscle.

A
  1. Binds β2-adrenoceptors (GPCR) coupled to Gs protein
  2. Increased activity of adenylyl cyclase results in higher levels of cAMP
  3. Protein kinase A activated resulting in myosin light chain kinase phosphorylation
  4. Airway smooth muscle relaxation
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17
Q

What effect do β2-agonists have on mast cells?

A

Inhibit degranulation

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18
Q

What are some of the possible side effects of β2-agonists?

A

Tremor

Increased heart rate

Hypokalaemia

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19
Q

What do muscarinic antagonists do?

A

Prevent smooth muscle contraction and mucus secretion

Acts on M3 receptors (smooth muscle)

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20
Q

What are two muscarinic antagonists and how long do their effects last?

A

Ipratropium bromide - 6 hours

Tiotropium bromide - 24 hours

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21
Q

What are the possible side effects of muscarinic antagonists?

A

Dry mouth = ulcers and cannot swallow/eat

Urinary retention

Constipation

Acute angle glaucoma

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22
Q

What is the structure of glucocorticosteroid drugs based on?

A

Endogenous steroids

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23
Q

How do glucocorticoid steroids work?

A
  1. Enters cells by simple diffusion
  2. Associates with a nuclear/steroid receptor in cytoplasm (receptor is conjugated with a chaperonin)
  3. Chaperonin dissociates and complex moves into nucleus
  4. Binds to DNA to alter transcription
24
Q

Give an example of a chaperonin protein.

A

Heat-shock protein 90

25
What do glucocorticosteroids generally do? (3)
Transactivation of annexin and β2-adrenoceptors Inhibits mitogen kinase phosphatase 1 Transrepression of NFkB and AP-1
26
What is another name for annexin?
Lipocortin
27
What is annexin? (2)
Resolvin protein which finishes the inflammatory response (anti-inflammatory) Inhibits PLA2
28
What is mitogen kinase phosphatase 1?
Pro-inflammatory enzyme
29
What are NFkB and AP-1?
Pro-inflammatory transcription factors which start de novo synthesis of pro-inflammatory mediators
30
Which inflammatory mediators are upregulated by NFkB and AP-1 and what do they do? (4)
Cytokines - activate immune cells Chemokines - cell motility Adhesion molecules - expressed on inflammatory cells and endothelium Pro-inflammatory enzymes - COX2, NOS
31
What are the actions of glucocorticosteroids in asthma? (4)
Inhibition of leukotriene and cytokine synthesis to stop inflammatory response and recruitment of cells Anti-oedema to increase air flow Increase β-adrenoceptor function to enhance bronchodilation (by other drugs) Decrease airway hyperresponsiveness
32
What are possible side effects of inhaled glucocorticosteroids? (2)
Oral candidiasis Hoarseness, cough, voice problems
33
What are possible side effects of oral/prolonged high dose glucocorticosteroids? (4)
Growth retardation, easy bruising Suppression of hypothalamic-pituitary axis Osteoporosis, water retention, diabetes Hypertension, weight gain, ocular hypertension
34
Why can stopping steroid treatment be dangerous?
Inflammation build up and a trigger could cause death
35
Which enzyme catalyses the formation of arachidonic acid from membrane phospholipids?
Phospholipase A2 (PLA2)
36
What does zileuton do?
Direct inhibitor of 5-lipoxygenase Prevents formation of leukotrienes
37
What type of drug is montelukast?
Cysteinyl leukotriene receptor antagonist
38
What do leukotrienes do? (4)
Cause: - Bronchoconstriction - Oedema - Cellular infiltration - Mucus production
39
What are leukotriene antagonists and 5-LO inhibitors best used to treat?
Severe asthma Aspirin-sensitive or exercise-induced asthma
40
What are possible side effects of leukotriene antagonists and 5-LO inhibitors? (2)
Headache GI disturbance (zileuton - hepatotoxicity and dyspepsia)
41
Give an example of a xanthine. (2)
Theophylline Aminophylline
42
How do xanthines work?
Inhibit phosphodiesterase Increased levels of cAMP More PKA activated and myosin light chain kinase phosphorylation Relaxation of airway smooth muscle
43
What common substance has a similar structure to theophylline?
Caffeine
44
Why must patients taking xanthine be monitored?
Narrow therapeutic window (10-20ug/ml) = watch out for side effects Numerous drug interactions can affect plasma levels
45
How does smoking affect xanthines?
Promotes plasma clearance of xanthines so decreases bioavailability
46
Give an example of a cromone.
Sodium cromoglicate Nedocromil sodium
47
What do cromones do?
Reduce inflammatory cell activation and recruitment
48
What are the possible side effects of xanthines?
Nausea, vomiting Arrhythmias, hypotension Hypokalaemia Seizures
49
How many times per day do you typically need to take leukotriene antagonists?
Once per day
50
What are the cons of cromones? (2)
Very short half-life Not as effective as glucocorticosteroids
51
How are cromones administered?
Inhaled
52
How are leukotriene antagonists administered?
Orally
53
How is anti-IgE administered?
Subcutaneous injection
54
What is IgE? (4)
Part of adaptive immune response Recognises allergens Produced by B-cells and sit on antigen-presenting cells with high affinity receptors Cause release of mediators when activated
55
Give an example of anti-IgE.
Omalizumab
56
How does omalizumab work? (2)
Sequesters IgE out of circulation so it does not bind high affinity receptors on antigen-presenting cells Decreases expression of high affinity receptors

BMS12 (7 decks)

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